The epidemiology of severe malaria in an area of low transmission in Thailand

Mahidol University, Krung Thep, Bangkok, Thailand
Transactions of the Royal Society of Tropical Medicine and Hygiene (Impact Factor: 1.84). 05/1997; 91(3):256-62. DOI: 10.1016/S0035-9203(97)90066-3
Source: PubMed


The predisposing factors, clinical presentation, and outcome of severe malaria in a Karen community living on the western border of Thailand were studied over a period of 2 years. This was an area of low malaria transmission (approximately one infection per person per year), where asymptomatic malaria is unusual. In a population of 4728 persons, who had good access to facilities for malaria diagnosis and treatment, there were 2573 cases of vivax malaria, none of whom died, and there were 5776 cases of falciparum malaria, 303 (5%) of whom had severe malaria and 11 (0.2%) of whom died-a case fatality rate of 1.9 per 1000 (95% confidence interval [CI] 1.0-3.3). The risks of developing severe malaria and dying declined steadily with age. The clinical features of severe malaria differed between children and adults. Anaemia was more common in children under 5 years old than in older children and adults, whereas the incidence of cerebral involvement increased with age. Severe malaria was 3 times (95% CI 1.4-6.2) more common in pregnant than in non-pregnant women, but was 4.2 times (95% CI 2.3-7.9) less common in patients with mixed Plasmodium falciparum and P. vivax infections than in those with P. falciparum alone, suggesting that P. vivax may attenuate the severity of P. falciparum malaria.

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    • "majority of malaria cases are treated with drugs, resulting in a strong selective pressure on the parasite population (Luxemburger et al. 1997). Consequently, drug resistance mutations are highly beneficial, with selection coefficients (s) on the order of 0.1 or higher (Nair et al. 2003). "
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    ABSTRACT: We explored the potential of pooled sequencing to swiftly and economically identify selective sweeps due to emerging artemisinin (ART) resistance in a South-East Asian malaria parasite population. ART resistance is defined by slow parasite clearance from the blood of ART-treated patients and mutations in the kelch gene (chr. 13) have been strongly implicated to play a role. We constructed triplicate pools of 70 slow-clearing (resistant) and 70 fast-clearing (sensitive) infections collected from the Thai-Myanmar border and sequenced these to high (~150-fold) read depth. Allele frequency estimates from pools showed almost perfect correlation (Lin's concordance = 0.98) with allele frequencies at 93 SNPs measured directly from individual infections, giving us confidence in the accuracy of this approach. By mapping genome-wide divergence (FST) between pools of drug resistant and drug sensitive parasites we identified two large (>150kb) regions (on chrs. 13 and 14) and 17 smaller candidate genome regions. To identify individual genes within these genome regions we re-sequenced an additional 38 parasite genomes (16 slow and 22 fast-clearing) and performed rare variant association tests. These confirmed kelch as a major molecular marker for ART resistance (p=6.03×10(-6)). This two-tier approach is powerful because pooled sequencing rapidly narrows down genome regions of interest, while targeted rare variant association testing within these regions can pinpoint the genetic basis of resistance. We show that our approach is robust to recurrent mutation and the generation of soft selective sweeps, which are predicted to be common in pathogen populations with large effective population sizes, and may confound more traditional gene mapping approaches. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.
    Molecular Biology and Evolution 12/2014; 32(4). DOI:10.1093/molbev/msu397 · 9.11 Impact Factor
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    • "In KwaZulu-Natal, the peak age of admission with malaria was in adolescents with case fatality over the age of 12 years (Soni and Gouws, 1996). Severe morbidities and mortalities have been reported from different malaria transmission settings among adolescent (Ejov et al., 1999; Luxemburger et al., 1997; Singh et al., 1992). "

    Acta Tropica 12/2014; 144. DOI:10.1016/j.actatropica.2014.12.009 · 2.27 Impact Factor
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    • "Observed rates of severe P. vivax in Southeast Asia and the Pacific have been high in several reports, accounting for up to 25% of severe malaria cases. While some have shown reduced risk of severe disease attributable to P. vivax and/or mixed infection in low transmission settings [28], others have shown risks of severe disease to be increased, particularly in young children and in areas with high grade chloroquine resistance, though the latter has not been reported in Cambodia [29]. Though P. vivax is typically thought of as a relatively benign disease, 14.5% of patients meeting the case definition of severe malaria at BRH during the study period had slide proven P. vivax, and there were four documented deaths. "
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    ABSTRACT: Despite recent malaria containment and control efforts leading to reduced incidence, Cambodia remains endemic for both Plasmodium vivax and multidrug-resistant Plasmodium falciparum malaria. Little has been reported in the peer-reviewed literature regarding the burden of severe malaria (SM) in Cambodia. Medical records for all patients admitted to the Battambang Referral Hospital (BRH) with an admitting or discharge diagnosis of SM from 2006 to 2009 (suspected SM cases) were reviewed. Those meeting the case definition of SM according to retrospective chart review and investigator assessment of probable cases, based on published national guidelines available at the time, were analysed for trends in demographics, mortality and referral patterns. Of the 537 suspected SM cases at BRH during the study period, 393 (73%) met published WHO criteria for SM infection. Despite limited diagnostic and treatment facilities, overall mortality was 14%, with 7% mortality in children 14 and under, but 19% in adults (60% of cases). Cerebral malaria with coma was relatively rare (17%), but mortality was disproportionately high at 35%. Mean time to hospital presentation was five days (range one to 30 days) after onset of symptoms. While patients with delays in presentation had worse outcomes, there was no excess mortality based on treatment referral times, distance travelled or residence in artemisinin-resistance containment (ARC) Zone 1 compared to Zone 2. Despite limitations in diagnosis and treatment, and multiple confounding co-morbidities, mortality rates at BRH were similar to reports from other countries in the region. Interventions to improve access to early diagnosis and effective treatment, combined with modest improvements in intensive care, are likely to reduce mortality further. Patients referred from Zone 1 did not have excess mortality compared to Zone 2 ARC areas. A steep decrease in SM cases and deaths observed in the first half of 2009 has since continued, indicating some success from containment efforts despite the emergence of artemisinin resistance in this area.
    Malaria Journal 06/2013; 12(1):217. DOI:10.1186/1475-2875-12-217 · 3.11 Impact Factor
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