Research Article: Multidrug-Resistant Plasmodium vivax Associated with Severe and Fatal Malaria: A Prospective Study in Papua, Indonesia

Date Published: June 17, 2008

Publisher: Public Library of Science

Author(s): Emiliana Tjitra, Nicholas M Anstey, Paulus Sugiarto, Noah Warikar, Enny Kenangalem, Muhammad Karyana, Daniel A Lampah, Ric N Price, Stephen Rogerson

Abstract: 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.

Partial Text: The burden of malaria in Asia has been under appreciated, despite recent evidence suggesting that the continent contributes almost 40% of the world’s malaria [1]. In sub-Saharan Africa the overwhelming majority of malaria-associated morbidity and mortality occurs with P. falciparum infections. In Asia, P. vivax often accounts for 50% of the malaria prevalence, and yet the morbidity associated with this infection and its spectrum of disease are largely ignored. Although P. vivax is widely regarded as benign, its propensity to recur is increasingly recognized by clinicians in endemic areas to result in appreciable disease, particularly in young children [2,3]. There have been increasing numbers of case reports describing severe manifestations of vivax malaria in recent years [3–5], however in the absence of a denominator, the true incidence of severe vivax malaria is unknown.

Our study in southern Papua, where high levels of resistance have emerged to P. vivax as well as P. falciparum, demonstrates that both species are associated with significant morbidity and mortality. In this region, malaria accounted for 16% of the all hospital outpatient consultations and 32% of admissions, a quarter of which were attributable to P. vivax. Severe disease was present in 22% of hospitalised patients, with a greater risk among patients infected with P. vivax than in those with P. falciparum (OR = 1.19). Inpatient case fatality rates of 1.6% of patients with P. vivax did not differ significantly from the 2.2% mortality among patients with pure P. falciparum infection. Importantly, whereas mixed infections have been associated previously with a lower risk of severe disease [16,17] and anaemia [18], in our study they were at significantly greater risk than either species alone.



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