The document outlines various aspects of malaria, highlighting its significant global impact, particularly on children under five, with a high number of cases and deaths reported. It details the transmission, life cycle, pathogenesis, clinical manifestations, and diagnostic criteria of malaria, emphasizing the critical nature of the disease caused by different Plasmodium species, especially P. falciparum. Additionally, the text mentions complications related to malaria during pregnancy and the importance of recognizing symptoms for timely diagnosis and treatment.

1. Infectious disease
Infectious disease

2. Out line
 Malaria
 Typhoid
 Schistosomiasis
 Leshmaniasis
 Tuberculosis
 Pediatrics' HIV
 Malaria
 Typhoid
 Schistosomiasis
 Leshmaniasis
 Tuberculosis
 Pediatrics' HIV

3. Malaria
 Malaria is an acute febrile illness characterized by
paroxysms of fever, chills, sweats, fatigue, anemia, and
splenomegaly
 Despite 37% reduction in malaria incidence and 60%
reduction in malaria mortality, malaria remains one of
the leading causes of morbidity and mortality
worldwide, with an estimated 214 million cases and
438,000 deaths in 2015.
 Malaria is an acute febrile illness characterized by
paroxysms of fever, chills, sweats, fatigue, anemia, and
splenomegaly
 Despite 37% reduction in malaria incidence and 60%
reduction in malaria mortality, malaria remains one of
the leading causes of morbidity and mortality
worldwide, with an estimated 214 million cases and
438,000 deaths in 2015.

4.  Malarial deaths in areas of high malaria transmission
occur primarily in children <5 yr of age, but in areas of
low transmission, a large percentage of deaths may
occur in older children and adults.

5. Etiology
 Plasmodium protozoa
 Five species:
 P. falciparum
 P. malariae
 P. ovale
 P. vivax
 P. knowlesi
 Plasmodium protozoa
 Five species:
 P. falciparum
 P. malariae
 P. ovale
 P. vivax
 P. knowlesi

6. Transmission
 Transmission:
 female Anopheles mosquitoes
 Blood transfusion
 Congenital.
 Transmission:
 female Anopheles mosquitoes
 Blood transfusion
 Congenital.

7. Epidemiology
 Malaria is a major worldwide problem, occurring in 95
countries that comprise
 approximately half the world's population
 The principal areas of transmission are Africa, Asia,
and South America. P. falciparum and P. malariae are
found in most malarious areas
 children <5 yr old were more likely to develop severe
malaria than were persons ≥5 yr old
 Malaria is a major worldwide problem, occurring in 95
countries that comprise
 approximately half the world's population
 The principal areas of transmission are Africa, Asia,
and South America. P. falciparum and P. malariae are
found in most malarious areas
 children <5 yr old were more likely to develop severe
malaria than were persons ≥5 yr old

8. Pathogenesis
 Plasmodium species exist in a variety of forms and
have a complex life cycle that enables them to survive
in different cellular environments in the human host
(asexual phase) and the mosquito (sexual phase)
 Asexual phase has 2-step process in humans, with the
1st phase in hepatic cells (exoerythrocytic phase) and
the 2nd phase in the RBCs (erythrocytic phase).
 Plasmodium species exist in a variety of forms and
have a complex life cycle that enables them to survive
in different cellular environments in the human host
(asexual phase) and the mosquito (sexual phase)
 Asexual phase has 2-step process in humans, with the
1st phase in hepatic cells (exoerythrocytic phase) and
the 2nd phase in the RBCs (erythrocytic phase).

9. Life Cycile

10.  Four important pathologic events:
 Fever occurs when erythrocytes rupture and release
merozoites.
 Anemia is caused by hemolysis, sequestration of
erythrocytes in the spleen and other organs, and bone
marrow suppression.
 Immunopathologic events- excessive production of
proinflammatory cytokines (TNF); polyclonal
activation; and immunosuppression.
 Tissue anoxia- Cytoadherence
 Four important pathologic events:
 Fever occurs when erythrocytes rupture and release
merozoites.
 Anemia is caused by hemolysis, sequestration of
erythrocytes in the spleen and other organs, and bone
marrow suppression.
 Immunopathologic events- excessive production of
proinflammatory cytokines (TNF); polyclonal
activation; and immunosuppression.
 Tissue anoxia- Cytoadherence

11.  Physiology and pathogenesis in malaria differ according to
species.
 Infection with all species leads to fever , caused by the host
immune response when erythrocytes rupture and release
merozoites into the circulation, and anemia , caused by
hemolysis and bone marrow suppression.
 Severe malaria is more common in P. falciparum because of
several process, including
 higher-density parasitemia, which may lead to excessive
production of proinflammatory cytokines;
 cytoadherence of P. falciparum -infected erythrocytes to the
vascular endothelium; and polyclonal activation, resulting in
both hypergammaglobulinemia and the formation of immune
complexes
 Physiology and pathogenesis in malaria differ according to
species.
 Infection with all species leads to fever , caused by the host
immune response when erythrocytes rupture and release
merozoites into the circulation, and anemia , caused by
hemolysis and bone marrow suppression.
 Severe malaria is more common in P. falciparum because of
several process, including
 higher-density parasitemia, which may lead to excessive
production of proinflammatory cytokines;
 cytoadherence of P. falciparum -infected erythrocytes to the
vascular endothelium; and polyclonal activation, resulting in
both hypergammaglobulinemia and the formation of immune
complexes

12.  Cytoadherence of infected erythrocytes to vascular
endothelium can lead to obstruction of blood flow and
capillary damage, with resultant vascular leakage of
blood, protein, and fluid and tissue anoxia.
 Parasite anaerobic metabolism may also lead to
hypoglycemia and metabolic acidosis.
 The cumulative effects of these pathologic processes
may lead to cerebral, cardiac, pulmonary, renal,and
hepatic failure.
 Cytoadherence of infected erythrocytes to vascular
endothelium can lead to obstruction of blood flow and
capillary damage, with resultant vascular leakage of
blood, protein, and fluid and tissue anoxia.
 Parasite anaerobic metabolism may also lead to
hypoglycemia and metabolic acidosis.
 The cumulative effects of these pathologic processes
may lead to cerebral, cardiac, pulmonary, renal,and
hepatic failure.

13.  Repeated episodes of infection occur because the
parasite has developed a number of immune-evasive
strategies,
 - intracellular replication,
 -vascular cytoadherence
 - rapid antigenic variation, and
 -alteration of the host immune system resulting in
partial immune suppression
 Repeated episodes of infection occur because the
parasite has developed a number of immune-evasive
strategies,
 - intracellular replication,
 -vascular cytoadherence
 - rapid antigenic variation, and
 -alteration of the host immune system resulting in
partial immune suppression

14.  Natural immune mechanisms that prevent infection
by Plasmodium spp.
 hemoglobin S (sickle erythrocytes) resist malaria
parasite growth,
 erythrocytes lacking Duffy blood group antigen are
resistant to P. vivax
 erythrocytes containing hemoglobin F (fetal
hemoglobin) and ovalocytes are resistant to P.
falciparum
 Natural immune mechanisms that prevent infection
by Plasmodium spp.
 hemoglobin S (sickle erythrocytes) resist malaria
parasite growth,
 erythrocytes lacking Duffy blood group antigen are
resistant to P. vivax
 erythrocytes containing hemoglobin F (fetal
hemoglobin) and ovalocytes are resistant to P.
falciparum

15.  In hyperendemic areas, newborns rarely become ill
with malaria, in part because of passive maternal
antibody and high levels of fetal hemoglobin.
 Children 3 mo to 2-5 yr of age have little specific
immunity to malaria species and therefore suffer
 yearly attacks of debilitating and potentially fatal
disease.
 Immunity is subsequently acquired, and severe cases
of malaria become less common
 In hyperendemic areas, newborns rarely become ill
with malaria, in part because of passive maternal
antibody and high levels of fetal hemoglobin.
 Children 3 mo to 2-5 yr of age have little specific
immunity to malaria species and therefore suffer
 yearly attacks of debilitating and potentially fatal
disease.
 Immunity is subsequently acquired, and severe cases
of malaria become less common

16. Clinical Manifestations
 Incubation period:
 9-14 days for P. falciparum
 12-17 days for P. vivax
 16-18 days for P. ovale
 18-40 days for P. malariae
 The IP can also be prolonged for patients with partial
immunity or incomplete chemoprophylaxis.
 Incubation period:
 9-14 days for P. falciparum
 12-17 days for P. vivax
 16-18 days for P. ovale
 18-40 days for P. malariae
 The IP can also be prolonged for patients with partial
immunity or incomplete chemoprophylaxis.

17.  A prodrome lasting 2-3 days is noted in some patients
before parasites are detected in the blood.
 Prodromal symptoms include headache,fatigue,
anorexia, myalgia, slight fever, and pain in the chest,
abdomen, and joints.
 classic pattern of fevers every other day (P.vivax and P.
ovale ) or every 3rd day (P. malariae ), periodicity is
less apparent with P. falciparum, and mixed infections
and may not be apparent early on in infection
 A prodrome lasting 2-3 days is noted in some patients
before parasites are detected in the blood.
 Prodromal symptoms include headache,fatigue,
anorexia, myalgia, slight fever, and pain in the chest,
abdomen, and joints.
 classic pattern of fevers every other day (P.vivax and P.
ovale ) or every 3rd day (P. malariae ), periodicity is
less apparent with P. falciparum, and mixed infections
and may not be apparent early on in infection

18.  fever (may be low-grade but is often >40°C
[104°F]),headache, drowsiness, anorexia, nausea,
vomiting, and diarrhea.
 Distinctive physical signs may include splenomegaly
(common), hepatomegaly, and pallor as a consequence
of anemia.
 Typical laboratory findings include anemia,
thrombocytopenia, and a normal or low leukocyte
count ,elevated ESR
 fever (may be low-grade but is often >40°C
[104°F]),headache, drowsiness, anorexia, nausea,
vomiting, and diarrhea.
 Distinctive physical signs may include splenomegaly
(common), hepatomegaly, and pallor as a consequence
of anemia.
 Typical laboratory findings include anemia,
thrombocytopenia, and a normal or low leukocyte
count ,elevated ESR

19.  P. falciparum is the most severe form of malaria and is
associated with higherdensity parasitemia > 60% and
a number of complications
 P. ovale, P. vivax, and P. malariae,which usually result
in parasitemias of <2%,
 P. falciparum is the most severe form of malaria and is
associated with higherdensity parasitemia > 60% and
a number of complications
 P. ovale, P. vivax, and P. malariae,which usually result
in parasitemias of <2%,

20. World Health Organization Criteria
for Severe Malaria
 Impaired consciousness
 Prostration
 Respiratory distress
 Multiple seizures
 Jaundice
 Hemoglobinuria
 Abnormal bleeding
 Severe anemia
 Circulatory collapse
 Pulmonary edema
 Impaired consciousness
 Prostration
 Respiratory distress
 Multiple seizures
 Jaundice
 Hemoglobinuria
 Abnormal bleeding
 Severe anemia
 Circulatory collapse
 Pulmonary edema

21.  Lab criteria for severe malaria:
 hypoglycaemia (RBS< 40 mg/dl)
 metabolic acidosis (bicarbonate < 15 mmol/l)
 severe normocytic anaemia (Hb < 5 g/dl)
 haemoglobinuria
 hyperparasitaemia (> 2%/100 000/μl in low intensity
transmission areas or > 5%/250 000/μl in areas of high
stable malaria transmission intensity)
 hyperlactataemia (lactate > 5 mmol/l)
 renal impairment (serum creatinine > 265 μmol/l).
 Lab criteria for severe malaria:
 hypoglycaemia (RBS< 40 mg/dl)
 metabolic acidosis (bicarbonate < 15 mmol/l)
 severe normocytic anaemia (Hb < 5 g/dl)
 haemoglobinuria
 hyperparasitaemia (> 2%/100 000/μl in low intensity
transmission areas or > 5%/250 000/μl in areas of high
stable malaria transmission intensity)
 hyperlactataemia (lactate > 5 mmol/l)
 renal impairment (serum creatinine > 265 μmol/l).

22. 22

23.  Nephrotic syndrome is a rare complication of P.
malariae infection
 Recrudescence after a primary attack may occur from
the survival of erythrocyte forms in the bloodstream
 Relapse is caused by release of merozoites from an
exoerythrocytic source in the liver, which occurs with
P.vivax and P. ovale , or from persistence within the
erythrocyte, which occurs with P. malariae and rarely
with P. falciparum
 Nephrotic syndrome is a rare complication of P.
malariae infection
 Recrudescence after a primary attack may occur from
the survival of erythrocyte forms in the bloodstream
 Relapse is caused by release of merozoites from an
exoerythrocytic source in the liver, which occurs with
P.vivax and P. ovale , or from persistence within the
erythrocyte, which occurs with P. malariae and rarely
with P. falciparum

24.  Congenital malaria is acquired from the mother
prenatally or perinatally
 It usually occurs in the offspring of a nonimmune
mother with P. vivax or P. malariae infection,
 although seen in any of the human malaria species.
 The first sign or symptom typically occurs between 10
and 30 days of age (range: 14 hr to several months of
age). Signs and symptoms include fever,
restlessness,drowsiness, pallor, jaundice, poor feeding,
vomiting, diarrhea, cyanosis, and hepatosplenomegaly
 Congenital malaria is acquired from the mother
prenatally or perinatally
 It usually occurs in the offspring of a nonimmune
mother with P. vivax or P. malariae infection,
 although seen in any of the human malaria species.
 The first sign or symptom typically occurs between 10
and 30 days of age (range: 14 hr to several months of
age). Signs and symptoms include fever,
restlessness,drowsiness, pallor, jaundice, poor feeding,
vomiting, diarrhea, cyanosis, and hepatosplenomegaly

25.  Malaria in pregnancy is a major health problem in
malaria endemic countries, can be severe, and is
associated with adverse outcomes in the fetus or
neonate, including intrauterine growth restriction and
low birth weight
 Malaria in pregnancy is a major health problem in
malaria endemic countries, can be severe, and is
associated with adverse outcomes in the fetus or
neonate, including intrauterine growth restriction and
low birth weight

26. Diagnosis
 Clinical:
 consider malaria on any child with fever or unexplained
systemic illness and has traveled or resided in a malaria-
endemic area.
 Geimsa stain:
 Thick smear- to scan large no. of erythrocytes
 Thin smear- to identify the malaria species
 Immunochromatographic test (rapid tests)
 PCR
 Clinical:
 consider malaria on any child with fever or unexplained
systemic illness and has traveled or resided in a malaria-
endemic area.
 Geimsa stain:
 Thick smear- to scan large no. of erythrocytes
 Thin smear- to identify the malaria species
 Immunochromatographic test (rapid tests)
 PCR

27.  3 negative blood smears to rule out malaria in children
in whom malaria is strongly suspected.
 3 negative blood smears to rule out malaria in children
in whom malaria is strongly suspected.

28. Differential DX
 viral infections- influenza and hepatitis
 Sepsis
 Pneumonia
 Meningitis
 Encephalitis
 Endocarditis
 Gastroenteritis
 Pyelonephritis
 Tuberculosis
 relapsing fever
 typhoid fever
 Hodgkin disease
 collagen vascular disease
 viral infections- influenza and hepatitis
 Sepsis
 Pneumonia
 Meningitis
 Encephalitis
 Endocarditis
 Gastroenteritis
 Pyelonephritis
 Tuberculosis
 relapsing fever
 typhoid fever
 Hodgkin disease
 collagen vascular disease

29. Complications of P.
Falciparum MALARIA
 anemia (hemoglobin level <5 g/dL) is the most
common severe complication of malaria in children
 Cerebral malaria is defined as the presence of coma in
a child with P.falciparum parasitemia and an absence
of other reasons for coma.
 most common in children in areas of midlevel
transmission and in adolescents or adults in areas of
very low transmission. It is less frequently seen in
areas of very high transmission.
 anemia (hemoglobin level <5 g/dL) is the most
common severe complication of malaria in children
 Cerebral malaria is defined as the presence of coma in
a child with P.falciparum parasitemia and an absence
of other reasons for coma.
 most common in children in areas of midlevel
transmission and in adolescents or adults in areas of
very low transmission. It is less frequently seen in
areas of very high transmission.

30.  has a fatality rate of 15–40% and is associated with
long-term cognitive impairment in children. Repeated
seizures are frequent in children with cerebral malaria.
Hypoglycemia is common, but children with true
cerebral malaria fail to arouse from coma even after
receiving a dextrose infusion that normalizes their
glucose level.
 has a fatality rate of 15–40% and is associated with
long-term cognitive impairment in children. Repeated
seizures are frequent in children with cerebral malaria.
Hypoglycemia is common, but children with true
cerebral malaria fail to arouse from coma even after
receiving a dextrose infusion that normalizes their
glucose level.

31.  Physical findings may include high fever, seizures,
muscular twitching, rhythmic movement of the head
or extremities, contracted or unequal pupils, retinal
hemorrhages, hemiplegia,absent or exaggerated deep
tendon reflexes, and a positive Babinski sign.
 Lumbar puncture reveals increased pressure and
mildly increased cerebrospinal fluid protein, typically
with no CSF pleocytosis and a normal CSF glucose.
 Physical findings may include high fever, seizures,
muscular twitching, rhythmic movement of the head
or extremities, contracted or unequal pupils, retinal
hemorrhages, hemiplegia,absent or exaggerated deep
tendon reflexes, and a positive Babinski sign.
 Lumbar puncture reveals increased pressure and
mildly increased cerebrospinal fluid protein, typically
with no CSF pleocytosis and a normal CSF glucose.

32.  Respiratory distress is a poor prognostic indicator in
severe malaria and appears to be caused by metabolic
acidosis rather than intrinsic pulmonary disease.
 Seizures are a common complication of severe malaria,
particularly cerebral malaria.
 Hypoglycemia is a complication of malaria that is
more common in children,pregnant women, and
patients receiving quinine therapy
 Respiratory distress is a poor prognostic indicator in
severe malaria and appears to be caused by metabolic
acidosis rather than intrinsic pulmonary disease.
 Seizures are a common complication of severe malaria,
particularly cerebral malaria.
 Hypoglycemia is a complication of malaria that is
more common in children,pregnant women, and
patients receiving quinine therapy

33.  Circulatory collapse (algid malaria) is a rare
complication that manifests as
 hypotension, hypothermia, rapid weak pulse, shallow
breathing, pallor, and vascular collapse. It is most
likely caused by bacterial superinfection, since up to
15% of children in endemic areas with severe malaria
may have concurrent bacteremia. Death may occur
within hours
 Circulatory collapse (algid malaria) is a rare
complication that manifests as
 hypotension, hypothermia, rapid weak pulse, shallow
breathing, pallor, and vascular collapse. It is most
likely caused by bacterial superinfection, since up to
15% of children in endemic areas with severe malaria
may have concurrent bacteremia. Death may occur
within hours

34.  Long-term cognitive impairment occurs in 25% of
children with cerebral malaria and also in children
with repeated episodes of uncomplicated disease

35.  Hyperreactive malarial splenomegaly (HMS) is a
chronic complication of P. falciparum malaria in which
massive splenomegaly persists after treatment of acute
infection.
 Major criteria include splenomegaly (>10 cm), IgM > 2
SD above local mean, high levels of antibodies to a
blood-stage P. falciparum antigen, and a clinical
response to an antimalarial drug.
 Hyperreactive malarial splenomegaly (HMS) is a
chronic complication of P. falciparum malaria in which
massive splenomegaly persists after treatment of acute
infection.
 Major criteria include splenomegaly (>10 cm), IgM > 2
SD above local mean, high levels of antibodies to a
blood-stage P. falciparum antigen, and a clinical
response to an antimalarial drug.

36.  acute kidney injury
 jaundice
 Prostration
 hemoglobinuria,
 abnormal bleeding, and
 pulmonary edema.
 acute kidney injury
 jaundice
 Prostration
 hemoglobinuria,
 abnormal bleeding, and
 pulmonary edema.

37. Management
 Treatment of uncomplicated malaria:
 P. falciparum: artemether-lumefantrine (coartum) Bid
for 3 days (1.7/12mg/kg/per dose).
 P.vivax, P.malariae or P. ovale: first-line drug of choice is
chloroquine.
 Second line- oral quinine plus doxycycline or
clindamycin.
 Supportive treatment
 Treatment of uncomplicated malaria:
 P. falciparum: artemether-lumefantrine (coartum) Bid
for 3 days (1.7/12mg/kg/per dose).
 P.vivax, P.malariae or P. ovale: first-line drug of choice is
chloroquine.
 Second line- oral quinine plus doxycycline or
clindamycin.
 Supportive treatment

38.  Severe malaria:
 Is the presence of one or more signs and symptoms of
sever illness and a demonstrable asexual P. falciparum
parasitaemia in peripheral blood sample.
 Severe malaria:
 Is the presence of one or more signs and symptoms of
sever illness and a demonstrable asexual P. falciparum
parasitaemia in peripheral blood sample.

39.  Cerebral malaria:
 The commonest complications of P. falciparum in
addition to severe anemia.
 Caused by Sluggish flow caused by sticky knobs on
parasitized red cells leading to stagnant hypoxia and
vascular damage.
 Management:
 Maintain airway
 place patient on his or her side
 exclude other treatable causes of coma (e.g. hypoglycaemia,
bacterial meningitis)
 Intubate if necessary
 Cerebral malaria:
 The commonest complications of P. falciparum in
addition to severe anemia.
 Caused by Sluggish flow caused by sticky knobs on
parasitized red cells leading to stagnant hypoxia and
vascular damage.
 Management:
 Maintain airway
 place patient on his or her side
 exclude other treatable causes of coma (e.g. hypoglycaemia,
bacterial meningitis)
 Intubate if necessary

40.  Hyperpyrexia:
 Administer antipyretic drugs.
 Paracetamol is preferred
 Convulsion:
 Maintain airways
 treat promptly with intravenous or rectal diazepam
 Check blood glucose.
 Hyperpyrexia:
 Administer antipyretic drugs.
 Paracetamol is preferred
 Convulsion:
 Maintain airways
 treat promptly with intravenous or rectal diazepam
 Check blood glucose.

41.  Severe anemia:
 Is due to destruction of parasitized RBCs, marrow
suppression
 Transfuse with screened fresh whole blood.
 Hypoglycemia:
 Is due to patient not feeding, consumption of glucose by
parasites, drug related (quinine).
 Check RBS
 correct hypoglycaemia (10% dextrose) and maintain with
glucose containing infusion.
 (note:40%dextrose not recommended for child)
 Severe anemia:
 Is due to destruction of parasitized RBCs, marrow
suppression
 Transfuse with screened fresh whole blood.
 Hypoglycemia:
 Is due to patient not feeding, consumption of glucose by
parasites, drug related (quinine).
 Check RBS
 correct hypoglycaemia (10% dextrose) and maintain with
glucose containing infusion.
 (note:40%dextrose not recommended for child)

42.  Pulmonary edema:
 Occurs due to increased pulmonary capillary
permeability.
 Prop patient up at an angle of 45°
 give oxygen, give a diuretic
 Stop IV fluids
 intubate and add CPAP in life-threatening hypoxaemia.
 Pulmonary edema:
 Occurs due to increased pulmonary capillary
permeability.
 Prop patient up at an angle of 45°
 give oxygen, give a diuretic
 Stop IV fluids
 intubate and add CPAP in life-threatening hypoxaemia.

43.  Acute Renal Failure:
 Is due to Acute tubular necrosis resulting from sluggish
blood flow and hypotension, hemoglobinuria.
 Exclude pre-renal causes
 check fluid balance
 If an established renal failure add dialysis
 Acute Renal Failure:
 Is due to Acute tubular necrosis resulting from sluggish
blood flow and hypotension, hemoglobinuria.
 Exclude pre-renal causes
 check fluid balance
 If an established renal failure add dialysis

44.  Spontaneous bleeding and coagulopathy:
 Transfuse with screened fresh whole blood
(cryoprecipitate, fresh frozen plasma and platelets, if
available)
 give vitamin K injection.
 Spontaneous bleeding and coagulopathy:
 Transfuse with screened fresh whole blood
(cryoprecipitate, fresh frozen plasma and platelets, if
available)
 give vitamin K injection.

45.  Metabolic acidosis:
 Exclude or treat hypoglycaemia, hypovolaemia and
septicaemia.
 If severe, add dialysis
 Shock/algid malaria:
 Hypotension, hypothermia, weak pulse, shallow
breathing, pallor, vascular collapse
 Suspect septicaemia, take blood for cultures
 give parenteral broad-spectrum antimicrobials
 correct haemodynamic disturbances.
 Metabolic acidosis:
 Exclude or treat hypoglycaemia, hypovolaemia and
septicaemia.
 If severe, add dialysis
 Shock/algid malaria:
 Hypotension, hypothermia, weak pulse, shallow
breathing, pallor, vascular collapse
 Suspect septicaemia, take blood for cultures
 give parenteral broad-spectrum antimicrobials
 correct haemodynamic disturbances.

46. Tx of sever malaria
 General measures (severe malaria):
 Admit to ICU
 Correct over/under hydration
 Correct hypoglycemia
 Monitor input/output
 Treat associated infection
 Control fever
• Parenteral anti malaria- quinine salt 20mg/kg loading
followed by 10mg/kg TID starting 8hrs after loading.
Dilute with 5% dextrose to run over 4hr
 General measures (severe malaria):
 Admit to ICU
 Correct over/under hydration
 Correct hypoglycemia
 Monitor input/output
 Treat associated infection
 Control fever
• Parenteral anti malaria- quinine salt 20mg/kg loading
followed by 10mg/kg TID starting 8hrs after loading.
Dilute with 5% dextrose to run over 4hr

47.  Artesunate, 2.4 mg/kg by intravenous or intramuscular*
injection, followed by 2.4 mg/kg at 12 hr and 24 hr;
continue injection once daily if necessary †
 Artemether, 3.2 mg/kg by immediate intramuscular*
injection, followed by 1.6 mg/kg daily
 Quinine dihydrochloride, 20 mg salt per kg infused during
4 hr, followed by maintenance of 10 mg salt per kg infused
during 2-8 hr every 8 hr (can also be given by
intramuscular injection* when diluted to 60-100 mg/mL).
 Artesunate is the treatment of choice. Artemether should
only be used if artesunate is unavailable.
 Quinine dihydrochloride should be given only when
artesunate and artemether are unavailable.
 Artesunate, 2.4 mg/kg by intravenous or intramuscular*
injection, followed by 2.4 mg/kg at 12 hr and 24 hr;
continue injection once daily if necessary †
 Artemether, 3.2 mg/kg by immediate intramuscular*
injection, followed by 1.6 mg/kg daily
 Quinine dihydrochloride, 20 mg salt per kg infused during
4 hr, followed by maintenance of 10 mg salt per kg infused
during 2-8 hr every 8 hr (can also be given by
intramuscular injection* when diluted to 60-100 mg/mL).
 Artesunate is the treatment of choice. Artemether should
only be used if artesunate is unavailable.
 Quinine dihydrochloride should be given only when
artesunate and artemether are unavailable.

48. Prevention
 ITN
 Antimalaria prophylaxis for travelers
 Insecticide spraying
 Drain marshy lands
 ITN
 Antimalaria prophylaxis for travelers
 Insecticide spraying
 Drain marshy lands

49. Typhoid( Enteric) fever
 Etiology
 Epidemiology
 Pathogenesis
 Clinical manifestation
 Complication
 Diagnosis
 DD
 Treatment
 Prognosis
 Prevention
 Etiology
 Epidemiology
 Pathogenesis
 Clinical manifestation
 Complication
 Diagnosis
 DD
 Treatment
 Prognosis
 Prevention

50. Typhoid fever cont..
 Is febrile illness remains endemic in many developing
countries.
 Etiology
 -S.Typhi
 - Salmonella Paratyphi A
 -S. Paratyphi B (Schotmulleri) and
 -S. Paratyphi C
 Is febrile illness remains endemic in many developing
countries.
 Etiology
 -S.Typhi
 - Salmonella Paratyphi A
 -S. Paratyphi B (Schotmulleri) and
 -S. Paratyphi C

51. Epidemiology
 It is estimated that >26.9 million typhoid fever cases
occur annually, of which 1% result in death
 In developed countries, the incidence of T. fever is <15
cases per 100,000 population, with most cases
occurring in travelers.
 In contrast, in the developing world, it range from
100-1,000 cases per 100,000 population.
 It is estimated that >26.9 million typhoid fever cases
occur annually, of which 1% result in death
 In developed countries, the incidence of T. fever is <15
cases per 100,000 population, with most cases
occurring in travelers.
 In contrast, in the developing world, it range from
100-1,000 cases per 100,000 population.

52. pathogenesis
 Occur with Ingestion of foods or water contaminated
with S. Typhi from human feces is the most common
mode of transmission
 infecting dose of about 10^5 -10^9organisms,
 incubation period ranging from 4-14 days
 After ingestion, S. Typhi organisms invade the body
through the gut mucosa in the terminal ileum
 Occur with Ingestion of foods or water contaminated
with S. Typhi from human feces is the most common
mode of transmission
 infecting dose of about 10^5 -10^9organisms,
 incubation period ranging from 4-14 days
 After ingestion, S. Typhi organisms invade the body
through the gut mucosa in the terminal ileum

53.  After passing through the intestinal mucosa, S. Typhi
organisms enter the mesenteric lymphoid system and then
pass into the bloodstream via the lymphatics (primary
bacteremia)
 The blood borne bacteria are disseminated throughout the
body and colonize the organs of the RES, where they may
replicate within macrophages.
 After a period of bacterial replication, S. Typhi organisms
are shed back into the blood, causing a secondary
bacteremia that coincides with the onset of clinical
symptoms and marks the end of the incubation period
 After passing through the intestinal mucosa, S. Typhi
organisms enter the mesenteric lymphoid system and then
pass into the bloodstream via the lymphatics (primary
bacteremia)
 The blood borne bacteria are disseminated throughout the
body and colonize the organs of the RES, where they may
replicate within macrophages.
 After a period of bacterial replication, S. Typhi organisms
are shed back into the blood, causing a secondary
bacteremia that coincides with the onset of clinical
symptoms and marks the end of the incubation period

54.  Infection with S. Typhi produces an inflammatory
response in the deeper mucosal layers and underlying
lymphoid tissue, with hyperplasia of Peyer patches and
subsequent necrosis and sloughing of overlying
epithelium.
 virulence of the infecting organisms, host factors and
immunity
 Infection with S. Typhi produces an inflammatory
response in the deeper mucosal layers and underlying
lymphoid tissue, with hyperplasia of Peyer patches and
subsequent necrosis and sloughing of overlying
epithelium.
 virulence of the infecting organisms, host factors and
immunity

55. Clinical manifestation
 Common Clinical Features of Typhoid Fever in Children*
 FEATURE RATE (%)
 High-grade fever …………………………………….95
 Coated tongue ……………………………………….76
 Anorexia…………………………………………………. 70
 Vomiting …………………………………………………..39
 Hepatomegaly…………………………………………… 37
 Diarrhea………………………………………………….. 36
 Toxicity…………………………………………………….. 29
 Abdominal pain …………………………………………21
 Pallor …………………………………………………………20
 Splenomegaly……………………………………………… 17
 Constipation ………………………………………………..7
 Headache ………………………………………………………4
 Jaundice ……………………………………………………….2
 Obtundation …………………………………………………2
 Ileus ……………………………………………………………1
 Intestinal perforation …………………………………..0.5
 Rose spot ……………………………………………………25
 Common Clinical Features of Typhoid Fever in Children*
 FEATURE RATE (%)
 High-grade fever …………………………………….95
 Coated tongue ……………………………………….76
 Anorexia…………………………………………………. 70
 Vomiting …………………………………………………..39
 Hepatomegaly…………………………………………… 37
 Diarrhea………………………………………………….. 36
 Toxicity…………………………………………………….. 29
 Abdominal pain …………………………………………21
 Pallor …………………………………………………………20
 Splenomegaly……………………………………………… 17
 Constipation ………………………………………………..7
 Headache ………………………………………………………4
 Jaundice ……………………………………………………….2
 Obtundation …………………………………………………2
 Ileus ……………………………………………………………1
 Intestinal perforation …………………………………..0.5
 Rose spot ……………………………………………………25

56. Complication
 hepatitis, jaundice, and cholecystitis
 Intestinal hemorrhage (<1%) and perforation (0.5–1%)
 delirium, psychosis, increased intracranial pressure,
acute cerebellar ataxia,chorea, deafness, and Guillain-
Barré syndrome
 Endocarditis,myocarditis,pericarditis,congestive heart
failure
 hepatitis, jaundice, and cholecystitis
 Intestinal hemorrhage (<1%) and perforation (0.5–1%)
 delirium, psychosis, increased intracranial pressure,
acute cerebellar ataxia,chorea, deafness, and Guillain-
Barré syndrome
 Endocarditis,myocarditis,pericarditis,congestive heart
failure

57. Diagnosis
 Blood culture
 Stool and urine culture
 widal test
 PCR
 Blood culture
 Stool and urine culture
 widal test
 PCR

58. Differential dig
 In endemic areas, typhoid fever may mimic many common
febrile illnesses
 acute gastroenteritis,
 bronchitis, and bronchopneumonia.
 malaria;
 sepsis
 tuberculosis,
 brucellosis,
 tularemia, leptospirosis,
 rickettsial diseases
 Dengue fever,
 acute hepatitis,
 infectious mononucleosis.
 In endemic areas, typhoid fever may mimic many common
febrile illnesses
 acute gastroenteritis,
 bronchitis, and bronchopneumonia.
 malaria;
 sepsis
 tuberculosis,
 brucellosis,
 tularemia, leptospirosis,
 rickettsial diseases
 Dengue fever,
 acute hepatitis,
 infectious mononucleosis.

59. Management
 general principles
 Adequate rest, and hydration,
 Hospitalize patients with complication
 Treat with oral antibiotics if no complication
 Antipyretic therapy (acetaminophen 10-15 mg/kg every
4-6 hr PO) should be provided as required.
 Admit if there is complication
 general principles
 Adequate rest, and hydration,
 Hospitalize patients with complication
 Treat with oral antibiotics if no complication
 Antipyretic therapy (acetaminophen 10-15 mg/kg every
4-6 hr PO) should be provided as required.
 Admit if there is complication

60.  Chloramphenicol 50-75 mg/kg/day in 4 divided dose
for 14-21 day.
 Amoxicillin 75-100mg/kg/day tid for 14 day.
 Fluoroquinolone(e.g., ciprofloxacin) 15 mg/kg/day bid
for 10-14day.
 Ceftriaxone 60mg/kg/day for 10-14 day.
 Chloramphenicol 50-75 mg/kg/day in 4 divided dose
for 14-21 day.
 Amoxicillin 75-100mg/kg/day tid for 14 day.
 Fluoroquinolone(e.g., ciprofloxacin) 15 mg/kg/day bid
for 10-14day.
 Ceftriaxone 60mg/kg/day for 10-14 day.

61. Prognosis
 depends on
 the rapidity of diagnosis and institution of appropriate antibiotic
therapy.
 patient/s, age,
 general state of health, and nutrition;
 the causative Salmonella serotype
 appearance of complications.
 Despite appropriate therapy, 2–4% of infected children may experience
relapse after initial clinical response to treatment.
 Individuals who excrete S.Typhi for ≥3 mo after infection are regarded
as chronic carriers, <2%
 A chronic urinary carrier state can develop in children with
schistosomiasis.
 depends on
 the rapidity of diagnosis and institution of appropriate antibiotic
therapy.
 patient/s, age,
 general state of health, and nutrition;
 the causative Salmonella serotype
 appearance of complications.
 Despite appropriate therapy, 2–4% of infected children may experience
relapse after initial clinical response to treatment.
 Individuals who excrete S.Typhi for ≥3 mo after infection are regarded
as chronic carriers, <2%
 A chronic urinary carrier state can develop in children with
schistosomiasis.

62. Prevention
 Hand washing before food preparation (food
handlers)
 Avoid street foods and cut fruits
 Water purification and chlorination if there is
epidemic due to water contamination with sewerage
system
 Vaccine for children and travelers to endemic area
 Vi-capsular polysacharide vaccine (IM)
 Oral live attenuated vaccine of Ty21a S.typhi strain
 Hand washing before food preparation (food
handlers)
 Avoid street foods and cut fruits
 Water purification and chlorination if there is
epidemic due to water contamination with sewerage
system
 Vaccine for children and travelers to endemic area
 Vi-capsular polysacharide vaccine (IM)
 Oral live attenuated vaccine of Ty21a S.typhi strain

63. Schistosomiasis (bilharzia)
 encompasses the acute and chronic inflammatory
disorders caused by human infection with
Schistosoma spp.
 Disease is related to both the systemic and the focal
effects of schistosome infection and its consequent
host immune responses triggered by parasite eggs
deposited in the tissues
 encompasses the acute and chronic inflammatory
disorders caused by human infection with
Schistosoma spp.
 Disease is related to both the systemic and the focal
effects of schistosome infection and its consequent
host immune responses triggered by parasite eggs
deposited in the tissues

64.  Etiology
 Schistosoma organisms are the trematodes, or flukes ,
that parasitize the bloodstream.
 Five schistosome species infect humans:
 -Schistosoma haematobium
 -S. mansoni
 - S. japonicum
 - S. intercalatum, and
 -S. mekongi .
 Etiology
 Schistosoma organisms are the trematodes, or flukes ,
that parasitize the bloodstream.
 Five schistosome species infect humans:
 -Schistosoma haematobium
 -S. mansoni
 - S. japonicum
 - S. intercalatum, and
 -S. mekongi .

65.  Epidemiology
 Schistosomiasis infects more than 300 million people
worldwide and puts more than 700 million people at
risk, primarily children and young adults.
 is the 2nd most disabling parasitic disease after
malaria.
 Humans are the main definitive hosts for the 5
clinically important species of schistosomes,
 Epidemiology
 Schistosomiasis infects more than 300 million people
worldwide and puts more than 700 million people at
risk, primarily children and young adults.
 is the 2nd most disabling parasitic disease after
malaria.
 Humans are the main definitive hosts for the 5
clinically important species of schistosomes,

66.  S. haematobium is prevalent in Africa and the Middle East;
 S. mansoni is prevalent in Africa, the Middle East, the
Caribbean, and South America; and
 S.japonicum is prevalent in China, the Philippines, and
Indonesia, with some
 S.intercalatum is found in West and Central Africa, and
 S. mekongi is found only along the upper Mekong River in the
Far East.
 Transmission depends on water contamination by human
excreta, the presence of specific intermediate snail hosts, and the
patterns of water contact and social habits of the population .
 The distribution of infection in endemic areas shows that
prevalence increases with age, to a peak at 10-20 yr old.
 S. haematobium is prevalent in Africa and the Middle East;
 S. mansoni is prevalent in Africa, the Middle East, the
Caribbean, and South America; and
 S.japonicum is prevalent in China, the Philippines, and
Indonesia, with some
 S.intercalatum is found in West and Central Africa, and
 S. mekongi is found only along the upper Mekong River in the
Far East.
 Transmission depends on water contamination by human
excreta, the presence of specific intermediate snail hosts, and the
patterns of water contact and social habits of the population .
 The distribution of infection in endemic areas shows that
prevalence increases with age, to a peak at 10-20 yr old.

67. Life cycle and transmission
 Humans are infected through contact with water
contaminated with cercariae ,the free-living infective stage
of the parasite,capable of penetrating intact human skin.
 S. haematobium adults are found in the perivesical and
periureteral venous plexus,
 S. mansoni in the inferior mesenteric veins, and
 S. japonicum in the superior mesenteric veins.
 S. intercalatum and S. mekongi are usually found in the
mesenteric vessels.
 Adult schistosome worms (1-2 cm long) are clearly adapted
for an intravascular existence.
 Humans are infected through contact with water
contaminated with cercariae ,the free-living infective stage
of the parasite,capable of penetrating intact human skin.
 S. haematobium adults are found in the perivesical and
periureteral venous plexus,
 S. mansoni in the inferior mesenteric veins, and
 S. japonicum in the superior mesenteric veins.
 S. intercalatum and S. mekongi are usually found in the
mesenteric vessels.
 Adult schistosome worms (1-2 cm long) are clearly adapted
for an intravascular existence.

69.  The eggs of the 3 main schistosome species have characteristic
morphologic features:
 S.haematobium has a terminal spine,
 S. mansoni has a lateral spine, and
 S.japonicum has a smaller size with a short, curved spine
 Parasite eggs provoke a significant granulomatous inflammatory
response that allows them to ulcerate through host tissues to reach the
lumen of the urinary tract or the intestines.
 They are carried to the outside environment in urine or feces
(depending on the species), where they will hatch if deposited in
freshwater.
 Motile miracidia emerge, infect specific freshwater snail intermediate
hosts, and divide asexually.
 After 4-12 wk, the infective cercariae are released by the snails
 The eggs of the 3 main schistosome species have characteristic
morphologic features:
 S.haematobium has a terminal spine,
 S. mansoni has a lateral spine, and
 S.japonicum has a smaller size with a short, curved spine
 Parasite eggs provoke a significant granulomatous inflammatory
response that allows them to ulcerate through host tissues to reach the
lumen of the urinary tract or the intestines.
 They are carried to the outside environment in urine or feces
(depending on the species), where they will hatch if deposited in
freshwater.
 Motile miracidia emerge, infect specific freshwater snail intermediate
hosts, and divide asexually.
 After 4-12 wk, the infective cercariae are released by the snails

71. Clinical manifestation
 Immediate Manifestations
 1, Swimmer’s Itching
 A maculopapular eruption may arise with in 2-3 days at
the site of penetration by the cercarial .
 It is a self-limiting entity.
 It is sever in those exposed to avian schisto
 Immediate Manifestations
 1, Swimmer’s Itching
 A maculopapular eruption may arise with in 2-3 days at
the site of penetration by the cercarial .
 It is a self-limiting entity.
 It is sever in those exposed to avian schisto

72.  2. Acute Schistosomiasis (Katayama Fever)
 Occur in heavly infected individual
 4-8 wk after exposure
 Manifested by ,acute onset of fever ,chills,cough
,sweating ,abdominal pain ,LAP,HSM,and eosinophilia
 2. Acute Schistosomiasis (Katayama Fever)
 Occur in heavly infected individual
 4-8 wk after exposure
 Manifested by ,acute onset of fever ,chills,cough
,sweating ,abdominal pain ,LAP,HSM,and eosinophilia

73.  Chronic Schistosomiasis
 Intestinal schistosomiasis
 Within few months patients can have bloody diarrhea and colicky
abdominal pain
 Chronic form: colonic plyposis
 Hepatosplenic Schistosomiasis
 Manifestation starts with in first year with hepatomegaly
 Periportal granuloma formation and fibrosis (Symmer’s Clay-Pipe
Stem fibrosis) leading to Portal hypertension and splenomegaly
 Esophageal varices with normal liver function
 Ascites and hypoalbuminemia are rare occurences
 Chronic Schistosomiasis
 Intestinal schistosomiasis
 Within few months patients can have bloody diarrhea and colicky
abdominal pain
 Chronic form: colonic plyposis
 Hepatosplenic Schistosomiasis
 Manifestation starts with in first year with hepatomegaly
 Periportal granuloma formation and fibrosis (Symmer’s Clay-Pipe
Stem fibrosis) leading to Portal hypertension and splenomegaly
 Esophageal varices with normal liver function
 Ascites and hypoalbuminemia are rare occurences

74.  Urinary Schistosomiasis
 S. hematobium
 Symptoms start early
 About 80% have Dysuria, frequency, gross hematuria
(can be terminal), frequent urinary tract infections
 Hydroureter and hydronephrosis occurs in 25-50% of
infected children
 May lead to Squamous cell ca of bladder
 Urinary Schistosomiasis
 S. hematobium
 Symptoms start early
 About 80% have Dysuria, frequency, gross hematuria
(can be terminal), frequent urinary tract infections
 Hydroureter and hydronephrosis occurs in 25-50% of
infected children
 May lead to Squamous cell ca of bladder

75.  Other organ involvement
 Embolization of eggs into the pulmonary circulation
leads to pulmonary Hypertension ( later causing
Corpulmonale)
 CNS Schistosomiasis
 Epilepsy ( S. japonicum)
 Transverse myelitis (S.mansoni and S.hematobium)
 Other organ involvement
 Embolization of eggs into the pulmonary circulation
leads to pulmonary Hypertension ( later causing
Corpulmonale)
 CNS Schistosomiasis
 Epilepsy ( S. japonicum)
 Transverse myelitis (S.mansoni and S.hematobium)

76. Diagnosis
 Acute Schistosomiasis
 Serology
 Chronic Schistosomiasis
 Serology: blood, CSF, Urine
 Stool and urine microscopy: Kato Method
 Rectal Snip
 Ultrasound of liver and portal structure
 Acute Schistosomiasis
 Serology
 Chronic Schistosomiasis
 Serology: blood, CSF, Urine
 Stool and urine microscopy: Kato Method
 Rectal Snip
 Ultrasound of liver and portal structure

77. Treatment
 The recommended treatment for schistosomiasis is
 praziquantel (40 mg/kg/day orally [PO] divided twice daily
[bid] for 1 day for schistosomiasis haematobia, mansoni,
and intercalatum;
 60 mg/kg/day PO divided 3 times daily [tid] for 1 day for
schistosomiasis japonica and mekongi).
 Children <5 yr old with S. mansoni may need up to 60
mg/kg/day PO tid for 1 day to achieve clearance.
 A 2nd treatment 4-6 wk after the 1st course may help in
eliminating residual infection.
 The recommended treatment for schistosomiasis is
 praziquantel (40 mg/kg/day orally [PO] divided twice daily
[bid] for 1 day for schistosomiasis haematobia, mansoni,
and intercalatum;
 60 mg/kg/day PO divided 3 times daily [tid] for 1 day for
schistosomiasis japonica and mekongi).
 Children <5 yr old with S. mansoni may need up to 60
mg/kg/day PO tid for 1 day to achieve clearance.
 A 2nd treatment 4-6 wk after the 1st course may help in
eliminating residual infection.

78. Prevention
 chemotherapy
 improved sanitation
 molluscicidals, and animal vaccination may prove
useful in breaking the cycle of transmission.
Prevention
 chemotherapy
 improved sanitation
 molluscicidals, and animal vaccination may prove
useful in breaking the cycle of transmission.

79. Leishmaniasis
 Leishmaniasis is syndrome caused by a group of
parasite in the genus Leishmania
 It is a vector-borne disease transmitted by
phlebotomine sand flies
 It can be a zoonosis, involving domestic and wild
animals as reservoir or an anthroponosis, human as a
reservoir
 Leishmaniasis is syndrome caused by a group of
parasite in the genus Leishmania
 It is a vector-borne disease transmitted by
phlebotomine sand flies
 It can be a zoonosis, involving domestic and wild
animals as reservoir or an anthroponosis, human as a
reservoir

80. Leishmaniasis
 Is caused by unicellular eukaryotic obligatory intracellular
protozoa of the genus Leishmania transmitted by
phlebotomine sandflies.
 Primarily affects the host's RES.
 Produce widely varying clinical syndromes ranging from
self-healing cutaneous ulcers to fatal visceral ds.
 Is grouped into 3:
(1) VL,
 (2) CL, &
 (3) ML
 Is caused by unicellular eukaryotic obligatory intracellular
protozoa of the genus Leishmania transmitted by
phlebotomine sandflies.
 Primarily affects the host's RES.
 Produce widely varying clinical syndromes ranging from
self-healing cutaneous ulcers to fatal visceral ds.
 Is grouped into 3:
(1) VL,
 (2) CL, &
 (3) ML

81.  Etiology
 Leishmania organisms are members of the
Trypanosomatidae family
 The parasite is dimorphic, existing as a flagellate
promastigote in the insect vector and as an aflagellate
amastigote that resides and replicates within
mononuclear phagocytes of the vertebrate host
 Etiology
 Leishmania organisms are members of the
Trypanosomatidae family
 The parasite is dimorphic, existing as a flagellate
promastigote in the insect vector and as an aflagellate
amastigote that resides and replicates within
mononuclear phagocytes of the vertebrate host

82.  Once within the macrophage,the promastigote
transforms to an amastigote and resides and replicates
within a phagolysosome.
 Transmission can be zoonotic and anthroponotic
through sandfly
 Once within the macrophage,the promastigote
transforms to an amastigote and resides and replicates
within a phagolysosome.
 Transmission can be zoonotic and anthroponotic
through sandfly

83. phlebotomine sandfly.
83

84. 6/18/2021 84

85.  Epidemiology
 The leishmaniases are estimated to affect 10-20 million
people in endemic tropical and subtropical regions on all
continents
 The different forms of the disease are distinct in their
causes,epidemiologic characteristics, transmission, and
geographic distribution.
 The leishmaniases may occur sporadically throughout an
endemic region or may occur in epidemic waves.
 Epidemiology
 The leishmaniases are estimated to affect 10-20 million
people in endemic tropical and subtropical regions on all
continents
 The different forms of the disease are distinct in their
causes,epidemiologic characteristics, transmission, and
geographic distribution.
 The leishmaniases may occur sporadically throughout an
endemic region or may occur in epidemic waves.

86.  Pathology
 intense chronic granulomatous inflammation involving the epidermis
and dermis with relatively few amastigotes.
 ML is characterized by an intense granulomatous reaction with
prominent tissue necrosis,
 In VL there is prominent reticuloendothelial cell hyperplasia in the
liver, spleen, bone marrow, and lymph Node
 Late in the course of disease,splenic infarction , centrilobular necrosis
and fatty infiltration of the liver occur, the normal marrow elements
are replaced by parasitized histiocytes,
 Pathology
 intense chronic granulomatous inflammation involving the epidermis
and dermis with relatively few amastigotes.
 ML is characterized by an intense granulomatous reaction with
prominent tissue necrosis,
 In VL there is prominent reticuloendothelial cell hyperplasia in the
liver, spleen, bone marrow, and lymph Node
 Late in the course of disease,splenic infarction , centrilobular necrosis
and fatty infiltration of the liver occur, the normal marrow elements
are replaced by parasitized histiocytes,

87.  Cellular immune mechanisms determine resistance or susceptibility to
infection with Leishmania.
 Resistance is mediated by interleukin (IL)-12–driven generation of a T
helper 1 (Th1) cell response, with interferon (IFN)-γ inducing classic
macrophage (M1) activation and parasite killing
 Susceptibility is associated with expansion of IL-4–producing Th2 cells
and/or the production of IL-10 and transforming growth factor (TGF)-
β, which are inhibitors of macrophage-mediated parasite killing, and
the generation of regulatory T cells and alternatively activated (M2)
macrophages.
 Cellular immune mechanisms determine resistance or susceptibility to
infection with Leishmania.
 Resistance is mediated by interleukin (IL)-12–driven generation of a T
helper 1 (Th1) cell response, with interferon (IFN)-γ inducing classic
macrophage (M1) activation and parasite killing
 Susceptibility is associated with expansion of IL-4–producing Th2 cells
and/or the production of IL-10 and transforming growth factor (TGF)-
β, which are inhibitors of macrophage-mediated parasite killing, and
the generation of regulatory T cells and alternatively activated (M2)
macrophages.

88.  Subclinical infection occurs considerably more frequently
than does active cutaneous or visceral disease.
 Host factors (genetic background, concomitant disease,
nutritional status),
 parasite factors (virulence,size of the inoculum), and
 vector -specific factors (vector genotype,
immunomodulatory salivary constituents)
 Subclinical infection occurs considerably more frequently
than does active cutaneous or visceral disease.
 Host factors (genetic background, concomitant disease,
nutritional status),
 parasite factors (virulence,size of the inoculum), and
 vector -specific factors (vector genotype,
immunomodulatory salivary constituents)

89.  Individuals with prior active disease or subclinical
infection are usually immune to a subsequent clinical
infection

90.  Clinical Manifestations
 The different forms of the disease are distinct in their
causes, epidemiologic features, transmission, and
geographic distribution
 Clinical Manifestations
 The different forms of the disease are distinct in their
causes, epidemiologic features, transmission, and
geographic distribution

91. Localized Cutaneous Leishmaniasis
 LCL (Oriental sore ) can affect individuals of any age, but children are
the primary victims in many endemic regions.
 It may present as 1 or a few papular,nodular, plaque-like, or ulcerative
lesions that are usually located on exposed skin, such as the face and
extremities
 The lesions typically begin as a small papule at the site of the sandfly
bite, which enlarges to 1-3 cm in diameter and may ulcerate over the
course of several weeks to months. The shallow ulcer is usually
nontender and surrounded by a sharp, indurated, erythematous
margin
 Regional lymphadenopathy and palpable subcutaneous nodules or
lymphatic cords
 LCL (Oriental sore ) can affect individuals of any age, but children are
the primary victims in many endemic regions.
 It may present as 1 or a few papular,nodular, plaque-like, or ulcerative
lesions that are usually located on exposed skin, such as the face and
extremities
 The lesions typically begin as a small papule at the site of the sandfly
bite, which enlarges to 1-3 cm in diameter and may ulcerate over the
course of several weeks to months. The shallow ulcer is usually
nontender and surrounded by a sharp, indurated, erythematous
margin
 Regional lymphadenopathy and palpable subcutaneous nodules or
lymphatic cords

92. Diffuse Cutaneous Leishmaniasis
 rare form caused by organisms of the L. mexicana
complex in the New World and L. aethiopica in the
Old World
 DCL manifests as large, nonulcerating macules,
papules, nodules, or plaques that often involve large
areas of skin and may resemble lepromatous leprosy.
 The face and extremities are most often involved.
 rare form caused by organisms of the L. mexicana
complex in the New World and L. aethiopica in the
Old World
 DCL manifests as large, nonulcerating macules,
papules, nodules, or plaques that often involve large
areas of skin and may resemble lepromatous leprosy.
 The face and extremities are most often involved.

93. Disseminated Leishmaniasis
 In rare cases, parasites can spread (likely by the hematogenous
route) in an immunocompetent host from a primary lesion to
cause DL.
 This is defined as >10 lesions (usually in the hundreds) involving
at least 2 noncontiguous areas of the skin.
 DL has been most often attributed to L. (V.) braziliensis
 The lesions are typically inflammatory papules or ulcers, in
contrast to the nodular and plaque-like lesions of DCL, and
 about one third of patients have mucosal involvement.
 In rare cases, parasites can spread (likely by the hematogenous
route) in an immunocompetent host from a primary lesion to
cause DL.
 This is defined as >10 lesions (usually in the hundreds) involving
at least 2 noncontiguous areas of the skin.
 DL has been most often attributed to L. (V.) braziliensis
 The lesions are typically inflammatory papules or ulcers, in
contrast to the nodular and plaque-like lesions of DCL, and
 about one third of patients have mucosal involvement.

94. Mucosal Leishmaniasis
 ML (espundia ) is an uncommon but serious manifestation of leishmanial
infection resulting from hematogenous spread of parasites to the nasal or
oropharyngeal mucosa from a cutaneous infection.
 It is usually caused by parasites in the L. (Viannia) complex.
 Approximately half of the patients with ML have had active cutaneous lesions
within the preceding 2 yr, but ML may not develop until many years after
resolution of the primary lesion.
 ML occurs in <5% of individuals who have, or have had, LCL caused by L. (V.)
braziliensis.
 Patients with ML typically have nasal mucosal involvement and present with
nasal congestion, discharge, and recurrent epistaxis.
 Marked soft tissue, cartilage, and even bone destruction occurs late in the
course ds.
 ML (espundia ) is an uncommon but serious manifestation of leishmanial
infection resulting from hematogenous spread of parasites to the nasal or
oropharyngeal mucosa from a cutaneous infection.
 It is usually caused by parasites in the L. (Viannia) complex.
 Approximately half of the patients with ML have had active cutaneous lesions
within the preceding 2 yr, but ML may not develop until many years after
resolution of the primary lesion.
 ML occurs in <5% of individuals who have, or have had, LCL caused by L. (V.)
braziliensis.
 Patients with ML typically have nasal mucosal involvement and present with
nasal congestion, discharge, and recurrent epistaxis.
 Marked soft tissue, cartilage, and even bone destruction occurs late in the
course ds.

95. Visceral Leishmaniasis
 VL (kala-azar ) typically affects children <5 yr old in
the New World and Mediterranean region (L.
infantum ) and older children and young adults in
Africa and Asia (L. donovani ).
 After inoculation of the organism into the skin by the
sandfly, the child may have a
 asymptomatic infection or
 an oligosymptomatic illness
 active kala-azar.
 VL (kala-azar ) typically affects children <5 yr old in
the New World and Mediterranean region (L.
infantum ) and older children and young adults in
Africa and Asia (L. donovani ).
 After inoculation of the organism into the skin by the
sandfly, the child may have a
 asymptomatic infection or
 an oligosymptomatic illness
 active kala-azar.

96.  During the 1st few wk to mo of disease evolution, the fever
is intermittent, there is weakness and loss of energy, and
the spleen begins to enlarge
 The classic clinical features of high fever, marked
splenomegaly, hepatomegaly, and severe cachexia typically
develop 3-6 mo after the onset of the illness,
 but a rapid clinical course over 1 mo has been noted in up
to 20% of patients .
 During the 1st few wk to mo of disease evolution, the fever
is intermittent, there is weakness and loss of energy, and
the spleen begins to enlarge
 The classic clinical features of high fever, marked
splenomegaly, hepatomegaly, and severe cachexia typically
develop 3-6 mo after the onset of the illness,
 but a rapid clinical course over 1 mo has been noted in up
to 20% of patients .

97.  At the terminal stages of kala-azar, the
hepatosplenomegaly is massive, there is gross wasting, the
pancytopenia is profound, and jaundice, edema, and
ascites, bacterial superinfection may be present
 A younger age , HIV coinfection, and underlying
malnutrition are risk factors for the development and more
rapid evolution of active VL.
 Death occurs in >90% of patients without treatment and in
4–10% of treated patients.
 At the terminal stages of kala-azar, the
hepatosplenomegaly is massive, there is gross wasting, the
pancytopenia is profound, and jaundice, edema, and
ascites, bacterial superinfection may be present
 A younger age , HIV coinfection, and underlying
malnutrition are risk factors for the development and more
rapid evolution of active VL.
 Death occurs in >90% of patients without treatment and in
4–10% of treated patients.

98. post–kala-azar dermal
leishmaniasis
 diffuse skin lesions, which develop in small
percentage of patients previously treated for VL.
 may appear during or shortly after therapy (Africa) or
up to several years later (India).
 hypopigmented, erythematous, or nodular and usually
involve the face and torso.
 They may persist for several months or for many years
 diffuse skin lesions, which develop in small
percentage of patients previously treated for VL.
 may appear during or shortly after therapy (Africa) or
up to several years later (India).
 hypopigmented, erythematous, or nodular and usually
involve the face and torso.
 They may persist for several months or for many years

99. Laboratory Findings
 Patients with CL or ML generally do not have abnormal
laboratory results unless the lesions are secondarily
infected with bacteria.
 Laboratory findings associated with classic kala-azar
include
 anemia(hemoglobin, 5-8 mg/dL),
 thrombocytopenia,
 leukopenia (2,000-3,000 cells/μL),
 elevated hepatic transaminase levels,
 hyperglobulinemia (>5 g/dL)
 Patients with CL or ML generally do not have abnormal
laboratory results unless the lesions are secondarily
infected with bacteria.
 Laboratory findings associated with classic kala-azar
include
 anemia(hemoglobin, 5-8 mg/dL),
 thrombocytopenia,
 leukopenia (2,000-3,000 cells/μL),
 elevated hepatic transaminase levels,
 hyperglobulinemia (>5 g/dL)

100. Differential Diagnosis
 LCL include sporotrichosis, blastomycosis, chromomycosis,
lobomycosis, cutaneous tuberculosis, atypical mycobacterial
infection, leprosy, ecthyma, syphilis, yaws, and neoplasms.
 ML , syphilis, tertiary yaws, histoplasmosis, and
paracoccidioidomycosis, as well as sarcoidosis, granulomatosis
with polyangiitis, midline granuloma, and carcinoma,
 VL, The clinical picture may also be consistent with that of
malaria,typhoid fever, miliary tuberculosis, schistosomiasis,
brucellosis, amebic liver abscess, infectious mononucleosis,
lymphoma, and leukemia.
 LCL include sporotrichosis, blastomycosis, chromomycosis,
lobomycosis, cutaneous tuberculosis, atypical mycobacterial
infection, leprosy, ecthyma, syphilis, yaws, and neoplasms.
 ML , syphilis, tertiary yaws, histoplasmosis, and
paracoccidioidomycosis, as well as sarcoidosis, granulomatosis
with polyangiitis, midline granuloma, and carcinoma,
 VL, The clinical picture may also be consistent with that of
malaria,typhoid fever, miliary tuberculosis, schistosomiasis,
brucellosis, amebic liver abscess, infectious mononucleosis,
lymphoma, and leukemia.

101. Diagnosis
 Clinical
 Serologic
 Tissue culture
 Geimsa stain
 Clinical
 Serologic
 Tissue culture
 Geimsa stain

102. Treatment
 not routinely indicated for uncomplicated LCL
 Lesions that are extensive, severely inflamed, or located
where a scar would result in disability (near a joint) or
cosmetic disfigurement (face or ear), that involve the
lymphatics, or that do not begin healing within 3-4 mo
should be treated.
 Cutaneous lesion caused by Viannia subgenus (New
World) and L. tropica (Old World), should be treated .
 All patients with VL or ML should receive therapy.
 not routinely indicated for uncomplicated LCL
 Lesions that are extensive, severely inflamed, or located
where a scar would result in disability (near a joint) or
cosmetic disfigurement (face or ear), that involve the
lymphatics, or that do not begin healing within 3-4 mo
should be treated.
 Cutaneous lesion caused by Viannia subgenus (New
World) and L. tropica (Old World), should be treated .
 All patients with VL or ML should receive therapy.

103.  sodium stibogluconate
 the recommended regimen is 20 mg/kg/day intravenously
(IV) or intramuscularly (IM) for 20 days (for LCL and DCL)
or 28 days (for ML and VL).
 Amphotericin B desoxycholate at doses of
 0.5-1.0 mg/kg every day or every other day for 14-20 doses.
 Miltefosine, 2.5 mg/kg/day orally for 20-28 days,
 sodium stibogluconate
 the recommended regimen is 20 mg/kg/day intravenously
(IV) or intramuscularly (IM) for 20 days (for LCL and DCL)
or 28 days (for ML and VL).
 Amphotericin B desoxycholate at doses of
 0.5-1.0 mg/kg every day or every other day for 14-20 doses.
 Miltefosine, 2.5 mg/kg/day orally for 20-28 days,

104. Prevention
 use of insect repellent and
 permethrin-impregnated mosquito netting.

105. Tuberculosis (Mycobacterium
tuberculosis)
 Etiology
 There are 5 closely related mycobacteria in the Mycobacterium tuberculosis
complex:
 M. tuberculosis,
 M. bovis,
 M. africanum,
 M. microti, and
 M. canetti.
 M. tuberculosis is the most important cause of tuberculosis (TB) disease in
humans.
 The tubercle bacilli are non–spore-forming, nonmotile, pleomorphic,weakly
gram-positive curved rods 1-5 μm long.
 Etiology
 There are 5 closely related mycobacteria in the Mycobacterium tuberculosis
complex:
 M. tuberculosis,
 M. bovis,
 M. africanum,
 M. microti, and
 M. canetti.
 M. tuberculosis is the most important cause of tuberculosis (TB) disease in
humans.
 The tubercle bacilli are non–spore-forming, nonmotile, pleomorphic,weakly
gram-positive curved rods 1-5 μm long.

106.  They are obligate aerobes
 These mycobacteria grow best at 37-41°C (98.6-105.8°F).
 A hallmark of all mycobacteria is acid fastness
 Mycobacteria grow slowly, with a generation time of 12-24 hr.
 Isolation from clinical specimens on solid synthetic media
usually takes 3-6 wk, and drug susceptibility testing requires an
additional 2-4 wk.
 Growth can be detected in 1-3 wk in selective liquid medium
using radiolabeled nutrients.
 They are obligate aerobes
 These mycobacteria grow best at 37-41°C (98.6-105.8°F).
 A hallmark of all mycobacteria is acid fastness
 Mycobacteria grow slowly, with a generation time of 12-24 hr.
 Isolation from clinical specimens on solid synthetic media
usually takes 3-6 wk, and drug susceptibility testing requires an
additional 2-4 wk.
 Growth can be detected in 1-3 wk in selective liquid medium
using radiolabeled nutrients.

107.  Clinical Stages
 There are 3 major clinical stages of tuberculosis:
 exposure,
 infection, and
 disease.
 Clinical Stages
 There are 3 major clinical stages of tuberculosis:
 exposure,
 infection, and
 disease.

108.  Exposure means a child has had significant contact (shared the
air) with an adult or adolescent with infectious tuberculosis but
lacks proof of infection.
 In this stage, the tuberculin skin test (TST) or interferon-γ
release assay (IGRA) result is negative, the chest radiograph is
normal, the physical examination is normal, and the child lacks
signs or symptoms of disease.
 However, the child may be infected and develop TB disease
rapidly, since there may not have been enough time for the TST
or IGRA to turn positive.
 Exposure means a child has had significant contact (shared the
air) with an adult or adolescent with infectious tuberculosis but
lacks proof of infection.
 In this stage, the tuberculin skin test (TST) or interferon-γ
release assay (IGRA) result is negative, the chest radiograph is
normal, the physical examination is normal, and the child lacks
signs or symptoms of disease.
 However, the child may be infected and develop TB disease
rapidly, since there may not have been enough time for the TST
or IGRA to turn positive.

109.  Tuberculosis infection (TBI) occurs when the individual
inhales droplet nuclei containing M. tuberculosis, which
survive intracellularly within the lung and associated
lymphoid tissue.
 The hallmark of TBI is a positive TST or IGRA result.
 In this stage the child has no signs or symptoms, a normal
physical examination, and the chest radiograph is either
normal or reveals only granuloma or calcifications in the
lung parenchyma
 Tuberculosis infection (TBI) occurs when the individual
inhales droplet nuclei containing M. tuberculosis, which
survive intracellularly within the lung and associated
lymphoid tissue.
 The hallmark of TBI is a positive TST or IGRA result.
 In this stage the child has no signs or symptoms, a normal
physical examination, and the chest radiograph is either
normal or reveals only granuloma or calcifications in the
lung parenchyma

110.  Disease occurs when signs or symptoms or radiographic
manifestations caused by M. tuberculosis become
apparent.
 Not all infected individuals have the same risk of
developing disease.
 An immunocompetent adult with untreated TBI has
approximately a 5–10% lifetime risk of developing disease.
 In contrast, an infected child <1 yr old has a 40% chance of
developing TB disease within 9 mo.
 Disease occurs when signs or symptoms or radiographic
manifestations caused by M. tuberculosis become
apparent.
 Not all infected individuals have the same risk of
developing disease.
 An immunocompetent adult with untreated TBI has
approximately a 5–10% lifetime risk of developing disease.
 In contrast, an infected child <1 yr old has a 40% chance of
developing TB disease within 9 mo.

111.  Epidemiology
 WHO estimates that since 2015, tuberculosis has
surpassed HIV/AIDS as the leading cause of death
from an infectious disease worldwide, and that almost
one third of the world's population(2.5 billion people)
is infected with M. tuberculosis.
 Approximately 95% of TB cases occur in the
developing world
 Epidemiology
 WHO estimates that since 2015, tuberculosis has
surpassed HIV/AIDS as the leading cause of death
from an infectious disease worldwide, and that almost
one third of the world's population(2.5 billion people)
is infected with M. tuberculosis.
 Approximately 95% of TB cases occur in the
developing world

112.  The global burden of tuberculosis is influenced by
several factors, including:
 the HIV pandemic;
 the development of multidrug-resistant (MDR)
tuberculosis ; and
 low access of populations to both diagnostic tests and
effective medical therapy.
 The global burden of tuberculosis is influenced by
several factors, including:
 the HIV pandemic;
 the development of multidrug-resistant (MDR)
tuberculosis ; and
 low access of populations to both diagnostic tests and
effective medical therapy.

113.  Most children are infected with M. tuberculosis in their home by
someone close to them,
 but outbreaks of childhood tuberculosis also have occurred in
 elementary and high schools,
 nursery schools,
 daycare centers and homes,
 churches,
 school buses, and
 sports teams.
 children with HIV infection are at increased risk for developing
tuberculosis after infection.
 Most children are infected with M. tuberculosis in their home by
someone close to them,
 but outbreaks of childhood tuberculosis also have occurred in
 elementary and high schools,
 nursery schools,
 daycare centers and homes,
 churches,
 school buses, and
 sports teams.
 children with HIV infection are at increased risk for developing
tuberculosis after infection.

114.  RISK FACTORS FOR PROGRESSION OF TUBERCULOSIS
INFECTION TO TUBERCULOSIS DISEASE
 Infants and children ≤4 yr old, especially those <2 yr old
 Adolescents and young adults
 Persons co-infected with human immunodeficiency virus
 Persons with skin test conversion in the past 1-2 yr
 Persons who are immunocompromised, especially in cases of
malignancy and solid-organ transplantation,
 immunosuppressive medical treatments including anti–tumor necrosis
factor therapies, diabetes mellitus,chronic renal failure, silicosis, and
malnutrition
 RISK FACTORS FOR PROGRESSION OF TUBERCULOSIS
INFECTION TO TUBERCULOSIS DISEASE
 Infants and children ≤4 yr old, especially those <2 yr old
 Adolescents and young adults
 Persons co-infected with human immunodeficiency virus
 Persons with skin test conversion in the past 1-2 yr
 Persons who are immunocompromised, especially in cases of
malignancy and solid-organ transplantation,
 immunosuppressive medical treatments including anti–tumor necrosis
factor therapies, diabetes mellitus,chronic renal failure, silicosis, and
malnutrition

115.  RISK FACTORS FOR DRUG-RESISTANT TUBERCULOSIS
 Personal or contact history of treatment for tuberculosis
 Contacts of patients with drug-resistant tuberculosis
 Birth or residence in a country with a high rate of drug resistance
 Poor response to standard therapy
 Positive sputum smears (acid-fast bacilli) or culture ≥2 mo after
initiating appropriate therapy
 RISK FACTORS FOR DRUG-RESISTANT TUBERCULOSIS
 Personal or contact history of treatment for tuberculosis
 Contacts of patients with drug-resistant tuberculosis
 Birth or residence in a country with a high rate of drug resistance
 Poor response to standard therapy
 Positive sputum smears (acid-fast bacilli) or culture ≥2 mo after
initiating appropriate therapy

116.  The incidence of drug-resistant tuberculosis has
increased dramatically throughout the world.
 MDR-TB is defined as resistance to at least isoniazid
and rifampin;
 extensively drug-resistant tuberculosis includes MDR-
TB plus resistance to any fluoroquinolone and at least 1
of 3 injectable drugs (kanamycin, capreomycin,
amikacin).
 The incidence of drug-resistant tuberculosis has
increased dramatically throughout the world.
 MDR-TB is defined as resistance to at least isoniazid
and rifampin;
 extensively drug-resistant tuberculosis includes MDR-
TB plus resistance to any fluoroquinolone and at least 1
of 3 injectable drugs (kanamycin, capreomycin,
amikacin).

117.  Transmission
 usually by inhalation of airborne mucus droplet
nuclei, particles 1-5 μm in diameter that contain M.
tuberculosis.
 rarely occurs by direct contact with an infected
discharge or a contaminated fomite.
 Transmission
 usually by inhalation of airborne mucus droplet
nuclei, particles 1-5 μm in diameter that contain M.
tuberculosis.
 rarely occurs by direct contact with an infected
discharge or a contaminated fomite.

118.  The chance of transmission increases when
 the patient has a positive acid-fast smear of sputum,
 an extensive upper lobe infiltrate or cavity,
 copious production of thin sputum, and
 severe and forceful cough.
 poor air circulation
 Most adults no longer transmit the organism within several days
to 2 wk after beginning adequate chemotherapy, but some
patients remain infectious for many weeks.
 The chance of transmission increases when
 the patient has a positive acid-fast smear of sputum,
 an extensive upper lobe infiltrate or cavity,
 copious production of thin sputum, and
 severe and forceful cough.
 poor air circulation
 Most adults no longer transmit the organism within several days
to 2 wk after beginning adequate chemotherapy, but some
patients remain infectious for many weeks.

119.  M. bovis can penetrate the gastrointestinal (GI)
mucosa or invade the lymphatic tissue of the
oropharynx when large numbers of the organism are
ingested.
 M. bovis can penetrate the gastrointestinal (GI)
mucosa or invade the lymphatic tissue of the
oropharynx when large numbers of the organism are
ingested.

120. Pathogenesis
 Tubercle bacilli  multiply within alveoli and alveolar
ducts macrophages lymphatic vessels regional
lymph nodes.
 The primary complex of tuberculosis (Ghon
complex),includes local infection at the portal of
entry (lung in >98%) and the regional lymph nodes
that drain the area.

 Tubercle bacilli  multiply within alveoli and alveolar
ducts macrophages lymphatic vessels regional
lymph nodes.
 The primary complex of tuberculosis (Ghon
complex),includes local infection at the portal of
entry (lung in >98%) and the regional lymph nodes
that drain the area.


121. Pathogenesis
 The tissue reaction in the lung parenchyma and lymph
nodes intensifies (2–12 wk) as the organisms grow in
number and tissue hypersensitivity develops.
 The parenchymal portion of the primary complex often
heals completely by fibrosis or calcification after
undergoing caseous necrosis and encapsulation.
 If caseation is intense, the center of the lesion liquefies and
empties into the associated bronchus, leaving a residual
cavity.
 The tissue reaction in the lung parenchyma and lymph
nodes intensifies (2–12 wk) as the organisms grow in
number and tissue hypersensitivity develops.
 The parenchymal portion of the primary complex often
heals completely by fibrosis or calcification after
undergoing caseous necrosis and encapsulation.
 If caseation is intense, the center of the lesion liquefies and
empties into the associated bronchus, leaving a residual
cavity.

122.  Inflamed caseous nodes can attach to the bronchial
wall and erode through it, causing endobronchial
tuberculosis or a fistula tract.
 The caseum causes complete obstruction of the
bronchus.
 The resulting lesion, a combination of pneumonitis
and atelectasis, has been called a collapse-
consolidation or segmental lesion
 Inflamed caseous nodes can attach to the bronchial
wall and erode through it, causing endobronchial
tuberculosis or a fistula tract.
 The caseum causes complete obstruction of the
bronchus.
 The resulting lesion, a combination of pneumonitis
and atelectasis, has been called a collapse-
consolidation or segmental lesion

123.  Tuberculous bacillus in lungs leads to one of four
possible outcomes
 Immediate clearance of the organism
 Chronic or latent infection
 Rapidly progressive disease (or primary disease)
 Active disease many years after the infection
(reactivation disease)
 Tuberculous bacillus in lungs leads to one of four
possible outcomes
 Immediate clearance of the organism
 Chronic or latent infection
 Rapidly progressive disease (or primary disease)
 Active disease many years after the infection
(reactivation disease)
123

124.  During the development of the primary complex,
tubercle bacilli are carried to most tissues of the body
through the blood and lymphatic vessels
 Disseminated tuberculosis occurs if the number of
circulating bacilli is large and the host's cellular
immune response is inadequate
 During the development of the primary complex,
tubercle bacilli are carried to most tissues of the body
through the blood and lymphatic vessels
 Disseminated tuberculosis occurs if the number of
circulating bacilli is large and the host's cellular
immune response is inadequate

125.  The time between initial infection and clinically apparent TB
disease is variable.
 Disseminated and meningeal tuberculosis are occurring within
2-6 mo of acquisition.
 lymph node or endobronchial tuberculosis within 3-9 mo.
 bones and joints take several years to develop,
 renal lesions decades after infection
 Extrapulmonary manifestations are more common in children
than adults and develop in 25–35% of children with tuberculosis,
vs approximately 10% of immunocompetent adults.
 The time between initial infection and clinically apparent TB
disease is variable.
 Disseminated and meningeal tuberculosis are occurring within
2-6 mo of acquisition.
 lymph node or endobronchial tuberculosis within 3-9 mo.
 bones and joints take several years to develop,
 renal lesions decades after infection
 Extrapulmonary manifestations are more common in children
than adults and develop in 25–35% of children with tuberculosis,
vs approximately 10% of immunocompetent adults.

126.  Immunity
 Cell-mediated immunity develops 2-12 wk after infection,
along with tissue hypersensitivity .
 The pathologic events in the initial TBI seem to depend on
the balance among
 the mycobacterial antigen load;
 cell-mediated immunity, which enhances intracellular
killing; and
 tissue hypersensitivity, which promotes extracellular
killing
 Immunity
 Cell-mediated immunity develops 2-12 wk after infection,
along with tissue hypersensitivity .
 The pathologic events in the initial TBI seem to depend on
the balance among
 the mycobacterial antigen load;
 cell-mediated immunity, which enhances intracellular
killing; and
 tissue hypersensitivity, which promotes extracellular
killing

127. Clinical manifestations and
diagnosis
 Infants:
 Nonproductive cough and mild dyspnea are the most
common symptoms.
 Systemic complaints such as fever, night sweats,
anorexia, and decreased activity occur less often.
 localized wheezing or decreased breath sounds that may
be accompanied by tachypnea or, rarely, respiratory
distress.
 Infants:
 Nonproductive cough and mild dyspnea are the most
common symptoms.
 Systemic complaints such as fever, night sweats,
anorexia, and decreased activity occur less often.
 localized wheezing or decreased breath sounds that may
be accompanied by tachypnea or, rarely, respiratory
distress.
127

128. Primary pulmonary disease
 The primary complex includes the parynchymal pulmonary
focus (70% sub pleural) + the regional LN
 The hall mark in the lung is the relatively large size of the
regional LAPS
 The usual sequence is hilar LAP →focal hyperinflation
→atelectasis:(collapse consolidation or segmental TB)
 Rarely, inflammed caseous LNS attach to endobronchial
wall-erosion through the wall →endobronchial TB (fistula
tract)
 The primary complex includes the parynchymal pulmonary
focus (70% sub pleural) + the regional LN
 The hall mark in the lung is the relatively large size of the
regional LAPS
 The usual sequence is hilar LAP →focal hyperinflation
→atelectasis:(collapse consolidation or segmental TB)
 Rarely, inflammed caseous LNS attach to endobronchial
wall-erosion through the wall →endobronchial TB (fistula
tract)
128

129. Progressive primary pulmonary
disease
 Rare and Serious complication
 Primary focus expansion→ large caseous center→
liquefaction → cavity (large number of bacilli)
 High fever, severe cough with sputum production, weight
loss, and night sweats are common.
 Physical signs include diminished breath sounds, rales, and
dullness or egophony over the cavity
 Rare and Serious complication
 Primary focus expansion→ large caseous center→
liquefaction → cavity (large number of bacilli)
 High fever, severe cough with sputum production, weight
loss, and night sweats are common.
 Physical signs include diminished breath sounds, rales, and
dullness or egophony over the cavity

130. Reactivation tuberculosis
 Rare in childhood
 Reactivation TB results when the persistent bacteria in a host suddenly
proliferate.
 Only 5 to 10 percent of patients with no underlying medical problems
who become infected develop active disease in their lifetime
 Involves the original parenchymal focus, lymph nodes, or the apical
seedings (Simon foci) established during the hematogenous phase of
the early infection.
 Remains localized to the lungs with little regional lymph node
involvement and less caseation.
 Occurs at the lung apices, and disseminated disease is unusual, unless
the host is severely immunosuppressed.
 Rare in childhood
 Reactivation TB results when the persistent bacteria in a host suddenly
proliferate.
 Only 5 to 10 percent of patients with no underlying medical problems
who become infected develop active disease in their lifetime
 Involves the original parenchymal focus, lymph nodes, or the apical
seedings (Simon foci) established during the hematogenous phase of
the early infection.
 Remains localized to the lungs with little regional lymph node
involvement and less caseation.
 Occurs at the lung apices, and disseminated disease is unusual, unless
the host is severely immunosuppressed.
130

131. Reactivation tuberculosis
 Older children and adolescents with reactivation
tuberculosis are more likely to experience fever,
anorexia, malaise, weight loss, night sweats,
productive cough, hemoptysis, and chest pain than
children with primary pulmonary tuberculosis.
 Radiography: extensive infiltrates or thick-walled
cavities in the upper lobes
 Older children and adolescents with reactivation
tuberculosis are more likely to experience fever,
anorexia, malaise, weight loss, night sweats,
productive cough, hemoptysis, and chest pain than
children with primary pulmonary tuberculosis.
 Radiography: extensive infiltrates or thick-walled
cavities in the upper lobes
131

132. Immunosuppressive conditions
associated with reactivation TB
 Diminution in CMI associated with old age,measeles
 Corticosteroid use
 Malignant lymphoma
 HIV infection and AIDS
 End-stage renal disease
 Diabetes mellitus
 Diminution in CMI associated with old age,measeles
 Corticosteroid use
 Malignant lymphoma
 HIV infection and AIDS
 End-stage renal disease
 Diabetes mellitus
132

133. Pleural effusion
 It is infrequent in children <6 yr of age and rare in children <2 yr of age
 Discharge of bacilli into pleural space (pulmonary focus or caseated LN)
 Fever, SOB, chest pain on deep inspiration, decreased breath sound
 Pleural fluid is usually yellow and only occasionally tinged with blood, specific gravity
1.012–1.025, protein 2–4 g/dL, and glucose may be low, (20–40 mg/dL).
 WBC shows early predominance of polymorphonuclear cells followed by a high
percentage of lymphocytes.
 Acid-fast smears of the pleural fluid are rarely positive.
 Cultures +ve in <30% of cases.
 Biopsy of the pleural membrane is more likely to yield a positive acid-fast stain or
culture,
 The prognosis is excellent, but radiographic resolution often takes months.
 It is infrequent in children <6 yr of age and rare in children <2 yr of age
 Discharge of bacilli into pleural space (pulmonary focus or caseated LN)
 Fever, SOB, chest pain on deep inspiration, decreased breath sound
 Pleural fluid is usually yellow and only occasionally tinged with blood, specific gravity
1.012–1.025, protein 2–4 g/dL, and glucose may be low, (20–40 mg/dL).
 WBC shows early predominance of polymorphonuclear cells followed by a high
percentage of lymphocytes.
 Acid-fast smears of the pleural fluid are rarely positive.
 Cultures +ve in <30% of cases.
 Biopsy of the pleural membrane is more likely to yield a positive acid-fast stain or
culture,
 The prognosis is excellent, but radiographic resolution often takes months.
133

134. Pericardial disease
 Rare ( 0.5-4%) of cases TB
 From Direct invasion or lymphatic drainage from subcarinal LNS
 low-grade fever, malaise, and weight loss
 Chest pain (unusual in children)
 Pericardial friction rub
 Distant heart sound
 Pulsus parodxus
 The pericardial fluid is typically serofibrinous or hemorrhagic.
 AFB rarely positive, but cultures are positive in 30–70% of cases.
 The culture yield from pericardial biopsy may be higher.
 Partial or complete pericardiectomy may be required when constrictive
pericarditis develops.
 Rare ( 0.5-4%) of cases TB
 From Direct invasion or lymphatic drainage from subcarinal LNS
 low-grade fever, malaise, and weight loss
 Chest pain (unusual in children)
 Pericardial friction rub
 Distant heart sound
 Pulsus parodxus
 The pericardial fluid is typically serofibrinous or hemorrhagic.
 AFB rarely positive, but cultures are positive in 30–70% of cases.
 The culture yield from pericardial biopsy may be higher.
 Partial or complete pericardiectomy may be required when constrictive
pericarditis develops.
134

135. Disseminated disease
(lymphohematogenous)
 If the bacterial growth continues to remain unchecked, the bacilli may spread
hematogenously to produce disseminated TB.
 Miliary TB describes a disseminated disease with lesions resembling millet
seeds
 Although the clinical picture may be acute, more often it is indolent and
prolonged, with spiking fever accompanying the release of organisms into the
bloodstream.
 Multiple organ involvement is common, leading to hepatomegaly,
splenomegaly, lymphadenitis in superficial or deep nodes, and papulonecrotic
tuberculids appearing on the skin. Bones and joints or kidneys also may
become involved.
 Meningitis occurs only late in the course of the disease.
 If the bacterial growth continues to remain unchecked, the bacilli may spread
hematogenously to produce disseminated TB.
 Miliary TB describes a disseminated disease with lesions resembling millet
seeds
 Although the clinical picture may be acute, more often it is indolent and
prolonged, with spiking fever accompanying the release of organisms into the
bloodstream.
 Multiple organ involvement is common, leading to hepatomegaly,
splenomegaly, lymphadenitis in superficial or deep nodes, and papulonecrotic
tuberculids appearing on the skin. Bones and joints or kidneys also may
become involved.
 Meningitis occurs only late in the course of the disease.
135

136. Milliary tuberculosis
 Milliary tuberculosis (TB) refers to clinical disease resulting from the
uncontrolled hematogenous dissemination of Mycobacterium
tuberculosis
 Originally a pathologic and then a radiologic description, the term
miliary TB is now used to denote all forms of progressive, widely
disseminated hematogenous TB, even if the classical pathologic or
radiologic findings are absent.
 most common in infants, young children and immunosuppressed.
 Lesions are often larger and more numerous in the lungs, spleen, liver,
and bone marrow than other tissues.
 Milliary tuberculosis (TB) refers to clinical disease resulting from the
uncontrolled hematogenous dissemination of Mycobacterium
tuberculosis
 Originally a pathologic and then a radiologic description, the term
miliary TB is now used to denote all forms of progressive, widely
disseminated hematogenous TB, even if the classical pathologic or
radiologic findings are absent.
 most common in infants, young children and immunosuppressed.
 Lesions are often larger and more numerous in the lungs, spleen, liver,
and bone marrow than other tissues.
136

137. Milliary tuberculosis
 onset is insidious with early systemic signs, including anorexia, weight
loss, and low-grade fever
 Generalized lymphadenopathy and hepatosplenomegaly develop
within several weeks in about 50% of cases.
 The fever may then become higher and more sustained, although the
chest radiograph usually is normal and respiratory symptoms are
minor or absent. Within several more weeks, the lungs may become
filled with tubercles, and dyspnea, cough, rales, or wheezing occur.
 respiratory distress, hypoxia, and pneumothorax, or
pneumomediastinum
 onset is insidious with early systemic signs, including anorexia, weight
loss, and low-grade fever
 Generalized lymphadenopathy and hepatosplenomegaly develop
within several weeks in about 50% of cases.
 The fever may then become higher and more sustained, although the
chest radiograph usually is normal and respiratory symptoms are
minor or absent. Within several more weeks, the lungs may become
filled with tubercles, and dyspnea, cough, rales, or wheezing occur.
 respiratory distress, hypoxia, and pneumothorax, or
pneumomediastinum

138. Milliary tuberculosis
 Signs or symptoms of meningitis or peritonitis are found in 20–
40% of patients with advanced disease.
 Cutaneous lesions include papulonecrotic tuberculids, nodules,
or purpura
 tuberculin skin test is nonreactive in up to 40% of patients with
disseminated tuberculosis
 The resolution of miliary tuberculosis is slow, even with proper
therapy. Fever usually declines within 2–3 wk of starting
chemotherapy, but the chest radiographic abnormalities may not
resolve for many months.
 corticosteroids hasten symptomatic relief.
 Signs or symptoms of meningitis or peritonitis are found in 20–
40% of patients with advanced disease.
 Cutaneous lesions include papulonecrotic tuberculids, nodules,
or purpura
 tuberculin skin test is nonreactive in up to 40% of patients with
disseminated tuberculosis
 The resolution of miliary tuberculosis is slow, even with proper
therapy. Fever usually declines within 2–3 wk of starting
chemotherapy, but the chest radiographic abnormalities may not
resolve for many months.
 corticosteroids hasten symptomatic relief.

139. Upper respiratory disease
 Laryngeal TB: have a croupy cough, sore throat,
hoarseness, and dysphagia. extensive upper lobe
pulmonary disease
 Tb of the middle ear(aspiration of infected pulmonary
secretions into the middle ear or hematogenous spread)
 unilateral otorrhea, tinnitus, decreased hearing, facial
paralysis, and a perforated tympanic membrane and LAP
 Diagnosis is difficult
 Laryngeal TB: have a croupy cough, sore throat,
hoarseness, and dysphagia. extensive upper lobe
pulmonary disease
 Tb of the middle ear(aspiration of infected pulmonary
secretions into the middle ear or hematogenous spread)
 unilateral otorrhea, tinnitus, decreased hearing, facial
paralysis, and a perforated tympanic membrane and LAP
 Diagnosis is difficult
139

140. Lymph node TB:
 often referred to as scrofula, is the most common form of
extrapulmonary TB.
 Most cases occur within 6–9 mo of initial infection.
 usually enlarge gradually in the early stages of lymph node disease.
 firm but not hard, discrete, and non tender.
 Disease is most often unilateral, but bilateral involvement may occur
 As infection progresses, multiple nodes are infected, resulting in a
mass of matted nodes.
 Systemic signs and symptoms other than a low-grade fever are usually
absent.
 often referred to as scrofula, is the most common form of
extrapulmonary TB.
 Most cases occur within 6–9 mo of initial infection.
 usually enlarge gradually in the early stages of lymph node disease.
 firm but not hard, discrete, and non tender.
 Disease is most often unilateral, but bilateral involvement may occur
 As infection progresses, multiple nodes are infected, resulting in a
mass of matted nodes.
 Systemic signs and symptoms other than a low-grade fever are usually
absent.

141. CNS disease
 Most serious Complication and fatal without prompt and
appropriate treatment
 metastatic caseous lesion in the cerebral cortex or meninges
→increases in size → discharges small numbers of tubercle
bacilli into the subarachnoid space→infiltrates the
corticomeningeal blood vessels →inflammation, obstruction,
and subsequent infarction of cerebral cortex
 Commenest site is brainstem and is associated with cranial
nerves III, VI, and VII involvement.
 The exudate also interferes with CSF in & out flow→
communicative hydrocephalus.
 Most serious Complication and fatal without prompt and
appropriate treatment
 metastatic caseous lesion in the cerebral cortex or meninges
→increases in size → discharges small numbers of tubercle
bacilli into the subarachnoid space→infiltrates the
corticomeningeal blood vessels →inflammation, obstruction,
and subsequent infarction of cerebral cortex
 Commenest site is brainstem and is associated with cranial
nerves III, VI, and VII involvement.
 The exudate also interferes with CSF in & out flow→
communicative hydrocephalus.
141

142. TB meningitis…
 is most common in children between 6 mo and 4 yr of age.
 complicates about 0.3% tuberculosis infections in children
 The clinical progression may be rapid or gradual.
 3 stages:
 The 1st stage: typically lasts 1–2 wk
 nonspecific symptoms, such as fever, headache, irritability, drowsiness, and
malaise.
 The 2nd stage: lethargy, nuchal rigidity, seizures, positive Kernig or
Brudzinski signs, hypertonia, vomiting, cranial nerve palsies, and other
focal neurologic signs.
 The 3rd stage : coma, hemiplegia or paraplegia, hypertension,
decerebrate posturing, deterioration of vital signs, and eventually
death.
 is most common in children between 6 mo and 4 yr of age.
 complicates about 0.3% tuberculosis infections in children
 The clinical progression may be rapid or gradual.
 3 stages:
 The 1st stage: typically lasts 1–2 wk
 nonspecific symptoms, such as fever, headache, irritability, drowsiness, and
malaise.
 The 2nd stage: lethargy, nuchal rigidity, seizures, positive Kernig or
Brudzinski signs, hypertonia, vomiting, cranial nerve palsies, and other
focal neurologic signs.
 The 3rd stage : coma, hemiplegia or paraplegia, hypertension,
decerebrate posturing, deterioration of vital signs, and eventually
death.

143. CNS TB: TB meningitis…
 Diagnosis:
 examination and culture of CSF:
 WBC- 10 to 500 cells/mm3, lymphocyte predominant
 glucose is typically <40 mg/dL.
 protein high (400–5,000 mg/dL)
 AFB is positive in up to 30% of cases
 culture is positive in 50–70% of cases
 CT or MRI - basilar enhancement and communicating
hydrocephalus with signs of cerebral edema or early focal
ischemia are the most common findings.
 Diagnosis:
 examination and culture of CSF:
 WBC- 10 to 500 cells/mm3, lymphocyte predominant
 glucose is typically <40 mg/dL.
 protein high (400–5,000 mg/dL)
 AFB is positive in up to 30% of cases
 culture is positive in 50–70% of cases
 CT or MRI - basilar enhancement and communicating
hydrocephalus with signs of cerebral edema or early focal
ischemia are the most common findings.

144. CNS TB: Tuberculoma
 a tumor-like mass resulting from aggregation of caseous tubercles that usually
presents clinically as a brain tumor.
 account for up to 40% of brain tumors in some areas of the world.
 in children they are often infratentorial, located at the base of the brain near
the cerebellum.
 often singular but may be multiple.
 The most common symptoms are headache, fever, and convulsions.
 CT or MRI - discrete lesions with surrounding edema. Contrast medium –ring
enhancing lesion.
 a tumor-like mass resulting from aggregation of caseous tubercles that usually
presents clinically as a brain tumor.
 account for up to 40% of brain tumors in some areas of the world.
 in children they are often infratentorial, located at the base of the brain near
the cerebellum.
 often singular but may be multiple.
 The most common symptoms are headache, fever, and convulsions.
 CT or MRI - discrete lesions with surrounding edema. Contrast medium –ring
enhancing lesion.

145. Bone and Joint TB:
 mostly involves the vertebrae.
 TB spondylitis progresses to Pott disease, in which destruction of the
vertebral bodies leads to gibbus deformity and kyphosis.

 Skeletal TB is a late complication of tuberculosis
 may resemble pyogenic and fungal infections, or bone tumors.
 A bone biopsy is essential to confirm the diagnosis.
 mostly involves the vertebrae.
 TB spondylitis progresses to Pott disease, in which destruction of the
vertebral bodies leads to gibbus deformity and kyphosis.

 Skeletal TB is a late complication of tuberculosis
 may resemble pyogenic and fungal infections, or bone tumors.
 A bone biopsy is essential to confirm the diagnosis.

146. GI TB:peritonitis
 Generalized peritonitis: hematogenous dissemination.
 Localized peritonitis :direct extension from an abdominal lymph node,
intestinal focus, or genitourinary tuberculosis.
 Rarely, the lymph nodes, omentum, and peritoneum become matted and can
be palpated as a “doughy” irregular nontender mass.
 Abdominal pain or tenderness, ascites, anorexia, and low-grade fever are
typical manifestations.
 diagnosis : paracentesis with appropriate stains and cultures
 Generalized peritonitis: hematogenous dissemination.
 Localized peritonitis :direct extension from an abdominal lymph node,
intestinal focus, or genitourinary tuberculosis.
 Rarely, the lymph nodes, omentum, and peritoneum become matted and can
be palpated as a “doughy” irregular nontender mass.
 Abdominal pain or tenderness, ascites, anorexia, and low-grade fever are
typical manifestations.
 diagnosis : paracentesis with appropriate stains and cultures

147. GI TB:Tb enteritis
 caused by hematogenous dissemination or by swallowing
tubercle bacilli.
 The jejunum and ileum near Peyer patches and the appendix are
the most common sites of involvement.
 shallow ulcers that cause pain, diarrhea or constipation, and
weight loss with low-grade fever.
 Diagnosis: Biopsy, acid-fast stain, and culture of the lesions
 caused by hematogenous dissemination or by swallowing
tubercle bacilli.
 The jejunum and ileum near Peyer patches and the appendix are
the most common sites of involvement.
 shallow ulcers that cause pain, diarrhea or constipation, and
weight loss with low-grade fever.
 Diagnosis: Biopsy, acid-fast stain, and culture of the lesions

148. GU TB:
 Renal Tb is rare in children.
 lymphohematogenous dissemination to kidney.
 Renal tuberculosis is often clinically silent in its early stages, marked
only by sterile pyuria and microscopic hematuria.
 Hydronephrosis or ureteral strictures may complicate the disease.
 Urine cultures positive in 80–90%, AFB positive in 50–70%
 IVP or CT
 Renal Tb is rare in children.
 lymphohematogenous dissemination to kidney.
 Renal tuberculosis is often clinically silent in its early stages, marked
only by sterile pyuria and microscopic hematuria.
 Hydronephrosis or ureteral strictures may complicate the disease.
 Urine cultures positive in 80–90%, AFB positive in 50–70%
 IVP or CT

149. Disease in HIV infected children
 Rate of TB disease is 30x
 Diagnosis difficult: due to absent skin test, similar clinical
conditions
 More severe
 Progressive
 Likely to occur in extrapulmonary sites
 CXR: lobar disease and lung cavitation are more common
 Rates of drug-resistant Tb is higher
 High mortality
 Rate of TB disease is 30x
 Diagnosis difficult: due to absent skin test, similar clinical
conditions
 More severe
 Progressive
 Likely to occur in extrapulmonary sites
 CXR: lobar disease and lung cavitation are more common
 Rates of drug-resistant Tb is higher
 High mortality
149

150. Impact of HIV/AIDS on TB
 HIV increases susceptibility to infection with M.
tuberculosis, the risk of progression to TB disease, and the
incidence and prevalence of TB.
 The annual risk of developing TB in PLHIV who is co-
infected with M. tuberculosis ranges from 5 to 15% as
compared to a 5 to 10% life time risk for HIV negative
individuals.
 increases the likelihood of re-infections and relapses of
TB.
 HIV increases susceptibility to infection with M.
tuberculosis, the risk of progression to TB disease, and the
incidence and prevalence of TB.
 The annual risk of developing TB in PLHIV who is co-
infected with M. tuberculosis ranges from 5 to 15% as
compared to a 5 to 10% life time risk for HIV negative
individuals.
 increases the likelihood of re-infections and relapses of
TB.

151. Impact of TB on HIV/AIDS
 TB increases HIV replication, which leads to increased viral
load.
 more rapid progression of HIV disease.
 TB increases occurrence of other OIs.
 The management of TB and HIV co-infected individual is
challenging because of:
 Pill burden,
 Increase adverse effect,
 Drug to drug interaction and IRIS
 TB increases HIV replication, which leads to increased viral
load.
 more rapid progression of HIV disease.
 TB increases occurrence of other OIs.
 The management of TB and HIV co-infected individual is
challenging because of:
 Pill burden,
 Increase adverse effect,
 Drug to drug interaction and IRIS

152. Perinatal disease
 Symptoms may occur at birth but more common by the second
or 3rd week of life
 Resp distress, Fever, HSM, Poor feeding, Lethargy or irritability
 LAP, Abdominal distension, Failure to thrive, EAR discharge,
Skin lesions
 CXR: milliary pattern
 Generalized lymphadenopathy and meningitis occur in 30–50%
of patients
 most important clue for rapid diagnosis of congenital
tuberculosis is a maternal or family history of tuberculosis.
 Symptoms may occur at birth but more common by the second
or 3rd week of life
 Resp distress, Fever, HSM, Poor feeding, Lethargy or irritability
 LAP, Abdominal distension, Failure to thrive, EAR discharge,
Skin lesions
 CXR: milliary pattern
 Generalized lymphadenopathy and meningitis occur in 30–50%
of patients
 most important clue for rapid diagnosis of congenital
tuberculosis is a maternal or family history of tuberculosis.

153. Perinatal disease
 The mortality rate of congenital tuberculosis remains very
high because of delayed diagnosis
 If the mother has suspected tuberculosis, the newborn
should be separated from the mother until the chest
radiograph is obtained.
 Isoniazid therapy for newborns has been so effective that
separation of the mother and infant is no longer
considered mandatory.
 Separation should occur only if the mother is ill enough to
require hospitalization.
 The mortality rate of congenital tuberculosis remains very
high because of delayed diagnosis
 If the mother has suspected tuberculosis, the newborn
should be separated from the mother until the chest
radiograph is obtained.
 Isoniazid therapy for newborns has been so effective that
separation of the mother and infant is no longer
considered mandatory.
 Separation should occur only if the mother is ill enough to
require hospitalization.

154. Pregnancy and the Newborn
 risk for prematurity, fetal growth retardation, low
birthweight, and perinatal mortality.
 Congenital tuberculosis is rare, and usually occurs
from a lesion in the placenta through the umbilical
vein then reach the fetal liver and infect many organs.
 For the neonate it is postnatal airborne transmission.
 risk for prematurity, fetal growth retardation, low
birthweight, and perinatal mortality.
 Congenital tuberculosis is rare, and usually occurs
from a lesion in the placenta through the umbilical
vein then reach the fetal liver and infect many organs.
 For the neonate it is postnatal airborne transmission.
154

155. Diagnosis
 Recommended approach to diagnose TB in children
 1. Careful history (including history of TB contact and
symptoms consistent with TB)
 2. Clinical examination (including growth assessment)
 3. Tuberculin skin testing
 4. Bacteriological confirmation whenever possible
 5. Investigations relevant for suspected pulmonary TB and
suspected extrapulmonary TB
 6. HIV testing (in high HIV prevalence areas)
 Recommended approach to diagnose TB in children
 1. Careful history (including history of TB contact and
symptoms consistent with TB)
 2. Clinical examination (including growth assessment)
 3. Tuberculin skin testing
 4. Bacteriological confirmation whenever possible
 5. Investigations relevant for suspected pulmonary TB and
suspected extrapulmonary TB
 6. HIV testing (in high HIV prevalence areas)

156. Diagnostic Tools
 Tuberculin Skin Testing (TST)
 Interferon-γ Release Assay (IGRA)
 CBC
 CXR
 Gene x-part
 AFB
 Culture
 Tuberculin Skin Testing (TST)
 Interferon-γ Release Assay (IGRA)
 CBC
 CXR
 Gene x-part
 AFB
 Culture

157. Key features suggestive of TB
 The presence of three or more of the following should
strongly suggest a diagnosis of TB:
 chronic symptoms suggestive of TB
 physical signs highly of suggestive of TB
 a positive tuberculin skin test
 chest X-ray suggestive of TB.
 No response to antibiotics
 The presence of three or more of the following should
strongly suggest a diagnosis of TB:
 chronic symptoms suggestive of TB
 physical signs highly of suggestive of TB
 a positive tuberculin skin test
 chest X-ray suggestive of TB.
 No response to antibiotics

158. Anti-TB treatment in children
 The main objectives of anti-TB treatment are to:
 1. cure the patient of TB (by rapidly eliminating most of
the bacilli);
 2. prevent death from active TB or its late effects;
 3. prevent relapse of TB (by eliminating the dormant
bacilli);
 4. prevent the development of drug resistance (by using
a combination of drugs);
 5. decrease TB transmission to others.
 The main objectives of anti-TB treatment are to:
 1. cure the patient of TB (by rapidly eliminating most of
the bacilli);
 2. prevent death from active TB or its late effects;
 3. prevent relapse of TB (by eliminating the dormant
bacilli);
 4. prevent the development of drug resistance (by using
a combination of drugs);
 5. decrease TB transmission to others.

159. Case definition
 New case (N):A patient who never had treatment for TB, or has been on previous anti-TB treatment
for less than four weeks.
 Relapse (R):A patient declared cured or treatment completed of any form of TB in the past, but who
reports back to the health service and is now found to be AFB smear-positive or culture positive
 Treatment Failure (F):A patient who, while on treatment, is smear-positive at the end of the fifth
month or later, after commencing. Treatment failure also includes a patient who was initially sputum
smear-negative but who becomes smear-positive during treatment.
 Return after default (D):A patient previously recorded as defaulted from treatment and returns to the
health facility with smear-positive sputum.
 Transfer out (T):A patient who started treatment in one treatment unit and is transferred to another
treatment unit to continue treatment.
 Chronic (C): A TB patient who remains smear-positive after completing a re-treatment regimen.
 Other (O): A patient who does not fit in any of the above mentioned categories (e.g., a PTB smear
negative who returns after treatment interruption).
 New case (N):A patient who never had treatment for TB, or has been on previous anti-TB treatment
for less than four weeks.
 Relapse (R):A patient declared cured or treatment completed of any form of TB in the past, but who
reports back to the health service and is now found to be AFB smear-positive or culture positive
 Treatment Failure (F):A patient who, while on treatment, is smear-positive at the end of the fifth
month or later, after commencing. Treatment failure also includes a patient who was initially sputum
smear-negative but who becomes smear-positive during treatment.
 Return after default (D):A patient previously recorded as defaulted from treatment and returns to the
health facility with smear-positive sputum.
 Transfer out (T):A patient who started treatment in one treatment unit and is transferred to another
treatment unit to continue treatment.
 Chronic (C): A TB patient who remains smear-positive after completing a re-treatment regimen.
 Other (O): A patient who does not fit in any of the above mentioned categories (e.g., a PTB smear
negative who returns after treatment interruption).

160. TB
Patient
type
Intensive
phase
Continuati
on phase
Patient registration groups receiving
the
regimen
Drug
susceptibl
e
TB case
(New and
Previously
treated)
New TB patients
Relapse
Treatment after LTFU
Treatment after failure of New regimen
Others
Drug
susceptibl
e
TB case
(New and
Previously
treated)
2 (RHZE)
4 (RH)
New TB patients
Relapse
Treatment after LTFU
Treatment after failure of New regimen
Others
2(RHZE)
10 (RH)
New patients with CNS TB( meningitis,
tuberculoma)
New TB patients involving vertebra and
Osteoarticular space

161. Pediatrics HIV
 Etiology
 HIV is a retroviridae family
 lentivirus genus
 Contains double stranded RNA
 HIV-1 and HIV-2 are major types
 HIV has three major groups (M,N,O)
 HIV-1 has several serotypes (A-H) in the M group Serotype
C predominates in East Africa
 Serotype B predominate in Europe and USA
 Etiology
 HIV is a retroviridae family
 lentivirus genus
 Contains double stranded RNA
 HIV-1 and HIV-2 are major types
 HIV has three major groups (M,N,O)
 HIV-1 has several serotypes (A-H) in the M group Serotype
C predominates in East Africa
 Serotype B predominate in Europe and USA

162.  HIV genome has 3 sections:
 GAG region; encodes the vital core proteins (P24,
P17,P9)
 POL region; encodes vital enzymes (Reverse
Transcriptase, Protease, Integrase)
 ENV region; encodes vital envelope proteins (gp120
,gp41 )
 HIV genome has 3 sections:
 GAG region; encodes the vital core proteins (P24,
P17,P9)
 POL region; encodes vital enzymes (Reverse
Transcriptase, Protease, Integrase)
 ENV region; encodes vital envelope proteins (gp120
,gp41 )
6/18/2021

163.  Epidemiology
 In 2015, WHO estimated that 1.8 million children < 15 yr of
age worldwide were living with HIV-1 infection;
 the 150,000 new infections annually in children was a 70%
reduction since 2000.
 80% of new infections in this age-group occur in sub-
Saharan Africa
 Notably, there are still 110,000 deaths worldwide of children
< 15 yr of age with HIV.
 Epidemiology
 In 2015, WHO estimated that 1.8 million children < 15 yr of
age worldwide were living with HIV-1 infection;
 the 150,000 new infections annually in children was a 70%
reduction since 2000.
 80% of new infections in this age-group occur in sub-
Saharan Africa
 Notably, there are still 110,000 deaths worldwide of children
< 15 yr of age with HIV.

164. Transmission from mother to child
 in majority of cases (>90%) the source of the child’s
HIV infection is the mother.
 It can occur during:
 Pregnancy
 Labor and delivery
 Breast feeding
Transmission from mother to child
 in majority of cases (>90%) the source of the child’s
HIV infection is the mother.
 It can occur during:
 Pregnancy
 Labor and delivery
 Breast feeding

165. Transmission
 Vertical transmission of HIV (25-52(>90%)% occur
 Intrauterine (20-30)%(5-10)%
 Intrapartum(10-15)%
 postpartum through breastfeeding(5-20)%
 Sexual abuse, traditional malpractices, blood
transfusion and operations could cause HIV infection
 Vertical transmission of HIV (25-52(>90%)% occur
 Intrauterine (20-30)%(5-10)%
 Intrapartum(10-15)%
 postpartum through breastfeeding(5-20)%
 Sexual abuse, traditional malpractices, blood
transfusion and operations could cause HIV infection

166. Several risk factors influence MTCT
of HIV. Some of the major factors
are:
Maternal factors: Infant factor:
.High viral load
.Low CD4 count with advanced disease
.Prolonged rupture of membrane
.HIV infection during pregnancy/breast
.feeding
.Mixed feeding
.Crackled nipples and breast abscess
.Prematurity <34 WK
.Oral thrush and ulcer
.Birth order (first twin) in twin
pregnancies
.Invasive fetal monitoring during labor
and delivery
,Instrumental delivery
.High viral load
.Low CD4 count with advanced disease
.Prolonged rupture of membrane
.HIV infection during pregnancy/breast
.feeding
.Mixed feeding
.Crackled nipples and breast abscess
.Prematurity <34 WK
.Oral thrush and ulcer
.Birth order (first twin) in twin
pregnancies
.Invasive fetal monitoring during labor
and delivery
,Instrumental delivery

167.  PATHOGENESIS
 Viral entry through abraded skin or mucosa
 Dendritic cells carry HIV to lymphoid tissue
 HIV selectively enter to CD4 T-cells through a chemokine
receptor (CCR5, CCXR)
 HIV genome is integrate to T-cell genome
 HIV genome replicate using T-cell’s energy
 Several HIV mature and emerge from a dying T-cell to
infect other new CD4 T-cells
 PATHOGENESIS
 Viral entry through abraded skin or mucosa
 Dendritic cells carry HIV to lymphoid tissue
 HIV selectively enter to CD4 T-cells through a chemokine
receptor (CCR5, CCXR)
 HIV genome is integrate to T-cell genome
 HIV genome replicate using T-cell’s energy
 Several HIV mature and emerge from a dying T-cell to
infect other new CD4 T-cells

168. 6/18/2021

169. progression of disease
 Three distinct patterns of disease are described in
children.
1. rapid progression course, ,15-25%with onset of AIDS
and symptoms during the first few months of life and a
median survival time of 6-9 mo if untreated.
2. slower progression of disease,60 -80 % with a median
survival time of 6 yr.
 Three distinct patterns of disease are described in
children.
1. rapid progression course, ,15-25%with onset of AIDS
and symptoms during the first few months of life and a
median survival time of 6-9 mo if untreated.
2. slower progression of disease,60 -80 % with a median
survival time of 6 yr.

170. 3.long-term survivors or long-term nonprogressors, who
have,5% minimal or no progression of disease with
relatively normal CD4 counts and very low viral loads
for longer than 8 yr.
Central nervous system (CNS) involvement is more
common in pediatric patients than in adults
3.long-term survivors or long-term nonprogressors, who
have,5% minimal or no progression of disease with
relatively normal CD4 counts and very low viral loads
for longer than 8 yr.
Central nervous system (CNS) involvement is more
common in pediatric patients than in adults

171. patterns of progression in children
 Category 1 (25–30%): Rapid progressors, who die by
the age of one and who are thought to have acquired
the infection in utero or during the early perinatal
period.
 Category 2 (50–60%): Children who develop symptoms
early in life, followed by a downhill course and death
by the age of three to five.
 Category 3 (5–25%): Long-term survivors, who live
beyond the age of eight.
 Category 1 (25–30%): Rapid progressors, who die by
the age of one and who are thought to have acquired
the infection in utero or during the early perinatal
period.
 Category 2 (50–60%): Children who develop symptoms
early in life, followed by a downhill course and death
by the age of three to five.
 Category 3 (5–25%): Long-term survivors, who live
beyond the age of eight.

172. Clinical manifestation
 Because HIV-related immunosuppression is imposed upon still-developing
immune, nervous and other systems,
 HIV disease tends to be more aggressive in children than in adults, and leads to
a range of unique problems
 Mostly infants are normal at birth
 Initial S/Sx (subtle): LAP,HSM or
 Non-specific: failure to thrive, chronic/recurrent diarrhea, interstitial
pneumonia or oral thrush
 C/ms more common in children than adults:
 Recurrent bacterial infections
 Chronic parotitis
 LIP
 Early onset progressive encephalopathy/neurologic deterioration
 Because HIV-related immunosuppression is imposed upon still-developing
immune, nervous and other systems,
 HIV disease tends to be more aggressive in children than in adults, and leads to
a range of unique problems
 Mostly infants are normal at birth
 Initial S/Sx (subtle): LAP,HSM or
 Non-specific: failure to thrive, chronic/recurrent diarrhea, interstitial
pneumonia or oral thrush
 C/ms more common in children than adults:
 Recurrent bacterial infections
 Chronic parotitis
 LIP
 Early onset progressive encephalopathy/neurologic deterioration

173.  Infections
 20% of AIDS-defining illnesses
 Recurrent and Common serious infections:
 Bacteremia/Sepsis
 Pneumonia
 Meningitis
 UTI
 Deep abscesses, bone/joint infections
 Infections
 20% of AIDS-defining illnesses
 Recurrent and Common serious infections:
 Bacteremia/Sepsis
 Pneumonia
 Meningitis
 UTI
 Deep abscesses, bone/joint infections

174.  Mild recurrent infections:
 Otitis media
 Sinusitis
 Skin & soft tissue infections
Opportunistic Infections
 Related with severe depression of CD4
 Mild recurrent infections:
 Otitis media
 Sinusitis
 Skin & soft tissue infections
Opportunistic Infections
 Related with severe depression of CD4

175. OIs of Respiratory System
 Pneumocystis Carinii Pneumonia
 ETIOLOGY:
 Pneumocystis jiroveci (previously Pneumocystis carinii) is classified as
a fungus on the basis of DNA sequence analysis
 Most common OI in children
 Higher mortality in infants
 Peak incidence at 3-6months of age
 highest mortality rate in children younger than 1 yr of age.
 The classic clinical presentation of PCP includes an acute onset of
fever, tachypnea, dyspnea, and marked hypoxemia;
 Pneumocystis Carinii Pneumonia
 ETIOLOGY:
 Pneumocystis jiroveci (previously Pneumocystis carinii) is classified as
a fungus on the basis of DNA sequence analysis
 Most common OI in children
 Higher mortality in infants
 Peak incidence at 3-6months of age
 highest mortality rate in children younger than 1 yr of age.
 The classic clinical presentation of PCP includes an acute onset of
fever, tachypnea, dyspnea, and marked hypoxemia;
6/18/2021

176.  diagnosis is established by demonstration of P. jiroveci
with appropriate staining of induced sputum or
bronchoalveolar fluid lavage
 diagnosis is established by demonstration of P. jiroveci
with appropriate staining of induced sputum or
bronchoalveolar fluid lavage

177.  Nontuberculous mycobacteria (NTM),
 MAC being most common
 IN <100 CD4 cells/μL is estimated to be as high as 10%,
 Disseminated MAC infection is characterized by fever,
malaise, weight loss, and night sweats; diarrhea,
abdominal pain, and, rarely, intestinal perforation or
jaundice
 Nontuberculous mycobacteria (NTM),
 MAC being most common
 IN <100 CD4 cells/μL is estimated to be as high as 10%,
 Disseminated MAC infection is characterized by fever,
malaise, weight loss, and night sweats; diarrhea,
abdominal pain, and, rarely, intestinal perforation or
jaundice

178.  diagnosis is made by the isolation of MAC from blood,
bone marrow, or tissue;
 Oral candidiasis is the most common fungal infection
seen in HIV-infected children
 Oral nystatin suspension (2-5 mL qid) is often
effective.
 Clotrimazole troches or fluconazole (3-6 mg/kg orally
qd) are effective alternatives
 diagnosis is made by the isolation of MAC from blood,
bone marrow, or tissue;
 Oral candidiasis is the most common fungal infection
seen in HIV-infected children
 Oral nystatin suspension (2-5 mL qid) is often
effective.
 Clotrimazole troches or fluconazole (3-6 mg/kg orally
qd) are effective alternatives

179.  Recurrent URTIs (otitis, sinusitis)
 Causes: typical pathogens (pneumococcus,
H.influenza,M.catarrhalis)
 Unusual pathogens (anaerobes, pseudomaonas)
 Pneumonia:
 recurrent
 Common
 Pneumococcus is most common etiology
 Others (gram negatives) are also common
 Recurrent URTIs (otitis, sinusitis)
 Causes: typical pathogens (pneumococcus,
H.influenza,M.catarrhalis)
 Unusual pathogens (anaerobes, pseudomaonas)
 Pneumonia:
 recurrent
 Common
 Pneumococcus is most common etiology
 Others (gram negatives) are also common
6/18/2021

180.  Lymphoid Interstitial Pneumonitis (LIP):
 Most common chronic LRT abnormality (25%)
 Chronic process with nodular lymphoid hyperplasia in the
bronchioles & bronchiolar epithelium leading to alveolar
capillary block
 Causes : not known (EBV, Immunologic)
 may result from an in situ lymphoproliferative response to
chronically presented viral antigens or cytokines and/or
recruitment of circulating lymphocytes
 Epstein-Barr virus
 HTLV type 1
 HIV type 1
 Lymphoid Interstitial Pneumonitis (LIP):
 Most common chronic LRT abnormality (25%)
 Chronic process with nodular lymphoid hyperplasia in the
bronchioles & bronchiolar epithelium leading to alveolar
capillary block
 Causes : not known (EBV, Immunologic)
 may result from an in situ lymphoproliferative response to
chronically presented viral antigens or cytokines and/or
recruitment of circulating lymphocytes
 Epstein-Barr virus
 HTLV type 1
 HIV type 1
6/18/2021

181.  C/ms:
 insidious onset of tachypnea, cough, & hypoxemia
 Normal or minimal rales on auscultation
 Clubbing & symptomatic hypoxemia
 CXR: chronic diffuse reticulonodular pattern, rarely
hilar LAP
 C/ms:
 insidious onset of tachypnea, cough, & hypoxemia
 Normal or minimal rales on auscultation
 Clubbing & symptomatic hypoxemia
 CXR: chronic diffuse reticulonodular pattern, rarely
hilar LAP
6/18/2021

182. Cardiovascular
 Subclinical, persistent and progressive cardiac
diseases are common
 dCMP and Left ventricular Hypertrophy are common
 CHF, sinus tachycardia, arrhythmia (?autonomic
neuropathy)
 Subclinical, persistent and progressive cardiac
diseases are common
 dCMP and Left ventricular Hypertrophy are common
 CHF, sinus tachycardia, arrhythmia (?autonomic
neuropathy)
6/18/2021

183. GIT
 GI:
 Common manifestation is persistent/recurrent diarrhea
 Failure to thrive
 Causes:
 bacteria (salmonella, MAC, campylobacter)
 Protozoa (giardiasis, cryptosporidiosis, isospora,
microsporidia)
 Viruse (CMV, HSV, rota)
 Fungi (candidisis)
 GI:
 Common manifestation is persistent/recurrent diarrhea
 Failure to thrive
 Causes:
 bacteria (salmonella, MAC, campylobacter)
 Protozoa (giardiasis, cryptosporidiosis, isospora,
microsporidia)
 Viruse (CMV, HSV, rota)
 Fungi (candidisis)
6/18/2021

184.  Infections may be localized or disseminated (oropharynx to
rectum)
 AIDS enteropathy:
 Malabsorption
 Partial villous atrophy
 Not associated with a specific pathogen
 Assumed to be the result direct HIV infection of the gut
 Dissacharade intolerance is common
 Infections may be localized or disseminated (oropharynx to
rectum)
 AIDS enteropathy:
 Malabsorption
 Partial villous atrophy
 Not associated with a specific pathogen
 Assumed to be the result direct HIV infection of the gut
 Dissacharade intolerance is common

185.  Chronic liver inflammation:
 Abnormal serum transaminases
 Etiology is not known but may be due to chronic HB
V,HCV,CMV,MAC
 Cholestasis may occur
 Hepatic failure and portal hypertension is common
 HAART may also affect the liver
 Pancreatitis: causes are drugs, MAC, CMV
 Chronic liver inflammation:
 Abnormal serum transaminases
 Etiology is not known but may be due to chronic HB
V,HCV,CMV,MAC
 Cholestasis may occur
 Hepatic failure and portal hypertension is common
 HAART may also affect the liver
 Pancreatitis: causes are drugs, MAC, CMV

186.  Oral thrush progresses to involve the esophagus in as
many as 20% of children with severe CD4 depletion,
presenting with symptoms such as anorexia,
dysphagia, vomiting, and fever.
 Treatment with oral fluconazole for 7-14 day
 HSV causes gingivostomatitis,
 Oral thrush progresses to involve the esophagus in as
many as 20% of children with severe CD4 depletion,
presenting with symptoms such as anorexia,
dysphagia, vomiting, and fever.
 Treatment with oral fluconazole for 7-14 day
 HSV causes gingivostomatitis,

187.  Disseminated CMV infection
 occurs in the setting of severe CD4 depletion (<50 CD4 cells/μL
for >6 yr) and may involve single or multiple organs.
 Retinitis, pneumonitis, esophagitis, gastritis with pyloric
obstruction, hepatitis, colitis, and encephalitis
 Ganciclovir and foscarnet are the drugs of choice
 Measles may occur despite immunization and may present
without the typical rash. It often disseminates to the lung or
brain with a high mortality rate in these patients.
 Disseminated CMV infection
 occurs in the setting of severe CD4 depletion (<50 CD4 cells/μL
for >6 yr) and may involve single or multiple organs.
 Retinitis, pneumonitis, esophagitis, gastritis with pyloric
obstruction, hepatitis, colitis, and encephalitis
 Ganciclovir and foscarnet are the drugs of choice
 Measles may occur despite immunization and may present
without the typical rash. It often disseminates to the lung or
brain with a high mortality rate in these patients.

188. Renal ds
 Nephropathy is common
 Causes:
 direct effect of HIV
 Immune-complexes
 Hyperviscosity of blood (hyperglobulinemia)
 Nephrotoxic drugs
 Histology:
 focal glomerulosclerosis, mesangial hyperplasia,segmental
necrotizing GN, minimal change disease
 Nephrotic syndrome is the most common manifestation
 Nephropathy is common
 Causes:
 direct effect of HIV
 Immune-complexes
 Hyperviscosity of blood (hyperglobulinemia)
 Nephrotoxic drugs
 Histology:
 focal glomerulosclerosis, mesangial hyperplasia,segmental
necrotizing GN, minimal change disease
 Nephrotic syndrome is the most common manifestation

189. CNS
 Involvement is common (50-60%)
 Median onset of symptoms is 19 months
 Neurological conditions in HIV patients may be due to:
 HIV(HIV encephalopathy)
 OIs (Toxoplasmosis, Crypotococcal meningitis,TB
meningitis)
 Neurosyphilis
 Malignancies (primary CNS lymphoma) and
 Drugs, example EFV, INH etc
 Involvement is common (50-60%)
 Median onset of symptoms is 19 months
 Neurological conditions in HIV patients may be due to:
 HIV(HIV encephalopathy)
 OIs (Toxoplasmosis, Crypotococcal meningitis,TB
meningitis)
 Neurosyphilis
 Malignancies (primary CNS lymphoma) and
 Drugs, example EFV, INH etc

190. Skin:
 Inflammatory or infectious
 Tend to be disseminated & respond less to drugs
 Seborrheic dermatitis or eczema
 Recurrent or chronic HSV, HZV, MC, candidia
 Allergic drug erruptions
 Pruritic Papular Erruption
Skin:
 Inflammatory or infectious
 Tend to be disseminated & respond less to drugs
 Seborrheic dermatitis or eczema
 Recurrent or chronic HSV, HZV, MC, candidia
 Allergic drug erruptions
 Pruritic Papular Erruption

191.  Hematology:
 Anemia (20-70%)– causes:
 Chronic infection
 Poor nutrition
 Autoimmune
 Virus-associated (e.g. parvo virus B19)
 Drug-induced (ZDV)
 Thrombocytopenia (10-20%)
 Immunologic (immune complexes or antiplatelet antibodies)
 Drug toxicity
 Idiopathic
 Leukopenia (33%)
 Antineutrophil antibodises
 Drugs
 Hematology:
 Anemia (20-70%)– causes:
 Chronic infection
 Poor nutrition
 Autoimmune
 Virus-associated (e.g. parvo virus B19)
 Drug-induced (ZDV)
 Thrombocytopenia (10-20%)
 Immunologic (immune complexes or antiplatelet antibodies)
 Drug toxicity
 Idiopathic
 Leukopenia (33%)
 Antineutrophil antibodises
 Drugs

192.  Clotting factor deficiency: II, VII, IX
 Hematologic manifestations may be the 1st
presentations
 Malignancy:
 Rare in children
 Only 2% of AIDS-defining illnesses
 NHL, primary CNS lymphoma, & leiomyosarcoma are
common
 Clotting factor deficiency: II, VII, IX
 Hematologic manifestations may be the 1st
presentations
 Malignancy:
 Rare in children
 Only 2% of AIDS-defining illnesses
 NHL, primary CNS lymphoma, & leiomyosarcoma are
common

193. Staging of AIDS
 To assess ds severity
 Monitor ds progression
 Criteria for ART therpy
 To assess ds severity
 Monitor ds progression
 Criteria for ART therpy

194.  Clinical stage 1
 Asymptomatic
 Persistent generalized lymphadenopathy
 Clinical stage 1
 Asymptomatic
 Persistent generalized lymphadenopathy

195.  Clinical stage 2
 Unexplained persistent hepatosplenomegaly
 Papular pruritic eruptions
 Extensive wart virus infection
 Extensive molluscum contagiosum
 Recurrent oral ulcerations
 Unexplained persistent parotid enlargement
 Lineal gingival erythema
 Herpes zoster
 Recurrent or chronic upper respiratory tract infections (otitis media,
otorrhoea,sinusitis, tonsillitis )
 Fungal nail infections
 Clinical stage 2
 Unexplained persistent hepatosplenomegaly
 Papular pruritic eruptions
 Extensive wart virus infection
 Extensive molluscum contagiosum
 Recurrent oral ulcerations
 Unexplained persistent parotid enlargement
 Lineal gingival erythema
 Herpes zoster
 Recurrent or chronic upper respiratory tract infections (otitis media,
otorrhoea,sinusitis, tonsillitis )
 Fungal nail infections

196.  Clinical stage 3
 Unexplained moderate malnutrition not adequately responding to standard therapy
 Unexplained persistent diarrhoea (14 days or more )
 Unexplained persistent fever (above 37.5 ºC, intermittent or constant, for longer than one
month)
 Persistent oral candidiasis (after first 6 weeks of life)
 Oral hairy leukoplakia
 Acute necrotizing ulcerative gingivitis/periodontitis
 Lymph node TB
 Pulmonary TB
 Severe recurrent bacterial pneumonia
 Symptomatic lymphoid interstitial pneumonitis
 Chronic HIV-associated lung disease including bronchiectasis
 Unexplained anaemia (<8.0 g/dl ),
 Clinical stage 3
 Unexplained moderate malnutrition not adequately responding to standard therapy
 Unexplained persistent diarrhoea (14 days or more )
 Unexplained persistent fever (above 37.5 ºC, intermittent or constant, for longer than one
month)
 Persistent oral candidiasis (after first 6 weeks of life)
 Oral hairy leukoplakia
 Acute necrotizing ulcerative gingivitis/periodontitis
 Lymph node TB
 Pulmonary TB
 Severe recurrent bacterial pneumonia
 Symptomatic lymphoid interstitial pneumonitis
 Chronic HIV-associated lung disease including bronchiectasis
 Unexplained anaemia (<8.0 g/dl ),

197.  Clinical stage 4
 Unexplained severe wasting, stunting or severe malnutrition not responding to standard therapy
 Pneumocystis pneumonia
 Recurrent severe bacterial infections (e.g. empyema, pyomyositis, bone or joint
 infection, meningitis, but excluding pneumonia)
 Chronic herpes simplex infection; (orolabial or cutaneous of more than one month’s
 duration, or visceral at any site)
 Extrapulmonary TB
 Kaposi sarcoma
 Oesophageal candidiasis (or Candida of trachea, bronchi or lungs)
 Central nervous system toxoplasmosis (after the neonatal period)
 HIV encephalopathy
 Cytomegalovirus (CMV) infection; retinitis or CMV infection affecting another organ,
 with onset at age over 1 month
 Extrapulmonary cryptococcosis (including meningitis)
 Disseminated endemic mycosis (extrapulmonary histoplasmosis, coccidiomycosis)
 Chronic cryptosporidiosis (with diarrhoea )
 Chronic isosporiasis
 Disseminated non-tuberculous mycobacteria infection
 Cerebral or B cell non-Hodgkin lymphoma
 Progressive multifocal leukoencephalopathy
 HIV-associated cardiomyopathy or nephropathy
 Clinical stage 4
 Unexplained severe wasting, stunting or severe malnutrition not responding to standard therapy
 Pneumocystis pneumonia
 Recurrent severe bacterial infections (e.g. empyema, pyomyositis, bone or joint
 infection, meningitis, but excluding pneumonia)
 Chronic herpes simplex infection; (orolabial or cutaneous of more than one month’s
 duration, or visceral at any site)
 Extrapulmonary TB
 Kaposi sarcoma
 Oesophageal candidiasis (or Candida of trachea, bronchi or lungs)
 Central nervous system toxoplasmosis (after the neonatal period)
 HIV encephalopathy
 Cytomegalovirus (CMV) infection; retinitis or CMV infection affecting another organ,
 with onset at age over 1 month
 Extrapulmonary cryptococcosis (including meningitis)
 Disseminated endemic mycosis (extrapulmonary histoplasmosis, coccidiomycosis)
 Chronic cryptosporidiosis (with diarrhoea )
 Chronic isosporiasis
 Disseminated non-tuberculous mycobacteria infection
 Cerebral or B cell non-Hodgkin lymphoma
 Progressive multifocal leukoencephalopathy
 HIV-associated cardiomyopathy or nephropathy

198. Diagnosis of HIV in Infants and
Children
 Complexities of Infant Diagnosis
 HIV infection is difficult to diagnosis in infants:
 Routine HIV antibody tests cannot be used
 Specialized virologic tests are necessary
 Not routinely available
 Sensitivity & specificity can vary with laboratory assay
 HIV infection is difficult to exclude:
 Infants who breast feed continue to be at risk for acquiring HIV
infection
 Risk of infection continues throughout duration of breast feeding
 Diagnosis of infants is an ongoing process and depends on good clinical
reasoning as well as laboratory results
 Complexities of Infant Diagnosis
 HIV infection is difficult to diagnosis in infants:
 Routine HIV antibody tests cannot be used
 Specialized virologic tests are necessary
 Not routinely available
 Sensitivity & specificity can vary with laboratory assay
 HIV infection is difficult to exclude:
 Infants who breast feed continue to be at risk for acquiring HIV
infection
 Risk of infection continues throughout duration of breast feeding
 Diagnosis of infants is an ongoing process and depends on good clinical
reasoning as well as laboratory results

199.  Specialized virologic tests must be used
 HIV DNA PCR
 HIV RNA PCR
 p24 Antigen
 Viral Culture
 Specialized virologic tests must be used
 HIV DNA PCR
 HIV RNA PCR
 p24 Antigen
 Viral Culture

200.  Management of HIV infection in children
 Provide comprehensive care
 Treat OI (PCP, TB, Candida, chronic GE etc)
 Early initiation of HAART
 OI prophylaxis (IPT, CTX, etc)
 Nutritional therapy
 Immunization
 Exclusive BF for 6months
 AFASS for those who can afford formula
 Management of HIV infection in children
 Provide comprehensive care
 Treat OI (PCP, TB, Candida, chronic GE etc)
 Early initiation of HAART
 OI prophylaxis (IPT, CTX, etc)
 Nutritional therapy
 Immunization
 Exclusive BF for 6months
 AFASS for those who can afford formula

201.  When to Start ART in Children?
 Start ART as early as possible to all children living with
HIV regardless of their WHO clinical stages and CD4
counts/percentage.
 Infants and young children infected with HIV have
exceptionally higher morbidity and mortality.
 Up to 52% and 75% of children die before the age of
two and five years respectively in the absence of any
intervention.
 When to Start ART in Children?
 Start ART as early as possible to all children living with
HIV regardless of their WHO clinical stages and CD4
counts/percentage.
 Infants and young children infected with HIV have
exceptionally higher morbidity and mortality.
 Up to 52% and 75% of children die before the age of
two and five years respectively in the absence of any
intervention.

202.  Treatment failure
 Clinical failure (new WHO stage IV )
 Immunologic failure (Decline in CD4 )
 Virologic failure (Reappearance of high VL)
 Treatment failure
 Clinical failure (new WHO stage IV )
 Immunologic failure (Decline in CD4 )
 Virologic failure (Reappearance of high VL)

203.  Preventive therapy
 Cotrimoxazole prophylaxis
 For all ages above 6wks with WHO clinical stage 3-4 until
CD4 count is normal for 6 months
 Not given in case of allergy, liver or renal disease
 INH preventive therapy
 For children living with HIV and PPD >5mm, TB contact
with house hold member
 INH not given if there is active TB, previous TB treatment
or INH prophylaxis, Liver disease
 Fluconazole for cryptococcal meningitis
 Preventive therapy
 Cotrimoxazole prophylaxis
 For all ages above 6wks with WHO clinical stage 3-4 until
CD4 count is normal for 6 months
 Not given in case of allergy, liver or renal disease
 INH preventive therapy
 For children living with HIV and PPD >5mm, TB contact
with house hold member
 INH not given if there is active TB, previous TB treatment
or INH prophylaxis, Liver disease
 Fluconazole for cryptococcal meningitis

204. Thank You !
Thank You !