This document defines and discusses various aspects of infectious diseases. It begins by defining key terms like infection, infestation, host, infectious disease, contagious disease, and communicable disease. It then discusses epidemiological patterns of disease spread including epidemic, endemic, sporadic, pandemic, and zoonosis. It also covers hospital-acquired infections, opportunistic infections, and iatrogenic disease. The document then focuses on specific infectious diseases like malaria and typhoid fever, describing their transmission, clinical features, diagnosis, treatment and differential diagnosis.

1. INFECTIOUS
DISEASE
M U L U G E TA ( M D ) 1

2. 2
INTRODUCTION
Definitions
Infection – the entry and development or multiplication of an
infectious agent in the body of human beings or animals
Infestation – the lodgment, development and reproduction
of arthropods on the surface of the body or in clothes
Host – the person or animal that affords subsistence or
lodgment to an infectious agent under natural conditions
Infectious disease – a clinically manifest disease of a man or
animal resulting from an infection
Contagious disease – a disease that is transmitted through
contact
Communicable disease – an illness due to a specific
infectious agents or its toxic products capable of being
directly or indirectly transmitted from man to man, animal to
animal or from environment to man or animal

3. 3
Epidemic – the unusual occurrence of disease in a
community or region, specific health related behavior or
events clearly in excess of expected occurrence
Endemic – constant presence of a disease or infectious
agent within a given geographic area or population group;
without importation from outside
Hyper endemic
Holoendemic
Sporadic – cases occur irregularly, haphazardly from time
to time and generally infrequent eg polio, tetanus, herpes
zoster
Pandemic – an epidemic affecting a large proportion of
the population occurring over a wide geographic area
Zoonosis – an infection transmissible under natural
conditions from vertebrate animals to man
Anthropozoonoses – eg rabies
Zooanthroponoses – human TB in animals

4. 4
Nosocomial (hospital acquired) – infection originating in
a patient while in hospital or other health care facility
New disorder associated with being in a health facility
It should not be present or incubating at time of
admission
It can be a residual infection from previous admission
It can be infection acquired in the hospital but
appearing after discharge
Opportunistic infection – an infection by organisms that
take the opportunity of defect in the host defense to
infect the host and cause disease
Eg herpes simplex, TB
Iatrogenic disease – any untoward or adverse
consequence of preventive, diagnostic or therapeutic
regimen or procedure that causes impairment, handicap,
disability or death resulting from physicians professional
activity or from the professional activity of other health

5. • Incubation period The time interval between invasion by infectious
agent and appearance of first sign or symptom of the disease.
• Fever - Fever is elevated body temperature due to altered
hypothalamic set point.
• - Hyperpyrexia when > 41.5
• Fever of unknown origin (FUO)-Repeated body temperature
record of 38.3 with no clear identified cause with clinical,
routine laboratoryincluding culture and radiology
evaluations
• Neutropenic – in those with neutrophil count <500/µl;
5

6. Sepsis and septic shock
-Systemic inflammatory response syndrome (SIRS) - Any 2 of:
• To>38 or <36
• RR>24 BPM;
• PR>90 BPM;
• WBC>12,000/ l or < 4000 / l or > 10% bands
-Sepsis: SIRS with suspected or proven microbial etiology
--Septic shock
6

7. • Infectious disease results from
– Bacteria
– Fungi
– Virus
– Parasites
• Acquiring infection depends on
– Host factors (age, immunization, prior illness, nutritional status,
pregnancy, coexisting illnesses and emotional status)
– Environmental ( altitude, geography, medical care, climate,
environment…)
– Microbial ( invasion, tropism and microbial virulence factors)
7

8. CONT…
Medical care itself could ↑ the patient's risk of acquiring an
infection in several ways: through
1. Contact with pathogens during hospitalization
2. Breaching of the skin (with IV devices or surgical incisions) or
mucosal surfaces (with ETT or bladder catheters)
3. Introduction of foreign bodies
4. Alteration of the natural flora with antibiotics, &
5. Treatment with immunosuppressive drugs
8

9. IMMUNE SYSTEM
• Two types
– Innate ( natural)
• First line
• Without previous exposure
• Non specific and has no memory
– Acquired
• Specific against specific organism
• Has memory
• Takes time to develop
9

10. IMMUNE SYSTEM
• Acquired immunity has two forms
– Cellular-
• Comprises T lymphocytes and NK-cells
– Humeral-
• Comprises B lymphocytes and antibodies produced by plasma cells
• Laboratory diagnosis
– Direct visualization-
• culture, microscopy
– Indirect tests-
• Detection of antibodies, antigens in body fluids, tissues and excreta from
the host
10

11. ACUTE FEBRILE ILLNESS
MALARIA
• is a protozoan disease transmitted to man by the bite of the
female anopheles mosquitoes
• Causes
– P. falciparum: also called malignant malaria
– P. vivax : tertian malaria
– P. ovale : tertian malaria
– P. malariae : quartan malaria
• Almost all deaths are caused by P. Falciparum
11

12. MALARIA
• Epidemiology
– Malaria is common in both high and low land areas
• In Ethiopia
– The disease is prevalent in 75% of the country with over 40 million
people at risk
– P.Falciparum and P. Vivax are the commonest accounting for 60%
and 40% of cases respectively
12

13. THE BASIC CHARACTERISTICS OF THE TWO
TRANSMISSION TYPES OF MALARIA
13
Stable Unstable
Mosquito life Long Short
Mosquito bites Frequent Rare
Human immunity High Low
Epidemics No (Only with rainy season and
migration of non immunes to
the area)
Yes
Eradication/control Difficult Possible

14. TRANSMISSION
• Is transmitted by bite of the female anopheles mosquitoes or
inoculation of Blood
• Requires high environmental temperature and collected water
body
14

15. CLINICAL FEATURE
• The incubation period varies between 10-14 days in P. vivax, P.
ovale, & P.falciparum, and 18 days to six weeks in P. malariae
• Early symptoms- non spcfc symptoms
– malaise, fatigue, headache, muscle pain, abdominal discomfort
– Then fever, nausea and vomiting
15

16. CLINICAL FEATURE
• Classical feature
– Paroxysmal fever, chillis and rigor every 2/3 days
– Has three stages
• Cold stage
– Cxzed by vasoconstriction of vessels & the temperature rises rapidly
– Pts fells cold and shivering
– Lasts 30min- one hr
• Hot stage
– Pts feel hot and uncomfortable
– Lasts two to six hours
• Sweating stage
– Profuse sweating
– Exhaustion
16

17. PHYSICICAL EXAMINATION
• Uncomplicated
– Fever
– Janundice
– Anemia
– Palpable spleen and liver
17

18. SEVERE AND COMPLICATED
MALARIA
• Is defined as life threatening malaria caused by P. falciparum,
and the asexual form of the parasite demonstrated in a blood
film
• Criteria
– Cerebral malaria: is a state of unarousable coma lasting for more
than 30 minutes and other causes of coma ruled out.
– Change of level of consciousness less marked than unarousable
coma
– Generalized tonic clonic seizure (> 2/day)
– Acute renal failure (Oliguria of < 400 ml/24 h and/or creatinine > 3
mg/dl)
18

19. SEVERE …..
– Severe Normocytic anemia (Hgb < 5 g/dl)
• RBC infection and rupture by the merozoites
• Infected RBC adhere to uninfected RBCs
• RBCs will be trapped by the spleen
• Hyper catabolic state
– Pulmonary edema or ARDS
– Metabolic acidociis ( lactic acidosis ) (pH < 7.25; plasma
bicarbonate < 15 mmol/l)
19

20. SEVERE……
– Hypoglycaemia (RBS < 40 mg/dl) is multi factorial The parasite
consumes glucose
• Catabolic state increases glucose demand of the host
• Anorexia associated with the illness
• Drugs like quinine can cause hypoglycaemia
– Circulatory collapse, shock ,septicaemia ( “ Algid Malaria “ ): systolic
BP < 80 mmHg, core vs. skin temperature difference > 10°C)
20

21. SEVERE…..
– Spontaneous bleeding / Disseminated Intravascular coagulation (
DIC)
– Hemoglobinuria
– Jaundice, bilirubine > 3 mg/dl
– Hyperparasitemia (>5 % of erythrocytes affected by plasmodium
or > 100.000 plasmodium/μl)
– P. falciparum malaria in pregnant women is also considered as
sever because it is associated with adverse out comes to the
mother and the foetus
• sever complications may occur singly, or, more commonly, in
combination in the same patient
21

22. DIAGNOSIS
• Demonstration of the parasite in blood film
– Thin film- to see the un-lyzed RBC’s
• Species identification is simple
• Percentage of RBC parasitized can be
– Thick film- the RBC’s are lysed and to see free parasites
• concentrates the parasite 20-40 times, this helps to determine parasite
concentration
– BF has to be done 4-6 times, a single negative result doesn’t rule
out malaria
• Rapid Diagnostic Test (RDT)
22

23. 23

24. DIAGNOSIS CONTINUED…
• Other Lab tests
– Hemoglobin
– Blood glucose
– Peripheral morphology- Normocytic normochromic anemia - Low
or normal WBC
– LP and CSF analysis ( when indicated to R/O Meningitis )
– BUN/ Cr, SGOT , SGPT , Serum electrolytes etc
24

25. TREATMENT
• P. Vivax, P. malarea and P. ovale
– Chloroquine
– Primaquine- for hypnozoites and gametocytes
• 15mg/day for two weeks
• P. falciparum- uncomplicated
– Artemether-lumefantrine (coartem)
25

26. TREATMENT OF
COMPLICATED MALARIA
• IV or IM artesunate (preferred)
• IM artemether (alternate)
• IV quinine infusion (if artesunate is not available)
• IM quinine (if artesunate is not available)
26

27. TREATMENT OF……
– Check renal function tests and blood sugar (beware of
hypoglycemia)
– For comatose or unconscious patients proper nursing care is
mandatory
• Position the patient on his/her sides; turn every 2 hours to avoid bed
sores
• Catheterize the bladder, monitor input-output.
• Insert NG tube
• Avoid fluid overload
• Monitor blood glucose regularly
• Ensure adequate nutrition
27

28. MALARIA DIFFERENTIAL
DIAGNOSIS
• Non complicated
– Relapsing fever
– Typhus fever
– Typhoid fever
– Fever with focal sign (urinary tract infection, respiratory tract
infections, otitis media, sinusitis, tonsillitis, osteomyelitis, arthritis,
dysentery)
– Influenza
– Visceral leishmaniasis
28

29. D.DX
• Complicated Malaria
Decreased Level of Consciousness
– Viral encephalitis
– Bacterial meningoencephalitis
– Cerebral typhoid
– Cerebro-vascular event
– Complicated typhus, relapsing fever
– Febrile illness with hypoglycaemia
– Sepsis
– Convulsion in a patient with fever
29

30. TYPHOID ( ENTERIC) FEVER
• Definition
– is a systemic infection characterized by fever and abdominal pain
– caused by non capsulated, gram negative motile bacteria
– Salmonella typhi, occasionally by S. paratyphi A and B
30

31. TRANSMISSION
• Contaminated food or water from the chronic carrier
• It affects all ages and sex
• Chronic carriers carry the infection in their gallbladder
• Endemic in most developing countries
31

32. PATHOGENESIS• Ingestion of the organism
• Intestinal( upper part)
• Payer’s patch
• Blood (bacteremia)
• Reticuloendothelial system ( liver,
spleen, lymphnode and bonemarrow)32

33. CLINICAL MANIFESTATION
• IP, 3-21 days
• Depends on
– Host defense
– Infectious dose
– Duration of the disease
• 1st week
– Step-ladder high grade fever
– Malaise, headache, abdominal pain
– Diarrheaconstipation
– Heapato-splenomegaly
– Relative bradycardia
– Epistaxis and rose spots=make up salmon colored, blanching,maculopapular rash located
primarely on trunk&chest
33

34. ROSE SPOTS
34

35. CLINICAL MANIFESTATION
• 2nd week
– Fever continues
– Severely ill, confused
– Delirious
– Comatose
• 3rd week typhoidal stage
– Disorientation, and “pea-soup” diarrhea
– Intestinal hemorrhage or perforation
• 4th week
– Resolution of symptoms
– Wt loss
• Relapse is – 10%
35

36. COMPLICATIONS
• Gastric perforation
– May occur even after resolution of the symptoms
• Others less common
– Hepatitis
– Meningitis
– Arthritis, osteomyelitis
– Parotitis and orchitis
– Nephritis
– Myocarditis
– Bronchitis and pneumonia
• All complications can be prevented by proper Dx and Rx
36

37. CHRONIC CARRIERS
• 1-5% of pts became chronic carriers
• They shed S. thyphi for >1 yr
• It is more common in females with gallbladder abnormality and
other GI malignancies
37

38. DIAGNOSIS
• Isolation of the organism
– Blood culture- 80% in the 1st week and 40 % in the 3rd week
– Stool and urine culture- negative in the first week and 75%posetive
in the 3rd week
– Bone marrow culture sensitivity 55-90%
• Widal test for H and O antigens
– O antigen - shows active infection
– H antigen – previous infection or immunization
• Non specific test and doesn’t have value to diagnose acute cases
38

39. TREATMENT
• Ciprofloxacilline 500 mg po BID for 5-7 days
• Ceftriaxone 1-2gm IM/IV for 7-14 days
• Other alternatives
– Azithromycine 1 gm PO daily for 5 days
– Chloramphenicol 500 mg Po QID for 14-21 days
– Norfloxacin 400mg twice daily for 10 days
• Parentral administrations are for critically ill patients
• Despite treatment, fever may persist up to 4-6 days
39

40. • Eradication of chronic carrier state requires prolonged
treatment with
– Ciprofloxacin for 4 weeks is effective and much better than the
other drugs
– Ampicillin or Amoxicillin 100mg/kg/d taken with Probenecid
30mg/kg/day for 6 weeks
– Co-trimexazole (160/800mg twice a day) plus Rifampicin 600mg
orally/d for 6 weeks
40

41. PREVENTION AND CONTROL
• Improve environmental sanitation
• Identification and treatment of Chronic carriers
• Avoid food handling by chronic carriers
• Vaccination for travelers to endemic areas
41

42. Relapsing fever :
Louse Born Relapsing Fever (LBRF):Epidemic,Borrelia recurrentis
Tick Born Relapsing Fever (TBRF): Endemic ,B. hermsi,B.
turicata,B.duttoni
Pathogenesis:
LBRF: crushed louse (scratching), in high lands of Ethiopia
TBRF: by bite of tick
42

43. CONT…
Clinical Manifestations:
• IP: 7 days for TBRF (range, 4–18) & 8 days for LBRF (range, 5–15)
• Are similar
• Sudden onset with fever, headache, shaking chills, sweats,
myalgia, Alteration of sensorium, nausea and vomiting
• Others: tachycardia, gallop, tender hepatosplenomegaly
• Diarrhea -25%
• Jaundice; CNS involvement; petechiae on the trunk,
extremities,& mucous membranes; epistaxis; & blood-tinged
sputum are more likely in LBRF
43

44. • Cranial nerve palsy and other neurologic manifestations are often
reversible. Neurologic findings may occur in 10–30% of cases and are
more common in LBRF.
• The average duration of the first episode of TBRF is 3 days (range, 12
h to 17 days), and LBRF is 5.5 days (range, 4–10 days).
44

45. CONT…
 Subsequent relapsing febrile episodes are typically of shorter
duration.
 average time b/n the 1st episode and the 1st relapse is 7 days
for TBRF and 9 days for LBRF
 During afebrile intervals, the patient may have symptoms (e.g.,
malaise) or may feel well.
45

46. Diagnosis
During asymptomatic intervals, relapsing fever borreliae are
undetectable in the bloodstream by microscopy. Laboratory
confirmation is made by the detection or isolation of
spirochetes from blood during a febrile episode.
46

47. DX, BF
GIEMSA STAIN OF BORRELIA
RECURRENTIS IN BLOOD
47

48. RX
RX: Relapsing Fever:
– Doxycycline, erythromycin, CAF, tetracycline
– LBRF: single dose
– TBRF:7 days(10)
• Delousing of patients with Relapsing fever is important to
prevent transmission and recurrence
48

49. PREVENTION AND CONTROL
OF RELAPSING FEVER
• Avoiding over crowding
• Apply hygienic practices that reduce the number of body lice
(washing clothes)
• Elimination of ticks
• Health education
• Early case detection and treatment of infected persons and close
contacts
• In out breaks of LBRF, empirical single dose treatment with
doxycycline
• Eradication of Rodents to control TBRF: ( Rodenticides )
49

50. CONT…Complications:
The Jarisch-Herxheimer reaction is an acute exacerbation of
symptoms that may occur on initial treatment of relapsing fever
with an effective antibiotic
JHR: Jarisch-Herxheimer Reaction
– Hypotension, tachycardia, chills, rigors, diaphoresis, & marked
elevation of body T ̊
– The reaction typically begins within 1–4 h of the 1st dose of
antibiotic, & the symptoms may be extremely severe
– More in LBRF
• Treatment of JHR
– Close monitoring of vital signs
– Care full fluid management
– Control high body Temperature
– Short term digoxin I.V administration in patients with evidence of myocardial
dysfunction
50

51. • Prognosis
 LBRF often occurs in settings of famine or overcrowding.
Among treated individuals, the fatality rate is 5% for LBRF and
much lower for TBRF.
51

52. Epidemic (Louse-Borne) Typhus
Etiology: R.prowazekii
 obligately intracellular, gram-negative coccobacilli and short bacilli
At risk populations:
Poor hygiene ,in cold areas
War
Disasters
Vector : Human body louse (Pediculus humanus corporis)
Clinical Manifestations:
IP 1–2 weeks, the onset of illness is abrupt
prostration, severe headache, and
fever rising rapidly to 38.8°–40.0°C
Cough is prominent- 70 % of patients
52

53. CONT…
Rash (5th day) sparing palms, soles
Photophobia
Renal & neurologic involvement
The signs of central nervous system involvement, commonly as
meningo-encephalitis, appear towards the end of the 1st week
progressing to seizure and coma
Diagnosis& treatment:-
– Serology (weil-felix test)
– Single dose doxycycline 200 mg
53

54. DIARRHEAL DISEASE
• Diarrhea-passage of watery or loose stool at
least 3 per day.
• Causes
-inflammatory
-secretory
-osmotic
-steatoreal
54

55. CHOLERA
• Etiology
• -caused by V. cholera(highly motile and curved shaped G-ve
rods.)
• Epidemiology
• ->90% of cases from Africa
• ->3million cases annually with 100,000 deaths
• Clinical manifestation
• -IP 24-48hr
• -painless watery diarrhea & vomiting
• -rice water apperance stool with flecks of mucus ,which has
inoffencive odur.
55

56. DIAGNOSIS
• Stool culture
• Antigen detection
treatment
• Rapid fluid replacement with ORS or
• IV ringer lactate
-Azithromycin 1 gm po stat
-erytheromycin 250 mg po QID for 3 days
-ciprofloxacillin 500mg po BID for 3 days
56

57. PROTOZOAL INFECTIONS:
Leishmaniasis:
– visceral leishmaniasis (VL)
– cutaneous leishmaniasis (CL), &
– Mucosal leishmaniasis (ML).
• Etiology:
 L. donovani L. infantum L. tropica
 L. major L. aethiopica
57

58. LESHI…
Transmission: sand fly
Phlebotomus
Lutzomyia
Leishmania organisms occur in two forms:
– Extracellular, flagellate promastigotes in the sand fly vector and
– Intracellular, nonflagellate amastigotes in vertebrate hosts,
including humans
58

59. PROMASTIGOTES
AMASTIGOTES , A MACROPHAGE
FILLED WITH AMASTIGOTES
59

60. LESHI…
• Epidemiology:
 98 countries
 Ethiopia:
– Northwest :
Metema
Humera,
Abderrafi,
libokemkem
– South; 60

61. CONT…
Visceral Leishmaniasis:
• kala-azar, "black fever“
• L. donovani complex,:-L. donovani and L. infantum
(the latter designated L. chagasi in the New World
• Organs of the reticuloendothelial system are
predominantly affected, with remarkable
enlargement of the spleen, the liver, and lymph
nodes in some regions
• Bone marrow dysfunction results in Pancytopenia.
61

62. PIC .VL PATIENT
• Profile view of a teenage
boy suffering from visceral
leishmaniasis. The boy
exhibits splenomegaly,
distended abdomen and
severe muscle wasting.
62

63. PIC VL PATIENT
• A 12-year-old boy suffering
from visceral leishmaniasis.
The boy exhibits
splenomegaly and severe
muscle wasting.
63

64. CONT…
Clinical Features:
moderate- to high-grade fever associated with rigor and chills
, night sweats, weakness (fatigue) ,weight loss & anorexia.
• Cachexia, wasting, Pallor
• Nontender, soft massive splenomegaly + perisplenitis
• Hepatomegaly + LAP
• Darkening of face/ashen grey appearance
• Bleeding 20 to thrombocytopenia
• Hypoalbuminemia may manifest as pedal edema and ascites
• Anemia (Pancytopenia)
64

65. CONT..
Laboratory Diagnosis:
• Anti body tests Rk-39
• Demonstration of amastigotes –gold
standard
– Splenic smear >95% sensitivity
– Bone marrow smears (60–85%)
– Lymph node aspirates (50%
65

66. CONT…
Differential Diagnosis:
• Malaria
• Typhoid fever
• Tuberculosis
• Brucellosis
• Schistosomiasis, and
• Histoplasmosis
• Portal hypertension
• Chronic myeloid leukemia
• Tropical Splenomegaly syndrome (HMS
66

67. TREATMENT
General Considerations:
 Correct anemia (blood transfusion)
• comorbid conditions should be managed promptly
Chemotherapy:
• Pentavalent Antimonials
– SSG ( 20 mg/kg IM) + paramomycine (15 mg/kg) for 17 days
• Pentavalent Antimonial Compounds
– SSG (20 mg/kg : IM, for 28–30 days)
• Amphotericin B
– (0.75–1.0 mg/kg on alternate days for a total of 15 infusions)
• Paromomycin
• Miltefosine
67

68. CONT..
Prognosis of Treated VL Patients:
• Recovery from VL is quick.
• Within a week of the start of treatment
• Regression of Splenomegaly
• Weight gain, and
• Recoveries of hematologic parameters are
evident.
• No parasite at end of Rx
68

69. PROGNOSIS
• Bad prognostic Sn and Sx
– Sever malnutrition
– Ascitis
– Liver damage ( jaundice)
– Sever pancytopenia
– HIV and other co-morbidities ( renal dysfunction)
69

70. CONT…
• VL in the Immunocompromised Host
(HIV/VL)
• Usually present with classic features
• But could have atypical manifestations
– Skin, oral mucosa, GI involvement, lung
• Parasites can be recovered from unusual sites such
as bronchoalveolar lavage fluid and buffy coat
• Treatment is more difficult(high toxcicity and less
effective)
70

71. CONT..
• Post –Kala-Azar Dermal Leishmaniasis
(PKDL):
– skin lesions concurrent with or after the cure of
VL
– hypo pigmented macules, papules, and/or
nodules
– or diffuse infiltration of the skin and sometimes
of the oral mucosa
– Spontaneous healing, or Rx with SSG
71

72. SPIROCHETAL DISEASES
Syphilis :
• Etiology: Treponema pallidum
• Transmission:
– Sexual contact - (mainly)
– nonsexual personal contact
– infection in utero
– blood transfusion and less common
– Organ transplantation.
72

73. NATURAL COURSE AND PATHOGENESIS OF
UNTREATED SYPHILIS
• T. pallidum intact MM or microscopic abrasions in
skin lymphatics & blood to systemic infection
and metastatic foci long before the appearance of a
primary lesion.
• IP 2-6 wks
• 1 ̊ lesion appears at the site of inoculation, usually
persists for 4–6 weeks, & then heals spontaneously
• 6–8 weeks a/r the chancre heals secondary syphilis
appear (mucocutaneous, parenchymal) & subside
within 2-6 wks
• Latent stage
• Tertiary syphlis
73

74. PRIMARY SYPHILIS
– Single
painless
chancre,
papular
– Later
eroded
,with
cartilaginou
s feel at its
edge & base
– Penis, labia,
cervix
74

75. SECONDARY SYPHILIS
• mucocutaneous lesions& generalized nontender
lymphadenopathy
• skin rash: macular, papular, pustular
• simultaneous d/t patterns of skin rash could be present
• non pruritic
• palms & soles involved
• hepatitis, nephropathy, GI involvement (hypertrophic gastritis,
patchy proctitis, arthritis, and periostitis---less common
75

76. SECONDARY SYPHILIS…
76

77. LATENT SYPHILIS
–+ve serology for syphilis
–-ve CSF
–Absent manifestations
–Early:<1 yr
–Late:1 yr, or unknown
duration
77

78. TERTIARY SYPHILIS:
• Neurosyphilis
– Meningeal
– meningovascular, and
– parenchymatous syphilis( general paresis & tabes
dorsalis)
• Cardiovascular Syphilis
– aortic regurgitation,
– saccular aneurysm (usually of the ascending aorta),
– or coronary ostial stenosis
78

79. DX
79

80. TREATMENT OF SYPHILIS
80

81. ACUTE BACTERIAL
MENINGITIS
• Bacterial meningitis is an acute purulent infection within the
sub-arachnoid space. It is associated with a CNS inflammatory
reaction that may result in decreased consciousness, seizures,
raised intracranial pressure (ICP), and stroke
• Is the most common CNS infection
81

82. ACUTE BACTERIAL
MENINGITIS
• Causes
– Streptococcus pneumoniae (50%),
– Neisseria meningitidis (25%),
– Group B streptococci (15%),
– Listeria monocytogenes (10%).
– Haemophilus influenzae type b accounts for <10%
– Others
• E.coli
• Staphylococci
• N. meningitidis is the causative organism of recurring epidemics of
meningitis
82

83. ACUTE BACTERIAL
MENINGITIS
• Risk factors
– Pneumonia
– Otitis media
– Diabetes
– Acute or chronic sinusitis
– Alcoholism
– Splenectomy
– Hypogammaglobulinemia,
– Complement deficiency
– head trauma with basilar skull fracture and CSF rhinorrhea
• The mortality rate remains 20% despite antibiotic therapy
83

84. ACUTE BACTERIAL
MENINGITIS
• Route of infection
– Droplet infection through the upper airways: E.g. In
Meningococcus meningitis, with possibly epidemic spread
– Haematogenous spread: e.g. in Pneumococcus pneumonia
– Contagious spread from adjacent sites : e.g. in otitis media ,
sinusitis
– Direct eg. Open trauma
84

85. ACUTE BACTERIAL
MENINGITIS
– Most of the manifestations and complications occur because of the
immune response for the invading organism than the direct effect
85

86. ACUTE BACTERIAL
MENINGITIS
• Clinical features
– Classic triads
• Fever
• Head ache
• Nuchal rigidity
– Decrease level of consciousness (>75% )( lethargy- coma)
– Nausea, vomiting and photophobia
– Seizure (20-40%)
86

87. ACUTE BACTERIAL
MENINGITIS
• Sx and Sn of raised ICP
– Reduced level of consciousness
– Papillae edema
– Sixth nerve palsy
– Dilated poorly reactive people
– decerebrate posturing
– The Cushing reflex (bradycardia, hypertension, and irregular
respirations)
• The most disastrous complication of increased ICP is cerebral
herniation
87

88. ACUTE BACTERIAL
MENINGITIS
• Specific clinical features include
– Rash of meningococcemia- diffuse erythematous maculo-papular
rash
– Petechia – rare on palms and soles
• Meningeal signs are clinical signs often sound in patients with
meningitis
– Neck stiffness: when head is flexed passively
– Kerning’s sign:
– Brudzinski’s sign:
88

89. COMPLICATIONS
• Moderate or severe sequelae occur in 25% of survivors,
although the exact incidence varies with the infecting
organism
– intellectual dysfunction
– Memory impairment
– Seizures
– Brain edema
– Hydrocephalus
– Brain abscess,
– Septic vein thrombosis
– Hearing impairment and dizziness
89

90. COMPLICATIONS
– Gait disturbance
– Fulminant meningococcal sepsis: Waterhouse-
Friedrichsen syndrome is a clinical condition
resulting from hemorrhagic necrosis of the
adrenal gland, with multi-organ failure
• hypotension or shock
• Disseminated intravascular coagulation (DIC)
• Skin and mucosal purpura
• Bleedings
90

91. DIAGNOSIS
• General sign of inflammation
– Leucocytosis
– Increased C reactive Protien (CRP)
– Increased ESR
• CSF analysis
– Polymorph nuclear leukocytosis, 10- 1000 cells/µl
– Low glucose <40mg/dl
– High protein
91

92. CSF ANALYSIS IN DIFFERENT
MENINGITIS
92

93. TREATMENT
• Supportive treatment
• Antibiotic
– a third- or fourth-generation cephalosporins +
– Vancomycine +
– Acyclovir +/or
• Dexamethasone
• Prophylaxis ( meningococal )
• Vaccination ( for meningococcal meningiti)
93

94. BAD PROGNOSTIC SIGN
• Decreased level of consciousness on admission
• Onset of seizures within 24 h of admission
• Signs of increased ICP
• Young age (infancy) and age >50
• The presence of co-morbid conditions including shock and/or the
need for mechanical ventilation
• Delay in the initiation of treatment
• Decreased CSF glucose concentration [<2.2 mmol/L (<40 mg/dL)]
and markedly increased CSF protein concentration [>3 g/L (> 300
mg/dL)
94

95. ACUTE VIRAL MENINGITIS
• High grade fever
• Headache frontal and retro orbital often associated with
photophobia and pain on moving the eyes
• Sn of meningeal irritation
• Constitutional symptoms
– Malaise, myalgia, anorexia, nausea and vomiting, abdominal pain,
and/or diarrhea
• Mild lethargy or drowziness
• presence of stupor, coma suggest involvement of the brain
95

96. ACUTE VIRAL MENINGITIS
• Commonest causes
– Enteroviruses
– Herpes simplex virus 2
– Arbovirus
– HIV
96

97. ACUTE VIRAL MENINGITIS
• Diagnosis
– LP and CSF analysis
• Lymphocytic pleocytosis
• Normal or slightly elevated protien
• Normal glucose concentration
• Normal or slightly elevated opening pressure
• PCR
• Viral serology
– CBC WITH DIFERENTIAL
– Liver and renal function tests
– Electrolyte
97

98. D. DX
• Untreated or partially treated bacterial meningitis
• Early stages of meningitis caused by fungi, mycobacteria, or
Treponema pallidum (neurosyphilis), in which a lymphocytic
pleocytosis is common
• Meningitis caused by agents such as Mycoplasma, Listeria spp.,
Brucella spp., Coxiella spp., Leptospira spp., and Rickettsia spp
• Parameningeal infections
• Neoplastic meningitis
• Meningitis secondary to noninfectious inflammatory diseases,
including hypersensitivity meningitis, SLE and other rheumatologic
diseases, sarcoidosis, and the uveomeningitic syndromes
98

99. TREATMENT
• Supportive treatment
– analgesics, antipyretics, and antiemetics
– Fluid and e-lyte balance as to be monitored
• Drug treatment
– Acyclovir for HSV-1,2
• Prognosis
– Very good but some will have some complications
99

100. ACUTE VIRAL ENCEPHALITIS
• Infection and inflammatory response to a virus that involve the
brain tissue
• Most of the time the meninges are also affected (
meningoencephalitis)
100

101. ACUTE VIRAL ENCEPHALITIS
• Clinical feature
– Acute febrile illness with sn and Sx of meningeal irritation
– Altered level of consciousness - confusion, behavioral
abnormalities
– Sign and Sx shows the site of the infection and inflamation
– Focal or diffuse neurological sign- ataxia, upper or lower motor
neuron patterns of weakness, involuntary movements (e.g.,
myoclonic jerks, tremor), and cranial nerve deficits (e.g., ocular
palsies, facial weakness) are the commonest ones
101

102. ACUTE VIRAL ENCEPHALITIS
• Commonest causes
– Herpes virus (HSV, EBV, VZV)
– Arboviruses
• Diagnosis
– Same as viral meningitis
– CSF PCR – for definitive diagnosis
– CSF culture
– Serology – week
– Imaging studies ( CT, MRI)
– Brain biopsy
102

103. ACUTE VIRAL ENCEPHALITIS
• Treatment
– Supportive
– Antivirals
• Acyclovir
• Ganciclovir
103

104. TB MENINGITIS…
• presents with a subacute febrile illness
• More than half of cases show evidence of old pulmonary lesions or a miliary pattern on chest
radiography
• progresses through 3 discernible phases
– Prodromal phase:- lasting 2 - 3 wks, cxd by insidious onset of malaise, lassitude,
headache, low-grade fever, & personality change
– Meningitic phase :-neurologic features, such as meningismus, protracted
headache, vomiting, lethargy, confusion, & varying degrees of cranial nerve &
long-tract signs
– Paralytic phase:-pace of illness may accelerate rapidly; confusion gives way
to stupor & coma, seizures& often hemiparesis
– In majority of unrxed pts, death ensues within 5 - 8 wks
104

105. TB MENINGITIS…
 Stage I:-pts are lucid with no focal neurologic
signs or evidence of hydrocephalus
 Stage II:- lethargy, confusion; ± mild focal signs
e.g. cranial nn palsy or hemiparesis
 Stage III:- delirium, stupor, coma, seizures,
multiple cranial nn palsies, &/or dense
hemiplegia
105

106. TB MENINGITIS ….
• Diagnosis
– LP:
• Cell count up to 1000/ul (lymphocyte
predominance)
• Low or normal protien
• AFB +ve in 1/3rd of cases
• Culture +ve in up to 80% - is the gold standard
– CXR
– Other routine tests ( CBC,
106

107. TB MENINGITIS ….
• Treatment
– category I anti-TB 2RHZE + 6-8RH + pyridoxine
– Steroid supp. For stage 2 and 3 disease
• Poor prognostic evidences
– Stage 2 & 3
– Delay in recognition and treatment
– Underlying disease – HIV, alcoholic, CLD….
– Low CSF cells
– Acute onset type disease
107

108. TETANUS
Etiology:
• Clostridium tetani: anaerobic, gram-positive, spore-forming
rod
• In ̴ 20% of cases of tetanus, no puncture entry wound is found
• Once in a suitable anaerobic environment, the organisms grow,
multiply, & release tetanus toxin:
– An exotoxin that enters the nervous system & causes
disease
– Very low concentrations of this highly potent toxin can
result in tetanus (minimum lethal human dose,2.5 ng/kg)
108

109. TETANUS…
Definitions:
• CDC defines tetanus as:-
– "the acute onset of hypertonia or. . .painful muscular
contractions (usually of the muscles of the jaw and neck) and
generalized muscle spasms without other apparent medical
cause."
• Neonatal tetanus is defined by (WHO) as :-
– "an illness occurring in a child who has the normal ability to
suck and cry in the first 2 days of life but who loses this
ability between days 3 and 28 of life and becomes rigid and
has spasms."
109

110. TETANUS…
Epidemiology& pathogenesis:
• C. tetani produces two exotoxins: tetanolysin &-
tetanospasmin
• Toxin transport is retrograde intra-axonal to motor nuclei of
the cranial nerves or ventral horns of the spinal cord
• Without ventilatory support, respiratory failure is the
commonest cause of death in tetanus
110

111. TETANUS…
Defns :
IP: time from infection to 1st symptom
Onset time: time from 1st symptom to 1st generalized spasm
Risus sardonicus – recession of the lips backward and a grinning like grimace
Opisthotonus – backward arched posture
Trismus (lockjaw) 20 to masseter muscle hypertonicity
• There are four forms of tetanus, genralized, localized , CNS and neonatal
DDX:
Strychnine poisoning
Oropharyngeal infection. For cephalic Tetanus
Hypocalcemia & meningoencephalitis are included in the DDX of
neonatal tetanus
111

112. TETANUS…
Genralized tetanus
• Most common presentation of tetanus
• Trismus (lockjaw) 20 to masseter muscle hypertonicity
• Neck shoulder and back muscle stiffness and pain
• Rigid abdomen and stiff proximal limb muscles
• Risus sardonicus, Arched back (Opisthotonus)
• Paroxysmal generalized muscle spasm apnea /Cyanosis
/laryngospasm (spontaneous or provoked)
• Hyperpyrexia with clear mentation
112

113. TETANUS…
113

114. TABLE : FACTORS ASSOCIATED
WITH A POOR PROGNOSIS IN
TETANUS
114

115. TETANUS…
Complications
• Aspiration pneumonia
• Vertebral fracture
• Muscle rupture
• DVT+PE (VTE)
• Decubitus ulcer
• Rhabdomyolysis (pigment-induced nephropathy)
• Autonomic dysfunction - Labile or sustained HTN, Tachycardia,
Hyperpyrexia, Profuse sweating, Bradycardia and hypotension
episodes, Sudden cardiac arrest
115

116. TREATMENT OF TETANUS
Wound: cleaned, and debrided of necrotic material
Metronidazole 500 mg IV QID for 7days (penicillin)
Antitoxin: Standard therapy is 3000–6000 IU of TIG or 10,000–20,000 U
of equine antitoxin as a single IM dose
Chlorpromazine or Phenobarbital
IV magnesium sulfate has been used as a muscle relaxant
Patients should be nursed in calm, quiet environments because light
and noise can trigger spasms.
Tracheostomy is usual method of securing the airway in severe tetanus
Recovery from tetanus may take 4–6 weeks
116

117. AMOEBIASIS
• Etiology:- Entamoeba histolytica
• Transmission and cycle
• - contaminated water, food or hands
• Clinical features
1. Intestinal amoebiasis
-IP = 2 - 6weeks
-Lower abdominal pain, Bloody mucoid diarrhea,
Fever (<40%), malaise
117

118. • 2. Amoebic liver abscess
- hepatomegaly /Wt loss/anorexia
-RUQ pain + Hepatic point tenderness
-Pathology : “ Anchovy paste”
• Complications of amoebic liver abscess
-Pleuropulmonary amoebiasis (20-30%)
-Hepato-bronchial fistula
-Rupture into the peritoneal space
-Rupture into the pericardium (left lobe site
118

119. DIAGNOSIS
1. Stool examination
2. Serologic test for invasive amoebiasis
-ELISA
-Agar-Gel diffusion assay
3. Liver imaging - US/CT scan
Treatment
-metronidazole 500-750mg po tid for 5-10days
-tinidazole 2gm po QD for 3 days
119

120. Prevention
• Adequate sanitation + Eradication of cyst
carriage
• Avoid unpeeled fruits/vegetables
• Use of bottled water
• Water disinfection by iodination
120

121. RABIES
• • Reservoir – mammals; primarily dogs
• • Transmission – bite or contact with rabid animal
• • Incubation period – 7 days to >1 year (average 1-2mths)
• retrograde
• axoplasmic transport (3mm/hr)
121

122. CLINICAL MANIFESTATIONS
• Prodromal period – lasts for about a week
- marked by fever, headache, myalgia, fatigue, anorexia, nausea, vomiting,
sore throat, dry cough.
• Encephalitic phase – lasts for about a week.
- excessive motor activities, excitation, agitation, confusion, hallucinations
- have high grade fever (eg 40.60C)
-hydrophobia or aerophobia
Laboratory evaluations
-Serum and CSF Ab
-PCR
-Negri bodies, intracytoplasmic inclusion bodies
122

123. TREATMENT
• No specific treatment, only supportive care.
Post exposure prophylaxis
-Whenever there is animal bite wound should be thoroughly
cleaned, TAT and antibiotic given.
- Modern cell culture vaccine on days 1, 3, 7, 14 and 28 days
-rabies Ig on day 0 (or up to the seventh day).
. Pre exposure prophylaxis
- 1ml modern cell culture vaccine on 0, 7 and 21 or 28 thday and
- Booster doses if exposed twice with 3 days interval.
123

124. TUBERCULOSIS
• Tuberculosis:
– usually affects the lungs,
– other organs are involved in up to one-third
of cases
– Etiology:
• M. tuberculosis
• M. bovis
• M.africanum
124

125. EPIDEMIOLOGY
• WHO Global TB Report 2011, estimated :-
– Global incidence: 8.8 million, in 2010,
• 1.1 million were among people living with HIV
– Ethiopian incidence: 220,000 (261 per 100,000) ,2010
– Ethiopian prevalence: 330,000 (394 per 100,000), 2010
– 29,000 deaths (35 per 100,000) due to TB, in Ethiopia
125

126. TRANSMISSION
• Inhalation of infected droplet nuclei (common)
• Small droplets vs large droplets
– Coughs, Talking
– Sneezing, spitting
– singing
• Consumption of raw milk containing M.bovis (rare)
Air-
droplets
126

127. TRANSMISSION …
• Two factors determine an individual’s risk of exposure:
1. concentration of droplet nuclei in contaminated air &
2. length of time spent breathing that air
• Risk of infection of susceptible person is thus high with :-
– close, prolonged, indoor exposure to a person with sputum smear-positive
pulmonary TB& if the patient is not on anti tb.
• After infection :-
– Great majority (90-95%) –latent infection
– Only 5-10% of the latent TB develop active disease
– Among HIV patients ,risk of progression to active disease is higher:-
• 10% per year
• 50% life-time risk
127

128. TABLE : COMPARISON OF
LTBI VS ACTIVE TB
128

129. NATURAL HISTORY
• Based on the time of occurrence TB can be classified in to:-
1. Primary TB:
• Children (< 5 years)
• Immunocompromised patients
• HIV/AIDS patients
• Affects middle & lower lobes
2. Postprimary TB:
• Upper lobes
129

130. NATURAL HISTORY OF
DISEASE…
Natural History of Disease:
• Untreated TB could be fatal.
• About 1/3 of patients die within 1 yr after dx &
• More than 50% die within 5 years
• The 5-year MR among sputum smear+ve cases is 65%.
• Of the survivors at 5 years, ̴ 60% have undergone spontaneous
remission, while the remainder are still excreting tubercle bacilli
130

131. CONT…
Clinical Manifestations:
• Pulmonary: 80%
• Extra pulmonary
131

132. CONT…
1.Pulmonary TB:
A. primary disease
• Middle, or lower lobe involvement
• Ghon focus & Ghon complex
• Hilar& paratracheal lymphadenopathy
• Young children & immunosuppressed (HIV)
132

133. CONT…
B.Postprimary (Adult-Type) Disease:
• reactivation or secondary TB
• apical and posterior segments of the upper lobes
• varies from small infiltrates to extensive cavitary lesions
Symptoms:
• Fever, night sweat
• Cough (90%) dry-productive
• Hemoptysis 20-30% of cases
133

134. CONT…
2.Extrapulmonary TB
• Extrapulmonary sites most commonly involved in TB are: in
decreasing frequency:-
Lymph nodes, pleura, genitourinary tract, bones and joints,
meninges, peritoneum, and pericardium.
134

135. CONT…
2.1 Lymph Node TB (Tuberculous Lymphadenitis):
• 35%
• presents as painless swelling of the lymph nodes
• mainly posterior cervical & supraclavicular LNs
• scrofula
• FNA up to 80% yield
• Culture positive in 70–80% of cases
135

136. CONT…
2.2 Pleural TB:
• ̴ 20% of extrapulmonary cases
• fever, pleuritic chest pain, and dyspnea
• AFB +ve only in 10-25% of cases
• Culture +ve in 25-75%
136

137. CONT…
2.3 Genitourinary TB:
• 10–15% of all extrapulmonary cases
• Up to 75% of patients have CXR abnormalities
• Urinary frequency, dysuria, nocturia,
and flank or abdominal pain are common
presentations
• U/A, culture, IV pyelography, abdominal CT, or
MRI
• Genital TB (fallopian tube, epididymis)
137

138. CONT…
2.4 Skeletal TB:
• 10% of extrapulmonary cases
• Weight-bearing joints (spine -40%, hips - 13% & knees - 10%)
mostly affected
• Spinal TB (Pott's disease or tuberculous spondylitis):
• upper thoracic spine is the most common site in children
• the lower thoracic and upper lumbar vertebrae are usually
affected in adults
• Gibbus, cold abscess
• Paraplegia
138

139. CONT…
2.5Tuberculous Meningitis & Tuberculoma:
• ̴ 5% of extrapulmonary cases
• TB meningitis results from:
– the hematogenous spread of primary or postprimary pulmonary TB or
– The rupture of a subependymal tubercle into the subarachnoid space.
• Headache and slight mental changes after a prodrome of weeks of low-grade
fever, malaise, anorexia, and irritability.
• severe headache, confusion, lethargy, altered sensorium, and neck rigidity
• meningeal involvement is pronounced at the base of the brain
• paresis of cranial nerves (ocular nerves in particular) is a frequent finding
139

140. CONT…
2.6 Gastrointestinal TB:
• Terminal ileum & cecum -most commonly
involved
• Abdominal pain and swelling, obstruction,
hematochezia,& palpable abdominal mass
• Fever, weight loss, anorexia, & night sweats are
also common
• TB peritonitis:non specific abdominal pain,fever
&ascites .
140

141. CONT…
2.7 Pericardial TB (TB Pericarditis):
• direct extension from adjacent
or hilar lymph nodes
• hematogenous spread
• dyspnea, fever, dull retrosternal pain, and
a pericardial friction rub
• pericardiocentesis
141

142. DIAGNOSIS OF TB
• Sputum AFB
– Spot, spot sampling
– Sensitivity (40-60%)
– 99% specificity
• Sputum culture
– allows diagnosis of less infectious cases
– Gold standard in mycobacterial detection
142

143. DIAGNOSIS OF TB…
• GeneXpert
• Radiology (Chest x-ray)
• Histopathology
– FNAC
– Pleural biopsy
– Peritoneal biopsy
143

144. CONT…
Treatment: Tuberculosis:
Goals of RX:
• 1. To interrupt transmission by rendering patients noninfectious
and
• 2 .to prevent morbidity & death by curing patients with TB while
preventing the emergence of drug resistance
• Drugs: isoniazid, rifampicin, pyrazinamide, ethambutol
144

145. HIV
 Retroviruses (lentivirus)
HIV-1: common worldwide
HIV-2: confined to West Africa
 Transmission:
sexual contact (both heterosexual & homosexual)
by blood & blood products
by infected mothers to infants intrapartum, perinatally, or via breast milk.
Presence of other STDs augment HIV infection
Rate of transmission is high during early stage of HIV infection& in advanced diseases
chronic, persistent infection is the hallmark of HIV disease
145

146. CONT…
• Epidemiology
– At the end of 2013, an estimated 35.0 million individuals were
living with HIV infection.
– An estimated 95% of people living with HIV/AIDS reside in low-
and middle-income countries.
– 50% are female, and 3.2 million are children <15 years.
– In 2013, an estimated 2.1 million new cases of HIV infection
occurred worldwide.
– Sub-Saharan Africa around 24.7 million cases.
146

147. PATHOGENESIS & HIV
REPLICATION
• Life Cycle of HIV
• Binding of GP 120 of virus with CD4 molecule of T cells or APCs
(monocytes/Macrophages/dendritic cells/ Langerhans cells)  fusion of HIV with target cell
via GP 41 molecule
• Co-receptors with CD4 molecule for viral fusion and entry into target cell
– CCR5 - Co-receptor of monocytes/ Macrophages
– CXCR4 - Co-receptor of T cells
• Replication
 uncoating of viral envelope and Internalization in to the cell  Reverse transcription of
viral RNA into proviral DNA  integration into host cell chromosome  Transcription of the
integrated proviral DNA into genomic RNA or mRNA  Translation of Viral mRNA Viral
protein synthesis, processing, modification and assembly  Assembly of viral envelope and
nucleocapsid  viral budding from target cell ---- and continue to infect other cells.
147

148. HIV EVASION METHODS
• Makes 10 billion copies/day  rapid mutation of HIV antigens
• Integrates into host DNA
• Depletes CD4 lymphocytes
• Down-regulation of MHC-I process
• Impairs Th1 response of CD4 helper T-lymphocyte
148

149. TISSUES WHERE HIV
REPLICATES
• Lymph nodes
• Spleen
• Bone marrow
• Gut associated lymphoid tissue (GALT)
• Brain
• Testis
149

150. LIFE SPAN OF HIV AND
INFECTED CELLS
• 109 - 1011 viral copies per day
• Average life-span of HIV in plasma is 30-60mins
• Average life-span of HIV-infected CD4 lymphocytes is ~1.6 days
• Integrated HIV genome can stay dormant within a cellular DNA
for many years
• Cellular activation plays an important role in the replication
cycle of HIV (e.g., TB)
150

151. 151
0
100
200
300
400
500
600
700
800
900
1000
0 1 2 3 4 5 1 2 3 4 5 6 7 8 9 10 11
CD4+cellCount
Months Years After HIV Infection
Natural Course of HIV Infection
Acute
HIV
infection
syndrome
Viral Load
Relative level of
Plasma HIV-RNA
Anti-HIV Ab
CD4+ T cells

152. Immunity
Natural (Innate)
Immunity
Physical (Skin)
Chemical
(HCl, peptides)
Cell (Phagocytosis)
Adaptive (acquired)
Immunity
Cell Mediated
Cellular Immunity
T-Lymphocytes
Cytotoxic Cells
(CD 8+ Cells)
Helper Cells
Antibody Mediated
Humoral Immunity
B-Lymphocytes
152

153. PATTERNS OF HIV DISEASE
PROGRESSION
153

154. OUTCOME OF HIV INFECTION
• Direct effect
– Nervous (encephalopathy and peripheral neuropathy)
– Kidney (HIVAN = HIV-associated nephropathy)
– Cardiac (HIV cardiomyopathy)
– Endocrine (hypogonadism in both sexes)
– GI tract (dysmotility and malabsorption)
• Indirect effect
– Opportunistic infections and tumors as a consequence of
immunosuppression
154

155. LABORATORY TESTS FOR
DIAGNOSIS• Direct detection of virus
– Viral culture
– Viral Load
• RNA or DNA PCR
– ANTIGEN (Ag) in plasma/serum (p24)
• Detection of Antibody
– Rapid tests
– ELISA
– Western blot
155
AVAILABLE IN MOST SETTINGS

156. WHO STAGING
A. Clinical stage 1:
 Asymptomatic infection
 PGL (Persistent generalized lymphadenopathy)
B. Clinical stage 2:
unexplained weight loss<10%
Seborrheic dermatitis
Angular chelitis
Herpes zoster (in last 2 yrs)
Recurrent URTI (sinusitis, otitis media…)
Recurrent oral ulceration
Fungal nail infections
156

157. WHO STAGE 2…
HERPES ZOSTER
PPE, ALWAYS EXLCUDE SCABIES,
INSECT BITES
157

158. 158
Stage 2
Seborrhoeic
dermatitis
Itchy scaly skin condition, especially affecting scalp, face,
upper trunk (also common in non-HIV)

159. WHO STAGING….
C. Clinical stage 3:
oral candidiasis
Unexplained weight loss >10%
Recurrent vaginal candidiasis
Persisntent oral hairy leukoplakia
Pul TB –recent
Unexplained chronic diarrhea > 1 month
Unexplained prolonged fever> 1 month
Severe bacterial infections( bacteramia ,pneumonia …
Unexplained hematologic abnormalities
Acute necrotizing ulcerative stomatitis , gingivitis or
periodontitis
159

160. WHO STAGE 3…
ORAL THRUSH ORAL HAIRY LEUKOPLAKIA
160

161. 161
Necrotising
stomatitis

162. WHO…
D. Clinical stage 4:
Chronic HSV infection
CMV infection (other than liver ,spleen, LN)
CNS toxoplasmosis
HIV wasting syndrome
PCP
Esophageal candidiasis, tracheal , bronchial
Extrapulmonary TB
Kaposi sarcoma
Invasive cervical ca
Cryptosporidiosis, microsporidiosis, isosporiosis
PMLE
VL
162

163. HIV WASTING: DEFINITION
163
Weight loss > 10%
PLUS
Unexplained chronic diarrhoea
> 1 month
OR
Unexplained prolonged fever
> 1 month

164. NATURAL HISTORY &CLINICAL MANIFESTATION
1.The Acute HIV Syndrome:-
Occurs in 50–70% of individuals with HIV infection
3–6 weeks after primary infection
occur along with a burst of plasma viremia
164
Table Clinical Findings in the Acute HIV Syndrome
General:-
a. Fever
b. Pharyngitis
c. Lymphadenopathy
d. Headache/retroorbital pain
e. Arthralgias/myalgias
f. Lethargy/malaise Anorexia/weight loss
g. Nausea/vomiting/diarrhea
Neurologic:-
I. Meningitis
II. Encephalitis
III. Peripheral neuropathy
IV. Myelopathy
Dermatologic:-
a) Erythematous maculopapular rash
b) Mucocutaneous ulceration

165. CONT…
2. Clinical latency
̴̴ mean 10 yrs
3. Symptomatic Disease
a. Diseases of the Respiratory System
 URTI (sinusitis, pharyngitis, otitis media)
 Recurrent bacterial pneumonia
 Tuberculosis, &
 Pneumonia due to the unicellular fungus P. jiroveci (PCP)
165

166. T-STAGING
• T-staging refers to clinical staging while on Antiretroviral treatment
for at least 6 months
• Used as an indicator for treatment outcome
• Prompts consideration to switch therapy
• Clinical events before the first six months of therapy are excluded
from this definition
– WHY?
166
Often represent IRIS
related to pre-existing
conditions

167. OPPORTUNISTIC
INFECTIONS
167

168. TOXOPLASMOSIS
• It is a protozoan disease
• Causes lymphadenopathy in immunocomptent
and self limiting disease
• It occurs late in AIDS with CD4 count < 100
• Etiology : Toxoplasma gondii
• Life cycle
– Intermediate host –Birds, mammals,
– Definitive host: cat and its prey
168

169. TOXOPLASMOSIS
• Transmission
– Oral transmission
• Ingestion of sporulated oocysts from contaminated
Soil
• Ingestion of bradyzoites from undercooked meat
– Blood transfusion and organ transplantation
– Vertical
169

170. CLINICAL FEATURE
– Altered mental status b/c of necrotizing encephalitis
/cerebral edema/ hydrocephalus/
Vasculitis/hemorrhage)
– Focal /localized head ache
– Fever
– Focal seizures
– Focal neurologic deficits: Motor deficits (hemiparesis),
CN palsy, Visual field defect, Aphasia
– Movement disorder
– Dysmetria/ataxia
170

171. DIAGNOSIS
• Presumptive clinical diagnosis
– AIDS pts with CD4
+ <200/l
– Clinical presentation
• Focal neurologic deficits
– History of exposure (evidenced by serology – IgG - past, IgM -
recent)
• No history of 10 prophylaxis for toxoplasmosis
• Radiologic evaluation: CT scan or MRI
• Remarkable Anti-Toxo treatment response within 1-2
weeks (95%)
171

172. CONT…
• Other diagnostic methods
– Serology
– ELISA
– Biopsy
– CT/MRI
• Treatment
– Trimethoprim/sulphamethoxazole
• Alternative regimen
– Pyrimethamine+ Clindamycin+ Leucovorin
– Pyrimethamine+ sulfadiazine+ Leucovorin
172

173. PROPHYLAXIS
• Primary
– For CD 4< 200
• Secondary
– Maintenance therapy in those with previous episode of
toxoplasmosis
– Discontinue when patients are asymptomatic and CD4+ > 200/l >
6 months after HAART
– Restart when CD4
+ < 200/l
173

174. CRYPTOCOCCAL
MENINGITIS
• Etiology: Cryptococcus neoformans, which is yeast- like fungus.
– Pigeon droppings commonly contain serotypes A or D
– Infection is acquired through inhalation
• Epidemiology:
– Is the leading cause of meningitis in patients with AIDS
– Is the initial AIDS defining illness
– Particularly common in patients with AIDS in Africa
174

175. CLINICAL FEATURES
• Occurs late in the course of HIV/AIDS – when CD4 count is,
100/mm3
• CNS and meningial involvement is seen in 67-85 % of patients
• Low grade fever, nausea , vomiting , headache
• Both fever and nuchal rigidity are often mild or lacking
• Papilledema is seen in one third of patients
• Neck stiffness , Photophobia – Meningial signs are seen in 30% of
patients
• Late manifestations : Confusion , altered state of consciousness,
comma
175

176. OTHER ORGAN SYSTEMS
AFFECTED
– Extra cranial manifestations: Occasionally appears as pulmonary or
disseminated disease that includes the skin (10%).
– Cutaneous Cryptococcosis: centrally umblicated multiple lesions on
the face (look very much like Molluscum contagiosum.)
– Pulmonary disease
– Fungemia
– Lymphadenopathy
– The prostate gland may be a reservoirs for smoldering infection
176

177. DIAGNOSIS AND TREATMENT
• LP- CSF
– Opening pressure is high
– WBC with differential, protein and glucose normal in 1/3 of patients
– Indian ink- positive in 60-80%
– CSF Cryptococcal antigen- Positive in 95-99 %
– Cryptococcal culture- Gold standard
• Rx
– Induction- Amphotericine B with flucytocine
– Consolidation- Fluconazole
– Maintenance phase- Fluconazole
– Secondary prophylaxis- Fluconazole CD4< 200
177

178. PNEUMOCYSTIC CARINNI
PNEUMONIA (PCP)
• Caused by P. jiroveci
• Transmitted by
– Air-Borne
• Predisposing factors
– HIV infection with CD4
+ <200/l
– Corticosteroid therapy
– Organ transplantation
– 10 immuno deficiency diseases
– Premature, malnourished infants
178

179. PCP….
• High index of suspicion required for early detection of PjP
• Sub-acute onset pneumonia with fever,
• Dyspnea
• Dry cough
• Tachycardia, Tachypnea, Cyanosis, minor findings on
auscultation
• Lymph node, spleen, liver, kidneys, pancreas, heart, thyroid,
adrenals can be involved
179

180. DIAGNOSIS AND TREATMENT
• Dx
– CXR:- Bilateral diffuse infiltrates beginning in perihilar regions is typical but
different
– LDH level is elevated in >90% of cases
– Broncho alveolar lavage
– Open lung biopsy
• Rx
– Trimethoprim- sulphamethoxazole (cotrimoxazole) 120mg/kg/day for three
weeks
– Adjunctive therapy
• Oxygen
• Steroids
– Is effective in 90% of patients
– Secondary prophylaxis
180

181. DIARRHEAL DISEASES
• Early (CD4 >200) – Gardiasis, amoebiasis,
salmonella, S. typhimurium, shigella, strongelloid,
• Late (CD4 <200) – isospora belli,
cryptosporidium, microsporidium, CMV,
lymphoma, M Tb, HIV enteropathy.
• Work up of diarrheal disease in HIV patient
• Characterized as chronic vs acute; watery vs
bloody
181

182. DIARRHEAL....
• Mechanism of diarrhea
– Adhesion to mucosal surface
– Enterotoxin
– Entero-invasion
– Atrophy of mucosal surface
• Diagnostic investigation
– Stool Microscopy
– Culture
– Intestinal biopsy
– Special stains: Modified AFB stain
182

183. DIAGNOSTIC….
– Stool microscopy for ova or parasite, inflammatory
cells … 3X
– Stool culture
– Modified AFB staining for cryptosporidium, isospora
belli
– Chromotrope based stains for microsporidium, or
biopsy
– Endoscopy and biopsy for CMV enteritis, lymphoma,
HIV enteropathy….
183

184. TREATMENT
• Fluid and electrolyte replacement, nutritional
support
• Treatment of identified parasite or infections
– Tinidazole or metronidazole for Giardia
– Tiabendazole for strongloidosis
– High dose cotrimoxazole for I. Belli (TMP-SMX;
160/800 mg four times daily for 10 days, and for HIV-
infected patients, then three times daily for 3 weeks)
– Albendazole (14 days) for microsporidium
– Cryptosporidium – trials with paramomycin,
nitazoxanide
184

185. TREATMENT OF HIV/AIDS
PRINCIPLES OF THERAPY
 Use multiple drugs with d/t MOA
 Avoid combining drugs with same MOA
 Adherence is vital
ARV Drugs:
a. Reverse Transcriptase Inhibitors
185
Nucleoside Reverse Transcriptase Inhibitor
(NRTI)
Zidovudine(AZT,ZDV
Stavudine (d4T)
Didanosine (ddI)
Lamivudine (3TC)
Emtricitabine (FTC)
Abacavir (ABC)
Zalcitabine (ddC)
Nucleotide analogues
Tenofovir (TDF)
Non-Nucleoside Reverse Transcriptase Inhibitor
(NNRT)
Nevirapine (NVP)
Efavirenz (EFV)

186. TREATMENT OF HIV/AIDS
b. Protease Inhibitors
Saquinavir (SQV)
Ritonavir (RTV)
Indinavir (IDV)
Nelfinavir (NFV)
Lopinavir (LPV)
Atazanavir (ATV)
186

187. TREATMENT OF HIV/AIDS
c. Fusion Inhibitors
Enfuvirtide (T-20)
d.Integrase Inhibitors
Raltegravir (RAL)
e.CCR5 Blockers
Maraviroc (MVC)
187

188. IRIS
Characteristics of Immune Reconstitution Inflammatory Syndrome (IRIS)
Can be:-
1. Paradoxical
2. Un masking
• Paradoxical worsening of clinical condition is seen following the initiation
of ART
• Occurs weeks to months following the initiation of antiretroviral therapy
• Is most common in patients starting therapy with a CD4count < 50/µL who
experience a precipitous drop in viral load
• Is frequently seen in the setting of tuberculosis
• Can be fatal
188

189. TREATMENT FAILURE
TYPE OF FAILURE DEFINITION
CLINICAL FAILURE New or recurrent WHO stage 4
condition
CD4 CELL FAILURE
Immunologic failure
•Fall of CD4 count to pre-Rx
baseline (or below);
•50% fall from the on-Rx peak
value (if known);
•Persistent CD4 levels below 100
cells/mm3
VIROLOGICAL FAILURE
Plasma VL above 1000 c/ml
189

190. HELIMINTHIASIS
• Intestinal nematodes:-
– Roundworms (1mm-many centimeters long)
– Most common in regions with poor fecal sanitation,
– Particularly in resource-poor countries in tropics & subtropics
– Not usually fatal, but they contribute to :
• malnutrition & diminished work capacity
– S.stercoralis & E.vermicularis, can be transmitted directly from person to
person
– Ascaris & hookworm require soil phase for development
190

191. ASCARIASIS
• The largest intestinal nematode in humans, reaching up to 40
cm in length
• Caused by Ascaris Lumbricoides
• Mostly asymptomatic (low worm burden)
• Symptoms are b/c of:-
– larval migration in the lungs or
– effects of the adult worms in the intestines
191

192. ASCARIASIS
• Life cycle:-
– Mature female Ascaris -240,000 eggs/day, w/h pass in feces
– Ascaris eggs:-
• remarkably resistant to environmental stresses
• become infective a/r several wks of maturation in the soil &
• can remain infective for yrs
– Adult worms live for 1–2 years
192

193. ASCARIASIS
• Transmission : feco - oral
• Clinical features:-
– During larval migration (~9-12 days a/r egg ingestion):-
• Irritating nonproductive cough
• Burning substernal discomfort (Pleuritic type)
• Dyspnea & blood-tinged sputum are less common
• Fever is usually reported
– Adult worms:-
• Usually cause no symptoms
• SBO (large bolus of worms esp., in children)
• Rarely: biliary colic, cholecystitis, cholangitis, pancreatitis, acute
appendicitis
193

194. ASCARIASIS
• Lab investigation :-
– Stool microscopy:-
• Ova of Ascaris
• Larvae can be found in sputum or gastric aspirates b/r diagnostic eggs
appear in the stool
– Treatment:-
• Albendazole (400 mg once)
• Mebendazole (100 g BID for 3 days or 500 mg once), or
• Pyrantel pamoate is safe in pregnancy
194

195. 2. HOOKWORM
• Two species (Ankylostoma duodenale and Necator americanus)
• Adult hookworms, w/h are ~1 cm long
• Use buccal teeth (Ancylostoma) or cutting plates (Necator)
• Attach to the small-bowel mucosa
• Suck blood (0.2 mL/d per Ancylostoma adult) & and interstitial
fluid
• Adult hookworms produce thousands of eggs daily
195

196. HOOKWORM…
• Life cycle:
– eggs ( deposited with feces in soil)---rhabditiform larvae -
infectious filariform larvae(within a wk)-Infective larvae
penetrate the skin ----lungs (via bloodstream)
– Adult hookworms may survive over a decade
– but usually live ~6–8 years for A. duodenale &
– 2–5 years for N. americanus
196

197. HOOKWORM…
• Clinical features:
– Most hookworm infections are asymptomatic
– Pruritic dermatitis ("ground itch") at site of penetration
– Mild transient pneumonitis (less than in ascaris)
– In the early intestinal phase, there may be epigastria pain,
inflammatory diarrhea or other GI symptoms
– major consequence of chronic hookworm infection is iron
deficiency anemia
197

198. HOOKWORM …
• Lab investigations:
– Stool microscopy:
• Ova of Hookworm
– Hypochromic microcytic anemia
• Treatment :
– Albendazole (400 mg once)
– Mebendazole (500 mg once), &
– Pyrantel pamoate (11 mg/kg for 3 days)
– Iron if anemic
198

199. STRONGYLOIDIASIS
• S. stercoralis -unique from helminths in replicating in human
host
• Autoinfection as infective larvae are internally produced
• Can persist for decades without re-exposure of host to
exogenous infective larvae
• Immunocompromised hosts, large numbers of invasive
Strongyloides larvae can disseminate widely & can be fatal
199

200. STRONGYLOIDIASIS…
• Clinical features:
– Many pts are asymptomatic or have mild cutaneous &/or
abdominal symptoms
– Recurrent urticaria, (often buttocks & wrists)
– Migrating larvae can elicit a pathognomonic serpiginous eruption,
larva currens ("running larva")
– Nausea, diarrhea, GI bleeding, mild chronic colitis,& weight loss
can occur
– Bacteremia may develop b/c of the passage of enteric flora via
disrupted mucosal barriers
200

201. STRONGYLOIDIASIS…
• Lab investigation:
– Stool microscopy
• Rhabditiform larvae
– Treatment
• Ivermectin (more effective)
• Albendazole
• Disseminated strongyloidiasis, Rx with Ivermectin should be extended
for at least 5–7 days or until the parasites are eradicated
201

202. TRICHURIASIS (WHIP-
WORM INFECTION)
• Caused by Trichuris trichiura
• The adult worms reside in the colon and caecum
• The adult worms may live for several years
Clinical presentation
– Most infections are asymptomatic.
– Large worm burden may be associated,
• Diarrhea of long duration,
• Dysentery
• Mucoid stools
• Abdominal pain and tenderness
– Dehydration, anemia, weight loss and weakness
– Rectal prolapse may occur, particularly in children
202

203. TRICHURIASIS
• Diagnosis
– Microscopy - lemon-shaped whip worm eggs
• Treatment
– Mebendazole 100mg twice daily for 3 days or
– Albendazole 4mg/kg as a single dose
203

204. SCHISTOSOMIASIS
,TREMATODE (FLATWORM)
• Etiologies
a) S. mansoni
b) S.japonicum
c) S. hematobium
d) S. Mekongi
e) S. intercalatum
204

205. LIFE CYCLE OF
SCHISTOSOMA
205

206. EPIDEMIOLOGY
Transmission
– penetration of intact skin with infective cercariae
• 200-300 million individuals infected worldwide
• ~20 million symptomatic
• Starts to be seen since age of 3-4 & maximum at ags 15-20
• Declines after age 40
206

207. PATHOGENESIS & IMMUNITY
• Cercarial invasion dermal &subdermal inflammatory
responses
• As oviposition commences, acute schistosomiasis or Katayama
fever may occur
• Eggs retained in host tissuesgranulomatous response
207

208. PIC HEPATOSPLENOMEGALY
208

209. CLINICAL FEATURES, 3
PHASES
1. Swimmer`s itch:
– phase of cercarial invasion, a form of dermatitis
– manifesting 2 or 3 days after invasion
– itchy maculopapular rash on the affected areas of the skin
– Cercarial dermatitis is a self-limiting clinical entity
2. Acute schistosomiasis (katayama fever):
– At the beginning of oviposition (i.e., 4–8 wks a/r skin invasion)
– fever, generalized lymphadenopathy, & hepatosplenomegaly—
may develop
– high degree of peripheral-blood eosinophilia
209

210. CLINICAL FEATURES, 3
PHASES…
3. Chronic schistosomiasis:
• species-dependent
– Urinary : S.hematobium
– Intestinal & hepatosplenic : the other species
– may begin a few months after infection & may last for years
– symptomatic patients characteristically have colicky abdominal pain,
bloody diarrhea, & anemia
– Patients could develop colonic polyposis
– hepatosplenic disease manifests early (during 1st yr of infection,)
• liver enlargement due to parasite-induced granulomatous lesions
210

211. CLINICAL FEATURES, 3
PHASES…
3. Chronic schistosomiasis:
• Hepatomegaly :-
– is seen in ~15–20% of infected individuals
– it correlates roughly with intensity of infection
– occurs more often in children
• presinusoidal blockage of blood flow leads to:
– portal hypertension & splenomegaly
– Esophageal varices
– Bleeding (vomiting)
– Ascites
211

212. CLINICAL FEATURES, 3
PHASES…
3. Chronic schistosomiasis:
• S. hematobium:-
– Up to 80% of children infected with S. haematobium have dysuria,
frequency, & hematuria
– Urine examination reveals blood & albumin
– hydroureter & hydronephrosis, may be seen in 25–50% of infected
children
– sandy patches visible on cystoscopy (fibrosis)
– Has association with squamous cell carcinoma of the bladder
212

213. CLINICAL FEATURES, 3
PHASES…
• Less common sites :
– pulmonary manifestations, CNS schistosomiasis
– Jacksonian epilepsy due to S. japonicum
– Transverse myelitis :S. mansoni & S. haematobium
• Diagnosis:-
– high-level peripheral-blood eosinophilia
– positive serologic assay for schistosomal antibodies
– stool / urine microscopy -ova
213

214. TREATMENT
• Praziquantel:
– PO in total of 40 or 60 mg/kg in 2 or 3 doses over a single day
– parasitologic cure in ~85% of cases
– reduces egg counts by >90%
214

215. CESTODES( TAPE WORMS)
Taeniasis saginata (beef tapeworm infection)
• is caused by the presence of the adult beef tapeworm,
T.Saginata, in the intestine of humans
• Is the large tape worm which measure 5-10 meters
• It is found in all countries whereraw met is ingested
• Human is the only definitive host
• Cysticercusis the stage of the tape worm which is found muscles
of a cattle
215

216. TAENIASIS SAGINATA
Clinical feature
• Usually patients are asymptomatic
• Patients pass proglottids ( segment of the worm) with stool or
alone
• Proglottids are motile and this causes perianal discomfort
during discharge
• Mild abdominal pain, nausea, anorexia and weight loss can
occur
216

217. TAENIASIS SAGINATA
• Dx- demostration of the egg or the proglotids in the stool
• Rx
– Praziquantile 5-10 mg/kg
– Niclosamide 2gm stat
217

218. TAENIASIS SOLIUM
• Is caused by T. solium ingestion from raw or undercooked
ppork
• The adult tape worm and the larvae (Cysticerca) infect human
• Human being is the definitive and intermediate host
218

219. TAENIASIS SOLIUM
• Mostly patients are asymptomatic
• Epigastric discomfort, nausea and weight loss
• Patients may note passage of proglottids
• Cysticerica (cysticercosis), they are distributed all over the body
– CNS with seizures, headache, raised intracranial pressure, mental
changes etc.
• Diagnosis: The diagnosis of intestinal T.solium infection is made by
the detection of eggs or proglottides
• RX
– intestinal – praziquantile
– CNS refer the patient to a hospital
219

220. HYMENOLEPIS NANA
(DWARF TAPEWORM)
• Is 25-40mm in length by 1mm in breadth
• It doesn't require intermediate host
• Hatching of eggs occurs in the small intestine where they penetrate
the villus and become cysticercoid
• Most infections are asymptomatic
• Severe infections may manifest with abdominal pain, anorexia and
diarrhea
• Dx – stool exam- ova
• RX- praziquantile 25mg/kg stat
– Niclosamide for 7days
220