Introduction & epidemiology Tropical disease

.

Aetiology & transmission Parasite :

plasmodum

I. P. vivax

II. P.falciparm

III. P. malariae

IV. P. ovale

V. P.knowlesi

Vectors : anopheles

I. A. culcifacies (rural)

II. A. fluvitalis( rice fields)

III. A. stephensi (urban)

IV. A. minimus

V. A. philippinesis

VI. A. sundaicus( costal)

Life cycle of malarial parasite

2 HOSTS–

DEFINITE HOST– female Anopheles-

SEXUAL PHASE

INTERMEDIATE HOST– Human

STAGES :

HEPATICphase / Tissue phase

Erythrocytic phase

:

RESISTANCE MECHANISMS INNATE RESISTANCE

Natural capacity of host to resist infection from malaria. ( which is due to

differences in surface receptors , intra erythrocytic factors or yet unknown

causes. )

In Endemic zones – repeated infection – development of resistance.

vulnerable to infection with one species – due to difference in genetic

constitution of species.

INNATE RESISTANCE

INTRA ERYTHROCYTIC FACTORS :

Resist penetration of cell by merozoites- Absence of duffy Ag.-vivax

Impede their development- HbS.

Assist their removal by RES.

Differences in cell membrane – decides attachment/penetration of

merozoites to receptors/cells.

Hb F & Ovalocytes- resist p. falciparum

ACQUIRED RESISTANCE

Sporozoites --- Liver cells --- No immunological response

Merozoites --- erythrocytes ---- Immunological response

First response – phagocytosis in spleen / hyperplastic RE cells.

Cell mediated immunity – -> through activated macrophages

Host defence - defervescence of fever.

ACQUIRED RESISTANCE

Protective antibodies against merozoites – IgM

Complement system not involved

Schizont infested cells – phagocytosed rapidly – after OPSONISATION

Antibodies against toxins

Antibodies and antigens may be transmitted to fetus trans placentally

Antibodies protect while antigens / antigen-antibody complexes help toacquire immunity.

Immune Evasion By Parasite :

Reasons for survival of parasite :

Antibodies against parasite may promote their survival instead ofdestruction

Infection may impair antibody synthesis

Handling & processing of antigens by macrophages is impaired

Sporozoites , schizonts & gametocytes are not destroyed by immunesystem.

immunopathologyAnaemia

Disproportionate to the damage to RBCs by parasite.

Formation of autoantibodies to RBCs & immune binding or adherence of

circulating Ag-Ab complexes to uninfected RBCs.

Hemolysis – blackwater fever – drug hypersensitivity.

Bone marrow suppression

Renal damage

Acute transient lesion as nephritis

May progress to ARF

ARF secondary to ATN

Development of proteinuria over a period of 1 to

2 weeks

ARF is reversible

Chronic progressive nephritic syndrome

Secondary to P. malariae infections

Soluble immune complexes deposits in

BM of Glomerular capillaries – glomerular

lesions

SPLENOMEGALY

Splenomegaly – elevated levels of IgM & Lymphocytosis in peripheral blood ,

bone marrow & liver sinusoids.

Sequestration of RBC.

Splenectomy – Relapse of latent infection.

CEREBRAL MALARIA

Pre school children

Common in PEM

Plugging of cerebral capillaries with infected erythrocytes with

char CYTOADHERENCE properrty.

Hemorrhages

Deposition of fibrin in vessels

Altered capillary permeability

Intravascular coagulation

Clinical features

High risk patients –depressed level of consciousness with

deep coma.

seizures

Irregular resp.

Hypoxia

Orthostatic Hypotension

Tachycardia

JAUNDICE, PUL. OEDEMA, RENAL FAILURE- RARE.

Dehydration

Hypoglycemia

Metabolic acidosis

Hyperkalemia

Children > 2 months (non immune ) – symptoms vary widely

Low grade fever to temp of 104 F with headache, drowsiness

Anorexia, nausea, vomiting, diarrhoea

Pallor, cyanosis

Splenomegaly

Hepatomegaly

Anaemia , Thrombocytopenia

Incubation period & stages of malaria

P. falciparum: 9 – 14 days

P. vivax: 12-17 days

P. ovale: 16 – 18 days

P. malariae: 18 – 40 days

Onset – sudden with fever , headache ,

loss of appetite , lassitude , pain in

limbs.

Initially – continuous or remittent fever

Later stages – classically remittent

fever

Clinical pattern in endemic zones

Atypical

Tolerance leading to less parastitemia

Mild symptoms

After sometime – inherited immunity ->( due to continuous heavy exposure

leading to poor immunological defence) –> severe form of disease->Cerebral

malaria Death/ Re-development of tolerance

Chronic malaria with marked HEPATOSPLENOMEGALY in highly endemic

zones.

Relapse & recrudescenceRecrudescence/ re occurrence/ late rx failure – reappearance of asexual

parasites with in 28 days of treatment

Optimising the drug therapy/ change to alt . Regimens wil be the cure.

Recurrence/true relapse - persistence of hypnozoite forms in liver in which

erythrocytic schizogony commences again.

Falciparum malaria – rare relapse

(since erythrocytic schizogony does not lead to exoerythrocytic phase.)

Vivax malaria – frequent relapse

(since erythrocytic schizogony can be started in these plasmodia)

complicationsCerebral malaria

Anemia

Gastrointestinal illness

Algid malaria

Blackwater fever

Renal lesions

Splenic rupture

Hypoglycemia

Hyperpyrexia

Convulsions

Spontaneous bleeding &

coagulopathy

Aspiration pneumonia

Cerebral malaria Most common non-traumatic encephalopathy

Adhering of P. falciparum infected erythrocytes to

brain capillaries causing coma & death.

key events influencing the disease were identified

as:

Pathophysiology :

Sequestration

Haemostasis dysfunction

Systemic inflammation

Neuronal damage

PfEMP-presentation,

platelet activation and

astrocyte dysfunction

It is manifested by coma or confusion.

Cerebral malarial fever d/d:

menigititis , encephalitis , head injury or tetanus

on investigation on examination

CSF is normal. splenomegaly

anaemiaIt is common in severe malaria.

Causes:

Haemolysis of infected & uninfected

erythrocytes.

Dyserythropoiesis./ BM DEPRESSION

Splenomegaly causing erythrocyte

sequestration & hemodilution.

Depletion of folate stores.

Gastrointestinal illness

Marked vomiting in infants

Diarrhoea

Dehydration

Dyselectrolytemia

Dark green or brownish stools tinged with blood

Symptoms relieved on antmalarial therapy

Algid malaria

It is charectorised by pheripheral circulatory failure and shock.

Usually occurs with falciparum inf in non immune children

Circulatory collapse – low BP , hypodermia , rapid thready pulse

Abdominal pain , vomitting , diarrhoea may be seen

Adrenal damage – congested , necrotic , haemorrhagic on post mortem

Blackwater fever Sudden severe hemolysis

Hemoglobinuria

Renal failure

Caused by hypersensitivity to antimalarial

drugs.

Nowadays – rare due to development of

synthetic drugs.

Repeated falciparum infection

Hypersensitivity

Anti erythrocyte antibodies&

Intravascular haemolysis

RBCs destroyed rapidly

Haemoglobinaemia & haemoglobinuria

Hypoglycaemia

It is a frequent complication of falciparum malaria.

It can occur due to various mechanisms:

Failure of hepatic gluconeogenesis.

Increased consumption of glucose by host & parasite.

Treatment with quinine results in stimulation of pancreas to

secrete insulin. The resulting hyperinsulinaemia causes

hypoglycaemia.

jaundice

It occurs due to severe hemolysis

& hepatic involvement.

Rare in children

Clinical manifestation include:

haematemesis or malaena

bleeding gums

epistaxis

petechiae

subconjuctival h’ages

Spontaneous bleeding

&

Disseminated intravascular coagulation

INVESTIGATIONS

Blood Film Examination

Thick and thin blood films (or “smears”) have remained the gold

standard for the diagnosis of malaria. The films are stained and

examined by microscopy.

• Thick blood film -

• detecting malaria:

• a larger volume of blood is examined

• detection of even low levels of parasitaemia

• determining parasite density

• monitoring the response to treatment.

• Romanowski stains(fields, giemsa,)

Thin blood film –

parasite morphology

species of Plasmodium.

Fixed with methanol n giemsa

Appearance of P. falciparum in thin blood films

Ring forms or trophozoites; many red cells infected – some with more than one parasite

Gametocytes (sexual stages); After a blood meal, these forms will develop in the mosquito gut

Other methods of diagnosis of malaria

Quantitative Buffy coat test:-

It involves staining of the centrifuged & compressed red cell layer

with acridine orange & its examination under UV light source.

Fast, easy & more sensitive than thick smear examination, abt

60microlitres of blood from a finger, ear, or heel puncture is

sufficient.

The parasites contain DNA which takes up acridine orange stain,

fluorescing parasites can be observed at the RBC/WBC interface

using standard white light microscope

Rapid diagnostic tests:-

Detects malarial antigens (PfHRP2/PMA/pLDH) from asexual &/or sexual forms of

the parasite.

Detected by colour changes on the antibody coated lines on the strip test such as

optiMAL assay and para sight F test are being increasingly employed.

optiMAL:- immunochromographic test that can be performed with a drop of finger

stick blood,

Detects LDH (parasite glycolytic enzyme) produced by all species of metabolizing

plasmodium parasites

The detection limit of test is >100-200 parasites/ microL for P.falciparum & P.vivax

Positive test indicates presence of viable parasitemia.

Polymerase chain reaction:-

Highly sensitive and specific test for detecting all species of malaria,

particularly in cases of low level parasitemia and mixed infections

10 fold more sensitive than microscopy

Other investigations:-

Complete blood counts

Blood levels of glucose

Bilirubin

Urea

Creatinine

Transaminases

prothrombin time

urine analysis may be done as required.

DIFFERENTIAL DIAGNOSIS

EARLY PHASE :

Typhoid fever

Non icteric

hepatitis

Septicemia

PAROXYSMAL

PHASE :

U.T.I.

Gm. –Ve

Septicemia

Liver abscess

CEREBRAL MALARIA:

Meningitis

Encephalitis

Lead encephalopathy

Heat stroke

GASTROINTESTINAL ILLNESS:

Non specific gastroenteritis

Cholera

E. coli diarrhoea

Abdominal emergencies

ALGID MALARIA:

Shock due to septicaemia

CHRONIC MALARIAL FEVER WITH SPLENOMEGALY:

Tuberculosis

Kala azar

Leukemia

TREATMENT

Uncomplicated P. vivax malaria

CHLOROQUINE:

10mg/kg stat followed by 10mg/kg 24, 5 mg/kg at 48 hrs total 25mg/kg

PRIMAQUINE :

o.25mg/kg 14 days

(relapse prevention)

• Frequent relapse: 0.5-0.75mg/kg primaquine

• No role with quinine/ sp regimen

uncomplicated P. falciparum malaria

No role for chloroquine

ACT THERAPY - RX OF CHOICE.

Artesunate 4mg/kg oral for 3 days

+Sulfodoxine 25mg/kg& pyrimethamine 1.25mg/kg as single dose (or)

artemeether + lumefantrine ( 20mg& 120 mg) pre formulated tablets six tablets tice daily for 3

days according to weight

+

Single dose of primaquine (0.75mg/kg)

Multidrug resistant p. falciparum un compl.(

to CQ & SP) Quinine

10mg/kg orally 3 times a day for 7 days

+

• Tetra cycline (4mg /kg 4 times a day for 7 days) or

• doxycycline ( 3.5mg/kg once a dsay for 7 days) or

• Clindamycin( 20mg/kg /day two divided doses)

CRITERIA FOR SEVERE/COMPLI. MALARIA Acidosis – Base excess < -8 / HCO3 <15 m eq

Parasitemia – low int. areas : > 2%

High stable trans .areas : >5%

Coma : Glassgow coma scale ≤ 8

Hypoglycemia : blood glucose level <2.2

mmol/ L(<40mg%)

Renal dysfunction : UO < 0.5ml/kg/hr.

Pulmonary oedema( radiologially)

Hyperlactatemia: lactate> 5 m mol/li

Haemoglobinuria & Hb<5g.dl/ pcv<15%

CLINICAL:

Impaired conciousness/coma

Prostration

Failure to feed

Multiple convulsions(>2/24hrs)

Acidotic breathing

Circulatory collapse(SBP <50mm )

Clinical jaundice/ other otrgan dysfunction

Abnormal spon. bleeding

Complicated / severe malaria QUININE:

20mg/kg of quinine salt in 10 ml of dns/ isotonic sol. Over 4 hrs f/w

10mg/ kg over 2 hrs repeated 8th hrly til he takes orally then orally for 7 days.

(+) single dose of primaquine

ARTESUNATE:

2.4 mg/kg iv stat then 12 & 24hrs FOLLOWED by oral combination with

artemeether + lumefantrine for 7 days.

Supportive therapiesAntibiotics:- tetracycline, doxycycline etc..,

Anticonvulsants:-

should be administered for seizures lasting more than 5mins,

benzodiazepines-mostly used,

other anticonvulsants-paraldehyde, phenytoin, phenobarbitone, fosphenytoin, etc,

Blood transfusions is life saving in severe malarial anemia

Exchange transfusions has thought to benefit patients with high parasite count

rationale is to remove parasite burden,( >20%)

to reduce antigen load,

to remove parasite derived toxins and metabolites and

to correct anemia.

Dialysis:- indicated in case of acute renal failure due to severe falciparum malaria,

Rapidly raise of creatinine level-most sensitive indicator.

Inotropic support:- shock- algid malaria,

Dopamine is used

Send blood culture and start on iv antibiotics.

Hypoglycemia:-

any blood sugar <40mg/dL should be treated with 5ml/kg of 10% dextrose IV

Raised intracranial pressure:- mannitol

Ventilation:-

Prevention