Congenital severe malaria: Artesunate for successful and safe treatment in neonates: A case report

Case report

A 30-day-old male was admitted with fever, cough, cold and gradually increasing tachypnoea for 3–4 days. Birth and postnatal history were uneventful. At admission, his general condition was poor; he was febrile (temperature of 39.2°C) with a tachycardia of 162 beats/min, tachypnoea of 78 breaths/min; and with subcostal and intercostal retractions and nasal flaring. On auscultation, there were bilateral coarse crepitations and ronchi. He had hepatosplenomegaly (liver 4 cm, and spleen 4 cm below the costal margins). He was irritable but with normal tone and reflexes and no focal deficit. His investigations revealed an anaemia (Hb 86 gm/l, leucocytosis 10 × 10⁹/l (polymorphs 43%, lymphocytes 53%) and platelets 260 × 10⁹/l, C-Reactive protein elevated (21.8 mg/dl).

He was immediately stabilised on oxygen, intravenous fluids and antipyretics, and intravenous ceftriaxone and amikacin were commenced in view of late-onset neonatal sepsis. For his worsening respiratory distress, he required mechanical ventilation, with peak inspiratory pressure of 20mBar, positive end expiratory pressure of 8mBar and FiO₂ of 60%. There was, however, no clinical improvement with these measures; hence antibiotics were upgraded after 48 h to meropenem.

On the third day, the peripheral smear showed the presence of trophozoites and schizonts of Plasmodium vivax. Intravenous artesunate was started at a dose of 3 mg/kg. After 48 h, the fever subsided. Enteral feeds were started. Ventilator settings were tapered gradually and the child was successfully extubated on the fifth day when antibiotics were stopped. Intravenous artesunate was changed to oral artemether with lumefantrine and a course of 7 days was completed. A repeat peripheral smear examination on the fifth and sixth days revealed no parasites. There were no adverse effects of artesunate noted. On reassessment, the mother confided that she had suffered from malaria and had received oral antimalarials 15 days prior to delivery.

Discussion

The prevalence of congenital malaria is estimated to be up to 46.7%.^{1, 2} It is important to document temperature in neonates and suspect malaria especially when a baby presents with hepatosplenomegaly. Congenital malaria is a mimicker of sepsis and therefore should be ruled out in all pyrexial neonates. ³ Evidence regarding the use of artemisinin-based combination therapy (ACT) in neonates with severe malaria is scarce. ² In a case series of four neonates from Uganda, two presented early at days 1 and 2 of life while other two presented late at days 14 and 16. ⁴ The mothers of early presenters had fever within 2 weeks of delivery while mothers of late presenters did not have any fever. ³ In other case reports, the age of neonates were 24 and 25 days, respectively, and the mother had no fever during pregnancy.^{5, 6} The case series from Uganda used intravenous artesunate at a dose of 4 mg/kg at 0, 12 and 24 h and then daily for 7 days. ³ The case from Nigeria used intravenous artesunate 2.4 mg/kg/dose at 0, 12, 24 and 48 h, and later changed to oral artemether–lumefantrine for 3 days. ⁵ The case from India used oral artesunate at a dose of 4 mg/kg on days 1 and 2 mg/kg for the next 6 days for the treatment of chloroquine unresponsive malaria. ⁶ The 2-day neonate from the recent report from Uganda received intravenous artesunate at admission, at 12 h and 24 h, then once a day for 5 days (doses not mentioned). ³ In our case, we administered intravenous artesunate 3 mg/kg for 4 days followed by oral artemether–lumefantrine (20/120 mg) one tablet for 3 days. None of these reports encountered any side effects of artesunate in neonates.

Currently, the WHO does not recommend monotherapy in such cases; thus oral therapy with artesunate alone was not continued. This may however be challenged. Such is, however, low-quality evidence; additional study of the efficacy and safety profile, dose and duration in neonates is urgently required.