BackgroundMultidrug-resistant Plasmodium vivax (Pv) is widespread in eastern Indonesia, and emerging elsewhere in Asia-Pacific and South America, but is generally regarded as a benign disease. The aim of the study was to review the spectrum of disease associated with malaria due to Pv and P. falciparum (Pf) in patients presenting to a hospital in Timika, southern Papua, Indonesia.Methods and FindingsData were prospectively collected from all patients attending the outpatient and inpatient departments of the only hospital in the region using systematic data forms and hospital computerised records. Between January 2004 and December 2007, clinical malaria was present in 16% (60,226/373,450) of hospital outpatients and 32% (12,171/37,800) of inpatients. Among patients admitted with slide-confirmed malaria, 64% of patients had Pf, 24% Pv, and 10.5% mixed infections. The proportion of malarial admissions attributable to Pv rose to 47% (415/887) in children under 1 y of age. Severe disease was present in 2,634 (22%) inpatients with malaria, with the risk greater among Pv (23% [675/2,937]) infections compared to Pf (20% [1,570/7,817]; odds ratio [OR] = 1.19 [95% confidence interval (CI) 1.08–1.32], p = 0.001), and greatest in patients with mixed infections (31% [389/1,273]); overall p < 0.0001. Severe anaemia (haemoglobin < 5 g/dl) was the major complication associated with Pv, accounting for 87% (589/675) of severe disease compared to 73% (1,144/1,570) of severe manifestations with Pf (p < 0.001). Pure Pv infection was also present in 78 patients with respiratory distress and 42 patients with coma. In total 242 (2.0%) patients with malaria died during admission: 2.2% (167/7,722) with Pf, 1.6% (46/2,916) with Pv, and 2.3% (29/1260) with mixed infections (p = 0.126).ConclusionsIn this region with established high-grade chloroquine resistance to both Pv and Pf, Pv is associated with severe and fatal malaria particularly in young children. The epidemiology of P. vivax needs to be re-examined elsewhere where chloroquine resistance is increasing.

In Papua, Indonesia, the antimalarial susceptibility of Plasmodium vivax (n ‫؍‬ 216) and P. falciparum (n ‫؍‬ 277) was assessed using a modified schizont maturation assay for chloroquine, amodiaquine, artesunate, lumefantrine, mefloquine, and piperaquine. The most effective antimalarial against P. vivax and P. falciparum was artesunate, with geometric mean 50% inhibitory concentrations (IC 50 In vitro drug susceptibility assays assess antimicrobial activity in the absence of the confounding effects of the host. Although such assays have become useful for monitoring the antimalarial resistance of Plasmodium falciparum, the assay has been of limited use with P. vivax. This is in part a consequence of a perception of the importance of antimalarial drug resistance with P. vivax, compounded by difficulties in standardizing a field-based assay. Over the last decade, a number of clinical studies have demonstrated the emergence of highgrade chloroquine resistance in Papua, Indonesia, and Papua, New Guinea (1, 18, 21), and its spread to other regions of Asia (6) and South America (20). However, assessment of the clinical efficacy of antimalarial drugs against P. vivax infection is confounded by the occurrence of both reinfections and relapses, making the attributable fraction of recurrent infections due to intrinsic parasite resistance difficult to gauge (2, 3, 10). To confirm the emergence of the spread of antimalarial drug resistance of P. vivax and to investigate alternative antimalarial drugs, it is critical that a standardized in vitro assay be developed and validated. The aim of this study was to define the in vitro susceptibility profiles of a range of antimalarial drugs and to investigate the confounding factors that modulate the derived estimate of drug efficacy. MATERIALS AND METHODS Field location and sample collection. Between March 2004 and May 2007,Plasmodium isolates were collected from patients attending malaria clinics in Timika, located in the southern part of Papua province, Indonesia. Timika is a region of endemicity for multidrug-resistant strains of P. vivax and P. falciparum, with a risk of treatment failure of 65% within 28 days after chloroquine monotherapy for P. vivax malaria and 48% failure after multidrug therapy with chloroquine-sulfadoxine-pyrimethamine for P. falciparum malaria (16). In 2004, treatment guidelines were changed accordingly to recommend an artemisinin combination therapy for both P. falciparum and P. vivax infection, precluding further clinical studies of the use of chloroquine monotherapy in this region (15). Patients with symptomatic malaria who presented to an outpatient facility were recruited into the study if they were singly infected with P. falciparum or with P. vivax, with a parasitemia of between 2,000 l Ϫ1 and 80,000 l Ϫ1 . Patients treated with antimalarials in the previous 3 weeks were excluded from this study. Venous blood (5 ml) was collected by venipuncture and, after the host white blood cells were removed using a CF11 column, 2 ml of packed infected red bl...

Ric Price and colleagues use hospital-based surveillance data to estimate the risk of severe anemia and mortality associated with endemic Plasmodium species in southern Papua, Indonesia. Please see later in the article for the Editors' Summary

BackgroundMultidrug resistance has emerged to both Plasmodium vivax and Plasmodium falciparum and yet the comparative epidemiology of these infections is poorly defined.MethodsAll laboratory-confirmed episodes of malaria in Timika, Papua, Indonesia, presenting to community primary care clinics and an inpatient facility were reviewed over a two-year period. In addition information was gathered from a house-to-house survey to quantify the prevalence of malaria and treatment-seeking behaviour of people with fever.ResultsBetween January 2004 and December 2005, 99,158 laboratory-confirmed episodes of malaria were reported, of which 58% (57,938) were attributable to P. falciparum and 37% (36,471) to P. vivax. Malaria was most likely to be attributable to pure P. vivax in children under one year of age (55% 2,684/4,889). In the household survey, the prevalence of asexual parasitaemia was 7.5% (290/3,890) for P. falciparum and 6.4% (248/3,890) for P. vivax. The prevalence of P. falciparum infection peaked in young adults aged 15–25 years (9.8% 69/707), compared to P. vivax infection which peaked in children aged 1 to 4 years (9.5% 61/642). Overall 35% (1,813/5,255) of people questioned reported a febrile episode in the preceding month. Of the 60% of people who were estimated to have had malaria, only 39% would have been detected by the surveillance network. The overall incidence of malaria was therefore estimated as 876 per 1,000 per year (Range: 711–906).ConclusionIn this region of multidrug-resistant P. vivax and P. falciparum, both species are associated with substantial morbidity, but with significant differences in the age-related risk of infection.

P. vivax malaria is a major cause of morbidity in early infancy. Preventive strategies, early diagnosis, and prompt treatment should be initiated in the perinatal period.