MALARIA

MALARIA
 Malaria is a protozoan disease transmitted by the
bite of infected female Anopheles mosquitoes.

 It is the most important of the parasitic diseases of

humans, with transmission in 107 countries

 Human malaria can be caused by four species of

the genus Plasmodium: P. falciparum, P. vivax, P.
ovale, P. malariae.
Parasitology
 The female mosquito becomes infected after taking a blood
meal containing gametocytes, the sexual form of the malarial
parasite .
 The developmental cycle in the mosquito usually takes 7-20
days, culminating in infective sporozoites migrating to the
insect's salivary glands.
 The sporozoites are inoculated into a new human host, and
those which are not destroyed by the immune response are
rapidly taken up by the liver.
 Here they multiply inside hepatocytes as merozoites: this is
pre-erythrocytic (or hepatic) sporogeny.
Parasitology (continue)

 After a few days the infected hepatocytes rupture,

releasing merozoites into the blood from where they
are rapidly taken up by erythrocytes.
 In the case of P. vivax and P. ovale, a few parasites
remain dormant in the liver as hypnozoites.
 These may reactivate at any time subsequently,
causing relapsing infection.
Parasitology (continue)
 Inside the red cells the parasites again multiply,
changing from merozoite, to trophozoite, to schizont,
and finally appearing as 8-24 new merozoites.
 The erythrocyte ruptures, releasing the merozoites to
infect further cells.
 Each cycle of this process, which is called
erythrocytic schizogony, takes about 48 hours in P.
falciparum, P. vivax and P. ovale, and about 72 hours
in P. malariae.
Parasitology (continue)
 A few merozoites develop not into trophozoites but
into gametocytes. These are not released from the red
cells until taken up by a feeding mosquito to
complete the life cycle.
PATHOGENESIS
 The pathology is related to anaemia, cytokine release, and in the case of P. falciparum,
widespread organ damage due to impaired microcirculation.
 The anaemia seen in malaria is multifactorial. In P. falciparum malaria, red cells containing
schizonts adhere to the lining of capillaries in the brain, kidneys, gut, liver and other organs.
As well as causing mechanical obstruction these schizonts rupture, releasing toxins and
stimulating further cytokine release.
 After repeated infections partial immunity develops, allowing the host to tolerate parasitaemia
with minimal ill effects.
 Certain genetic traits also confer some immunity to malaria.
 Certain haemoglobinopathies (including sickle cell trait) also give some protection against the
severe effects of malaria
 Iron deficiency may also have some protective effect.
 The spleen appears to play a role in controlling infection, and splenectomized people are at
risk of overwhelming malaria.
 Some individuals appear to have a genetic predisposition for developing cerebral malaria
following infection with P. falciparum.
 Pregnant women are especially susceptible to severe disease.
 Causes of anaemia in malaria

 Haemolysis of RBCs.
 Enlarged spleen causing sequestration of RBCs .

 Dyserythropoiesis.

 Folate deficiency due to depletion of stores .

 Drug-induced (chloroquine, primaquine) haemolysis in

patients with G6PD deficiency.
CLINICAL FEATURES
Clinical syndromes may be classified as
i. Uncomplicated acute malaria
ii. Severe (complicated) malaria, including cerebral
malaria
iii. Chronic malaria
iv. Sequelae : tropical splenomegaly syndrome
v. Complications : splenic rupture (rare)
Uncomplicated acute malaria
 This is the commonest presentation of malaria.
 Infection is mostly caused by P. vivax, and to less

extend being due to P. falciparum.

 After an incubation period of 8-14 days, initial

malaise, fatigue and headache are followed by typical

paroxysms of fever.
 The cold phase lasts for 20-60 minutes. The patient

experiences abrupt onset of chills and covers himself

with many layers of blankets. This is associated with
uncontrollable shivering (rigors).
Uncomplicated acute malaria (cont.)

 The hot phase follows and the temperature may reach

40°-41.7°C, associated with headache, flushing and
tachycardia.
 After 3-8 hours, even in the absence of treatment,
fever abruptly remits over the next half hour with
profuse sweating, leaving the patient drenched in
sweat — the wet phase.
 The paroxysms correspond with RBC lysis and are
due to the release of cytokines like tumour necrosis
factor and interleukin-1.
 Uncomplicated acute malaria(cont.)

 After about a week the life cycles of individual parasites may

synchronise and the characteristic periodicity of fever is seen.
 Infection with vivax and falciparum species produces tertian
malaria — fever recurs every 48 hours.
 Between paroxysms the patient is usually asymptomatic and
may even go to work.
 The only physical findings may be mild anaemia and mild
splenomegaly . Uncommon features are dry cough, diarrhoea
and herpes labialis.
 Symptoms and signs are identical in vivax and falciparum
malaria and differentiation is impossible without laboratory
tests.
Relapses
Once the acute attacks subside, recurrence of fever
does not occur in falciparum malaria.
 In vivax malaria, however, batches of merozoites

may be released from the hepatic hypnozoites for 8-

10 years, which cause febrile relapses after 2-3
months in up to 30% of patients.
 Subsequent relapses are milder and of shorter

duration.
Severe (pernicious) malaria
 About 1% of patients with Plasmodium falciparum
infection may develop more severe manifestations
culminating in failure of various organ systems.
 This does not occur with P. vivax infection because
the vivax parasites undergo their entire erythrocytic
life cycle in circulating RBCs.
 The infected cells develop small protrusions
(knobs) on their cell membranes which serve to
attach to the capillary endothelium.
 The parasites probably get some nutrition from the
endothelium and mature into schizonts and
merozoites.
 This results in microcirculatory obstruction.
 Moreover, unlike P. vivax which infect only young
RBCs, P. falciparum can infect RBCs of all ages,
producing heavier parasitaemia.
 Cerebral malaria
 Of all the manifestations of severe malaria, cerebral malaria
is the commonest and carries a mortality rate of 25-30%.
 It is more common in children, pregnant women,
splenectomised individuals and in non-immune travellers
visiting endemic regions.
 Typical acute febrile malaria may be complicated by gradual
onset of coma or convulsions. Hyperpyrexia is common.
 Examination reveals no focal neurological deficit except for
squint .
 Neck rigidity is absent, helping to differentiate it from
pyogenic meningitis.
Cerebral malaria(cont.)
 Pallor and splenomegaly are common. Some patients
may develop jaundice and haemoglobinuria due to
massive haemolysis.
 Hypoglycaemia is frequent and may cause
irreversible brain damage if uncorrected.
 These patients need hospitalisation and intensive care.
 The peripheral smear is teeming with parasites and
when 10% or more of RBCs are infected, mortality
exceeds 50%.
Chronic malaria
 Patients with persistent hepatic P. vivax infection
may develop partial immunity which permits
asymptomatic low-grade parasitaemia.
 The resulting immune stimulation may result in
progressive splenomegaly.
 The enlarged spleen may at times rupture
spontaneously or following trauma.
Tropical splenomegaly syndrome

 In some patients residing in endemic regions,

massive splenomegaly is seen in the absence of
parasitaemia on repeated blood smear examination.
 These patients have elevated serum IgM levels,
demonstrable antimalarial antibodies in the blood,
and hepatic sinusoidal lymphocytic infiltration.
 This is thought to be an excessive immunological
response to repeated infection by any species of
plasmodia.
 Tropical splenomegaly syndrome
(cont.)
 Symptoms may be due to the mass effect or
hypersplenism.
 Marked regression of the splenomegaly with
prolonged malarial chemoprophylaxis (particularly
with proguanil) confirms the diagnosis.
Other forms of malaria
-Plasmodium ovale infection
 causes benign tertian malaria like P. vivax. It tends to cease

after a few paroxysms even without treatment. Hepatic

hypnozoites may persist for years.
-Plasmodium malariae infection
 causes fever with a 72 hours periodicity (benign quartan

fever); its incubation period is longer (18-40 days).

 Serious renal damage may occur due to progressive

glomerulonephritis due to deposition of immune complexes.

The glomerulonephritis does not respond to antimalarial
drugs or corticosteroids.
DIAGNOSIS
 The diagnosis is easily confirmed by demonstration
of asexual forms of parasites in RBCs in the
peripheral smear .
 Giemsa-stained thick and thin smears must be
made on a clean glass slide and dried in air.
 At least three films should be examined before
malaria is declared unlikely.
 Parasitaemia is quantitated by counting percent of
parasitised cells per 1000 RBCs.
DIAGNOSIS (cont.)
 An alternative microscopic method is quantitative
buffy coat analysis (QBC), in which the centrifuged
buffy coat is stained with a fluorochrome which 'lights
up' malarial parasites.
 A number of antigen-detection methods for
identifying malarial proteins and enzymes have been
developed. Some of these are available in card or
dipstick form, and are potentially suitable for use in
resource-poor settings.
 Serological tests are of no diagnostic value.
DIAGNOSIS (cont.)
Other findings include
 normochromic normocytic anaemia.

 polymorphonuclear leucocytes laden with malarial

pigment,
 elevated ESR.

 In severe falciparum malaria there may be

metabolic acidosis, hyperbilirubinaemia,

thrombocytopenia, hypoalbuminaemia, azotaemia,
hypoglycaemia and elevated liver enzymes
 TREATMENT

1. Acute uncomplicated malaria

a)    P. vivax, malariae and ovale infection :
 Oral chloroquine 10 mg/kg (maximum 600 mg)

followed by 5 mg/kg (maximum 300 mg) after 6, 24

and 48 hours.
 Radical cure is necessary as chloroquine is

ineffective against hepatic forms. Hence oral

primaquine (15 mg/day for 14 days) is required to
prevent relapses in vivax and ovale infection. It is
not given in pregnancy and in G6PD-deficient
patients.
TREATMENT (cont.)
b)    Plasmodium falciparum infection
 The artemisinin-based combination therapy

(ACT) is the recommended oral treatment for

uncomplicated falciparum malaria
 Treatment of severe falciparum malaria is IV

artesunate, ICU facilities including ventilation

and dialysis, transfusion in severe anemia
PROPHYLAXIS
 Vector control methods
 Public health measures include case detection
and radical cure of asymptomatic persons
 Personal protection to avoid mosquito bites
 Chemoprophylaxis is advised to nonimmune
visitors to endemic areas and to pregnant
mothers. Prophylaxis should be started 1-2
weeks before exposure and continued for 4
weeks after returning from the endemic area.
Malaria prophylaxis for adult travellers

Area visited Prophylactic regimen Alternatives

No chloroquine resistance Chloroquine 300 mg Proguanil 200 mg daily
weekly
Limited chloroquine Chloroquine 300 mg Doxycycline 100 mg daily
resistance weekly
  plus or
  Proguanil 200 mg daily Mefloquine 250 mg
weekly
Significant chloroquine Mefloquine 250 mg Doxycycline 100 mg daily
resistance weekly
    or
    Malarone 1 tablet daily
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