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UNUSUAL PRESENTATION OF MALARIA AND ITS MANAGEMENT

Jayendra Kapadia

Family Physician, Surat (Gujarat).

INTRODUCTION

Malaria continues to be a major killer of mankind and the most important parasitic disease in the world. Approximately one million die each year of malaria round the globe. More than half to the world’s population is under the shadow of the disease. Mortality in malaria directly related to promptness of diagnosis and institutions of early specific treatment.

Usual Clinical Presentation in Malaria also Known as Characteristic Clinical Syndrome

Incubation Period :

P. Vivax 18-40 Days

P. Falciparum 9-14 days

1. Cold stage onset occurs with

• Lassitude
• Headache often severe
• Nausea followed by vomiting
• Chilly sensations followed by rigors.
• Skin feels cool; later it becomes hot.
• Parasite is usually demonstrable in the blood.
• Pulse rapid and may be weak.

2. Hot Stage
-Patient feels hot,
-Skin is hot and dry to the touch,
-Headache is intense but nausea diminishes.
-Pulse is full and respiration rapid.

3. Sweating stage
-Profuse sweating
-Body temperature drops rapidly to normal.
-Skin is cool and moist
-Pulse rate becomes slower
-Patient feels relieved and often falls to asleep.

4. This is followed by afebrile interval of 48-78 hours hence typical malarial fever is usually observed on alternate days.

5. Latent period : In this period the patient is usually free of symptoms but in P. vivax hypnozoites persist in the liver and in P. Falciparum infection, following inadequate treatment parasites persist in the blood.

Recrudescences

It is a renewed manifestation of infection within days or weeks.

It is a result of continued survival or presence in the blood of asexual forms of parasite because of no treatment or inadequate treatment.

Relapses

It is the result from maturation of hypnozoites in the liver with liberation of merozoites in to the blood.

It varies according to the species and even according to the group or strain.

It can occur even three years after the primary infection.

Peripheral smears

Microscopic diagnosis finding of malarial parasite in the blood and their identification is essential for the confirmation of the diagnosis of malaria.

Thick film is reliable in searching for parasite.

Thin is valuable for confirming the species of parasite present in the blood.

The result of parasitological examination often provide better measure of severity of disease than the initial clinical examination.

Serological Diagnosis

Demonstration of malaria antibodies in the serum is of limited value in the diagnosis of recent malaria infection. It is of no value in acute malaria infection since they become positive two weeks or more after the primary infection.

Remember : Chance of detecting parasite is more when blood slide taken soon after chills than during febrile period. Clinical picture of malaria varies greatly, particularly when caused by P. Falciparum.

Fig 1
Fig 1

Pattern of fever

May be irregular or continuous.

When more than two breeds of parasites are involved daily paroxysms may be observed.

The pattern may be varied by use of antipyretics and chemoprophylaxis.

UNUSUAL PRESENTATION OF MALARIA

Simple malaria

Unusual malaria means we are tempted to diagnose something else than the malaria, it is a matter of experience and when you come across management of large number of cases of malaria one can recognize them earlier.

Uncomplicated malaria in adult and older patients may present as a following symptoms

- bodyache, headache and no fever
- throat pain, bodyache and mild fever
- severe headache
- diarrhoea, jaundice, urticaria,
- pain in epigastrium

Uncomplicated malaria in children may present as following symptoms:

- Vomiting, cough, Urticaria
- No rhinitis and clear throat
- Child becomes irritable, crying and not looking healthy.

Unusual presentation of malaria may be detected when, following information available for the clinical judgement

1. Stage of the disease

2. Endemicity

3.
Role of immunity in manifestations

4. Pathogenesis of complicated malaria

5. Type of organisms

6. Age of the patients

Causes of fever when malaria is likely to be confused are:

- URTI

- UTI

- Influenza

- Dengue

- Typhoid and paratyphoid fever

- Tuberculosis

- Amoebic liver abscess

- Brain abscess, endocarditis

When malaria is associated with Jaundice

- Viral Hepatitis

- Leptospirosis

- Cholangiohepatitis

- The most important step in diagnosis to think of the possibility that malaria may be the cause of patient’s illness.

Anaemia

- Anaemia is an inevitable consequence of malaria, because of the great proportion of erythrocytes which became parasitized in malarial infection.

- Release of more malaria antigens result into marked immunohaemolytic anaemia.

- Growth of parasite within erythrocyte leads to consistent drop in the haematocrit level which leads to shortening of the life span of RBC even in the absence of overt infection.

- It is more common and more marked in children than in adults.

- Malaria may be the cause of sudden and catastrophic fall in Hb% in pregnant women.

Remember : In any illness with or without fever sudden or persistent fall in Hb%, think of malaria first.

Fig 2
Fig 2

Jaundice

Jaundice with palpable liver and spleen is common finding in falciparum malaria.

Degree of icterus correlates well with the amount of haemolysis.

Clinical signs of hepatic failure is rarely seen.

Raised serum bilirubin, to SGPT, SGOT level in the liverprofile study is also observed in malaria.

Bile pigment in the urine usually increased during the malaria.

Remember : Fever in the presence of jaundice suggest malaria rather than viral hepatitis in which the fever has usually resolved by the time jaundice develops. Gastro intestinal involvement

Vomiting is a common feature of severe malaria particularly in children.

Diarrhoea in case of malaria may be seen as a result from necrosis and damage to the intestinal wall.

Sweating, vomiting and diarrhoea may combine to produce dehydration.

Remember : Any GIT symptoms can be caused by malaria, but a blood film to exclude malaria should always be taken.

Fig 3
Fig 3

SEVERE COMPLICATED MALARIA

Cerebral Malaria

Any manifestation of cerebral dysfunction in a patient with malaria is evident of cerebral malaria.

Occurs particularly when nonimmune persons have remained untreated for 3 to 7 days after the development of primary fever.

Patient’s condition may deteriorate rapidly with increasing headache and drowsiness which later merge into confusion and coma.

Inspite of treatment given the condition may deteriorate further into deep coma.

When the coma is light, patient may be able to talk and answer questions, although later patient will have no recollection of having done so.

In severe infections, delirium and coma may develop suddenly and may even occur early during the course of the febrile illness.

Patients with cerebral malaria may present with convulsions, hallucinations and a state of agitation.

Hyperpyrexia is not unusual, focal neurological deficits and signs of meningeal irritation are rare. CSF is usually normal on examination.

Acute renal failure

Malaria with associated dehydration and hypotension may lead to oliguria, anuria, and ultimately acute renal failure.

Intravascular haemolysis and secondary infection may further aggravate the situation.

A reduction in urine output 400 ml or less per day indicate renal failure.

Raised blood urea and serum creatinine.

If effective treatment not employed may reach high levels.

Remember : A careful watch on a urinary out put and raised blood urea and serum creatinine is a good clue in the early diagnosis of ARF due to malaria.

PULMONARY MANIFESTATIONS IN MALARIA

Malaria may present with signs and symptoms suggestive of respiratory disease like pneumonia, bronchial asthma, bronchitis and more grave ARDS.

Most commonest presentation are fever with or without chills, cough with expectoration or dry cough, chest pain and dyspnea. Haemoptysis is uncommon.

Hepatomegaly and splenomegaly are for less clinical observation. Drop in haematocrit level, but no specific abnormality trends seen in total or differential leucocyte count.

Peripheral blood film examination reveals the type of malaria.

If not treated in time ARDS is the most common complication in pulmonary manifestations and where management is extremely difficult and prognosis is also poor.

Pulmonary Oedema

This could be a grave and fatal complication due to P. Falciparum Malaria.

The pathogenesis of this condition remains unclear.

The first indication of pulmonary oedema is cough usually dry, difficulty in breathing, tightness in the chest.

Dyspnoea may increase rapidly in severity.

The respiratory rate goes up - crepitation may appear

Haemoptysis is usually absent.

Serious signs such as frothing from the mouth, cyanosis, convulsions, deterioration of the level of consciousness may lead to grave complication like ARDS.

Remember : Incidence of respiratory manifestations in malaria are far more than described in the literature. Suspicion of malaria should be kept and peripheral smear examination help in decreasing morbidity and mortality.

Hypoglycaemia

It is a quite frequent observation in malaria.

It may contribute to the neurological disturbances.

In pregnant woman suffering from malaria hypoglycaemia appears to be a common clinical observation.

It may present during early convalescence or patient receiving 5% dextrose during treatment, not because of liver glycogen depletion or starvation but due to glucose consumption by the malaria, and stimulation of insulin secretion by quinine.

Remember : Any patient with symptoms of hypoglycaemia may be misdiagnosed as a case of cerebral malaria.

Glucometer is a more powerful tool in visit bag or in a clinic than stethoscope.

CIRCULATORY COLLAPSE

Marked hypotension were systolic BP less than 80 mm of Hg in supine position.

Cold clammy, cyanotic skin

Constricted peripheral vessels may occur in severe falciparum malaria.

Circulatory collapse may occur suddenly if it is associated with severe dehydration, gram negative septicaemia and massive GI haemorrhage.

This grave emergency in past was also known as ‘Algid Malaria’.

Urticaria as an allergic manifestation

Sinusitis,

Occasionally retinal and sub conjunctival haemorrhage may also present as an unusual presentation in malaria.

Common errors in diagnosis

Failure to do a malarial blood film (Thick and thin smear)

Failure to take a detail history e.g. travel history, previous malarial infection

Misjudgement of severity of the disease

False parasitological diagnosis

Missed hypoglycaemia

Missed diagnosis e.g. influenza, viral hepatitis, typhoid fever

Failure to perform fundoscopic examination to rule out presence of retinal haemorrhage.

Fig 7
Fig 7

 

MANAGEMENT OF UNUSUAL PRESENTATION OF MALARIA

General Principle

If parasitiological confirmation of malaria is not readily available, a blood film should be made and the treatment started on the basis of clinical presentation.

In severe malaria, anti malarial therapy must be given Intravenously or Intramuscularly, oral treatment should be substituted as early as possible.

Doses must be calculated in on a mg/kg of body weight. It is important to weigh the patient, this is particularly important for children.

Do not confuse the doses of salt and base. Quinine doses are prescribed as salt (10 mg of salt 8.3 mg of base). Chloroquine and mefloquine are prescribed as a base.

Good nursing care is vital.

Maintain adequate fluid balance, to avoid overhydration or underhydration.

Initial check of blood glucose is vital.

Frequent monitoring for hypoglycaemia are important.

Frequent monitoring of the therapeutic response is important.

Anaemia

Keep haemoglobin level above 7 gm per cent.

If required a slow transfusion of 5 ml-10 ml/kg pcv or 10-20 ml/kg whole blood may be given.

In children with severe anaemia with associated tachycardia inj. frusemide (1-2 mg/kg) may be given.

Administer appropriate anti malarial therapy with proper dosage calculation.

Supplement iron and folic acid during convalescent period is helpful. Pulmonary oedema

It may be caused by fluid overload, so careful fluid management is vital.

Along with strict control of fluid intake propped patient at an angle of 45o

Maintain CVP

Give high concentration of oxygen by any convenient method.

IV frusemide (40-120 mg) should be tried first, if CVP does not fall use other vasodilators in well equipped ICU

If required fluid can be removed by dialysis.

For a family physician it is of great importance to think of pulmonary oedema and refer patient to a well equipped hospital.

HYPOGLYCAEMIA

Prompt IV glucose is essential and life saving.

Pregnant woman with malaria closely monitor both, hypoglycaemia and foetal distress.

50% glucose (up to 1.0 ml/kg) followed by IV infusion of 10-20% dextrose should be given.

The possible recurrence of hypoglycaemia, when patient on IV quinine should be kept in mind.

Hyper pyrexia and associated management

Cooling by fanning, tepid lukewarm water sponging

Use appropriate antipyretic,

Pneumonia, urinary tract infection, typhoid fever should be treated with appropriate antibiotics

Be careful in using nephrotoxic drugs such as sulphonamides, aminoglycosides and tetracycline if there is renal insufficiency or hepatotoxic antibiotic in case of complicated jaundice or altered LFT.

Acute renal failure

It is because of haemoglobinaemia may lead to oliguria and ARF.

Continue appropriate anti malarial treatment

Maintain haematocrit level above 20% or 7 gm

Correct fluid and electrolyte deficit

Treatment of hypotension and shock is of vital importance.

If oliguria (below 400 ml/24 hrs.) is present preventive measure for the development of ARF should be instituted.

Patient with G6PD deficiency should be screened carefully.

ARF demands skillful management hence refer patient to a well equipped centre, because these patient may require peritoneal dialysis.

DRUG THERAPY

Quinine

Still it is a drug of choice for the treatment for severe and complicated malaria.

It should always be given by rate controlled infusion never by bolus IV injection.

Switch on to oral administration as early as possible.

Common side effect are tinnitus, hearing loss, nausea, uneasiness, restlessness and blurring of vision.

Serious CVS and neurological toxicity is rare.

Hypoglycaemia is the most frequent adverse side effect.

IM injection of quinine is not recommended.

In suspected quinine poisoning activated charcoal given orally or by nasogastric tube accelerates elimination.

Dosage Schedule : Dose 10 mg salt/kg Infusion Volume : 10 ml/kg if pt is normally hydrated. 20 ml/kg if pt is dehydraded.

5 ml/kg. if the pt. is overhydrated. Infusion time : 2.5 hours. Infusion interval : 8 hours.

CHLOROQUINE

Chloroquine is still the more widely prescribed drug in the tropics.

It should always be given by slow rate controlled IV infusion, and never by bolus injection.

Oral therapy should be substituted as early as possible.

Side effects include headache, nausea, vomiting, uneasiness, blurred vision, hypotension and pruritus.

Dosage Schedule

Dose 5 mg. base/kg

Infusion Volume : 10 ml/kg Infusion Time 4.6 hours.

Infusion interval 8 hours

IM chloroquine injection may be given as 5 mg base/kg in two divided doses of 2.5 mg/kg in the gluteal region at an interval of one hour and repeated every 12 hours, never to be given in single dose. Avoid in infants and in children.

Oral route

10 mg of base/kg on day -1 as a loading dose followed by 5 mg of base/kg after 6 hours. 6 mg base/kg on day -2 and day -3.

Mefloquine

Chemically related to quinine

It is a long acting schizontocide

It is effective against multidrug resistant parasite

Single oral dose is sufficient to effect cure

Dose 20 mg to 25 mg/kg taken as a single dose

Side effect may include GI upset, dizziness, fatigue, asymptomatic bradycardia and occasionally acute psychosis.

Artemisine (Artesunate)

It is ancient Chinese herbal medicine

Artesunate is a semisynthetic derivative of artemisine.

Dose:

IV 9.6 mg/kg. divided in over 5 days.

IM 2 mg/kg as first dose.

Followed by 1 mg/kg 12 hourly till patient can take oral treatment.

Oral : 10-14 mg/kg given over a period of 4.7 days.

Side effect : GI upset.

Relatively safe drugs

Arteether

It is a arthisinin derivative.

It has a ‘reserve status’ in WHO essential drug, means they should be reserved for multi drug resistant malaria.

So far no significant toxicity or drug resistance to these compound has been reported.

Compliance of patient is excellent.

Cost of therapy is comparable to other second line antimalarial drugs.

Dose : 150 mg deep IM once daily on three consecutive days.

PRESUMPTIVE TREATMENT

(Before the result of the smear is known)

It is given to all fever cases or cases with history of fever during the preceding 15 days immediately after the blood smear is collected and also to fever cases where blood smears are not collected.

Chloroquine base

Day 1

10 mg/kg

600 mg adult

Primaquine

Day 1

0.75 mg/kg

45 mg adult

Chloroquine base

Day 2

10 mg/kg

600 mg adult

Chloroquine base

Day 3

5 mg/kg

300 mg adult

G6 PD deficiency

It is a myth that person with G6PD deficiency are more protected from P. falciparum malaria.

They suffer more frequently from P. vivax malaria.

Intravascular haemolysis may occur in G6PD deficient person, due to action of anti malarial drugs on older erythrocytes.

As a family physician one should be careful of G6PD deficiency in certain ethnic group e.g. Parsi, Khatri, Sindhis

Primaquine can produce massive haemolysis and may cause severe anaemia, and renal failure.

RADICAL TREATMENT

(All microscopically positive cases)

All microscopically positive cases of malaria are to be given radical treatment with Primaquine for its gametocytocidal and anti-relapse properties.

Age-wise dosage of radical treatment

Age in yearsChloroquinePrimaquine Single Dose Single Dose Mg base No. of Tablets

< 1

75

1/2

Nil

Nil

1-4

150

1

7.5

1/2

5-8

300

2

15

1

9-14

450

3

30

2

> 15

600

4

45

3

TAKE HOME MESSAGE

Malaria continues to be major killer of Mankind

Approximately one million die each year of malaria around the globe.

We must take note of changing pattern of malaria.

The malaria prone areas are now the metro cities and urban India.

Newer development of ‘Resistant Malaria’ has to be kept in mind.

Some strains which are sensitive and other strains which are resistant to different type of anti malarial drugs.

Treatment is complicated because of phenomenon of existence of many strains.

Right choice of drug is absolutely important.

Role of a family physician against this menace like "little drop of water make the ocean wide", little things like personal protection and source reduction and get tuned to the final battle against malarial mosquitoes. The future will be ours.

REFERENCES

1. Gilles HM, Warrell DA. Brace Chwatt’s Essential Malariology. Third Edition. Plates: 1, 2, 3, 4, 6, 25 Pg. 44.

2. The Clinical Management of Acute Malaria. WHO regional publications. South East Asia - Series No. 9. Pgs. 19, 27, 37, 46, 47, 50, 51, 54, 68.

3.
Management of severe and complicated malaria practical handbook. HM Gilles WHO Geneva. Pg. 20, 35, 46.

4. A closer look at Malaria’ General Practitioners’ Association Surat Publication. Pg. 67, 68.

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