This document provides an overview of malaria, including its epidemiology, pathogenesis, clinical manifestations, diagnosis and treatment. Some key points: - Malaria is caused by Plasmodium parasites transmitted via mosquito bites and remains a major global health problem. P. falciparum causes the most severe disease and majority of deaths. - Clinical features vary by parasite species but can include fever, anemia, jaundice, cerebral malaria and more. Severe malaria affects vital organs and has high mortality without prompt treatment. - Diagnosis is by microscopic examination of blood films. Treatment depends on severity but involves artemisinin-based combinations or parenteral artesunate for severe cases. Prevention focuses on vector control

1. Fitsum Getahun
MD, Assistant prof. of internal medicine
August 2016

3.  Introduction
 Epidemiology
 Pathogenesis
 Clinical features
 Severe malaria
 Diagnosis
 Treatment
 Prevention

4.  Humanity has but three great enemies: Fever,
famine and war; of these by far the greatest, by far
the most terrible, is fever.
William Osler

5.  Malaria is a protozoan disease transmitted by the bite
of infected Anopheles mosquitoes
 It is the most important of the parasitic disease of
humans-107 countries, 3 billion people, 1-3 million
deaths/yr
 Eliminated from few countries but resurged in many
parts of the tropics
 Resistance of the parasite and the vector

6.  Malaria occurs throughout most of the tropical regions
of the world.
 Global distribution
 Prevalence of 500 million people/yr
 Two million death/yr

7.  40% of the world population living in
tropical/subtropical climates are exposed to malaria.
 Endemicity is defined in terms of parasitemia rates or
palpable-spleen rates in children 2-9 yrs of age as-
hypo/meso/hyper/holo-endemic
 Epidemic can occur under some conditions

8.  Malaria is one of the leading public health problems
in Ethiopia
 75% of the country is malarious (<2000m), with about
68% of the population (50 million) at risk
 Major impediment to socio-economic development,
coincides with major planting and harvesting season

9.  Major Malaria Parasites
 P. falciparum ( 60%)
 P. vivax ( 40%)
 P. malariae (rare)
 Major Malaria Vectors
 An. arabiensis (family of An. gambiae comlex)= primary
vector
 An. funestus
 An. phareonsis
 An. nili

10.  Bimodal type of transmission:
 Major: Sep - Dec, following the main rainy season from Jun to
Aug
 Minor: Apr–May, following a short rainy season from Feb to
Mar
 Major epidemics occur every 5-8 years, focal outbreaks
are common
 Distribution varies from place to place depending on
climate and altitude

12. Unstable malaria
 Seasonal
 Lack of immunity
 Epidemic common
 All age groups
affected
Stable malaria
 Intense, perennial
 High immunity
 Epidemic uncommon
 Children & pregnant
women more affected

13.  More than 600,000 confirmed and >9 million clinical
cases each year
 Cause about 70,000 deaths each year
 Health and health related indicator (2005/06) of the
FMOH:
 18% of OPD cases (1st)
 14% of admission (2nd)
 9% of hospital deaths (2nd)
 Reduction in Malaria

14.  Four species of the genus plasmodium cause nearly all
malarial infections in humans.
 P. falciparum ( 60%)
 P. vivax ( 40%)
 P. malariae (rare)
 P.ovale
 Almost all deaths are by P. falciparum.
 The disease in human beings is caused by the direct effects
of RBC invasion and destruction by the asexual parasite and
the hosts reaction.

17.  Hgb consumption and degradation
 Detoxify heme into nontoxic hemozoine (malaria
pigment)
 Alter the RBC membrane by changing its transport
properties , exposing cryptic surface antigens and
inserting new parasite-derived proteins.
 The RBC becomes more irregular in shape, more
antigenic, and less deformable

18.  In Pf infections , membrane protuberances appears on
the erythrocyte’s surface=12-15 h after the cell’s
invasion.
 These ‘knobs’ extrude a HMW, antigenically variant,
strain-specific erythrocyte memebrane adhesive
protein (pfEMP) that mediates attachement to
receptors on venular and capillary endothelium-an
event termed cytoadherence.
 Several vascular receptors have been identified of w/c
ICAM-1 is probably the most important in brain,
chondrotin sulphat-B in the placenta, & CD36 in most
other organs.

19.  Thus the infected erythrocyte stick inside and
eventually block capillaries and venules; at the
same time these Pf infected RBCs may adhere to un
infected RBCs (to form rosettes) and to other
parasitisized erythrocytes (aggulitnation)
 The process of cytoadherance, rosetting and
aggultination are central to the pathogenesis of Pf
malaria

20.  They result in:
 Sequestration of the infected erythrocytes
 Escape host defence mechanism
 Under estimates level of parasitemia
 Decreased deformability of the uninfected RBCs

21.  Non-specific defence mechanisms
 Certain genetic disorders confers protection
 Formation of specific immunity
 Several factors retard the development of cellular
immunity to malaria:
 The absence of MHC antigens on the surface of infected RBCs
 Malaria antigen specific unresponsiveness
 The enormous strain diversity of malarial parasite
 Ag variation

22.  Malaria is a very common cause of fever in
tropical countries.
 Non-specific symptoms

23.  Depends on the type of malaria:
P. falciparum:
 The most dangerous type.
 Insidious onset
 Malaise, headache, vomiting
 Fever
 Cough, diarrhea
 Jaundice
 Tender hepatosplenomegaly
 Anemia develops rapidly

24. P.vivax and P.ovale:
 Fever: classically every 48 h
 Rigors
 Gradual hepatosplenomegaly.
 Anemia develops slowly
 Relapse is common

25. P.malariea:
 Fever: every third day.
 Mild symptoms.
 Parasitaemia may persist for many years.
 Causes glomerulonephritis and nephrotic
syndrome in children.

26. P.FALCIPARUM OTHERS
 Cerebral malaria ( coma )
 Convulsions
 Hyperpyrexia
 Severe anemia
 Metabolic (Lactic) Acidosis
 Jaundice
 Renal failure
 Pulmonary odema & ARDS
 Hypoglycemia
 Hypotention & shock
 Bleeding & clotting disorder
 Haemoglobinuria
 Hyperparasitemia
 Associated infection
 Rupture of spleen
 Hepatic dysfunction
 Thrombocytopenia
 Severe anemia
 Malarial nephropathy

28.  Extremes of age.
 Pregnancy, especially in primigravidae and in 2nd half
of pregnancy.
 Immunosuppressed - patients on steroids, anti-cancer
drugs, immunosuppressant drugs.
 Immunocompromised - patients with advanced
tuberculosis, HIV and cancers.
 Splenectomy
 Lack of previous exposure to malaria (non-immune) or
lapsed immunity
 Pre-existing organ failure.

29.  If treated early MR<0.1%

30.  Causes of neurological manifestations in malaria:
 High-grade fever
 Antimalarial drugs
 Hypoglycemia
 Hyponatremia
 Severe anaemia
 Acidosis and uremia

31.  Coma is a characteristic and ominous feature (MR
15-20% despite treatment).
 10% of all admissions and 80% of deaths are due to
the C.N.S. involvement
 Any obtundation, delirium, or abnormal behaviour
should be taken seriously.

32.  Cerebral malaria manifests as diffuse symmetrical
encephalopathy
 No meningial sign
 Primitive reflexes are absent
 Corneal reflexes are reserved
 muscle tone either increase or decrease
 Flexor or extensor posturing may be seen.
 Approximately 15% of pts have retinal haemorrhage

33.  Generalized convulsion(50%)
 Neurological deficit in 3-15%
 1o% of children has language deficit
 The incidence of epilepsy increase
 Life expectancy decrease among these children.

34.  Plasma glucose level of <2.2mmol/l(<40mg/dl)
 Indicate poor prognosis
 Dxic difficulty
 Causes:
 Failure in hepatic gluconeogensis
 Increase consumption
 drugs

35.  Arterial PH<7.25 or plasma bicarbonate level of <
15mmol/l; venous lactate level of>5mmol/l
 manifest as laboured deep breathing often termed
“respiratory distress”
 it is a sign of poor prognosis
 It results from accumulation of organic acid.

36.  Hyperlactatemia commonly coexists with
hypoglycaemia.
 In adults, coexisting renal impairment often compounds
the acidosis
 Other still-undefined organic acids are major
contributor of acidosis.
 The plasma concentration of bicarbonate or lactate are
the best biochemical prognosticators in severe malaria
 often followed by circulatory failure

37.  Causes:
 Anaerobic glycolysis
 Hypovolemia
 Lactate production
 Decreased clearance
 the prognosis of severe acidosis is poor.

38.  The pathogenesis of this variant of ARDS is unclear.
 The MR is >80%
 This condition can be aggravated by overly
vigorous administration of IV fluids

39.  Common among adults
 Pathogenesis is unclear but may be related to
erythrocyte sequestration in renal microcirculatory
flow and metabolism
 Clinically and pathologically, this syndrome manifests
as ATN, but renal cortical necrosis never occur.

40.  ARF may occur with other vital-organ dysfunction
in w/c case mortality will be high
 Early dialysis or hemofiltration considerably
enhances the likelihood of a patient’s survival ,
particularly in acute hyper catabolic renal failure.
 In survivors urine flow resumes within 4 days and
serum creatnine normalizes with in 17 days.

41.  Anaemia occurs as a result of:
 Accelerated all RBC removal by the spleen
 Obligatory RBC destruction at parasite schizogony
 Ineffective erythropoiesis
 In severe malaria both infected and uninfected RBCs
show reduced deformability, which correlates with
prognosis and development of anaemia.

42.  In areas with unstable transmission anemia can
develop rapidly and transfusion is often required.
 Anaemia is a common consequence of anti malarial
drug resistance , which results in repeated or
continued infection.

43.  Mild to severe jaundice
 Results from haemolysis, hepatocyte injury and
cholestasis
 It is associated with different complications-
hypoglycaemia, acidosis & impaired drug
metabolism
 Carries poor prognosis when associated with other
vital organ dysfunction

44.  Septicaemia may complicate severe malaria,
particularly in children
 In endemic areas Salmonella bacteraemia has been
associated specifically with Pf infection
 In comatose pts(for >3 days) chest infection,
catheter induced UTI, aspiration pneumonia
 Recrudescence, relapse, re infection

45.  Low birth wt(~ reduction in BWT of 170 gm)
 In areas with unstable transmission severe infection
results in- oedema, fetal distress, premature
labour, and still birth or LBW.

47.  HIV infection is associated with increased
susceptibility, higher parasitemia, and an increased
risk for recurrent malaria infection, particularly in
patients with CD4 counts <200 cells/microL
 Dual infection with HIV and malaria during pregnancy
leads to adverse maternal and perinatal outcomes.
 ART decreases the incidence of malaria in malaria-
endemic areas.

48.  Malaria can be transmitted by blood transfusion,
needle prick injury, sharing of needles by infected
injection drug users, or organ transplantation.
 IP in this condition is short b/c no pre erythrocytic
stage of development.

49.  TROPICAL SPLENOMEGALY (HMS)
 Chronic or repeated malarial infections produce
hypergammaglobulinemia, NCNC anaemia, and in certain
situations, splenomegaly.
 Abnormal immune response to repeated infection leads to
massive splenomegaly, hepatomegaly,
 marked elevation in serum titer of IgM and malarial
antibody,
 hepatic sinusoidal lymphocytosis, and (in Africa) peripheral
B cell lymphocytosis.

50.  This syndrome has been associated with the production
of cytotoxic IgM Abs to CD5+ T-lymphocytes, and an
increase of CD4+ to CD8+ T cells.
 These events may lead to uninhibited B cell production
of IgM and the formation of cryoglobulins (IgM
aggregates and immune complexes).
 This immunologic process stimulates RES hyperplasia
and clearance activity and eventually produces
splenomegaly—with all its consequences.

51.  Chronic or repeated infections with P.malariea may
cause soluble immune-complex injury to the renal
glomeruli, resulting in nephrotic syndrome.
 The histological appreance is that of focal or
segmental GN with splitting of the capillary BM.
 Quartan nephropathy usualy responds poorly to
treatment with either antimalarial agents or
glucocorticoides, and cytotoxic drugs.

52.  Malaria related immuno-suppression provokes
infection with lymphoma viruses.
 The prevalence of BL is high in malarious areas of
Africa.

53.  Clinical diagnosis
 Microscopic (Thin and Thick Blood films)
 Serology (rapid diagnostic test)
PfHRP2
PLDH

54. Light microscopy
Giemsa stained blood film
Thick and Thin Blood Smears
Thick smears -detect parasite
Thin smears - for species

55.  General management
 Treat complications
 Specific anti malarial treatment
 Two classes of drugs
 Cinchona alkaloids (quinine and quinidine)
 Artemisinin derivatives (artesunate, artemether &
artemotil)

56.  In endemic areas, the WHO now recommends
artemisinin-based combinations as first-line
treatment for uncomplicated falciparum malaria
everywhere.

57.  Second-line treatment/treatment of imported malaria
 Either artesunate (2 mg/kg qd for 7 days) or quinine (10 mg
of salt/kg tid for 7 days)
plus 1 of the following 3:
1. Tetracycline (4 mg/kg qid for 7 days)
2. Doxycycline (3 mg/kg qd for 7 days)
3. Clindamycin (10 mg/kg bid for 7 days) or Atovaquone-
proguanil (20/8 mg/kg qd for 3 days with food)

58.  Severe Falciparum Malaria
 Artesunate(2.4 mg/kg stat IV followed by 2.4 mg/kg at 12 and 24
h and then daily if necessary) or
 Artemether (3.2 mg/kg stat IM followed by 1.6 mg/kg qd
 Quinine dihydrochloride (20 mg of salt/kg infused over 4 h,
followed by 10 mg of salt/kg infused over 2–8 h q8h
 Quinidine (10 mg of base/kg infused over 1–2 h, followed by 1.2
mg of base/kg per hourwith electrocardiographic monitoring).

59.  In large studies conducted in Asia, parenteral
artesunate,has been shown to reduce mortality rates in
severe falciparum malaria among adults by 35% from
rates obtained with quinine.
 Recently, the largest trial ever in severe malaria showed
that parenteral artesunate reduced the mortality rate
among African children by 22.5% compared with that
obtained with quinine.

60.  RBS < 40 mg/dL should mandate Rx with IV dextrose.
 All patients treated with IV quinine or quinidine should
receive a continuous infusion of 5–10% dextrose.
 if the hematocrit falls to <20%, then whole blood
(preferably fresh) or packed cells should be transfused
slowly, with careful attention to circulatory status.
 If the level of parasitemia does not fall below 25% of the
admission value in 48 h or if parasitemia has not cleared
by 7 days (and adherence is assured), drug resistance is
likely and the regimen should be changed.

61.  To eradicate persistent liver stages and prevent
relapse (radical treatment), primaquine (0.25–0.5 mg
of base/kg, adult dose) should be given daily for 14
days to patients with P. vivax or P. ovale infections
after laboratory tests for G6PD deficiency have
proved negative.

62.  Fluid Balance
 Therapeutic Response
 Input and output
 Oxygenation.
 V/s, level of consciousness
 RBs (4-6hrs)
 Hct and parasite count (6-12 hrs)
 RFT- daily

66.  Rapid Dx and Rx.
 Mosquito Avoidance .
 Remaining in screened areas.
 Bed nets.
 Suitable clothing.
 Applying insect Repellent.
 Use of insecticides.
 Elimination of mosquito breeding sites.
 Chemoprophylaxis.
 Vaccination- no safe & effective vaccine.

67. .General measures
- Rapid diagnosis and prompt treatment.
- Early detection and containment of epidemics.
-Mechanical method
-draining water collections and swampy areas.
-use of chemical impregnated bed nets.
-wire mesh across windows
-use of long sleeved shirts & trousers.
- insecticide/chemical
-use insecticide spray aerosol
-apply insecticide repellents
-DDT spray

68. -Indicated for ; pregnant women in endemic area.
; 3 mths -4 yrs old children in endemic
area (born to non-immune mother)
; travelers to malarious area.
-In areas of chloroquine resistant p.f.
- mefloquine , doxycycline , maloprim
-In areas of chloroquine sensitive p.f. -
- chloroquine, atovaquone - proguanil

71.  Typhoid/enteric fever is endemic in most developing
countries in Africa, Asia and Latin America
 It is primarily a disease of children and young adults
 In developed countries it occurs in travelers to endemic
regions
 Man is the ONLY reservoir of Salmonella typhi
 It is transmitted by ingestion of food/water
contaminated by feces of patients/carriers

72.  Up to 10% of patients continue to excrete the
organism in feces for three months
 1-4% become chronic carriers; excrete the organism
for > six months
 S. typhi had become increasingly resistant to a
number of 1st line antibiotics

73.  S. Typhi and S. Paratyphi serotypes A, B, and C—have no
known hosts other than humans.
 Food-borne or waterborne, Homosexual , Occupational
 poor sanitation and lack of access to clean drinking water
→ high incidence.
 In endemic regions, common in urban than rural areas and
among young children and adolescents
 There were an estimated 22 million cases of enteric fever,
with 200,000 deaths, in 2002.

75.  Typhoid fever is caused by S. typhi;
S. enterica, subspecies enterica, serotype typhi
 It is a Gram negative, aerobic, non spore forming
organism
 It contains:
 LPS, lipolysaccharide
 Oligosaccharide somatic antigen “O” antigen
 Flagella “H” antigen
 Virulence “Vi’ antigen

76.  The portal of entry is the gastrointestinal tract
 Infecting dose, ID50, is 1,000,000 organism
 Organism destroyed by acid in stomach
 Achlorhydria, treatment with H-2 receptor antagonists
lowers the infecting dose
 Incubation period is 5-21 Days
 Organism multiplies within mononuclear
phagocytic cells of the intestinal lymphoid follicles

77.  After initial intracellular replication the organism is
released into the circulation:
 Sustained bacteremia
 Widely disseminated and seeds the liver, spleen, bone
marrow, gall bladder, Peyer’s patches
 It induces local and systemic humoral and cellular responses
 Endotoxin may activate clotting/fibrinolytic cascade
 Local inflammation at Peyer’s patches may cause tissue
necrosis

79.  Typically, infection of untreated typhoid fever is divided
into 4 individual stages (each lasting ~1 week) IP = 5-21
Days
 In the first week,
 Slowly rising temperature with relative bradycardia
 Malaise, headache, and cough.
 Epistaxis
 Abdominal pain
 Leukopenia,with eosinopenia and relative
lymphocytosis,
 Positive blood cultures
 The classic Widal test is negative in the first week.

80.  Patient prostrated
 high fever in plateau around
40 °C ,bradycardia
 Nervous fever: delirium
 Rose spots
 Abdominal pain
 Diarrhea
 Constipation
 Hepatosplenomegaly
 Elevation of liver
transaminases
 Widal reaction is strongly
positive with antiO and
antiH antibodies
 Blood cultures positive

81.  In the third week of typhoid fever, a number of complications can
occur:
 Intestinal hemorrhage
 Intestinal perforation
 Encephalitis
 Neuropsychiatric symptoms
 Metastatic abscesses, cholecystitis, endocarditis and
osteomyelitis
 The fever is still very high and oscillates very little over 24 hours.
Dehydration ensues and the patient is delirious (typhoid state).
 By the end of third week the fever has started reducing this
(defervescence).
 This carries on into the fourth and final week

82. Symptoms Frequency %
Headache 80%
Chills 35-45%
cough 30%
diarrhea 22–28%)
constipation 13-16%
vomiting 18%
Myalgia 20%
Arthralgia 4%
splenomegaly 5–6%
abdominal tenderness 30-40%
Clin Infect Dis.2006;42(9):1247

83.  With appropriate therapy mortality <1%
 mortality rates were >/=15 % in the preantibiotic era
 Perforation is the most serious complication
 Occurs in about 1-3% of patients
 GI bleeding, in about 10% of patients
 Neurologic manifestations occur in 2–40% of patients
and include meningitis, GBS, neuritis, and
neuropsychiatric symptoms

84.  Rose spots
 The rash is evident in ~30%
of patients and resolves
without a trace after 2–5
days.
 Salmonella can be cultured
from punch biopsies of these
lesions
 Relative bradycardia in < 50%

85.  10% of patients develop mild relapse, usually within
2–3 weeks of fever resolution
 10% of untreated patients with typhoid fever excrete S.
Typhi in the feces for up to 3 months, and
 1–4% develop chronic asymptomatic carriage,
shedding S. Typhi in either urine or stool for >1 year.
 Chronic carriage is more common among:
 Women
 biliary abnormalities
 bladder abnormality or infection with Schistosoma
haematobium

86.  In 15–25% of cases, leukopenia and neutropenia
are detectable.
 Leukocytosis is more common in cases
complicated by intestinal perforation or secondary
infection.
 moderately elevated liver function tests and muscle
enzyme levels.
 The definitive diagnosis is isolation of it.

87.  BC + in only 50-70%, need at least
15ml of blood – highest yield in
first week of illness
 BM culture + 95% (higher
bacterial burden) - positive even
if AB taken for up to 5d
 Duodenal string test + in 58%
 Stool culture: + in 30%

88. 20
30
10
0
100
90
80
70
60
50
40
7
6
5
3
2 8
4
1 Weeks
%
Positive
Presence of S. typhi in blood urine and
stool, and rise of antibodies after
ingestion of the organism
Blood culture
Urine Culture
Stool culture
Serum agglutinins

89.  Serological test, the Widal test becomes positive in 7-10
days
 A four-fold rise in titer
 A single titer of >1/160 with compatible clinical illness
 False positive/negative results are common
 cross reactions with other salmonella species
 Vi agglutination reaction: more helpful to detect carriers

90.  The aim of management is to kill the organism and
correct effect of septicemia
 Most patients are treated at home
 Multi drug resistant S. typhi increasing
 For hospitalized patients, good nursing care, adequate
nutrition, fluid/electrolytes
 Recognition and management of complications

91.  For drug-susceptible, fluoroquinolones cure
rates of ~98% and relapse and fecal carriage
rates of <2%.
 For MDR : ceftriaxone, azithromycin, or high-
dose ciprofloxacin with:
 Failure rates of ~5–10%
 Fecal carriage rates of <3%
 Relapse rates of 3–6%.

92.  With shock and obtundation→ dexamethasone (3-
mg initial dose followed by eight doses of 1 mg/kg
every 6 h) ↓MR than treatment with
chloramphenicol alone (10% vs 55%)???????????
 Perforation is usually managed by surgery
 Sever GI bleeding may require blood transfusion

94.  Treatment with oral amoxicillin, TMP-SMX,
ciprofloxacin, or norfloxacin is ~80% effective in
eradicating chronic carriage of susceptible organisms
(2-4 weeks Rx) .
 -/+ surgical correction.

95.  Two typhoid vaccines are commercially available:
 Ty21a, an oral live attenuated S. Typhi vaccine (given on
days 1, 3, 5, and 7, with a booster every 5 years) min age
= 6 years
 effecacy @ 3yr=51%
 Vi CPS, a parenteral vaccine consisting of purified Vi
polysaccharide from the bacterial capsule (given in 1
dose, with a booster every 2 years). Min age =2 years
 effecacy @ 3yr=55%
 Vaccine for traveler to endemic area
 Sanitation
 Food handler & child care giver screening

97.  A group of acute infections caused by arthropod born
spirochetes of the genus Borrelia.
 Characterized by recurrent cycles of febrile episodes,
separated by asymptomatic intervals of apparent recovery.

98.  Borrelia recurrentis, is the cause of louse borne RF.
 Several different Borrelia species cause tick born
relapsing fever.
 In Africa Borreli duttoni, and Borrelia croicuidare are the
predominant species.
 Borrelia are slender actively motile spirochetes.
 measure10-20µ long and 0.2-0.5µ wide, with 4-10 loose coils.

99.  can give rise to as many as 30 antigenic variants
 The antigenic variation generated by sequential expression of
previously silent vmp genes
 They readily stain with aniline dyes e.g. Wright stain.
 Several Species of tick borne Borrelia, and recently B.recurrentis
had been cultivated and propagated in artificial media.

100. There are two epidemiological forms:
Louse borne relapsing fever
Tick borne relapsing fever
 Louse borne relapsing fever is transmitted:
 Only between humans, by the body louse, Pediculus humanus,
var corporis.
 It is endemic in Ethiopia, the Sudan, and Rwanda.
 It is a disease of poverty, overcrowding, poor personal hygiene,
and infestation with lice.

101.  Tick borne relapsing fever is a zoonosis,
maintained in nature between ticks and its natural host, often
wild rodents.

102. Characteristics LBRF TBRF
Etiology B.Recurentus >15
Borreli duttoni, and
Borrelia croicuidare
(Africa)
Vector P.Humanus corporis d/t species of
Ornithodoros
Reservoir Humans Rodents & small animals
Geography Endemic to East Africa Except
Antartica,Austeralia,sout
h west pacific
Feeding habit With cloths proximity to
the body
Night time,painless
5-20min several times a
day
Transmission Only the hemolymph Excreta ,saliva,tissue
To offspring Not Yes
Life span of vectors 10-60days >15years

103.  Portal of entry, infected lice crushed into abraded skin.
High level spirochetemia.
 Incubation period, 5-10 days.
 Patients’ producing neutralizing antibodies,
clearing of the circulating strain Borrelia in 3-5 days
 New ANTIGENIC VARIANTS appear
 Recurrence of clinical symptom/signs;
 up to 3-5 relapses may occur

104. SYMPTOMS
 Incubation period, 5-10 days,
average 7 days.
 abrupt onset of fever, 39-40.
 Headaches
 Arthralgia/myalgia
 Dry cough
 Epistaxis/gum bleeding
SIGNS
 Temperature
 Tachycardia
 Hepatomegaly
 Splenomegaly
 Petechie/
Subconjunctival
bleeding
 Jaundice
 Confusion/Meningism

105.  WBC : normal - slighlty increased & can be low during crisis
 Mild-moderate normocystic anemia
 Low platelet
 Deranged liver test
 CSF –Pleocytosis,↑protien ,normal glucose, spirocheate (12%)
 ECG--- may reveal a prolonged QTc interval in patients with
myocarditis.
 Some such patients have cardiomegaly and pulmonary edema
on chest radiograph

106.  The definitive diagnosis of relapsing fever is
established by the demonstration of
borreliae in the peripheral blood of febrile
patients.
 Organisms are rarely found during afebrile
periods.
 The diagnostic yield can be increased by
the examination of acridine orange–
stained smears by fluorescence microscopy
or buffy coat smears

107. COMPLICATIONS
POORER PROGNOSTIC
FEATURES
 Coma
 Liver dysfunction
 Meningitis
 Myocarditis -- may
lead to arrhythmias
 Pneumonia
 Seizures
 Shock
 Widespread bleeding
 Stupor or coma on
admission
 Diffuse bleeding
 Myocarditis
 Poor hepatic function
 Bronchopneumonia
 Coinfection with typhus,
typhoid , or malaria

108.  Penicillins and tetracyclines have been the antibiotics
of choice for several decades
 There is no evidence resistance to this antibiotics.
 Relatively resistant to rifampin, sulfonamides,
fluoroquinolones, metronidazole, and aminoglycosides
 Undetectable spirochetes in the blood within 8hrs of
the first dose of an effective antibiotic

109.  In LBRF the recurrence rate after antibiotics is less than
5% ( single dose TTC) & in TBRF is 20% or higher after
single dose treatments ,which is probably due to brain
invasion by TBRF spirochetes.
 For pregnant women, erythromycin or penicillin may
be preferred, given the potential adverse effects of
tetracyclines.

111.  Jarish- Herxheimer reaction:
 The first dose of appropriate antibiotic causes
transient worsening of clinical symptoms/signs.
 Occurring in approximately 80% of treated LBRF &
54% TBRF patients.
 associated with increased mortality.
 Penicillin therapy appears to cause a more
prolonged reaction than TTC
 These reactions tend to occur within 1-4hrs of
antibiotic administration

112.  Physiologic change:
 chills phase lasts10–30 min
 rise in BP, pulse, and respiratory rate;
 flush phase,
 BP falls dramatically
 There is a marked, but transient rise in circulating level of
 TNF, IL-6, and IL-8 at the peak of the reaction
 Rx
 Vital signs must be monitored carefully during this period of
the reaction, which usually lasts 8 h.
 Close monitoring of fluid balance, arterial and venous
pressures, and myocardial function is advised in supportive
management

113. OUTCOME
 The mortality rates for untreated LBRF 10 -70%and
 In TBRF- it ranges of 4-10 %
 With prompt treatment with appropriate antibiotics,
the death rate for LBRF is 2 -5%
 TBRF is less than 2 %.

114.  PREVENTION AND CONTROL —
 Decreasing louse and tick
 hygiene & Delousing
 postexposure treatment with doxycycline (200 mg on day
one followed by 100 mg daily for four days)
 There is not a vaccine for either LBRF or TBRF.

116.  Rickettsial diseases are acute febrile illnesses caused by
bacterial of the genus Rickettsia.
 They are transmitted to humans by arthropod vectors
such as, lice, fleas, ticks, and mites.

117. Disease Causative
agent
Geographic
distribution
Arthropod
vector
Natural host
Typhus fever group
• Epidemic typhus &
Brill Zinsser disease
•Endemic typhus
R. Prowazekii
R. typhi
World wide
World wide
Body lice
Flea
Man
Small rodents
Spotted fever group
•Rocky Mountain
Spotted fever
•Mediteranian
spotted fever
R.ricketssii Western
hemisphere Ticks
Wild rodents,
dogs
R.conorii
Africa,
Middle east,
Europe Ticks
Wild rodents,
dogs
There are several clinical and epidemiological forms, the major forms are:

118. Disease Causative
agent
Geographic
distribution
Arthropod
vector
Natural
host
Others,
• Q fever
•Trench
fever
Coxeiella
burnetii
Bartonella
quintana*
World wide
World wide
Ticks
Body lice
Small
Mammals
Man
Forms Contd…

119. Most rickettsial diseases are zoonoses,
 maintained in nature by a cycle between arthropod vector
and mammalian host
 Man is the ONLY reservoir in louse borne typhus
 Is endemic in the highlands of Ethiopia,
 is a classic disease of poverty, overcrowding, and
infestation with lice.
 Persons at risk, prisoners, soldiers, homeless, medical
personnel.

120.  Transmission is through contamination of skin
abrasions/bit wound by infected lice feces.
 The infective dose, ID50, is less than 10 organisms.
 Ricketssia multiply inside endothelial cells of small
blood vessels in skin, brain, liver heart and kidneys.

121. ↑permiabilty ,vasculities,edema ,thrombosis
Injury to d/t organs → C/F
Endothelium ,macrophage,PMN,fibroblast
Replicate in cytosol →→ Cell lysis + inflam.response
Enter through skin ( feces or tissue)
Blood stream Lymphatics

122.  IP of 8 -16 days and a prodrome of 2 days.
 Prodromal symptoms, malaise, myalgia, headache.
 Abrupt onset of fever and chills.
 Rash appears after 4-5 days.
 Rash progresses through macules that disappear on
pressure to maculopapules with petechiae.
 The face, palms, and soles are usually spared
 60% of African patients have spotless epidemic typhus

124.  Neurological complications, delirium,coma.
 Macro vascular injuries, mainly gangrene, hemiplegia.
 Brill-Zinsser disease, recrudescent typhus,

125.  Recrudescent epidemic typhus
 Establish latency in lymph
nodes
 Occurs in elderly or
immunocompromised persons -
> malnourishment, poverty,
and war!
 Milder disease (including
absence of fever) and lower
mortality
 RESERVOIR FOR NEW TYPHUS
EPIDEMICS!

127.  A compatible clinical illness, with positive serological test
 Detection of antibodies with a fourfold rise in titer in
convalescence.
 Proteus vulgaris OX-19 agglutination (Weil-Felix reaction)
has been demonstrated to be poorly sensitive and
nonspecific
 Usually, a diagnostic titer is detected during the second
week of illness
 The standard serologic method is indirect
immunofluorescence assay, and an immunoglobulin (Ig) G
titer of 128 or an IgM titer of 32 confirms the diagnosis
 PCR

128.  Tetracycline and
chloramphenicol are the only
effective agents for epidemic
typhus.
 The drug of choice is doxycycline
for 7 - 10 days .
 In the series from Rwanda, 29 of
37 patients were afebrile 48
hours after therapy was started
 Other antibiotics,
including β-lactams,
aminoglycosides, and
sulfonamides, are
ineffective.
 Administration of
quinolones has been
associated with treatment
failure
 Supportive

129. PREVENTION
PROGNOSIS
 Sanitation & Delousing
 Antibiotic prophylaxis
 chloramphenicol
 tetracycline .
 Vaccination —moderate
degree of protection.
 Environmental control
 is dependent upon age,
underlying nutritional status, and
health of the patient and the
speed with which therapy is
administered.
 Untreated disease is fatal in 7–
40% of cases.
 Overall, 12% of patients with
epidemic typhus have neurologic
involvement