A stratified random survey of the proportion of poor quality oral artesunate sold at medicine outlets in the Lao PDR – implications for therapeutic failure and drug resistance

<p>Abstract</p> <p>Background</p> <p>Counterfeit oral artesunate has been a major public health problem in mainland SE Asia, impeding malaria control. A countrywide stratified random survey was performed to determine the availability and quality of oral artesunate in pharmacies and outlets (shops selling medicines) in the Lao PDR (Laos).</p> <p>Methods</p> <p>In 2003, 'mystery' shoppers were asked to buy artesunate tablets from 180 outlets in 12 of the 18 Lao provinces. Outlets were selected using stratified random sampling by investigators not involved in sampling. Samples were analysed for packaging characteristics, by the Fast Red Dye test, high-performance liquid chromatography (HPLC), mass spectrometry (MS), X-ray diffractometry and pollen analysis.</p> <p>Results</p> <p>Of 180 outlets sampled, 25 (13.9%) sold oral artesunate. Outlets selling artesunate were more commonly found in the more malarious southern Laos. Of the 25 outlets, 22 (88%; 95%CI 68–97%) sold counterfeit artesunate, as defined by packaging and chemistry. No artesunate was detected in the counterfeits by any of the chemical analysis techniques and analysis of the packaging demonstrated seven different counterfeit types. There was complete agreement between the Fast Red dye test, HPLC and MS analysis. A wide variety of wrong active ingredients were found by MS. Of great concern, 4/27 (14.8%) fakes contained detectable amounts of artemisinin (0.26–115.7 mg/tablet).</p> <p>Conclusion</p> <p>This random survey confirms results from previous convenience surveys that counterfeit artesunate is a severe public health problem. The presence of artemisinin in counterfeits may encourage malaria resistance to artemisinin derivatives. With increasing accessibility of artemisinin-derivative combination therapy (ACT) in Laos, the removal of artesunate monotherapy from pharmacies may be an effective intervention.</p

Is staying overnight in a farming hut a risk factor for malaria infection in a setting with insecticide-treated bed nets in rural Laos?

<p>Abstract</p> <p>Background</p> <p>Overnight stays in farming huts are known to pose a risk of malaria infection. However, studies reporting the risk were conducted in the settings of poor net coverage. This study sought to assess whether an overnight stay in a farming hut is associated with an increased risk of malaria infection if insecticide-treated bed nets (ITNs) are properly used.</p> <p>Methods</p> <p>A pair of cross-sectional surveys was carried out in the Lamarm district of Sekong province, Laos, in March (dry season) and August (rainy season) in 2008. Questionnaire-based interviews and blood examinations were conducted with farmers and their household members from three randomly selected villages in March (127 households, 891 people) and August (128 households, 919 people). Logistic regression analysis, adjusted for potential confounding factors, was used to assess the association between malaria infection status and frequency of overnight stays for the two weeks prior to the study in both the seasons.</p> <p>Results</p> <p>In March, 13.7% of participants reported staying overnight in a farming hut at least once in the previous two weeks. The percentage increased to 74.6% in August. Not only adults but also young children stayed overnight as often as adults. The use of an ITN the preceding night was common both in farming huts (66.3% in March, 95.2% in August), and in main residences (85.8% in March, 92.5% in August). Logistic regression analysis showed no statistical association between malaria infection status and frequency of overnight stays in farming huts in either study period. However, people sharing one family type net with five people or more were significantly more likely to have malaria than those sharing a net with up to two people in the dry season.</p> <p>Conclusions</p> <p>This study showed that staying overnight in farming huts was not associated with an increased risk of malaria infection in the setting where ITNs were widely used in farming huts. It suggests that malaria infection during overnight stays in farming huts might be preventable if ITNs are properly used in rural Laos.</p

Piloting a surveillance system to monitor the global patterns of drug efficacy and the emergence of anthelmintic resistance in soil-transmitted helminth control programs: a Starworms study protocol

To eliminate soil-transmitted helminth (STH) infections as a public health problem, the administration of benzimidazole (BZ) drugs to children has recently intensified. But, as drug pressure increases, the development of anthelmintic drug resistance (AR) becomes a major concern. Currently, there is no global surveillance system to monitor drug efficacy and the emergence of AR. Consequently, it is unclear what the current efficacy of the used drugs is and whether AR is already present. The aim of this study is to pilot a global surveillance system to assess anthelmintic drug efficacy and the emergence of AR in STH control programs. For this, we will incorporate drug efficacy trials into national STH control programs of eight countries (Bangladesh, Cambodia, Lao PDR, Vietnam, Ghana, Rwanda, Senegal and a yet to be defined country in the Americas). In each country, one trial will be performed in one program implementation unit to assess the efficacy of BZ drugs against STHs in school-aged children by faecal egg count reduction test. Stool samples will be collected before and after treatment with BZs for Kato-Katz analysis and preserved to purify parasite DNA. The presence and frequency of known single nucleotide polymorphisms (SNPs) in the β-tubulin genes of the different STHs will subsequently be assessed. This study will provide a global pattern of drug efficacy and emergence of AR in STH control programs. The results will provide complementary insights on the validity of known SNPs in the ß-tubulin gene as a marker for AR in human STHs as well as information on the technical and financial resources required to set up a surveillance system. Finally, the collected stool samples will be an important resource to validate different molecular technologies for the detection of AR markers or to identify novel potential molecular markers associated with AR in STH

Cost-effectiveness analysis of G6PD diagnostic test for Plasmodium vivax radical cure in Lao PDR: an economic modelling study

Background Plasmodium vivax (Pv) infections were 68% of the total malaria burden in Laos in 2019. The parasite causes frequent relapses, which can be prevented by primaquine (PMQ). Testing for glucose-6-phosphate-dehydrogenase (G6PD) deficiency is recommended before giving PMQ to avoid haemolysis. Because of the risk of haemolysis in G6PD intermediate deficiencies among females, Laos uses the PMQ 14-days regimen only in G6PD normal females. Among G6PD point-of-care tests, qualitative tests cannot differentiate between G6PD normal and intermediate females. Quantitative tests are required to differentiate between G6PD normal and intermediate deficiencies. However, the quantitative test lacks the cost-effectiveness evidence necessary for decision-making for large-scale adoption. This study examined the cost-effectiveness of quantitative G6PD test, with either supervised PMQ treatment or unsupervised PMQ treatment, against the usual unsupervised PMQ 8-weeks strategy. Supervised PMQ 8-weeks strategy without G6PD testing was also compared against the unsupervised PMQ 8-weeks strategy since the former had recently been adopted in malaria high burden villages that had village malaria volunteers. A budget impact analysis was conducted to understand the incremental cost and effect needed for a nationwide scale-up of the chosen strategy. Methods A decision tree model compared the cost-effectiveness of implementing four strategies at one health facility with an average of 14 Pv cases in one year. The strategies were unsupervised PMQ strategy, supervised PMQ strategy, G6PD test with unsupervised PMQ strategy, and G6PD test with supervised PMQ strategy. Disability Adjusted Life Years (DALYs) was the effect measure. Costs were calculated from a payer perspective, and sensitivity analyses were conducted. One Gross Domestic Product (GDP) per capita of Laos was set as the cost-effectiveness threshold. Budget impact analysis was conducted using the health facility wise Pv data in Laos in 2020. Findings Supervised PMQ strategy was extendedly dominated by G6PD test strategies. When compared against the unsupervised PMQ strategy, both G6PD test strategies were more costly but more effective. Their Incremental Cost-Effectiveness Ratios (ICER) were 96.72US$for the G6PD test with unsupervised PMQ strategy and 184.86US$ for the G6PD test with supervised PMQ strategy. Both ICERs were lower than one GDP per capita in Laos. Following the sensitivity analysis, low adherence for PMQ 14 days made both G6PD test strategies less cost-effective. The lower the Pv case number reported in a health facility, the higher the ICER was. In the budget impact analysis, the expected budget need was only half a million US$ when the G6PD test rollout was discriminately done depending on the Pv case number reported at the health facilities. Indiscriminate roll out of G6PD test to all health facilities was most expensive with least effect impact

Falciparum malaria in the north of Laos: the occurrence and implications of the <em>Plasmodium falciparum</em> chloroquine resistance transporter (pfcrt) gene haplotype SVMNT

OBJECTIVE: The Pfcrt-gene encodes a transmembrane protein located in the Plasmodium falciparum digestive vacuole. Chloroquine resistant (CQR) strains of African and Southeast Asian origin carry the Pfcrt-haplotype (c72-76) CVIET, whereas most South American and Papua New Guinean CQR stains carry the SVMNT haplotype. METHOD: Eighty-eight samples from an area with reported in vivo Chloroquine and in vitro Amodiaquine-resistance were screened for the K76T mutation and their Pfcrt-haplotype (c72-76) using a new SSOP-ELISA. RESULTS: Hundred percent of the analysed samples showed the K76T mutation which is highly associated with in vivo drug failure. This very high rate of a CQR-marker is alarming in an area were CQ is still used as first line drug. The distribution of the three main Pfcrt-haplotypes was as follows: 68% CVIET, 31% SVMNT, 0% CVMNT. CONCLUSIONS: These data show, for the first time, the South American/PNG -haplotype (SVMNT) on mainland Southeast Asia. SVMNT-haplotype and others might be associated with a decreased efficacy of Amodiaquine and could therefore be potential markers for of amodiaquine resistance (AQR). If there is a correlation between AQR and the SVMNT-haplotype as suggested, 31% prevalence of a potential resistance marker is cause for concern