Trypanosomiasis

Mugendi AG
Introduction
 These are protozoan pathogens of man
 They are flagellates
 There are two groups of diseases that are caused by this
pathogen
 African trypanosomiasis – sleeping sickness
 South American trypanosomiasis – chaga’s disease
 African trypanosomiasis is endemic in a belt across sub
Saharan Africa (14˚N and 20˚S)
African trypanosomiasis
 Caused by trypanosomes that are subspecies of Trypanosoma
brucei
 Tsetse flies are the insect vector
 The human parasites are
 T.brucei gambiense, occurring in the riverine areas of west and
central Africa(Uganda, Senegal and Angola)
 T.brucei rhodesience, a parasite common in the savannah plains
of east Africa. Cattle and wild antelopes are reservoirs of
infection
 T.brucei brucei, found all over the continent
Pathogenesis
 Infection occurs through the bite of an infected tsetse fly.
Both male and female bite, during the day.
 There are various species of the tsetse flies
 Glossina morsitans – T.b. rhodesiense
 Glossina swynertoni
 Glossina palpalis – T.b.gambiense
 Glossina submorsitans
 A localized trypanosomal chancre forms though transiently
 Hematologic spread is rapid with multiplication and the
appearance of non specific symptoms
Tse tse fly
Pathogenesis
 The patient maybe febrile and may present with
lymphadenitis
 Untreated, the disease progresses to involve the CNS with
sleeping sickness and death eventually.
Clinical presentation
 Localized chancre at the bite site.
 Adenitis
 Fever
 Lymphadenitis especially around the neck – winter bottom's
sign
 Splenomegally and hepatomegally
 CNS involvement in the chronic form with severe headaches,
confusion, continuous or episodic sleep
 Coma or death in severe infection
Clinical presentation
 T.brucei rhodesience has a more acute, fulminating course
lasting a few months
 T.brucei gambiense progresses slowly over several years
Diagnosis
 Peripheral blood smears may reveal trypanosomes in the
parasitaemic stage
 Examination of lymph node exudate
 Examination of CSF aspirate with the following
characteristics
 Lymphocytosis
 Presence of morula cells (plasma cells)
 High pressure
 Elevated protein
 Elevated IgM levels
Treatment
 Therapeutic options are limited
 Most of the drugs used are toxic and expensive
 Prognosis is good if treatment is begun early before the brain
is invaded
Treatment
 Prior to brain invasion

 For rhodesciense - IV suramin 1 g (20mg/kg) on days

1,3,7,14,21 for a total dose of 5g (this is after giving a test
dose of 100-200mg)
 For gambiense infections – IV pentamidine 4mg/kg for 10
days
Treatment
 After nervous system invasion –rhodesciense
 Melarsoprol 2-3.6mg/kg/day IV 1st course
 Then 3.6mg/kg/day thereafter
 1st and 2nd courses are separated by 7 days
 2nd and 3rd courses are separated by 10-21 days
 Acute encephalopathy, hepatorenal toxicity and peripheral
neuropathy are common
 Administer melarsoprol with prednisolone 1mg/kg up to
40mg started 1-2 days before, continued during and tapered
after treatment to reduce side effects (
Treatment
 After CNS invasion – gambiense

 Eflornithine 100 and 150mg/kg IV 6 hourly for 14 days for

adults and children respectively
South American trypanosomiasis
Chaga’s disease
Introduction
 Widely distributed in the rural areas of south and central
america
 Caused by T.cruzi transmitted to humans in the faeces of
reduviid bugs
 Blood tranfusion may account for 5% of cases in some areas
 Occasionally, congenital transmission occurs
Clinical features – acute phase

 Clinical features in this phase are only seen in 1-2% of cases

infected before 15 yrs of age
 Most common in 1-5 yrs olds
 It often passes unnoticed
 A firm reddish papule is seen at the site of entry
 There may be regional lymphadenopathy
 Swelling of the eyelid in conjuctival infection may occur
leading to closure of the involved eye – Romana’s sign
Romana’s sign
Clinical features – acute phase

 Fever
 Hepatosplenomegally
 Rarely meningoencephalitis
 Acute infection is fatal in infants
Clinical features- chronic phase
 A period of latency follows lasting many years
 10-30% develop chronic chaga’s disease
 10-30% develop chronic myocarditis– conduction
abnormalities, arrhythmias, aneurysm formation and
cardiomegally
 10% damage of the Auerbach’s plexus causes –
megaoesophagus (causing dysphagia and aspiration
pneumonia) and megacolon (causing severe constipation)
 Dilation of the bronchi and bile ducts are also possible
sequelae
Diagnosis
 Trypanosomes in the stained blood smear
 Serology
 Xenodiagnosis
Management and control
 Nirfutimox, PO 10mg/kg/day divided into 3 equal doses for
60-90 days (children 15mg/kg/day)
 Benznidazole PO 5-10mg/kg/day in 2 divided doses for 60
days (children 10mg/kg/day)
 Both are toxic

 Antiarrhythmic drugs and pacemakers – cardiac disease

 Surgery for GI complications
Leishmaniasis
Introduction
 Leishmania are intracellular parasites of the reticulo-
endothelial system
 The parasites are transmitted by female phlebotomine
sandflies in various parts of the world
 There are 21 leishmanial species which cause several diverse
clinical symptoms broadly categorized as
 Visceral leishmaniasis –kalar azar, dum dum fever
 Cutaneous leishmaniasis – oriental sore
 Mucosal leishmaniasis – espundia
Distribution of visceral and cutaneous
leishmaniasis
Leishmaniaisis and HIV coinfection
Visceral leishmaniasis – kalar azar
 Caused by the Leishmania donovani complex of
 L.donovani
 L.infantum
 L.chagasi
 90% of the cases are found in India, Sudan, Bangladesh and
Brazil
 Other regions are east africa, china, arabia, israel.
 May also be transmitted through blood transfusions
Clinical features

 In India, adults and children are equally affected

 Elsewhere, children and infants are most afflicted
 Incubation period is typically 1-2 months, but may be several
months.
 Most people remain asymptomatic
 The spleen, liver, bone marrow and lymph nodes are
affected.
Clinical features
 First sign of infection is a high fever.
 The fever may be intermittent
 This is accompanied by rigors and chills
 Splenomegally develops quickly and may become massive
with disease progression
 Moderate hepatomegally occurs later
 Lymphadenopathy is common in african kalar azar
 Blackish discoloration of the skin occurs
 Progressively, the patient becomes pancytopenic, wasted and
immunosuppressed
Body parts affected
Clinical features
 Moderate to severe anemia develops rapidly leading to CCF
 Thrombocytopenia may lead to bleeding from the retina,
GIT and nose.
 In severe cases, hypoalbuminemia may present as pedal
edema, ascites and anasarca.
 Bacterial infections – TB, penumonia, GE, boils, cellulitis
occur
 Death occurs within a year due to either uncontrolled
bleeding or bacterial infection
Investigations
 Stained smears of the aspirates of bone marrow, lymph
nodes, spleen or liver to demonstrate amastigotes
 FBC to demonstrate pancytopenia with granulocytopenia and
monocytosis
 Polyclonal hypergammaglobulinemia chiefly IgG followed by
IgM
 Hypoalbuminemia
 Serodiagnosis using ELISA or immunoflorescence antibody
test
Differential diagnosis
 Malaria
 Typhoid
 Tuberculosis
 Schistosomiasis
Management – pentavalent
antimonials
 First to be used and remain the mainstay in many developing
countries
 Exception is India (Bihar state) where 2/3 of the cases are
refractory to antimony. Meglumine antimonate is used.
 Sodium stibogluconate (100mg/ml)
 Meglumine antimonate (85mg/ml)
 Daily dose is 20mg/kg body weight IV or IM for 21-30 days
 Side effects are common – arthralgias, myalgias, pancreatitis,
raised hepatic transaminases and severe cardiotoxicity
Amphotericin B
 Given IV once daily or on alternate days at a dose of 0.75-
1.00mg/kg for 15-20 doses
 The liposomal form is preferrable
 First line in regions with significant Sb unresponsiveness
 Side effects – renal and hepatic toxicity, hypokalemia and
thrombocytopenia
Other drugs - miltefosine
 An alkyl phospholipid
 Daily oral dose of 50mg (patient body weight <25kg) to
100mg (>25Kg) or 2.5mg/kg body weight for children, for
28 days
 Side effects – skin allergy, renal or liver toxicity.
 Terogenic, CI in pregnancy
 Female patients are advised not to get pregnant during
treatment and 3 months thereafter
Paromomycin
 Aminoglycoside
 Highly effective if given IM at 11mg/kg body weight of
paromomycin base daily for 3 weeks
 No significant auditory or renal toxicity is seen
 Approved for use in India
Post kala azar dermal
leishmaniasis (PKDL)
PKDL
 Occurs in few patients

 Mostly seen in India and the Sudan

 Is a dermatological manifestation of local parasitic infection

Clinical features
 INDIA
 Dermatologic changes occur 6 months to more than 3 years
after initial infection
 Presents as macules, papules, nodules (most frequently) and
plaques which have a predilection for the face, especially
around the chin.
 Face appears erythrematous
 Hypopigmented papules occur all over the body
 Absence of systemic symptoms and spontaneous healing
PKDL
Clinical features – sudan
 Approximately 50% of patients with VL develop PKDL

 May experience skin manifestations concurrently with VL or

within 6 months afterwards

 A micropapular rash may be seen all over the body

 Children are more frequently affected than in India

 Spontaneous healing occurs in about ¾ of cases within a year

Investigations and management
 Diagnosis is clinical
 Demonstrate scanty parasites in lesions by slit skin smear and
culture
 Treatment is difficult
 In India, SB for 120 days or several courses of Amphotericin
B infusions are required
 In Sudan, Sb for 2 months is adequate
 PKDL patients are human reservoirs
Cutaneous leishmaniasis (CL)
Oriental sore
Introduction
 CL occurs both in the old world and the new world (the
Americas)

Old world
 L.major and L.tropica are found in Russia and Eastern Europe,
central Asia, the mediterranean littoral and sub-saharan
africa.
 L.aethopica – highlands of Ethiopia and Kenya
Introduction
New world
 L.mexicana complex – mexico, guatemala, brazil, venezuela,
panama.
 Complex consists of L.mexicana, L.amazonensis and
L.venezuelensis
Pathogenesis and clinical features
 Following a sandfly bite, leishmania amastigotes multiply in
dermal macrophages.
 Incubation period is 2-3 months
 Single or multiple painless red papules occur on exposed
areas with raised borders
 These enlarge- reaching 2-10cm in diameter- and ulcerate
with a characteristic erythrematous raised border
 The ulcer develops a few weeks to months after the bite
 An overlying crust may develop
CL
CL
Pathogenesis and clinical features
 Lesions heal slowly over months to years leaving a disfiguring
scar
 Regional lymphadenopathy, pain, pruritus and secondary
bacterial infections may occur.
Diagnosis and treatment
 Often done clinically in patients who have been in endemic
areas
 Giemsa stain on a split skin smear will demonstrate
leishmania parasites
 PCR
 Small lesions require no treatment
 Large lesions – curettage, cryotherapy or topical antiparasitic
agents.
 Systemic treatment is less successful
 L.aethiopica is not sensitive to antimonials
Treatment of CL
 Topical application of paromomycin 15% plus
methylbenzethonium chloride 12% is beneficial
 Intralesional antimony (Sb:0.2-0.8ml/lesion) up to 2g

 Systemic therapy with parenteral antimony at 20mg/kg/day

given over 20 days or
 Liposomal amphotericin B as for VL (also used to treat
refractory CL)
 Also – 2-4 doses (2-4mg/kg) of alternate day administration
of pentamidine in new world CL
Treatment of CL
 Ketoconazole 600mg daily for 4 weeks has potential against
L.mexicana

 Fluconazole 200mg daily for 6 weeks reduced healing times

and cured 79% of patients with CL due to L.major in Saudi
Arabia

 Itraconazole 200mg daily for 6 weeks had favourable results

in CL in India.
Mucosal leishmaniasis (ML)
ML
 Occurs in 3-10% of infections with L.brasiliensis

 Most common in Bolivia and Peru

 The cutaneous sores are followed months to years later by

indurated or ulcerating lesions affecting mucosa or cartilage,
typically on the lips or nose (espundia)

 Characterized by thickening and erythema of the nasal

mucosa, typically starting at the junction of the nose and
upper lip.
ML
 May remain static or may progress over months or years
affecting the nasopharynx, uvula, palate and upper airways.

 Leads to destruction of mentioned structures with

considerable suffering and deformity

 There is no spontaneous healing

 Death may result from severe respiratory tract infections due

to massive destruction of the pharynx
ML
Diagnosis and treatment
 PCR
 Serology

 With multiple lesions, parenteral Sb at 20mg/kg/day for 28

days
 Liposomal amphotericin B (VL doses)
 Amphotericin B is used to treat refractory ML
 8 injections of pentamidine -4mg/kg on alternate days