Features and Prognosis of Severe Malaria Caused by Plasmodium falciparum, Plasmodium vivax and Mixed Plasmodium Species in Papua New Guinean Children

BACKGROUND: Mortality from severe pediatric falciparum malaria appears low in Oceania but Plasmodium vivax is increasingly recognized as a cause of complications and death. The features and prognosis of mixed Plasmodium species infections are poorly characterized. Detailed prospective studies that include accurate malaria diagnosis and detection of co-morbidities are lacking. METHODS AND FINDINGS: We followed 340 Papua New Guinean (PNG) children with PCR-confirmed severe malaria (77.1% P. falciparum, 7.9% P. vivax, 14.7% P. falciparum/vivax) hospitalized over a 3-year period. Bacterial cultures were performed to identify co-incident sepsis. Clinical management was under national guidelines. Of 262 children with severe falciparum malaria, 30.9%, 24.8% and 23.2% had impaired consciousness, severe anemia, and metabolic acidosis/hyperlactatemia, respectively. Two (0.8%) presented with hypoglycemia, seven (2.7%) were discharged with neurologic impairment, and one child died (0.4%). The 27 severe vivax malaria cases presented with similar phenotypic features to the falciparum malaria cases but respiratory distress was five times more common (P=0.001); one child died (3.7%). The 50 children with P. falciparum/vivax infections shared phenotypic features of mono-species infections, but were more likely to present in deep coma and had the highest mortality (8.0%; P=0.003 vs falciparum malaria). Overall, bacterial cultures were positive in only two non-fatal cases. 83.6% of the children had alpha-thalassemia trait and seven with coma/impaired consciousness had South Asian ovalocytosis (SAO). CONCLUSIONS: The low mortality from severe falciparum malaria in PNG children may reflect protective genetic factors other than alpha-thalassemia trait/SAO, good nutrition, and/or infrequent co-incident sepsis. Severe vivax malaria had similar features but severe P. falciparum/vivax infections were associated with the most severe phenotype and worst prognosis

Overlapping clinical phenotypes of severe malaria caused by <i>Plasmodium falciparum</i>.

<p>Overlapping clinical phenotypes of severe malaria caused by <i>Plasmodium falciparum</i>.</p

Uncomplicated and severe malaria numbers, and incidence of severe malaria, by infecting <i>Plasmodium</i> species from a longitudinal surveillance study of 264 children followed over 17 months in neighbouring East Sepik Province.

<p>Data are from Lin <i>et al.</i><a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0029203#pone.0029203-Lin1" target="_blank">[32]</a>.</p><p>*Single or mixed infections with <i>P. malariae</i> or <i>P. ovale</i>;</p>¶<p>(95% confidence intervals);</p>†<p><i>P</i><0.05 vs <i>P. vivax</i>.</p

Consort diagram outlining categorization of children presenting to Modilon Hospital, Madang Province, during the study period.

<p>Severe malaria cases were identified by clinical and laboratory features at presentation including blood film microscopy, and subsequent nPCR for <i>Plasmodium</i> speciation.</p

Baseline clinical and laboratory data for children with severe malaria categorized by <i>Plasmodium</i> species.

<p>Data are, unless otherwise stated, median and [inter-quartile range].</p>a<p><i>P</i><0.05 for post-test comparison between <i>P. falciparum</i> vs <i>P. falciparum/vivax</i>;</p>b<p><i>P</i><0.05 for post-test comparison between <i>P. falciparum</i> vs <i>P. vivax</i>;</p>c<p><i>P</i><0.05 for post-test comparison between <i>P. vivax</i> vs <i>P. falciparum/vivax</i>;</p><p>*Kruskal-Wallis or Chi-squared test;</p>#<p>Mann-Whitney test for <i>P. falciparum</i> vs <i>P. falciparum/vivax</i>; wt, wildtype; α^del/wt, heterozygous for either 3.7 or 4.2 kb deletions; α^del/α^del, homozygous or compound heterozygous for either 3.7 or 4.2 kb deletion.</p