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.
Case Report
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.
Discussion
ARDS is an uncommon complication in malaria
but carries a high mortality rate [4]. There is no precise data
regarding the prevalence of ARDS during malaria infection;
however, it is predicted nearly 20-30% of malaria patients
admitted to ICU develop ARDS [5]. Proposed mechanism of
development of ARDS is pulmonary vasculature dysfunction
secondary to liberation of inflammatory mediators which increase
vascular permeability, and parasitized RBCs’ sequestration cause
injury. Clinically, patients developing sudden onset tachypnea
and dyspnea. Life threatening hypoxemia may develop within a few
hours. Two of our patients developed ARDS, one died and other
required mechanical ventilation.
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.
Thus, we had a family of three children, all
with falciparum malaria with three unusual complications
occurring in the same family.
Contributors: All authors contributed to
the case report, drafting and approval.
Funding: None; Competing interests:
None stated.
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