Malaria-related hospitalization during childhood in Papua, Indonesia: A retrospective cohort study.

BACKGROUND: In endemic regions, the age distribution of malaria varies according to the infecting Plasmodium species. We aimed to delineate the pattern of malaria-related hospitalization from birth in Timika, Papua-an area co-endemic for P. falciparum and P. vivax. METHODS: Between April 2004 and December 2013, infants born at Mitra Masyarakat Hospital, or presenting within the first 7 days of life, were enrolled retrospectively into a cohort study and followed passively using routinely-collected hospital surveillance data. Outcomes were stratified by the presence or absence of Plasmodium parasitemia and included re-presentation to hospital, requirement for hospital admission and death. RESULTS: Overall, 11,408 infants were enrolled into the cohort. Median follow-up was 4.3 (maximum 9.7) years. In total, 7,847 (68.9%) infants made 90,766 re-presentations to hospital, 18,105 (19.9%) of which were associated with Plasmodium parasitemia. The incidence of re-presentations with malaria during the first year of life was 213 per 1,000 person-years (py) for P. vivax and 79 per 1,000py for P. falciparum (Incidence Rate Ratio (IRR) = 2.69, 95% Confidence Interval (95%CI): 2.48-2.92). After the age of 5 years, the incidence of P. vivax had fallen to 77/1,000py and the incidence of P. falciparum had risen to 95/1,000py (IRR = 0.80, 95%CI: 0.73-0.88). Overall, 79.7% (14,431/18,105) of malaria re-presentations were recurrences rather than initial infections. Malaria accounted for 31.7% (2,126/3,120) of all hospital admissions. The infant mortality rate in this study was 52 deaths per 1,000 live births. Beyond the early neonatal period, 13.4% of deaths were associated with Plasmodium parasitemia. CONCLUSIONS: In Papua, Indonesia, malaria is a major cause of hospital presentation and admission in early life. The initial predominance of P. vivax over P. falciparum inverts after five years of age. Malaria is directly associated with nearly one in seven deaths after the early neonatal period.

Early and late mortality after malaria in young children in Papua, Indonesia.

BACKGROUND: In southern Papua, Indonesia, malaria is highly prevalent in young children and is a significant cause of morbidity and early mortality. The association between malaria and delayed mortality is unknown. METHODS: Routinely-collected hospital surveillance data from southern Papua, Indonesia, were used to assess the risk of recurrent malaria and mortality within 12 months of an initial presentation with malaria in all children younger than 5 years old attending the local hospital. Analysis was primarily by Kaplan Meier and Cox regression methods. RESULTS: In total 15,716 children presenting with malaria between April 2004 and December 2013 were included in the analysis; 6184 (39.3%) with Plasmodium falciparum, 7499 (47.7%) with P. vivax, 203 (1.3%) with P. malariae, 3 with P. ovale and 1827 (11.6%) with mixed infections. Within 1 year, 48.4% (7620/15,716) of children represented a total of 16,957 times with malaria (range 1 to 11 episodes), with the incidence of malaria being greater in patients initially presenting with P. vivax infection (1334 [95%CI 1307-1361] per 1000 patient years) compared to those with P. falciparum infection (920 [896-944]). In total 266 (1.7%) children died within 1 year of their initial presentation, 129 (48.5%) within 30 days and 137 (51.5%) between 31 and 365 days. There was no significant difference in the mortality risk in patients infected with P. vivax versus P. falciparum either before 30 days (Hazard Ratio (HR) 1.02 [0.69,1.49]) or between 31 and 365 days (HR = 1.30 [0.90,1.88]). Children who died had a greater incidence of malaria, 2280 [95%CI 1946-2671] per 1000 patient years preceding their death, compared to 1141 [95%CI 1124-1158] per 1000 patient years in those surviving. CONCLUSIONS: Children under-5 years old with P. vivax malaria, are at significant risk of multiple representations with malaria and of dying within 1 year of their initial presentation. Preventing recurrent malaria must be a public health priority in this vulnerable population.

Safety of primaquine in infants with Plasmodium vivax malaria in Papua, Indonesia.

BACKGROUND: Primaquine (PQ) prevents relapses of vivax malaria but may induce severe haemolysis in glucose-6-phosphate dehydrogenase (G6PD) deficient patients. Data on the safety of primaquine in infants are limited. METHODS: A retrospective, hospital-based cohort study of infants aged 1-12 months with vivax malaria was carried out in Timika, Papua province, Indonesia. Risks of admission, death and severe haematological outcomes within 30 days of first presentation were compared between infants who did and did not receive primaquine. Infants were not tested routinely for G6PD deficiency as per local guidelines. RESULTS: Between 2004 and 2013, 4078 infants presented to the hospital for the first time with vivax malaria, of whom 3681 (90.3%) had data available for analysis. In total 1228 (33.4%) infants were aged between 1 and 6 months and 2453 (66.6%) between 6 and 12 months of age. Thirty-three (0.9%) patients received low-dose primaquine (LDP), 174 (4.7%) received high-dose primaquine (HDP), 3432 (93.2%) received no primaquine (NPQ) and 42 patients received either a single dose or an unknown dose of primaquine. The risk of the Hb concentration falling by > 25% to less than 5 g/dL was similar in the LDP or HDP groups (4.3%, 1/23) versus the NPQ group (3.5%, 16/461). Three infants (1.4%) died following receipt of PQ, all of whom had major comorbidities. Seventeen patients (0.5%) died in the NPQ group. None of the infants had documented massive haemolysis or renal impairment. CONCLUSIONS: Severe clinical outcomes amongst infants treated with primaquine in Papua were rare. The risks of using primaquine in infancy must be weighed against the risks of recurrent vivax malaria in early life.