The risk of morbidity and mortality following recurrent malaria in Papua, Indonesia: a retrospective cohort study

Abstract

Background: An acute episode of malaria can be followed by multiple recurrent episodes either due to reinfection, recrudescence of a partially treated parasite or, in the case of Plasmodium vivax or P. ovale, relapse from the dormant liver stage of the parasite. The aim of this study was to quantify the impact of recurrent malaria episodes on morbidity and mortality in Papua, Indonesia. Methods: We undertook a retrospective analysis of routinely collected data from malaria patients attending the primary referral hospital in Papua, Indonesia, between April 2004 and December 2013. Multi-state modelling was used to estimate the effect of recurring malaria episodes on re-presentation and admission to hospital and death. The risks of early (≤ 14 days) and late (15 to 365 days) hospital admission and death were estimated separately in our study to distinguish between the direct and indirect effects of malaria recurrence on adverse outcomes. Results: A total of 68,361 patients were included in the analysis, of whom 37,168 (54.4%) presented initially with P. falciparum, 22,209 (32.5%) with P. vivax, and 8984 (13.1%) with other species. During 12 months of follow-up after each of the first four malaria episodes, 10,868 (15.9%) patients were admitted to hospital and 897 (1.3%) died. The risk of re-presenting to the hospital with malaria increased from 34.7% (95% CI 34.4%, 35.1%) at first episode to 58.6% (57.5%, 59.6%) following the third episode of malaria. After adjusting for co-factors, infection with P. vivax was a significant risk factor for re-presentation (hazard ratio (HR) = 1.48 (95% CI 1.44, 1.51)) and late admission to hospital (HR = 1.17 (1.11, 1.22)). Patients infected with P. falciparum had a greater overall rate of mortality within 14 days (HR = 1.54 (1.25, 1.92)), but after multiple episodes of malaria, there was a trend towards a higher rate of early death in patients infected with P. vivax compared to P. falciparum (HR = 1.91 (0.73, 4.97)). Conclusions: Compared to patients initially infected with P. falciparum, those infected with P. vivax had significantly more re-presentations to hospital with malaria, and this contributed to a high risk of inpatient admission and death. These findings highlight the importance of radical cure of P. vivax to eliminate the dormant liver stages that trigger relapses.

Severity and mortality of severe Plasmodium ovale infection: A systematic review and meta-analysis

“…The highest prevalence of P. ovale has been reported in Papua New Guinea (15%) [4] and Nigeria (15%) [5]. However, the most recent retrospective cohort study conducted in Papua, Indonesia during 2004-2013 demonstrated a low prevalence of P. ovale infections (0.06%) among 68,361 patients [6]. Other recent studies demonstrated that P. ovale infections accounted for 2.5% of malaria cases in Uganda [7] and 2.7% of malaria cases in China [8].…”

Severe vivax malaria trends in the last two years: a study from a tertiary care centre, Delhi, India

“…The outcome of the malaria disease is influenced by various factors like infecting Plasmodium species, host immunity and efficacy of treatment [ 4 ]. In endemic areas, some of the important risk factors responsible for the severity of disease including the age of the patient, early and frequent relapses with limited access to early diagnosis and treatment, along with prevalence of comorbidities such as bacterial co-infections [ 5 – 7 ].…”

The risk of adverse clinical outcomes following treatment of Plasmodium vivax malaria with and without primaquine in Papua, Indonesia

“…The reduction of all-cause hospitalization if confirmed, argues that reduction in P . vivax relapses by the provision of effective radical cure would also reduce vulnerability to other non-malaria illnesses [ 12 , 19 , 25 ]. Reassuringly, we observed no overall increased risk of mortality or massive Hb reductions in patients treated with PQ.…”

“…Since recurrent episodes of P . vivax malaria are associated with a cumulative risk of anaemia and both direct and indirect mortality [ 11 , 12 ], the analysis was limited to patients presenting with their first episode of P . vivax , alone or mixed with another Plasmodium species, and all associated clinical events occurring within the ensuing 30 days.…”

“…The HRN was used to link clinical and laboratory data with the pharmacy records. Since recurrent episodes of P. vivax malaria are associated with a cumulative risk of anaemia and both direct and indirect mortality [11,12], the analysis was limited to patients presenting with their first episode of P. vivax, alone or mixed with another Plasmodium species, and all associated clinical events occurring within the ensuing 30 days. Pharmacy records reported the number of tablets prescribed and the actual mg per kg dose of PQ prescribed were derived for each individual patient by applying estimated mean body weights within each age, sex, and ethnicity strata derived from a cross sectional survey [13].…”