Introduction

Malaria, particularly pernicious malaria (falciparum malaria) poses a diagnostic dilemma at early stage as the disease can mimic many other conditions₁. Even after proper diagnosis, it can pose problem due to associated complications which unless anticipated earlier or diagnosed at proper stage can cause death.

The aim of WHO's Roll Back Malaria programme has been early diagnosis and prompt treatment to reduce the mortality to a great extent. There is a great need for early diagnosis and recognition of the complications of malaria at local centre, and if warranted, to be sent to a higher centre for management of the complications at an early stage to avoid mortality due to complications.

There are certain difficulties in the diagnosis and management of malaria. We like to make a brief review of these issues.

Difficulty In The Diagnosis And Treatment Of Malaria

Problems in the management of malaria

In many dedicated and advanced centres, it has been seen that despite institution of proper therapy for severe and complicate malaria, the death rates are high as many of these patients are brought to hospital quite late in irreversible state. In cerebral malaria, if acute renal failure sets in, the mortality is approximately 40% and in the presence of acute lung injury, it reaches almost 80 to 90% even in most advanced centres ¹ .

Prevention of ARDS by prophylactic artificial respiratory support is still controversial.₁₀ .

At times, despite early diagnosis and institution of prompt therapy, patients proceed to have MODS with disastrous outcome. Most of the complications can be anticipated, viz. anaemia in presence of haemolysis, ARDS in presence of ARF etc. But there is no marker or scale to predict the complications. The estimation of TNF, thromboxane B orIL-6 may be raised in the severely ill patients; but in most centres these facilities are not available, and if available it cannot be repeated frequently due to prohibitive cost factor.

Considering the above facts, it can be said that the therapeutic challenge can be met with institution of proper agent at proper dose, proper route of administration, rate of infusion, duration of therapy, correction of electrolytes, calories, antibiotics and supportive therapy as indicated. Anticipation, close monitoring with recognition of the complications at an early stage will be of immense value.

There are certain differences in the presentation of severe malaria in the children ¹,²,¹⁰,₁₂

Figure 1

Table-1 :Differences in adult and children

Clinical Features Of Severe Malaria In Pregnant Women

Pregnant women are more prone to develop multiple complications of malaria. There are several factors that make pregnant women more vulnerable to malaria and its complications including mortality⁷,⁸, ₁₃,₁₄:

Malaria parasites are preferentially sequestrated in the placenta,

Anaemia : In India, women have a lower haematocrit because of dietary habits, frequent pregnancies, folate deficiency etc. Malaria increases the incidence of anemia. Mild anaemia doesn't influence the mortality but moderate or severe anaemia is associated with increased morbidity & mortality in pregnant women. It is associated with an increased risk of perinatal mortality, maternal morbidity, PPH and pulmonary oedema.

Cerebral malaria- Although incidence of cerebral malaria is same as that of non-pregnant women, however once they develop cerebral malaria, the mortality is three times higher in pregnant women.

Hypoglycemia - This may be present in pregnant women at the time of admission or may develop after quinine infusion. Commonly it is asymptomatic. Abnormal behaviour, sweating & sudden loss of consciousness are the usual manifestations. It may be missed if blood glucose estimation is not done. It should be treated with intravenous 50% glucose 50 ml or 25% dextrose 100ml; followed by IV infusion of 10% dextrose. Continue monitoring blood glucose levels is desirable. If glucose infusions are not available, glucose solutions can be given through mouth or nasogastric tube. It may be associated with lactic acidosis, a dreaded accompaniment with mortality upto 70%. Women in second or third trimester of pregnancy may develop hypoglycemia even with low parasitemia.

Pulmonary oedema : This is a serious complication. It may be present on admission, may develop unexpectedly several days later or may develop immediately after childbirth.

Premature labour: In non immunised females, foetal distress and premature labour is common and may occur at the height of fever. Foetal prognosis with premature labour is invariably poor. In endemic areas, pregnant women tolerate heavy parasitemia better than the pregnant women from non endemic areas.

Septicaemia: Pregnancy increases susceptibility to pneumococcal infections and may lead to pneumonia or meningitis. Septicaemia following bladder catheterisation is common in pregnant women with heavy parasitemia ¹ .

Safety Of Antimalarials During Pregnancy

Management Of Various Complications In Severe Malaria

Cerebral malaria is the most important complication of severe malaria. These patients need close monitoring and meticulous management. This can lead to death if left untreated, and 15 to 30% die even with treatment. The patrasitemia may clear, but still the patient can die. Hence there is a need to understand the pathophysiology of cerebral malaria. The prognosis becomes worse in the presence of MODS. Prophylactic use of anticonvulsants is debatable. Use of steroids in this situation has not been without side effects. ₁₅

Severe anaemia in malaria is due to

Anaemia due to acute malaria is usually normochromic normocytic in nature. The presence of microcytic hypochromic anaemia indicates either iron deficiency, nutritional anaemia or hemoglobinopathies; which are not uncommon in tropical countries. The preexisting anaemia due to nutritional deficiency or haemogloboinopathy may be aggravated in malaria. Severe anaemia (Haemoglobin below 5 g/dl) or a rate of fall of more than 2g in 24 hrs may induce cerebral anoxia and cardiac failure. Patients with heavy parasitemia, pregnancy or delivery, and children are vulnerable to develop severe anemia.

Indications of blood transfusion in severe malaria

The presence of severe or rapidly progressing anaemia in malaria needs prompt treatment, as it is associated with poor prognosis.

Blood transfusion of whole blood or packed cell is indicated when haemoglobin is below 5 g/dl; a rate of fall of > 2g in 24 hrs; haematocrit < 20 or in patients with features of cerebral anaoxia.

Volume overload must be avoided by giving only packed cells. Injection furosemide 20-to 40 mg should be administered prior to blood transfusion when impending cardiac failure is suspected or already present.

Jaundice as such is a not a grave complication, unless very severe. It is a non fatal complication when occurs alone. It however accompanies other severe complications like cerebral malaria, anaemia, renal failure etc. Usually jaundice is mild to moderate; infrequently the serum bilirubin may go beyond 20 mg %. It is predominantly unconjuagated hyperbilirubinemia, occasionally associated with marginally raised liver enzymes. Liver cell failure due to malaria is relatively rare. ₂₀

No specific management is needed to reduce hyperbilirubinemia. However when associated with very high bilirubin levels ( > 28 mg/dl) in children, exchange transfusion is needed. Severe haemolysis may lead to consequent anaemia, which may need blood transfusion, if severe. ₂₁

Dose modification in severe malaria in the presence of jaundice?

Renal failure increases the mortality three fold. The institution of dialysis is needed at an early stage; and not when the acute renal failure is established or when ARDS has set in. Biochemical parameters need to be checked at least 12 hourly. Urinary estimation of sodium (Na) is required to establish ATN.

Blackwater fever a rare complication . It is suspected when patient passes of black or cola colored urine resulting from massive haemolysis. Urine examination reveals haemoglobinuria without RBC. It may be associated with acute renal failure or DIC.

The management of this rare complication is maintenance of good hydration, blood transfusion, if associated with severe anemia or thrombocytopenia. If associated with renal failure, consider for haemodialysis or peritoneal dialysis. Quinine should not be discontinued or reduced in the first 48 hours of therapy.

Patients with G6PD deficiency are prone to this complication when on quinine therapy.

The newer antimalarials are quite effective and useful in both uncomplicated and complicated malaria.₁₆,₁₇ . However, it should be used with caution, as these have neurological and cardiovascular side effects ₁₈,₁₉ . It may have deleterious effect in pregnancy and infancy.

Severe P. vivax malaria usually does not cause much problem other than haemolysis and anaemia. But acute complications include splenic rupture and at times hepatic dysfunction. Though cerebral malaria has been described in P vivax malaria, the authenticity of these reports is questionable. Probably mixed infections with P falciparum were missed.

Figure 2

Table-2: Check list for management in severe malaria

Figure 3

Table-3: Conditions mimicking malaria 1,2