Multidrug-resistant Plasmodium vivax associated with severe and fatal malaria: a prospective study in Papua, Indonesia

Abstract

Background: Multidrug-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 findings: Data 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).

Conclusions: In 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.

Figure 1. Age Stratified Proportions of Hospital Patients with Malaria

Bars represent proportion of all patients attending outpatients (A) or admitted to hospital (B) who were parasitaemic.

Figure 2. Age-Stratified Percentage of Females in Patients Hospitalised with P. falciparum (Squares) and P. vivax Infection (Diamonds)

Error bars represent 95% CI, and dotted line denotes males and females present in equal proportions.

Figure 3. The Prevalence of Severe Disease in Patients Hospitalised with Malaria Stratified by Species of Infection and Age Group

Severe disease defined by respiratory distress (RDS), coma, and SMA. For each age group the upper number above each column represents the total number of patients with severe disease (numerator), and the lower number is the total number of patients with the species of infection (denominator). Data on age were unavailable in 50 patients.

Figure 4. Age-Specific Risk of Severe Disease in Patients Admitted with P. falciparum (Bold Line), P. vivax (Hashed Line), and Mixed (Dotted Line) Infections

Lines represent predicted values from a logistic regression model in which age was entered as a linear effect, along with an interactive term for age and species.

Figure 5. Prevalence, Overlap, and Mortality for Criteria of Severe Malaria Associated with Infection of P. falciparum, P. vivax, and Mixed Infections

Total numbers are given in parentheses, and mortality is given as a percentage. The sizes of the circles represent the relative proportions of patients with malaria with different severe manifestations of disease for each species. Data on mortality are missing in 129 (1.1%) patients, 95 with P. falciparum, 21 with P. vivax, and 13 with mixed infections.