Received: June 7, 2011;
Initial review: June 29, 2011;
Accepted: August 21, 2011.
 

Malaria due to Plasmodium falciparum is responsible for significant morbidity and mortality amongst nonimmune patients. ARDS may develop as a severe complication of malaria and has a high mortality rate (80%) [1,2]. Hemophagocytosis characterized by proliferation of macrophages that exhibit phagocytosis of haemopoeitic elements is commonly associated with viral infections but rarely with malaria [3]. We describe 3 patients with complicated falciparum malaria from a single family.

The first child was a 2 year old male, who developed fever and vomiting since 2 days followed by sudden onset breathlessness. Peripheral smear was positive for P.falciparum with a parasite index of 80%. The chest X-ray showed bilateral fluffy infiltrates and the child was unable to maintain saturation even with 60% FiO2. The child was intubated and put on ventilator but died within a few hours due to respiratory failure. Following the death of the first child, the family was referred to us for further management.

The second child was a 10 year old girl brought with complaints of fever with chills and vomiting of 7 days, respiratory distress, generalized edema and jaundice of 3 days. Peripheral smear was positive for Plasmodium falciparum. Vitals were suggestive of hypotensive shock, there was decreased air entry bilaterally and bilateral crepitations were present; along with hepatos-penomegaly. Investigations revealed 7.2g/dL hemoglobin, platelet-35000 mm3, total bilirubin 8.8 mg/dL (direct 7.2 mg/dL). Child was not maintaining saturation with FiO2 0f 60% and ABG was pH-7.23, pCO2 67.6, pO2 64.4, HCO3 _ 27.3, SO2 88%. Chest roentgenogram revealed bilateral fluffy infiltrates. With bilateral pulmonary infiltrates, inability to maintain saturations with a very high FiO2 and normal cardiac function on admission, a diagnosis of ARDS was made. The child was intubated and ventilated on volume control mode with low tidal volumes and high PEEP. Intravenous artesunate was continued and circulatory support was given with dopamine. In view of persistent tachycardia, a 2D-echocardiography was done, which was suggestive of myocardial dysfunction with serial ejection fractions of 45%, 35% and 25%, which gradually improved to 55% with fluid restriction and ACE inhibitors. As the child improved, settings were reduced and child was extubated. As soon as the child stabilized, she was administered a combination of artmether and halofantrine orally for 3 days.

The third child was a 12 year old girl brought with complaints of weakness and fatiguability of 6 days and fever of 3 days. The peripheral smear was positive for P. falciparum. Pallor, icterus and hepatosplenomegaly were present. There was no respiratory distress and the chest radiograph was normal. On admission her hemoglobin was 7.4 g/dL, platelet count was 46000mm3, and total bilirubin was 4 mg/dL. She was started on intravenous artesunate and a packed cell transfusion was given. She improved over a period of 4 days after which there was a sudden drop of hemoglobin and platelet count. Fever spikes reappeared and were present every day. Blood culture was negative and ultrasound of the abdomen was normal. She was administered artemether plus halofantrine for 3 days followed by mefloquine since her fever persisted and her hemoglobin kept dropping. Bone marrow aspiration was suggestive of hemophagocytosis. Serum ferritin was 2136 ng/dL, serum triglyceride levels were 484 mg/dL and G6PD was normal. Investigations for other etiologies of hemophagocytosis such as EBV and HIV were negative. Child improved spontaneously with supportive treatment and was discharged with normal hemoglobin and platelet counts.

Hemophagocytosis is associated with malignant, genetic, and autoimmune diseases. Viral infections as a cause are mainly limited to EBV infection. Malaria is a very rare cause and the mechanism of hemophagocytosis in malaria is unknown [3]. High levels of cytokines have been reported in malaria patients with hemophagocytosis which resolves soon after successful treatment of malaria [6-9]. Prolonged hemophagocytosis, has not been reported in patients with falciparum malaria. Once the cytokine cascade is triggered, hemophagocytosis may continue independent of the presence of the malarial parasite.

9. Zvulunov A, Tamary H, Gal N. Pancytopenia resulting from hemophagocytosis in malaria. Pediatr Infect Dis J. 2002;21:1086-8.