hematological manifestations of tropical diseases

1. Haematological aspects of
tropical diseases

2. • We will try to cover tropical diseases in which
organisms can be visualized in the blood or
bone marrow and those that cause secondary
haematological abnormalities.
• In 2010, 3% of the world’s population lived
outside their country of origin. The majority
were economic migrants, often moving from
tropical countries to temperate areas.

3. • The platelet counts in healthy West Indians and
Africans may be 10–20% lower than in Europeans
living in the same environment.
• Eosinophilia with Counts of up to 2 × 109/L have
been described in healthy blood donors in Africa.

4. Malaria
• Until 2004, only four species of plasmodia were
known to cause malaria in humans:
• Plasmodium(P) falciparum (most morbidity and mortality)
• P. vivax
• P. ovale
• P. malariae;
• since then there have been increasing numbers of
cases of infection by a fifth plasmodium, i.e. P.
knowlesi , initially reported in South-east Asia

5. • Malaria rates were highest in immigrants returning
from visits to their countries of origin (1/3 all reports).
• It has also been reported in travellers who have
transited through airports in malarious areas.
• The majority of those are travellers had not taken
malaria prevention tablets.
• Infrequently, through blood transfusion, bone marrow
transplantation and transplacentally (0.5% of all UK
cases).
• transmission in aircraft or near airports in temperate
zones due to infected mosquitoes being brought to
non-malarious areas.

6. • Malaria is transmitted by the bite of an
infected female Anopheles mosquito. The
infecting agent is the spindle-shaped
sporozoite and thousands of these may be
injected by a single bite.
• P. knowlesi is transmitted by Anopheles
latens. Its absence in Africa may partly be due
to the absence of its reservoir hosts.

8. • Within a few hours of an infected bite, the
sporozoites enter the hepatocytes, where
they divide.
• Rupture of the hepatocyte releases the
parasites into the blood, where they attach to
red cell membranes using specific receptors.
• In the red cells, asexual replication of the
trophozoites (ring forms) occurs, giving rise to
erythrocyte schizonts.

9. • The schizonts mature into merozoites and are
released into the circulation to re-infect other
red cells.
• The periodicity of this release varies with the
species and is responsible for the classical cyclic
nature of malaria fevers.
• Relapses, which can occur months or years after
the primary illness, are characteristic of infection
with P. vivax and P. ovale, and are due to
maturation of persistent hypnozoites in the liver.

10. • A few of the trophozoites develop into male
and female banana-shaped gametocytes and
are taken up by the mosquito at a blood meal.
• Inside the midgut of the mosquito, they
undergo sexual reproduction and sporozoites
migrate to the salivary glands, ready to infect
another host when the mosquito bites.

12. • Unlike the schizonts of P. vivax, P. ovale P. malariae and
P. knowlesi, those of P. falciparum are not commonly
seen in the peripheral blood of the human host.
• This is because P. falciparum-infected cells have surface
cytoadherence molecules that enable them to be
sequestered in the deep tissues.
• Therefore P. falciparum schizonts only appear in the
blood in very severe infections or in splenectomized
patients.
• Sequestration is responsible for some of the severe
clinical consequences of P. falciparum malaria, such as
cerebral malaria.

13. Clinical features
• The time between the infected bite and the
appearance of clinical symptoms and parasites
in the peripheral blood varies between
species.
• It is 7–30 days (mean 10 days) in P. falciparum,
but can be months, or even years,with other
species, particularly P. vivax and P. ovale,
because of their hypnozoite stage.

14. • All five Plasmodium species produce factors that cause
release of tissue cytokines, especially from leucocytes.
• These cytokines produce fever and contribute to
anaemia through marrow suppression.
• Splenomegaly is a common feature of acute malaria
and mild jaundice may also occur secondary to
haemolysis. Other clinical features vary with different
species.
• Maximal immunity to malaria takes around 10 years to
develop and is lost over the course of 1–5 years if the
individual leaves a malarious area and is no longer
exposed to infections.

15. Plasmodium falciparum
• Plasmodium falciparum is the only species
associated with complicated and severe disease.
though recently Plasmodium vivax has also been
associated with severe and fatal disease.
• In P. falciparum infections, death may occur after
a single exposure to malaria, particularly in those
with no immunity, such as non-immune travellers
or young children in endemic countries.

16. • In addition to fever with rigors, nausea, and
hot and cold phases, P. falciparum infection
can also present with diarrhoea and cough
• Serious complications include severe anaemia,
cerebral involvement and failure Of major
organs such as kidneys and liver.

17. • During pregnancy, immunity to malaria is
reduced and parasite density increases.
• Even when parasites cannot be visualized in
the peripheral blood, they may be
sequestered in the placenta and compromise
fetal development.
• Malaria is an important cause of low birth
weight in neonates and anaemia in pregnant
women.

21. Plasmodium malariae
• The incubation period of P. malariae may be
several weeks. It is associated with recurrent
fever, anaemia and enlargement of the liver and
spleen.
• Without treatment or following incomplete
treatment of the primary infection, re-
crudescences may occur with decreasing severity
over many years.
• Clinical symptoms of malaria have been reported
up to 30 years after the initial infection.

22. Plasmodium vivax and Plasmodium
ovale
• These species cause a similar clinical picture
with bouts of fever occurring periodically up
to 5 years after the initial infection. These are
relapses, due to reinvasion of red cells by
hypnozoites.
• The trigger for hypnozoites to reactivate after
dormancy is unknown.

23. Plasmodium knowlesi
• The incubation period of P. knowlesi infection
is about 11 days. It causes severe, and
occasionally fatal, malaria. This is because the
parasite invades red cells of all ages and has a
short life cycle of 24 hours.

25. Haematological abnormalities
• Normochromic normocytic anaemia is common.
• Haemoglobin may fall by up to 2 g/dcL each day.
• In malaria-endemic regions other causes of
anemia may be compounded by anaemia due to
malaria.
• In chronically anaemic patients, the oxygen
dissociation curve is shifted to the right so they
are better able to tolerate further falls in
haemoglobin.
• The clinical effects are due to a combination of
the degree and rate of fall of haemoglobin.

26. • Anaemia due to malaria has multiple
aetiologies:
infected red cells are removed from the circulation
by the reticuloendothelial system.
there is accelerated destruction of non-parasitized
cells and dyserythropoiesis in the bone marrow.
Both parasitized and non-parasitized red cells lose
deformability and the high shear rates in the
spleen enhance their removal.

27. • In acute malaria, reticulocyte response is suppressed and
erythropoietin levels are elevated, although this may be less
than expected for the degree of anaemia.
• Uncommon complications of malaria that can exacerbate the
anaemia are hyper-reactive malarial splenomegaly (HMS) and
‘blackwater fever’.
• HMS is massive splenomegaly with hypersplenism due to
disordered immune response to malaria.
• Blackwater fever is severe intravascular haemolysis with
haemoglobinuria, acute renal failure. associated with
antimalarial drugs(quinine) .associated with (G6PD)
deficiency.

28. • Case fatality rates of children with severe
anaemia in Africa are 9–18% and mortality
rises steeply at haemoglobin concentrations of
less than 4 g/dcL.
• Severe decompensated malarial anaemia can
be accompanied by hypovolaemia and
acidosis and therefore requires careful
rehydration and blood transfusion

29. • In Milder forms of anemia avoid giving blood
transfusions which is associated with
increased risk.
• Antimalarial prophylaxis, prompt treatment of
malaria and avoidance of mosquito bites are
valuable in reducing malaria infections and
anaemia in vulnerable groups, such as
pregnant women and young children.

30. • The white cell count in malaria is usually normal, but
may be raised in severe disease.
• a leucoerythroblastic response, monocytosis,
eosinopenia and a reactive eosinophilia during the
recovery phase.
• Neutrophil activation may be apparent in severe
malaria.
• Thrombocytopenia due to increased splenic clearance,
raised thrombopoietin levels is usually mild with
counts around 100 × 109/L (marked in P. knowlesi ).
• Pancytopenia without massive splenomegaly has also
been described.

31. • The bone marrow shows prominent dyserythropoiesis.
This may persist for weeks after the acute infection and
is caused by intramedullary cytokines produced by the
infection.
• Erythrophagocytosis and macrophages containing
malaria pigment are frequently seen in marrow
samples.
• Although thrombocytopenia and activation of the
coagulation cascade and fibrinolytic system, bleeding
and haemorrhage are uncommon(even when
prothrombin and partial thromboplastin times
prolonged).

32. • Disseminated intravascular coagulation is not
common.
• Fibrinogen levels are increased with rapid
fibrinogen turnover and consumption of
antithrombin and factor XIII resulting in
increased fibrin degradation products.
• increased levels of circulating active von
Willebrand.

33. • Haematological indicators of a poor prognosis in severe
malaria include:
 leucocytosis >12 × 109/L
 severe anaemia (packed cell volume <15%)
 thrombocytopenia <50 × 109/L
 prolonged prothrombin time (>16 s)
 prolonged partial thromboplastin time (>40 s)
 reduced fibrinogen (<2 g/L)
 hyperparasitaemia >100,000/μL (high mortality >500,000/
μL)
 >20% of parasites are pigment-containing trophozoites
and schizonts
 >5% of neutrophils contain visible malaria pigment

34. Genetic haematological protection
mechanisms
• Plasmdium vivax and P. knowlesi need Duffy blood
group antigen as a receptor to enter red cells. This
antigen is absent in at least two-thirds of all Africans
who consequently have a natural resistance to
infection with P. vivax and P. knowlesi.
• Hb AS has a substantial (up to 10 times) protective
effect against severe malaria and a similar, but less
marked protection is associated with other genetic red
cell abnormalities such as G6PD deficiency,
thalassaemia trait and Hb C trait.

35. Diagnosis
• Direct visualization of parasites by light
microscopy using a combination of thick and
thin blood films is the gold-standard
diagnostic technique for malaria.

36. • The disadvantages of basing a diagnosis of
malaria on blood film examination include the
following:
 An initial negative film does not exclude malaria: at
least three films taken during episodes of fever should
be examined in the absence of antimalarial drugs to
confirm a negative blood film.
 A positive film does not prove that symptoms are due
to malaria: asymptomatic parasitaemia is common in
adults from endemic areas.
 P. malariae and P. knowlesi cannot be distinguished
morphologically.

37. Parasites, particularly P. falciparum gametocytes,
may be washed off the slide during staining and
bulk staining may result in transfer of parasites
between slides.
 Parasite density does not necessarily correlate
with disease severity, although heavy
parasitaemia (>5% of red cells infected) indicates a
poor prognosis.
• Malaria pigment may persist in phagocytic cells for
several weeks after an acute attack andmay be helpful in
retrospective diagnosis of malaria.

38. Antigen detection
• detection of the malaria antigen histidine-rich protein
(HRP)2 or parasite lactate dehydrogenase (pLDH) for
rapid diagnosis.
• HRP2 protein may remain positive for 14 days after
successful treatment and false positives due to
rheumatoid factor have been reported.
• pLDH is only produced by viable parasites so it
becomes negative 2–3 days after successful treatment.
• These tests should not replace microscopy, but are
useful in on-call or emergency situations or when no
experienced microscopist is available.

39. Antibody detection
• Malarial antibodies can remain in the blood
after the eradication of parasites, so their
detection is not useful for diagnosis in the
acute attack.
• The main uses of malarial antibody detection
are for excluding malaria as a cause of
recurrent fever, for population surveys and as
a screening test for blood donors in non-
endemic areas.

40. DNA-based methods
• DNA probes have been developed for malaria
diagnosis, but their use is generally restricted to
research and epidemiological surveys.
• Although the current prevalence of P. knowlesi
infections is relatively low, it may be
misdiagnosed as P. malariae, especially when
microscopy is used.
• P. knowlesi can only be accurately distinguished
from P. malariae using PCR assay and/or
molecular characterization.

41. Haematological implications of
treatment for falciparum malaria
• Current widely recommended first-line
treatment for malaria is with combination
therapy which includes artemisinin.
• Pyrimethamine is used in combination with a
long-acting sulfonamide, such as sulfadoxine
(as in Fansidar), a dihydrofolate reductase
inhibitor, which may therefore induce
megaloblastic anaemia and other cytopenias.

42. • The sulfur component of these combinations
may also cause methaemoglobinaemia.
• The sulfur component of these combinations
may also cause methaemoglobinaemia.
• Dapsone acts by inhibiting the synthesis of
dihydrofolic acid and may be associated with
haemolytic anaemia, methaemoglobinaemia
and eosinophilia.

43. • Primaquine, an inhibitor of protein synthesis, is
active against the hypnozoites of P. vivax and the
gametocytes of P. falciparum.
• It causes oxidant haemolysis in patients with
G6PD deficiency and, rarely,
methaemoglobinaemia.
• Quinine is usually reserved for life-threatening
infections. It acts by disrupting the food vacuole
of the parasite. Rarely, it is associated with
immune thrombocytopenia and severe
intravascular haemolysis.

44. • Mefloquine, halofantrine and artemisinin-related
compounds do not commonly cause significant
haematological side-effects.
• A combination of artemether and lumefantrine
(Coartem or Riamet) is commonly used as first-
line treatment in endemic areas.
• Some antibacterial drugs, such as doxycycline,
clindamycin, trimethoprim and sulfonamides,
have also been used for their antimalarial effect
and may be associated with haematological side-
effects.

45. • For malaria due to P. vivax, P. ovale, P.
malariae and P. knowlesi, chloroquine is still
widely used for treatment, as resistance is
generally low; primaquine is added to prevent
relapses in vivax, ovale and knowlesi malaria.
• Travellers on warfarin should begin malaria
chemoprophylaxis one week (2–3 for
mefloquine) before travelling and the INR
should be stabilized before travel.

46. Babesiosis in the differential
diagnosis of malaria
• Primarily a disease of animals and rarely infects
humans. It is due to a protozoan parasite transmitted
by the bite of the ixodid tick.
• Following the bite, the organisms penetrate red
cells,where they take on an oval, round or pear shape.
• The erythrocytic ring forms of Babesia microti and B.
divergens may be confused with malaria P. falciparum
rings, but they do not produce pigment or cause
alterations in red cell morphology.
• A minority of organisms take on a folded shape and
are thought to be gametocytes.

47. Filariasis
• There are two groups of human filariasis: the
blood (lymphatic filariasis) and the skin
(onchocerciasis).
• Three species of filarial worms cause
lymphatic filariasis
Wuchereria bancrofti (most widespread,90%in asia)
Brugia timori (indonesia)
Brugia malayi (China, Indo-China, Thailand, Malaysia,
Indonesia, the Philippines and south-west India)

49. Other filariae with blood-inhabiting
larvae
• Loa loa
 This occurs especially in West Africa. The adult wormsmigrate
through the subcutaneous tissues, including the conjunctiva, and
occasionally can be seen passing across the eye.
• Mansonella perstans
 This is a common infection in Africa. It can cause angioedema,
pruritus, abdominal pain and eosinophilia. These organisms often
coexist in the blood with W. bancrofti, but can be distinguished by
their smaller size and absence of a sheath.
• Mansonella ozzardi
 This is probably non-pathogenic and occurs in the West Indies and
South America. The adult worm lives in the body cavities and
mesentery, rarely causing any symptoms.

50. Clinical presentation
• May occur 6 months or more after the infective
bite.
• The symptoms and signs are due to lymphangitis.
• fever with heat, redness and pain over lymphatic
vessels,the lymphangitis can be seen to spread
distally
• In W. bancrofti infection, these repeated episodes
of inflammation result in the typical chronic
picture of filariasis (hydrocele, lymphoedema and
elephantiasis, chyluria and tropical pulmonary
eosinophilia).

51. • The clinical picture in B.malayi infection is
similar, but it does not cause hydrocele or
chylous urine. B. timori causes lymphodema
characteristically limited to the leg below the
knee.

52. Haematological abnormalities in
filariasis
• Eosinophilia is the major haematological
abnormality.
• Tropical pulmonary eosinophilia is unusual
happens due to an immunological hyper-
responsiveness to microfilariae in the lungs. It is
more common in men than women.
• Although microfilariae are absent from the blood
in this syndrome, they may be seen in lung
biopsies and adult worms can be visualized in
lymphatics on ultrasound.

53. • There is an extreme eosinophilia, with eosinophil
counts of greater than 10 × 109/L; the level of
eosinophilia is not related to the severity of symptoms.
• A study of filariasis in India in 2013 found that, in
addition to eosinophilia, there was leucocytosis,
neutrophila, thrombocytosis, raised erythrocyte
sedimentation rate and raised mean corpuscular
volume.
• Haemoglobin, total red cell count, lymphocytes,
basophils, monocytes, mean corpuscular haemoglobin
and mean corpuscular haemoglobin concentration
were reduced.

54. • In tropical pulmonary eosinophilia,
diethylcarbamazine treatment reduces the
eosinophil count and produces resolution of
symptoms.
• This rapid response to treatment distinguishes
filariasis from other causes of marked
eosinophilia associated with helminths such as
Ascaris, Strongyloides, Schistosoma subsp.
trichinosis and Toxocara.

55. Diagnosis of filariasis
• The adult worms residing in the lymphatics
are inaccessible, so diagnosis is based on
finding microfilariae in the peripheral blood.
• The level of filaraemia is inversely related to
the clinical signs because much of the damage
is due to immunological responses to the
microfilariae rather than to the organisms
themselves.

56. • To optimize the chances of finding scant
microfilariae in the blood, the sample should
be taken at the appropriate time for the
expected peak concentration of microfilariae
(i.e. around midnight or midday for
nocturnally and diurnally periodic forms,
respectively).

57. • Detection of circulating antigen by enzyme-linked
immunosorbent assay (ELISA) or
immunochromatography (ICT) has replaced
microscopy for the diagnosis of bancroftian, but
not brugian, filariasis. An antigen ICT card test is
available for the detection of W. bancrofti, which
does not react with other filariae and is highly
sensitive (100%) and specific (92%).
• Filarial DNA can be detected by PCR, and
ultrasound scans can help identify adult worms
within the lymphatic system.

59. • Serological tests are not very helpful as most
individuals from endemic areas have
antibodies to crude filarial antigens and there
is cross-reactivity with other filariae and
nematodes.

60. Haematological implications of
treatment for filariasis
• Oral diethylcarbamazine is the drug of choice in
all forms of lymphatic filariasis, including
subclinical infection.
• Alternative treatments include combinations of
albendazole and ivermectin.
• None of these drugs has common, serious
haematological sideeffects.
• Depletion of Wolbachia endobacteria, a symbiont
of Onchocerca, by tetracycline antibiotics leads to
long-lasting sterility of adult female worms.

61. African trypanosomiasis (sleeping
sickness)
• caused by the haemoflagellate protozoa Trypanosoma
brucei gambiense in West and Central Africa, and T.
brucei rhodesiense in eastern Africa.
• These parasites are fusiform in shape, 12–35 μm long
And morphologically indistinguishable from each other.
• The disease is transmitted by the bite of the tsetse
fly,which is only found in Africa.
• The trypanosomes multiply by fission in the vicinity of
the infected bite and are then disseminated by the
bloodstream.
• Congenital transmission has also been described.

62. Clinical features
• The bite of a tsetse fly is very painful and causes a
small indurated lesion that may persist for some days.
The local multiplication of the trypanosomes may
cause a marked inflammatory reaction (a chancre) that
regresses after 2–3 weeks.
• Entry of the trypanosomes into the bloodstream is
associated with fever, which tends to be less marked in
West African trypanosomiasis than in the East African
variety.
• East African trypanosomiasis is primarily a disease of
cattle and only enters human hosts by accident.(less
well tolerated and more aggressive).

63. • The early stages of sleeping sickness can be
associated with prominent lymphadenopathy,
particularly of the posterior cervical nodes,
and mild splenomegaly. These features may
be suggestive of infectious mononucleosis,
tuberculous lymphadenitis or a
lymphoproliferative disorder.
• Severe anaemia, haemorrhages and
petechiae may occur at this stage.

64. • Both types cause a febrile illness which, despite the
name, is not always associated with drowsiness. Death
is inevitable if the disease is left untreated.
• As the disease progresses, parasitaemia decreases,
trypanosomes invade the central nervous system (CNS)
and neurological disturbances due to inflammatory
chronic meningoencephalitis supervene.
• In West African trypanosomiasis, the disease runs its
course over several years, but in East African
trypanosomiasis infection CNS involvement may occur
within weeks.

65. Haematological abnormalities
• Anaemia : multifactorial but primarily due to
phagocytic removal of immune complex-coated
red cells.
• Trypanosomes liberate haemolytic factors that
contribute to this process
• There is a failure to incorporate iron into red cell
precursors and the resulting dyserythropoiesis
means that the bone marrow is unable to
compensate for the fall in haemoglobin.

66. • Moderate leucocytosis with increased
monocytes, lymphocytes and plasma cells.
• Mott morular cells have also been described
in sleeping sickness.
• The bone marrow is hypercellular, with fat cell
atrophy, focal loss of haematopoietic cells and
deposition of extracellular gelatinous
substances, which histochemically are
mucopolysaccharides, rich in hyaluronic acid.

67. • As the disease advances, a bleeding tendency
may develop due to thrombocytopenia, vascular
injury and coagulopathy.
• Platelet dysfunction has also been described and
is manifest as clumping and abnormal
aggregation responses.
• DIC with raised FDPs may occur in the later
stages. Although some of these haematological
changes can be linked to the non-specific
polyclonal activation of B cells, overall the
underlying mechanisms are not well understood.

68. Diagnosis
• Trypanosomes can be seen on stained thin
blood films, but the number of trypanosomes
in the circulation can vary considerably and is
often low, so concentration techniques are
usually required.
• Quantitative buffy coat method is the
technique of choice for diagnosis of African
sleeping sickness.

69. • Wet preparations of fluid aspirated from the
lymph nodes, bone marrow or cerebrospinal fluid
(CSF) may also reveal live motile organisms.
• The highly specific and sensitive serological card
agglutination test for trypanosomiasis (CATT) may
be used in conjunction with a direct visualization
method. If these tests are positive, then CSF
examination is mandatory to determine the stage
of the illness.

70. Haematological implications of
treatment
• Pentamidine and suramin are the drugs of choice
for the early stages.
• cure rate (90%) but only modest CSF
concentrations so cannot be used for later stages.
• The most common haematological side effects
are leucopenia, thrombocytopenia and anaemia.
• Suramin has serious side-effects, including
haemolytic anaemia and bone marrow toxicity.

71. • Melarsoprol, an arsenic-based compound, has
been the drug of choice for late-stage sleeping
sickness, but is highly toxic, with a mortality of 4–
12%. Its main adverse effect is a fatal
encephalopathic syndrome; haematological
toxicity is not a problem.
• Eflornithine is expensive, but is of benefit in late-
stage, particularly West African, disease; 25–50%
of patients treated with this drug exhibit bone
marrow toxicity with pancytopenia.

72. American trypanosomiasis (Chagas
disease)
• caused by T. cruzi, which is transmitted by
triatomine bugs that infest poor-quality
housing. It can also be transmitted through
blood transfusions and congenitally.

73. Clinical features
• incubation period 7-14 days, may exceed 40 days
if transmission through blood transfusion.
• In the acute phase, swelling at the site of entry of
the organism (chagoma), may be accompanied by
fever, hepatosplenomegaly and
lymphadenopathy.
• The trypanosomes multiply intracellularly in
muscle tissue, particularly the heart, colon and
oesophagus.
• Once infection has occurred, the organisms will
be present for life unless treatment is given.

74. • The chronic phase of the disease is associated with
heart disease in 30% of cases, manifesting as
arrhythmias and cardiomegaly.
• Also gastrointestinal tract and other hollow organs,
resulting in loss of peristalsis and organ failure.
• Asymptomatic infection is common and threaten blood
transfusion services, so routine screening blood for
American trypanosomiasis.
• Many cases do not become symptomatic until the
chronic stage, which can occur 5 to 40 years after
infection.

75. Diagnosis
• Microscopy of blood smears can be helpful,
but only in the acute phase of infection when
parasites are circulating in blood.
• Sensitive serological tests based on enzyme
immunoassay or immunofluorescence are
therefore more commonly used as the
primary diagnostic tool. Diagnosis is generally
made based on at least two different serologic
tests. PCR may also be useful.

76. Haematological implications of
treatment
• Treatment of T. cruzi infection is with
nifurtimox or benznidazole and if started
early, the disease is curable.
• Major haematological side-effects are
uncommon with either drug, although
agranulocytosis has been reported with
benznidazole.

77. Leishmaniasis
• Visceral and cutaneous leishmaniases are caused
by protozoan flagellates that are transmitted
through the infective bite of a phlebotomine
sandfly.
• Leishmaniasis is second only to malaria as the
most common parasitic cause of mortality.
• Following an infected bite, parasites spread from
the inoculation site to the mononuclear
phagocytic system.
• Only the visceral form (kala-azar) is associated
with organisms in haemopoietic tissues.

78. • Visceral leishmaniasis is due to the species
Leishmania donovani and L. infantum.
• A concomitant HIV infection increases the risk
of developing active visceral leishmaniasis by
between 100 and 2320 times. In southern
Europe, up to 70% of cases of visceral
leishmaniasis in adults are associatedwithHIV
infection.

79. Clinical features
• This depends on both the genotypic potential of
the parasite and the immunological response of
the patient. Incubation period varies from days to
years but is generally 2–6months.
• Onset can be sudden with high fever, or gradual
with intermittent fever.
• Diarrhoea, joint pain, weight loss and bleeding
gums occur in the acute phase. This is followed
by progressive muscle wasting, protuberant
abdomen, fever, weight loss, anaemia and
hepatosplenomegaly.

80. Haematological abnormalities
• Normochromic normocytic anaemia
• haemoglobin levels of 7–10 g/dcL are
common
• The massive splenomegaly results in
hypersplenism with consequent pancytopenia.
• Liver dysfunction with jaundice, ascites and
deranged coagulation may occur in the late
stages and has a poor prognosis.

81. • The bleeding tendencymay be exacerbated by
thrombocytopenia. In all patients with
unexplained splenomegaly, pancytopenia or
fever, a high index of suspicion of
leishmaniasis needs to be maintained to
prevent fatalities.

82. Diagnosis
• Definitive diagnosis is based on detection of
the parasites, or their DNA, in smears of bone
marrow, splenic aspirate or fluid aspirated
from enlarged lymph nodes.
• On microscopy Leishmania are usually seen as
intracellular amastigotes in mononuclear cells,
but can also be seen extracellularly

83. • Microscopy is less sensitive than molecular
diagnosis, particularly when there is
coinfection with HIV.
• PCR can be performed on lesion
aspirate,marrow, blood and biopsymaterial.
The indirect fluorescent antibody tests ELISA
and DAT are useful for detecting antibodies to
visceral leishmaniasis, but results may be
inconclusive in immunosuppressed patients.

84. Haematological implications of
treatment
• Sodium stibogluconate is the most used. can cause
worsening anaemia and thrombocytopenia, although
its most sideeffects are on cardiac function. Resistance
levels to antimonials are high so other options
including amphotericin, paromomycin and miltefosine.
• HIV-coinfected patients do not respond well to
antimonials, so amphotericin is the drug of choice.
• Amphotericin causes normocytic normochromic
anaemia, but its most toxicity is related to renal,
cardiac, neurological and hepatic dysfunction.

85. Hookworm infection
• Hookworms (Ancylostoma duodenale) and Necator
americanus) are common in the tropics and subtropics
and affect 600 million people worldwide. They cause
significant iron deficiency anaemia in all age groups,
including 30–50% of anaemia in pregnancy.
• The hookworm eggs are generally transmitted between
humans through contact with faeces. Most infections
are asymptomatic, but chronic blood loss through the
gut eventually leads to severe iron deficiency anaemia,
and even cardiac failure.

86. • Other symptoms include itch, rash and abdominal
discomfort.
• Eosinophilia is common and characteristic eggs
can be seen on faecal microscopy.
• Albendazole or mebendazole are the usual
treatments and iron deficiency should also be
treated.
• Transfusion is rarely necessary, and may be
harmful since the anaemia develops very slowly
and cardiac function may be compromised in
severe anaemia.

87. Schistosomiases (Bilharzia)
• common intravascular infection caused by
trematode worms acquired through contact
with contaminated water.
• Schistosoma. mansoni, intercalatum, japonica
and mekongi all cause intestinal
schistosomiasis, whilst S. haematobium causes
urinary schistosomiasis.

88. • There is an acute stage (Katayama syndrome),
and chronic and advanced stages.
• Schistosomiasis is the second most common
cause of iron deficiency worldwide after
hookworm infection. It is due to blood loss
from the urinary and gastrointestinal tracts
and may be severe.

89. • Eosinophilia occurs in 80% of cases.
• Anaemia of chronic disease, massive
splenomegaly with hypersplenism,
hepatomegaly and generalized
lymphadenopathy can all occur.
• Iron deficiency should be treated and
schistosomiasis treatment is with
praziquantel, which has no significant
haematological complications.

90. Viral haemorrhagic fevers
• caused by arenaviruses, filoviruses, bunyaviruses and
flaviviruses and are classified according to their
reservoir hosts and their primary means of
transmission into:
– rodent-associated viruses (e.g. Lassa fever, hantaviruses);
– arthropod-borne viruses (e.g. dengue, yellow fever and
Chikungunya viruses);
– unknown vectors or hosts (e.g. Marburg, Ebola).
• occur in epidemics, have human-to-human
transmission and, in non-tropical settings, may only be
suspected if a relevant travel history is reported.

91. Dengue
• 4 types of virus belong to flaviviruses transmitted by
Aedes mosquitoes.
• infection in young children is usually asymptomatic.
• Older children and adults develop acute fever,
headache and myalgia (‘breakbone fever’).
• Leucopenia may accompany this stage of the illness.
Severe complications may arise in those with previous
infection. These include hypotensive shock, bone
marrow hypoplasia with neutropenia and abnormal
megakaryopoiesis, leading to severe thrombocytopenia
and spontaneous bleeding.

92. Yellow fever
• Yellow fever virus is transmitted by Aedes
mosquitoes and exists throughout equatorial
Africa, northern and central southern
America. Ninety percent of cases and deaths
each year occur in Africa, and the number of
cases has been increasing over the past two
decades possibly due to a decline in
population immunity.

93. • The virus invades hepatocytes, causing
hepatocellular dysfunction. After an incubation
period of 3–4 days, fever, myalgia and back pain
may be followed by jaundice, bleeding and, in the
most severe cases, renal failure.
• Haematological changes include leucopenia with
relative neutropenia, thrombocytopenia as part
of a consumptive coagulopathy, initial
haemoconcentration, and subsequent
haemorrhage and haemodilution.

94. • Coagulation abnormalities include reduced
fibrinogen and clotting factors II, V, VII, VIII, IX
and X, with increased PT and APTT, as well as
the presence of fibrin degradation products.
• In 85% of cases there is spontaneous
improvement, with the disappearance of
symptoms in 3–4 days. The remaining 15%
enter a toxic phase which has a 50% mortality.

95. • Diagnosis can be difficult, as yellow fever
(preventable by vaccination) can be confused
with several febrile and haemorrhagic
illnesses.Antibodies can be detected in the
serumand treatment is symptomatic.

96. Lassa fever, Ebola virus and Marburg
virus
• These are endemic in equatorial Africa and are
important because they cause potentially fatal
infections and have the ability to spread fromperson to
person.
• Only about 10%of infected individuals become ill. Of
these 1–2% develop fatal disease.
• The clinical features are similar and are characterized
by headache, fever and oesophagitis. Spontaneous
bleeding occurs in 25% of hospitalized patients and is
thought to be due to increased vessel permeability and
abnormal platelet function.

97. • Death is due to multi-organ failure and shock.
Case reports suggest that treatment with
ribavirin may be helpful and a promising
vaccine against Ebola virus has recently been
tested in clinical trials in west Africa.