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MALARIA

Nainesh Parikh
Paediatrician, Surat.

Malaria is a protozoan disease transmitted by the bite of infected female anopheles mosquitoes. It is the most important parasitic disease of human being affecting 5% of the world population at a given time. 200 million cases of malaria occur every year with world wide mortality rate of about over 1 million per year. The great antiquity of malaria infection is confirmed by the fact that well over 100 species of plasmodia similar to those of man are found in a wide range of vertebrates from reptiles or birds to higher apes. None of these plasmodia can be transmitted by human beings except for those found in some monkeys.

LIFE CYCLE AND MORPHOLOGY

Let us recapitulate the terminologies with clinical importance.

Sporogony - exogenous sexual phase with multiplication in certain Anopheles mosquitoes.

Schizogony - multiplication in the vertebrate host.

Erythrocytic Schizogony - The development in the parenchymal cells of the liver, also known as the tissue stage.

In the tissue stage, one should distinguish between the primary or Pre-erythrocytic Schizogony which follows the development of the sporozoite and the delayed Exo-erythrocytic Schizogony which is related to relapses.

Out of the four species of plasmodia found in human beings, Viz. P. vivax, P. falciparum, P. malaria and P. ovale, first two accounts for around 95% of total infections.

P. vivax and P. ovale have persistent hepatic phase and trophozoites in hepatocytes may remain dormant for considerable period and give rise to relapses of malaria for about 2 to 3 years. P. falciparum and P. malaria do not have persistent hepatic phase and they do not have true relapse; recrudesce with this plasmodia is related to subclinical therapy and ineffective immune host responses.

Morbidity as well as mortality is less with P. vivax as number of parasitized RBCs with latter infection rarely exceeds 1%. The reason being.

1. Less initial hepatic merozoites load (< 10,000).

2. Invasion of younger RBCs only. With P. falciparum, initial merozoites load exceeds (> 40,000). Can invade younger as well as older RBCs.

3. Due to formation of knobs and increase stickiness of infected RBCs and occurrence of erythrocytic schizogony in capillaries of internal organs (visceral tide), parasite density often exceeds 10%. Levels of 30% to 60% have been observed in fatal cases.

THE CLINICAL COURSE

Sporogony (development in mosquitoes) averages to 10 days and incubation period (between mosquito bite and the presence of parasite in the blood) varies with the species; with P. falciparum it is 10-13 days, with P. vivax and P. ovale 12-16 days and with P. malaria 27-37 days. Clinical manifestation does not appear until enough erythrocytic cycles have occurred to produce the amount of parasitic material, pigment and red cell debris to induce febrile or other reactions.

Classically, the duration of erythrocytic cyclewhich is 48 hrs for P. falciparum, P. vivax and P. ovale malaria and 72 hrs for P. malariae responsible for tertian and quarton fever characteristic respectively. With development of distinct broods of single species, this character may be lost.

In case of mixed infections, P. falciparum overshadows, P. vivax and P. vivax overshadows P. malariae. Only when sufficient immunity is developed to the dominant strain does the other begin to produce clinical manifestation.

In non immune infants and children who contract an acute primary attack manifest clinically with restlessness or becomes drowsy, refuses food, unusual crying and disturbances of sleep. Fever may be absent or increase gradually for 1-2 days, as the onset may be sudden with temperature up to 40.6 degree F (105 degree F) or higher, with or without prodromal chill. After varying periods of time, the temperature falls to normal or below and sweating occurs. The febrile paroxysm may last for 2-12 hrs; its characteristic pattern is usually obscured in children less than 5 years of age. If convulsions occur, they abate when the fever falls. As the temperature rises, thirst become more marked which in breast fed infants is displayed by frequent attempts to suck the breast, but soon this is abandoned due to nausea. Vomiting is often marked.

Older children often complain of headache, nausea, generalised aching particularly of the back, and occasionally pain in abdomen where the spleen has swollen or due to enlarged tender liver. In the primary attack of non immune children, many days may pass before clinical splenomegaly. Splenomegaly develops earlier in vivax, less rapidly in falciparum and very slowly in quartan malaria.

In infants in highly endemic area, manifestation are more variable due to inherited immunity. There may be slight restlessness, lack of appetite, sweating, anaemia and occasional spikes of temperature. As inherited immunity declines, the clinical attacks become more severe.

In children in highly endemic area without any protection and continuous exposure to the infection, many of them die either of cerebral malaria or of an acute general infection. Some, after several successive attacks, achieve a relative tolerance to the infection and in these cases, the clinical picture may be mild fever, fretfulness, tiredness, cough, diarrhoea etc. Many have hepatosplenomegaly and +ve blood for MP without any other signs of the disease other than a degree of anaemia.

Herpetic lesion of the mouth are not uncommon. The RBC count and Hb level decrease with variable leucopenia and monocytosis.

In falciparum malaria, fever is less characteristic and may be continuous and over shadowed by other systemic manifestations.

Cerebral Malaria has gradual or sudden onset. Occurs in 2% of non-immune subjects, less common in malnourished patients.

* Neurological signs of UMN type and brain stem disturbances.

* Convulsions common even before the onset of coma.

* CSF pressure increase otherwise NAD.

* Leucocytosis not unusual.

* Mortality about 20%.

* Neurologic sequaelae about 18%.

Cerebral malaria is a form of disseminated vasculomyelopathy a hyperergic response of the CNS where ‘T’ helper, IgM and complement are playing important role.

Algid Malaria - a rare condition resembling surgical shock accompanied by vomiting and diarrhoea - possible related to adrenal involvement.

Gastro intestinal symptoms may imitate cholera or dysentery.

RENAL INVOLVEMENT

Slight proteinuria with granular cast common, severe involvement with clinical evidence of acute renal shut-down with uraemia is rare.

The Nephrotic Syndrome is seen with P. malariae infection in malnourished children in endemic area - poor prognosis not responding to steroids, antimalarial and azothiaprine.

Hypoglycaemia is common whereas pneumonia like manifestation, acute pulmonary oedema, neuritis, hypotension are rare.

Black Water Fever - Rare complication of P. falciparum infection is associated with haemoglobinuria due to severe and sudden intravascular haemolysis - may lead to anuria and death from uraemia.

Symptomatology is less severe with sickle cell anaemia. G6PD deficiency as far as P. falciparum is concerned. Relations with other Haemoglobinopathies like HbE/HBC is not certain. Hbf offers some degree of resistance.

Tropical Splenomegaly Syndrome may constitute abnormal immune response in malnourished children in endemic areas. Hepatosplenomegaly not responding well to antimalarials is accompanied by lymphocytic infiltration, elevated fluorescent antibody titre with without scanty parasitaemia.

Anaemia : Severe anaemia may develop with recurrent attacks or severe parasitaemia - may be a presenting feature.

Fig 1
Fig 1: Diagram of action of antimalarial compounds in relation to the stage of development of the malaria parasite in Anopheles and in the human host.

It results from haemolysis, shortened survival of unparasitised RBCs, hypersplenism and RBC sequestration, immune RBC destruction, Dyserythropoiesis and marrow suppression, folate deficiency due to compensatory erythroid hyperplasia and due to antifolate antimalarials.

Apart from specific chemotherapy, supportive treatment should include treatment for hyperpyrexia fluid and electrlyte balance once acute phase is over consider Vit Bl and Iron therapy for replacement.

The Criteria for Referral to Hospital

1. Difficulty in talking, sitting up, standing or walking without any other obvious cause.

2. Unexplained oliguria, anuria or passage of dark coloured urine.

3. A change of behaviour, confusion or drowsiness;

4. Altered consciousness or coma;

5. Convulsion (s);

6. Jaundice and/or severe anaemia;

7. Circulatory collapse or shock;

8. Difficulty in breathing.

TREATMENT

It falls in 4 categories

1. Specific chemotherapy for acute attacks,

2. Specific chemotherapy for prophylaxis,

3. Specific chemotherapy to destroy or sterilise gametocyte for protection of community,

4. Supportive treatment and management of complications.

Care of patients with severe falciparum malaria (Mainly after White and Warrell, 1983 - Essential Malariology)
Initial handling
Dealing with severe symptoms
      
Weight the patient Check airway
Coma (cerebral malaria)
Maintain airways, nurse on side,exclude meningitis, avoid corticoster- oids, heparin and adrenaline
Make rapid clinical assessment*
         
        
Take blood film for examination and collect specimens for laboratory tests
Hyperpyrexia
Tepid sponging, fanning, dipyrone injection
Start intravenous infusion ofchloroquine or quinine**
Convulsions
Maintain airway, Diazepam orparaldehyde injection
Assess state of hydration
Severe anaemia(PCV less than 20%)
Transfuse fresh whole blood
Check urine output and specific gravity, Catheter if necessary. Decide on fluid requirement
Acute pulmonary oedema
Prop up in bed, give oxygen, stop iv fluid, consider blood letting
If rectal temperature over 39.5oC start tepid sponging and fanning
Acute renal failure
Exclude dehydration, strict fluid balance, peritoneal dialysis
Perform lumbar puncture to exclude meningitis
Coagulopathy withspontaneous bleeding
Fresh blood transfusionVitamin K injection
Consider additional drugs : anti convulsants, antibiotics, etc.
Lactic acidosis
Exclude or treat hypoglycaemia,hypovolaemia and Gram-negativesepticaemia
Assess need for blood transfusion
HypoglycaemiaGram-negativesepticaemia
Give oxygen Give 50% dextrose by injection, followed by 5-10% infusion Parenteral antimicrobials correct haemodynamic disturbance
Aspiration pneumonia Parenteral antimicrobials, oxygen, physiotherapy
*Depending on facilities:haematocrit, serum electrolytes, urea, creatinine, glucose (rapid test using ‘Stir’ test), blood culture, blood grouping. **In areas with chloroquine resistance quinine should be used.


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