Severe malaria in children in Papua New Guinea

QJ Med 1996; 89:779-788

Severe malaria in children in Papua New Guinea S.J. ALLEN 1 ' 2 , A. O ' D O N N E L L 1 ' 2 , N.D.E. ALEXANDER 2 and J.B. CLEGG 1 From the1 Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, UK, and 2 Papua New Guinea Institute of Medical Research, Madang, PNG Received 1 August 1996

Summary level of plasma lactate ( ^ 5 mmol/l) was common (20%) and was the major predictor of death in multiple regression analysis. Raised plasma creatinine and decreased plasma bicarbonate were also independent predictors of mortality. Coma was not predictive of death, although a high proportion of children with profound coma died. Investigation of the causes of acidosis in children with malaria is a high research priority. In view of the short time interval between admission and death in many children, emphasis must be placed on the prevention or early recognition and treatment of acidosis in the district health clinic as well as the central hospital.

Introduction In many tropical and sub-tropical regions, malaria remains a major cause of mortality, with most deaths occurring in children. The W H O have proposed concise clinical and laboratory criteria to identify severe manifestations of malaria1 and multiple regression analysis has been used to identify those associated with mortality in African children. Amongst 1844 Kenyan children admitted to hospital with malaria, impaired consciousness, respiratory distress, hypoglycaemia and jaundice were the major predictors of death.2 Of 180 Gambian children with severe malaria, coma with extensor posturing, hypoglycaemia, hyperlactataemia, raised pulse or respiratory rates, a high parasite count ( > 5 0 0 0 0 0 / J J J ) or a high proportion of mature stages of parasites in the peripheral blood, and biochemical markers of impaired renal function were all independently associated with death.3

Malaria is a prominent cause of mortality in children in the South Pacific region. Mortality surveillance in 35 villages in Madang Province, Papua New Guinea in the early 1980s determined that at least 1 1 % of all deaths in children aged less than 10 years were attributable to malaria.4 Analysis of Madang hospital records showed 3968 paediatric admissions during 1994 and 1995, of whom 186 died. In children in whom a diagnosis was assigned, 752/3912 (19.2%) of all admissions and 27/177 (15.3%) of all deaths were considered to be due to malaria (case fatality rate 3.6%; S. Allen, unpublished data). The establishment of a prospective study to evaluate the protective effect of haemoglobin and erythrocyte genetic variants against severe malaria in children admitted to Madang hospital provided an opportunity to investigate the clinical features of severe malaria and identify risk factors for mortality in this region.

Address correspondence to Dr S.J. Allen, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford OX3 9DU © Oxford University Press 1996

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The clinical features of severe falciparum malaria and risk factors for mortality were studied in 489 children admitted with malaria to Madang Hospital, Papua New Guinea. The most common severe manifestations of malaria were severe anaemia (22%) and coma (16%). Children with severe anaemia were younger than those with coma (median age 2.2 vs. 3.7 years) and had been ill for longer before admission (median 7 vs. 4 days, respectively). Although the clinical features of coma in Madang children with malaria resembled closely those reported in African children, mortality was lower (8% vs. 17-25%, respectively). Overall, 17 (3.5%) children died, most within 12 h of admission. A high

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Methods Study site Madang is situated 5° south of the equator on the north coast of Papua New Guinea. Annual rainfall is 3500 mm and the wet season is from October to May. Plasmodium falciparum (P. falciparum) malaria is transmitted throughout the year by mosquitoes of the Anopheles punctulatus complex, and the inoculation rate in six Madang villages was determined to vary between 0 and 0.68 infective bites per night during the 1985 wet season.5 Malaria is hyperendemic; in surveys undertaken during the wet season, 70% of children aged 1-9 years living in Madang villages had a palpable spleen and 57% had malaria parasitaemia (P. falciparum accounted for 76%, P. vivax for 20% and P. malariae for 4% of all infections).6 Malariometric indices were only slightly lower during the dry season.

Children were eligible to join the study if they had lived in Madang Province for ^ 1 2 months. Initial treatment was administered in the emergency department. Clinical details were recorded on to standard forms, an examination was performed and samples were collected on admission to the ward. All children were reviewed by the project clinician (SA) either on admission or within 6 h. The duration of illness was recorded in days, with a maximum value of 30 days. Residence was classified as either rural villages, periurban settlements or Madang town, and ethnicity according to the region of origin of the languages spoken by each of the child's parents. Blood was collected by venepuncture into EDTA for blood count (MD8, Coulter Electronics) and into heparin and fluoride oxalate for biochemical analyses (dry-slide chemistry, Kodak Ektachem). Thick blood films were stained with Giemsa, and the number of malaria parasites per 200 white blood cells was counted. All slides were read twice independently, and a third time if there was disagreement. P. falciparum density per uJ of whole blood was calculated using the measured white cell count. Lumbar puncture was performed on admission without sedation using a 22G spinal needle in all comatose children in whom there were no contraindications. Cerebrospinal fluid (CSF) opening pressure, measured with a paediatric spinal manometer, was recorded if children were quiet and a swing with respiration was observed.7 CSF was collected immediately post-mortem from a few children who died shortly after admission. CSF collected into plain containers was examined by microscopy, stored at —20 °C and sent on dry-ice to the University of

Definitions of severe malaria Definitions of severe and complicated malaria were based on WHO criteria.1 Severe malarial anaemia was defined as a febrile illness with Hb