Prevalence and risk factors for asymptomatic malaria and genotyping of glucose 6-phosphate (G6PD) deficiencies in a vivax-predominant setting, Lao PDR: implications for sub-national elimination goals

Abstract

BackgroundLao People Democratic Republic (PDR; Laos), a landlocked country in Southeast Asia, has made important progress in reducing malaria morbidity and mortality in the past 5–6 years, and the northern provinces have very low reported incidence. To support national progress towards elimination, it is critical to verify and understand these changes in disease burden.MethodsA two-stage cluster cross-sectional survey was conducted in four districts within four northern provinces (Khua, Phongsaly Province; Paktha, Bokeo Province; Nambak, Luang Prabang, and Muang Et, Huaphanh Province). During September and October 2016, demographics and malaria risk factors were collected from a total of 1492 households. A total of 5085 persons consented to collection of blood samples for testing, by rapid diagnostic test (RDT) and polymerase chain reaction (PCR)-based testing. Risk factors for infection were examined using logistic regression; and a randomized subset of males was tested for glucose-6-phosphate dehydrogenase (G6PD) deficiencies using a combined PCR and sequencing approach.ResultsThere were zero positives by RDT, and PCR detected Plasmodium infections in 39 (0.77%; 95% CI 0.40–1.47%) of 5082 analysable samples. The species distribution was Plasmodium vivax (28 total); Plasmodium falciparum/P. vivax (5); P. falciparum (3), Plasmodium malariae (2), and P. vivax/P. malariae (1). In multivariable analysis, the main risk factors included having any other cases within the household [aOR 12.83 (95% CI 4.40 to 37.38), p < 0.001]; and lack of bed net ownership within the household [aOR 10.91 (95% 5.42–21.94), p < 0.001]; age, sex and forest-travel were not associated with parasitaemia. A total of 910 males were tested for the six most common G6PDd in SE Asia; and 30 (3.3%; 95% CI 2.1–5.1%) had a G6PD variant allele associated with G6PD deficiency, with the majority being the Union (14) and Viangchan (11) polymorphisms, with smaller numbers of Canton and Mahidol.ConclusionThis is the first rigorous PCR-based population survey for malaria infection in Northern Lao PDR, and found a very low prevalence of asymptomatic Plasmodium infections by standard PCR methods, with P. vivax predominating in the surveyed districts. Clustering of cases within households, and lack of a bed nets suggest reactive case detection, and scale-up of coverage should be prioritized. The predominance of infections with P. vivax, combined with moderate levels of serious G6PD deficiencies highlight the need for careful rollout of primaquine towards elimination goals.Electronic supplementary materialThe online version of this article (10.1186/s12936-018-2367-5) contains supplementary material, which is available to authorized users.

Molecular characterization of G6PD mutations reveals the high frequency of G6PD Aures in the Lao Theung population&nbsp;

“…A comparison of the G6PD mutation data collected in this and previous studies of non-speci ed Lao ethnic populations is summarized in Table 2. The most common G6PD mutation in the Lao Theung population was G6PD Aures c.143T>C (6.75%); this result is different from that in a previous report, which found that the G6PD Viangchan mutation was the most common mutation in the Laotian population (1.21-6.76%) (20)(21)(22)(23)(24)(25). The G6PD Jammu mutation is an 871G>A mutation identical to the G6PD Viangchan mutation but different from the polymorphism at nucleotide 1311 (nt1311C) detected in this study, whereas the previous report found only G6PD Viangchan in the Laotian population (21).…”

Molecular Characterization of G6PD Mutations Reveals the High Frequency of G6PD Aures in the Mon-Khmer Population

“…A comparison of the G6PD mutation data collected in this and previous studies of non-speci ed Lao ethnic populations is summarized in Table 2. The most common G6PD mutation in the Mon-Khmer population was G6PD Aures c.143T > C (6.75%); this result is different from that in a previous report, which found that the G6PD Viangchan mutation was the most common mutation in the Laotian population (1.21-6.76%) (20,26,27,(29)(30)(31). The G6PD Jammu mutation is an 871G > A mutation identical to the G6PD Viangchan mutation but different from the polymorphism at nucleotide 1311 (nt1311C) detected in this study, whereas the previous report found only G6PD Viangchan in the Laotian population (30).…”

“…In the beginning of G6PD mutation screening, the study of G6PD mutations focused only on the detection of the G6PD Viangchan mutation or identi ed the G6PD mutation only in males that presented with severe hemolytic anemia (20,26,29). Only six previous studies ( Table 2) have revealed that the prevalence of G6PD de ciency in the Lao population ranges from 3.30-21.98% in males and 2.50-11.24% in females (20,26,27,(29)(30)(31). Our study revealed severe G6PD de ciency more frequently in males than in females, whereas moderate and mild G6PD de ciencies were more common in females than in males.…”

Molecular characterization of G6PD mutations reveals the high frequency of G6PD Aures in the Lao Theung population&nbsp;

“…In the beginning of G6PD mutation screening, the study of G6PD mutations focused only on the detection of the G6PD Viangchan mutation or identi ed the G6PD mutation only in males that presented with severe hemolytic anemia (20,21,23). Only six previous studies ( Table 2) have revealed that the prevalence of G6PD de ciency in the Lao population ranges from 3.30-21.98% in males (20)(21)(22)(23)25) and 4.50-11.24 % in females (21,23). Our study revealed severe G6PD de ciency more frequently in males than in females, whereas intermediate G6PD de ciencies were more common in females than in males.…”