Dataset Information

Prevalence of G6PD deficiency in selected populations from two previously high malaria endemic areas of Sri Lanka.

ABSTRACT: Glucose-6-Phosphate Dehydrogenase (G6PD) enzyme deficiency is known to offer protection against malaria and an increased selection of mutant genes in malaria endemic regions is expected. However, anti-malarial drugs such as primaquine can cause haemolytic anaemia in persons with G6PD deficiency. We studied the extent of G6PD deficiency in selected persons attending Teaching Hospitals of Anuradhapura and Kurunegala, two previously high malaria endemic districts in Sri Lanka. A total of 2059 filter-paper blood spots collected between November 2013 and June 2014 were analysed for phenotypic G6PD deficiency using the modified WST-8/1-methoxy PMS method. Each assay was conducted with a set of controls and the colour development assessed visually as well as with a microplate reader at OD450-630nm. Overall, 142/1018 (13.95%) and 83/1041 (7.97%) were G6PD deficient in Anuradhapura and Kurunegala districts respectively. The G6PD prevalence was significantly greater in Anuradhapura when compared to Kurunegala (P<0.0001). Surprisingly, females were equally affected as males in each district: 35/313 (11.18%) males and 107/705 (15.18%) females were affected in Anuradhapura (P = 0.089); 25/313 (7.99%) males and 58/728 (7.97%) females were affected in Kurunegala (P = 0.991). Prevalence was greater among females in Anuradhapura than in Kurunegala (P<0.05), while no such difference was observed between the males (P>0.05). Severe deficiency (<10% normal) was seen among 28/1018 (2.75%) in Anuradhapura (7 males; 21 females) and 17/1041 (1.63%) in Kurunegala (7 males; 10 females). Enzyme activity between 10-30% was observed among 114/1018 (11.20%; 28 males; 86 females) in Anuradhapura while it was 66/1041 (6.34%; 18 males; 48 females) in Kurunegala. Screening and educational programmes for G6PD deficiency are warranted in these high risk areas irrespective of gender for the prevention of disease states related to this condition.

SUBMITTER: Gunawardena S

PROVIDER: S-EPMC5289554 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Prevalence of G6PD deficiency in selected populations from two previously high malaria endemic areas of Sri Lanka.

Gunawardena Sharmini S Kapilananda G M G GM Samarakoon Dilhani D Maddevithana Sashika S Wijesundera Sulochana S Goonaratne Lallindra V LV Karunaweera Nadira D ND

PloS one 20170202 2

Glucose-6-Phosphate Dehydrogenase (G6PD) enzyme deficiency is known to offer protection against malaria and an increased selection of mutant genes in malaria endemic regions is expected. However, anti-malarial drugs such as primaquine can cause haemolytic anaemia in persons with G6PD deficiency. We studied the extent of G6PD deficiency in selected persons attending Teaching Hospitals of Anuradhapura and Kurunegala, two previously high malaria endemic districts in Sri Lanka. A total of 2059 filte ...[more]

PMID: 28152025

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Project description:BackgroundPrimaquine is essential for malaria control and elimination since it is the only available drug preventing multiple clinical attacks by relapses of Plasmodium vivax. It is also the only therapy against the sexual stages of Plasmodium falciparum infectious to mosquitoes, and is thus useful in preventing malaria transmission. However, the difficulties of diagnosing glucose-6-phosphate dehydrogenase deficiency (G6PDd) greatly hinder primaquine's widespread use, as this common genetic disorder makes patients susceptible to potentially severe and fatal primaquine-induced haemolysis. The risk of such an outcome varies widely among G6PD gene variants.MethodsA literature review was conducted to identify surveys of G6PD variant frequencies among representative population groups. Informative surveys were assembled into two map series: (1) those showing the relative proportions of the different variants among G6PDd individuals; and (2) those showing allele frequencies of G6PD variants based on population surveys without prior G6PDd screening.ResultsVariants showed conspicuous geographic patterns. A limited repertoire of variants was tested for across sub-Saharan Africa, which nevertheless indicated low genetic heterogeneity predominated by the G6PD A(-202A) mutation, though other mutations were common in western Africa. The severe G6PD Mediterranean variant was widespread across western Asia. Further east, a sharp shift in variants was identified, with high variant heterogeneity in the populations of China and the Asia-Pacific where no single variant dominated.ConclusionsG6PD variants exhibited distinctive region-specific distributions with important primaquine policy implications. Relative homogeneity in the Americas, Africa, and western Asia contrasted sharply with the heterogeneity of variants in China, Southeast Asia and Oceania. These findings will inform rational risk assessments for primaquine in developing public health strategies for malaria control and elimination, and support the future development of regionally targeted policies. The major knowledge gaps highlighted here strongly advocate for further investigation of G6PD variant diversity and their primaquine-sensitivity phenotypes.

Project description:BackgroundPrimaquine is a key drug for malaria elimination. In addition to being the only drug active against the dormant relapsing forms of Plasmodium vivax, primaquine is the sole effective treatment of infectious P. falciparum gametocytes, and may interrupt transmission and help contain the spread of artemisinin resistance. However, primaquine can trigger haemolysis in patients with a deficiency in glucose-6-phosphate dehydrogenase (G6PDd). Poor information is available about the distribution of individuals at risk of primaquine-induced haemolysis. We present a continuous evidence-based prevalence map of G6PDd and estimates of affected populations, together with a national index of relative haemolytic risk.Methods and findingsRepresentative community surveys of phenotypic G6PDd prevalence were identified for 1,734 spatially unique sites. These surveys formed the evidence-base for a Bayesian geostatistical model adapted to the gene's X-linked inheritance, which predicted a G6PDd allele frequency map across malaria endemic countries (MECs) and generated population-weighted estimates of affected populations. Highest median prevalence (peaking at 32.5%) was predicted across sub-Saharan Africa and the Arabian Peninsula. Although G6PDd prevalence was generally lower across central and southeast Asia, rarely exceeding 20%, the majority of G6PDd individuals (67.5% median estimate) were from Asian countries. We estimated a G6PDd allele frequency of 8.0% (interquartile range: 7.4-8.8) across MECs, and 5.3% (4.4-6.7) within malaria-eliminating countries. The reliability of the map is contingent on the underlying data informing the model; population heterogeneity can only be represented by the available surveys, and important weaknesses exist in the map across data-sparse regions. Uncertainty metrics are used to quantify some aspects of these limitations in the map. Finally, we assembled a database of G6PDd variant occurrences to inform a national-level index of relative G6PDd haemolytic risk. Asian countries, where variants were most severe, had the highest relative risks from G6PDd.ConclusionsG6PDd is widespread and spatially heterogeneous across most MECs where primaquine would be valuable for malaria control and elimination. The maps and population estimates presented here reflect potential risk of primaquine-associated harm. In the absence of non-toxic alternatives to primaquine, these results represent additional evidence to help inform safe use of this valuable, yet dangerous, component of the malaria-elimination toolkit. Please see later in the article for the Editors' Summary.

Project description:BackgroundG6PD deficiency is common in malaria endemic regions and is estimated to affect more than 400 million people worldwide. Treatment of malaria patients with the anti-malarial drug primaquine or other 8-aminoquinolines may be associated with potential haemolytic anaemia. The aim of the present study was to investigate the prevalence of G6PD variants in Thai population who resided in malaria endemic areas (western, northern, north-eastern, southern, eastern and central regions) of Thailand, as well as the Burmese population who resided in areas along the Thai-Myanmar border.MethodsThe ten common G6PD variants were investigated in dried blood spot samples collected from 317 Thai (84 males, 233 females) and 183 Burmese (11 males, 172 females) populations residing in malaria endemic areas of Thailand using PCR-RFLP method.ResultsFour and seven G6PD variants were observed in samples collected from Burmese and Thai population, with prevalence of 6.6% (21/317) and 14.2% (26/183), respectively. Almost all (96.2%) of G6PD mutation samples collected from Burmese population carried G6PD Mahidol variant; only one sample (3.8%) carried G6PD Kaiping variant. For the Thai population, G6PD Mahidol (8/21: 38.1%) was the most common variant detected, followed by G6PD Viangchan (4/21: 19.0%), G6PD Chinese 4 (3/21: 14.3%), G6PD Canton (2/21: 9.5%), G6PD Union (2/21: 9.5%), G6PD Kaiping (1/21: 4.8%), and G6PD Gaohe (1/21: 4.8%). No G6PD Chinese 3, Chinese 5 and Coimbra variants were found. With this limited sample size, there appeared to be variation in G6PD mutation variants in samples obtained from Thai population in different regions particularly in the western region.ConclusionsResults indicate difference in the prevalence and distribution of G6PD gene variants among the Thai and Burmese populations in different malaria endemic areas. Dosage regimen of primaquine for treatment of both Plasmodium falciparum and Plasmodium vivax malaria may need to be optimized, based on endemic areas with supporting data on G6PD variants. Larger sample size from different malaria endemic is required to obtain accurate genetic mapping of G6PD variants in Burmese and Thai population residing in malaria endemic areas of Thailand.

Project description:BackgroundPlasmodium vivax parasites are the predominant cause of malaria infections in the Brazilian Amazon. Infected individuals are treated with primaquine, which can induce haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals and may lead to severe and fatal complications. This X-linked disorder is distributed globally and is caused by allelic variants with a geographical distribution that closely reflects populations exposed historically to endemic malaria. In Brazil, few studies have reported the frequency of G6PD deficiency (G6PDd) present in malaria-endemic areas. This is particularly important, as G6PDd screening is not currently performed before primaquine treatment. The aim of this study was to determine the prevalence of G6PDd in the region of Alto do Juruá, in the Western Brazilian Amazon, an area characterized by a high prevalence of P. vivax infection.MethodsFive-hundred and sixteen male volunteers were screened for G6PDd using the fluorescence spot test (Beutler test) and CareStart™ G6PD Biosensor system. Demographic and clinical-epidemiological data were acquired through an individual interview. To assess the genetic basis of G6PDd, 24 SNPs were genotyped using the Kompetitive Allele Specific PCR assay.ResultsTwenty-three (4.5%) individuals were G6PDd. No association was found between G6PDd and the number of malaria cases. An increased risk of reported haemolysis symptoms and blood transfusions was evident among the G6PDd individuals. Twenty-two individuals had the G6PDd A(-) variant and one the G6PD A(+) variant. The Mediterranean variant was not present. Apart from one polymorphism, almost all SNPs were monomorphic or with low frequencies (0-0.04%). No differences were detected among ethnic groups.ConclusionsThe data indicates that ~1/23 males from the Alto do Juruá could be G6PD deficient and at risk of haemolytic anaemia if treated with primaquine. G6PD A(-) is the most frequent deficiency allele in this population. These results concur with reported G6PDd in other regions in Brazil. Routine G6PDd screening to personalize primaquine administration should be considered, particularly as complete treatment of patients with vivax malaria using chloroquine and primaquine, is crucial for malaria elimination.

Project description:BackgroundAntibodies against the merozoite surface protein 1-19 (MSP1-19) and the apical membrane antigen 1 (AMA1) of the malaria parasite (Plasmodium vivax) are proven to be important in protection against clinical disease. Differences in the production/maintenance of antibodies may be due to many factors including host genetics. This paper discusses the association of 4 anti-malarial antibodies with selected host genetic markers.MethodsBlood was collected from individuals (n = 242) with a history of malaria within past 15 years for DNA and serum. ELISA was carried out for serum to determine the concentration of anti-malarial antibodies MSP1-19 and AMA1 for both vivax and falciparum malaria. 170 SNPs related to malaria were genotyped. Associations between seropositivity, antibody levels and genetic, non-genetic factors were determined.ResultsAge ranged 13-74 years (mean age = 40.21 years). Majority were females. Over 90% individuals possessed either one or more type(s) of anti-malarial antibodies. Five SNPs were significantly associated with seropositivity. One SNP was associated with MSP1-19_Pv(rs739718); 4 SNPs with MSP1-19_Pf (rs6874639, rs2706379, rs2706381 and rs2075820) and1 with AMA1_Pv (rs2075820). Eleven and 7 genotypes (out of 15) were significantly associated with either presence or absence of antibodies. Three SNPs were found to be significantly associated with the antibody levels viz. rs17411697 with MSP1-19_Pv, rs2227491 with AMA1_Pv and rs229587 with AMA1_Pf. Linkage of the markers in the two groups was similar, but lower LOD scores were observed in seropositives compared to seronegatives.Discussion and conclusionsThe study suggests that several SNPs in the human genome that exist in Sri Lankan populations are significantly associated with anti-malarial antibodies, either with generation and/or maintenance of antibodies for longer periods, which can be due to either individual polymorphisms or most probably a combined effect of the markers.

Project description:BackgroundLeishmaniasis is a notifiable disease in Sri Lanka since 2008. Previous studies show a gap in the notification of leishmaniasis. The purpose of the present study was to determine the Knowledge, attitudes and practice of medical officers regarding leishmaniasis.MethodsA cross-sectional study was conducted in the Anuradhapura district which reported the highest case load of leishmaniasis. Medical officers from public and private health care institutes in the area filled a self-administered questionnaire in the presence of the investigators.ResultsOne hundred and eighty-eight (188) medical officers completed the questionnaire. Of them, 95.7% were aware of leishmaniasis as a parasitic infection and 84.7% correctly identified Leishmania donovani as the causative organism in Sri Lanka. From the respondents, 181 (96.8%) knew that the vector of leishmaniasis is sand fly. Cutaneous leishmaniasis was reported as the most prevalent form of leishmaniasis in the country by 176 (94.1%). Nearly half of the respondents (98, 54.1%) were aware of the fact that the Anuradhapura district has the highest disease burden. Many of them had the idea that leishmaniasis is an emerging disease (155, 84.3%,) and early diagnosis is important in controlling the disease (163, 89.1%). Although about three fourth (123, 73.7%,) of the participants mentioned that leishmaniasis should be notified at first clinical suspicion, only 74 (42.5%) were aware that it is a legal requirement. Some medical officers (39, 22%) believed that the current notification system in the country is not effective. Unavailability of notification forms (60, 36.8%) heavy workload (85, 50.3%) and inadequate supportive staff (55, 35.1%) were reported as barriers for timely notification. Even though 105 (58.0%) of medical officers had suspected leishmaniasis during the last 8 years period only 35 (19.4%) had notified.ConclusionsEven though more than 90% of the participants had good theoretical knowledge about leishmaniasis; notification of leishmaniasis is considerably inadequate. This study emphasizes the need for greater efforts to improve the notification of leishmaniasis in Sri Lanka.

Dataset Information

Prevalence of G6PD deficiency in selected populations from two previously high malaria endemic areas of Sri Lanka.

Publications

Prevalence of G6PD deficiency in selected populations from two previously high malaria endemic areas of Sri Lanka.

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