[Show abstract][Hide abstract]ABSTRACT: In a recent study one third of Lao patients presenting with uncomplicated Plasmodium falciparum malaria had biochemical evidence of thiamin deficiency, which was associated with a higher incidence of adverse events. Thiamin supplementation might, therefore, reduce adverse events in this population.
An exploratory, double-blind, parallel group, placebo-controlled, superiority trial of thiamin supplementation in patients of all ages with uncomplicated and severe falciparum malaria was conducted in Xepon District, Savannakhet Province, southern Laos. Patients were randomly assigned to either oral thiamin 10 mg/day for 7 days immediately after standard anti-malarial treatment then 5 mg daily until day 42, or identical oral placebo.
After interim analyses when 630 patients (314 in thiamin and 316 in placebo groups) had been recruited, the trial was discontinued on the grounds of futility. On admission biochemical thiamin deficiency (alpha ≥ 25%) was present in 27% of patients and 9% had severe deficiency (alpha > 31%). After 42 days of treatment, the frequency of thiamin deficiency was lower in the thiamin (2%, 1% severe) compared to the placebo (11%, 3% severe) groups (p < 0.001 and p = 0.05), respectively. Except for diarrhoea, 7% in the placebo compared to 3% in the thiamin group (p = 0.04), and dizziness on day 1 (33% vs 25%, p = 0.045), all adverse events were not significantly different between the groups (p > 0.05). Clinical, haematological, and parasitological responses to treatment did not differ significantly between the two groups.
Thiamin supplementation reduced biochemical thiamin deficiency among Lao malaria patients following anti-malarial drug treatment, but it did not reduce the frequency of adverse events after anti-malarial therapy or have any detected clinical or parasitological impact.
[Show abstract][Hide abstract]ABSTRACT: Background
Malaria morbidity and mortality have been significantly reduced through the proper use of insecticide-treated mosquito nets, but the extra protection afforded by the insecticide diminishes over time. The insecticide depletion rates vary according to location where wash frequency and wear are influenced by cultural habits as well as the availability of water. Monitoring of available insecticides on the net surface is essential for determining the effective life of the net. Therefore, a rapid and inexpensive colorimetric field test for cyanopyrethroids (Cyanopyrethroid Field Test or CFT) was used to measure surface levels of deltamethrin on insecticide-coated polyester nets (PowerNets™) in rural Lao PDR over a two-year period.
Net surface levels of deltamethrin were measured by wiping the net with filter paper and measuring the adsorbed deltamethrin using the CFT. A relationship between surface levels of deltamethrin and whole net levels was established by comparing results of the CFT with whole levels assayed by high-performance liquid chromatography (HPLC). An effective deltamethrin surface concentration (EC80) was determined by comparing mosquito mortality (WHO Cone Test) with CFT and HPLC results. Five positions (roof to bottom) on each of 23 matched nets were assayed for deltamethrin surface levels at 6, 12, and 24 months. Mosquito mortality assays (WHO Cone Tests) were performed on a subset of eleven 24-month old nets and compared with the proportion of failed nets as predicted by the CFT.
At six months, the nets retained about 80% of the baseline (new net) levels of deltamethrin with no significant differences between net positions. At 12 months, ~15-40%, and at 24 months <10% of deltamethrin was retained on the nets, with significant differences appearing between positions. Results from the CFT show that 93% of the nets failed (deltamethrin surface levels </= EC80) at 24 months. This value is in agreement with 91% failure as determined by the WHO Cone Test on a subset of 11 nets. The CFT results show that 50% of the nets from Laos failed at 12 months of normal use.
The CFT is a useful and accurate indicator of net efficacy and may be substituted for mosquito bioassays.
[Show abstract][Hide abstract]ABSTRACT: Abstract Background The Lao Government changed the national policy for uncomplicated Plasmodium falciparum malaria from chloroquine to artemether-lumefantrine (AL) in 2005. Since then, no information on AL efficacy has been reported. With evidence of resistance to artemisinin derivatives in adjacent Cambodia, there has been a concern as to AL efficacy. Monitoring of AL efficacy would help the Lao Government to make decisions on appropriate malaria treatment. Methods The efficacy of a three-day, twice daily oral artemether-lumefantrine for the treatment of uncomplicated falciparum malaria in Xepon District, Savannakhet Province, southern Laos was studied over 42 days follow-up. This was part of a trial of thiamin supplementation in falciparum malaria. Results Of 630 patients with P. falciparum enrolled in the trial of thiamin treatment, 549 (87%, 357 children ≤15 years and 192 adults) were included in this study. The per protocol 42-day cure rates were 97% (524/541) [96% (337/352) for children and 99% (187/189) for adults, p = 0.042]. By conventional intention-to-treat analysis, the 42-day cure rates adjusted for re-infection, were 97% (532/549) [96% (342/357) in children and 99% (190/192) in adults, p = 0.042]. The proportion of patients who remained parasitaemic at day 1 after treatment was significantly higher in children [33% (116/356)] compared to adults [15% (28/192)] (p
[Show abstract][Hide abstract]ABSTRACT: We conducted an open-label, randomized clinical trial to assess parasite clearance times (PCT) and the efficacy of 4 mg/kg (group 1, n = 22) and 2 mg/kg (group 2, n = 22) of oral artesunate for three days followed by artemether-lumefantrine in patients with uncomplicated Plasmodium falciparum malaria at Xepon Interdistrict Hospital, Savannakhet Province in southern Laos. Slides were read in duplicate. The overall mean (95% confidence interval; range) PCT in hours was 23.2 (21.2-25.3; 12-46) and 22.4 (20.3-24.5; 12-46) for the first and second microscopists, respectively (P = 0.57). Ten (23%) patients remained parasitemic on day 1 after treatment (4 [18%] in group 1 and 6 [27%] in group 2; P = 0.47). No patient had patent asexual parasitemia on the second and third days of treatment. The 42-day polymerase chain reaction-corrected cure rates were 100% in both treatment groups. Serious adverse events did not develop during or after treatment in any patients. In conclusion, no evidence of P. falciparum in vivo resistance to artesunate was found in southern Laos.
Full-text Article · Mar 2012 · The American journal of tropical medicine and hygiene
[Show abstract][Hide abstract]ABSTRACT: Schistosomiasis mekongi is prevalent in the Khong district of Lao PDR, made up of one big island, Khong, and numerous small islands in the Mekong River. Schistosoma mekongi is spread by Neotricula aperta as the intermediate host along the Mekong River. Therefore, even if an epidemic of S. mekongi were stamped out in a certain village, infection may recur if the source of infection is a village located in the upper reaches of the Mekong River. The purpose of this study was to construct a mathematical model for the transmission of S. mekongi among villages from the upper to lower Mekong River to estimate the effect of control measures against it. The chief characteristic of the present model is competence in dealing with the spread of infection among villages through the Mekong River in consideration of the reduction in longevity of cercariae and miracidia and their diffusion in the river. The model also takes into account seasonal fluctuation in the water level of the Mekong River, which affects human behavior in terms of water contact. The results of simulations indicated that the prevalence of schistosomiasis mekongi would be suppressed to a low level for a long time in a village further downstream when universal mass treatment is performed in villages further upstream simultaneously.
[Show abstract][Hide abstract]ABSTRACT: We conducted a 28-day follow-up of 17 Laotian patients diagnosed with uncomplicated Plasmodium falciparum malaria treated with mefloquine (Mephaquine, MQ) alone to determine the efficacy. All patients were completely cured with MQ, without reappearance of asexual stage parasitemia at follow-up. Of the 7 isolates tested for genotypic analysis, one isolate was a Y86 mutant type of the pfmdr1 gene, the others were N86 wild. These findings suggest no MQ resistance in the study area possibly because the drug is rarely used in southern Lao PDR.
Full-text Article · Jul 2011 · The Southeast Asian journal of tropical medicine and public health
[Show abstract][Hide abstract]ABSTRACT: We assessed the insecticidal efficacy of Olyset nets after 5 years of use in rural villages of Lao PDR and evaluated the relationship between the physical condition of the nets and their insecticidal effect. Our results showed that most of the Olyset nets remained effective after 5 years of use; however, there was no significant relationship between the physical condition of the nets (ie, presence of holes, level of stains) and the insecticidal effect. The presence of large holes in polyester nets compared to the Olyset nets suggest the Olyset nets are stronger; however, nearly half of Olyset nets had small holes or had been previously repaired. Interestingly, the insecticide concentration and knockdown (KD) rate for 3 stored nets was low compared to the other nets routinely used in the house. To maintain the effectiveness of Olyset nets in rural villages of Lao PDR and other areas, residents should be advised to repair and store the nets appropriately and avoid exposure to high temperatures and direct sunlight for long periods.
Full-text Article · Mar 2011 · The Southeast Asian journal of tropical medicine and public health
[Show abstract][Hide abstract]ABSTRACT: Schistosomiasis found in communities along the Mekong River in Cambodia and Lao People's Democratic Republic (Lao PDR) is caused by the blood fluke Schistosoma mekongi. Early observations on patients in 1957 revealed severe intestinal and hepatosplenic disease. High mortality rates and widespread disease were reported from the provinces of northern Cambodia (Stung Treng and Kratié) and southern Lao PDR (Champasack) in the early 1970s and 1990s. Control programmes built around mass drug administration, with praziquantel, and combined with information and education campaigns, were carried out. In Cambodia, such programmes were started in 1995 in the endemic provinces and sustained until today; these efforts resolved the public health problem of schistosomiasis mekongi and led to a significant reduction in transmission. In Lao PDR, the interventions started in the late 1980s, but suffered several interruptions which permitted transmission to resume. Today, a number of small foci continue to show substantial prevalence rates. The snail intermediate host, Neotricula aperta, is present in the Mekong River and some of its tributaries. There is evidence that the snail might not yet have reached its full geographical distribution emphasising the need to sustain vigilance. New infections with S. mekongi occur in the endemic population and travellers alike. Comprehensive guidelines for the elimination of S. mekongi and bilateral efforts between Cambodia and Lao PDR are required.
[Show abstract][Hide abstract]ABSTRACT: 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.
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.
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.
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.
[Show abstract][Hide abstract]ABSTRACT: We conducted an open, randomized clinical trial of oral dihydroartemisinin-piperaquine (DP) versus artesunate-mefloquine (AM) in 300 patients in Laos with uncomplicated Plasmodium falciparum malaria as part of a multicentre study in Asia. Survival analysis and adjustment for re-infection showed that the 63-day cure rates (95% confidence interval [CI]) were 100% for AM and 99.5% (96.4-99.8%) for DP. The 63-day cure rates per protocol were 99% (97 of 98) for AM and 99.5% (196 of 197) for DP (P = 0.55). The difference (AM minus DP) in cure rates (95% CI) was -0.5% (-5.1 to 2.0%), which is within the 5% non-inferiority margin. The median fever and parasite clearance times were also similar for AM and DP. The proportion of patients with at least one recorded potential adverse event was significantly higher in the AM group (38 of 87, 44%) than in the DP group (57 of 182, 31%) (relative risk = 0.6, 95% CI = 0.4-0.9; P = 0.04). Dihydroartemisinin-piperaquine is not inferior to AM in the treatment of uncomplicated P. falciparum malaria in Laos and is associated with fewer adverse effects. The results of this study were similar to those of the larger multicentre study.
Full-text Article · Dec 2010 · The American journal of tropical medicine and hygiene
[Show abstract][Hide abstract]ABSTRACT: A large-scale cross-sectional seroprevalence study of dengue (DEN) and Japanese encephalitis (JE) was conducted in Khammouane province, Lao PDR, as part of the initial baseline health impact assessment of the Nam Theun 2 hydroelectric dam construction project. Health surveys were performed between May 2007 and February 2008 with serum samples collected from healthy individuals involved in the resettlement program of 16 villages (total surveyed population 4,369). Hemagglutination inhibition assay using flavivirus antigens (DENV1, DENV3, and JEV) performed on 1,708 plasma specimens revealed 30.4% (519) cross-reactive positives, and 10% (172) and 1.3% (22) positives to JEV or DENV, respectively. Entomological surveys conducted during the rainy season of 2008 indicated the presence of competent flavivirus vectors (Culex vishnui group and Aedes albopictus), although Aedes aegypti was not found. Continued surveillance and investigation is warranted to assess the clinical disease burden of flaviviruses in this area that is undergoing rapid ecological and demographic change.
Full-text Article · Nov 2010 · The American journal of tropical medicine and hygiene
[Show abstract][Hide abstract]ABSTRACT: Naturally occurring bithyniid snails, Bithynia siamensis goniomphalos (Prosobranchia: Bithyniidae), and their intermediate hosts were sampled from Khammouane Province, the Lao People's Democratic Republic, and the prevalence of the carcinogenic human liver fluke, Opisthorchis viverrini, was examined. The presence of O. viverrini cercariae in snails was examined by cercarial shedding test and then confirmed by specific hybridization probe-based real-time fluorescence resonance energy transfer (FRET) PCR method. The real-time FRET PCR method is based on a fluorescence melting curve analysis of a hybrid between an amplicon produced from the pOV-A6 specific sequence (Genbank accession no. S80278), a 162-bp repeated sequence specific to O. viverrini, and specific fluorophore-labeled probes. Mean melting temperature of O. viverrini DNA from the cercariae and each of two positive snails by shedding test was 66.3 ± 0.1. The O. viverrini infection rate in snails was 2.47% (2/81) by cercarial shedding test but was 8.52% (4/47) by real-time FRET PCR method. The real-time FRET PCR method is rapid and effective in examining a large number of snail samples simultaneously. Validation using molecular evidence from this procedure provides another tool for surveying the prevalence of O. viverrini-infected snails in Southeast Asian countries.
[Show abstract][Hide abstract]ABSTRACT: Background
Accurate information on the geographical distribution of malaria is important for efficient resource allocation. The Lao People's Democratic Republic has experienced a major decline in malaria morbidity and mortality in the past decade. However, efforts to respond effectively to these changes have been impeded by lack of detailed data on malaria distribution. In 2008, a countrywide survey on Plasmodium falciparum diagnosed in health centres and villages was initiated to develop a detailed P. falciparum risk map with the aim to identify priority areas for malaria control, estimate population at risk, and guide resource allocation in the Lao People's Democratic Republic.
P. falciparum incidence data were collected from point-referenced villages and health centres for the period 2006-2008 during a country-wide survey between December 2008 and January 2009. Using the highest recorded annual rate, continuous surfaces of P. falciparum incidence were produced by the inverse distance weighted interpolation technique.
Incidence rates were obtained from 3,876 villages and 685 health centres. The risk map shows that P. falciparum is highly heterogeneous in the northern and central regions of the country with large areas of no transmission. In the southern part, transmission is pervasive and the risk of P. falciparum is high. It was estimated that 3.4 million people (60% of the population) live at risk of malaria.
This paper presents the first comprehensive malaria risk map of the Lao People's Democratic Republic based entirely on empirical data. The estimated population at risk is substantially lower than previous estimates, reflecting the presence of vast areas with focal or no malaria transmission as identified in this study. These findings provide important guidance for malaria control interventions in the Lao People's Democratic Republic, and underline the need for detailed data on malaria to accurately predict risk in countries with heterogeneous transmission.
[Show abstract][Hide abstract]ABSTRACT: This study aimed to examine the care-seeking choices for treatment of a febrile illness compatible with malaria in the public and private sectors in Lao PDR. We conducted interviews with 745 heads of household in 14 villages in the Sekong province, using a structured-questionnaire. We asked each about who the care-providers were for febrile illness episodes affecting their household members during the past year. If patients used more than one care-provider for a single episode over a period of time, we identified patterns of the care-sequences for the initial and subsequent care choices. Then, we analyzed the relationship between the initial care choices and secondary care choices for care-providers by Chi-square test, categorizing care-providers into public (hospital, health centre, and village health volunteer) and private care-providers (private pharmacy, informal retailer, faith healing and herbs). As a result, we found that 624 patients sought care at least once, 255 (40.9%) twice, and 66 (10.6%) three times or more during a single episode. Of 138 patients who started with a public care-provider and then sought a secondary care, 71 (51.4%) switched to a private care-provider. In contrast, of 117 patients who started with a private care-provider and then sought a secondary care, 82 (70.1%) switched to a public care-provider (p<0.001). In conclusion, although most patients who failed being treated by a private care-provider switched to a public one, some exclusively relied on care within the private sector. An intervention is necessary to make the private sector an integral component of malaria treatment in Lao PDR.
[Show abstract][Hide abstract]ABSTRACT: Insecticide-treated nets (ITNs) are a key intervention to control malaria. The intervention coverage varies as a consequence of geographical accessibility to remote villages and limitations of financial and human resources for the intervention. People's adherence to the intervention, i.e., proper use of ITNs, also affects malaria health outcome. The study objective is to explore the impact of the intervention coverage and people's adherence to the intervention on malaria health outcome among targeted villages in various geographic locations.
Geographic information system (GIS) maps were developed using the data collected in an active case detection survey in Khammouane province, Laos. The survey was conducted using rapid diagnostic tests (RDTs) and a structured questionnaire at 23 sites in the province from June to July, the rainy season, in 2005. A total of 1,711 villagers from 403 households participated in the survey.
As indicated on the GIS maps, villages with malaria cases, lower intervention coverage, and lower adherence were identified. Although no malaria case was detected in most villages with the best access to the district center, several cases were detected in the distal villages, where the intervention coverage and adherence to the intervention remained relatively lower.
Based on the data and maps, it was demonstrated that malaria remained unevenly distributed within districts. Balancing the intervention coverage in the distal villages with the overall coverage and continued promotion of the proper use of ITNs are necessary for a further reduction of malaria cases in the province.
[Show abstract][Hide abstract]ABSTRACT: 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).
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.
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).
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.
[Show abstract][Hide abstract]ABSTRACT: Details of samples of artesunate blisterpacks collected in Laos by stratified random sampling. The table describes the packaging détails and chemistry data for all the samples collected.
[Show abstract][Hide abstract]ABSTRACT: In Khammouane province, Laos, over 5000 slide-positive malaria cases were reported at local health facilities in 1997. To combat the spread of malaria, insecticide-treated nets (ITNs) and community health education were provided to the people in this province by the Lao Ministry of Health and the Japan International Cooperation Agency. In order to document the current malaria situation, an active case detection (ACD) survey using rapid diagnostic tests was conducted at 23 sites from June to July, the rainy season, in 2005. A total of 1711 villagers from 403 households participated in the survey. The proportion of positive cases was 0.7% (12/1711) with a range in each village of 0-8.2%. The low infection rate observed in this ACD survey was consistent with the decrease in the number of slide-positive malaria cases at local health facilities (from over 5000 cases to 536 cases), indicating the substantial progress made in malaria control. Although the reduction of malaria cases can be attributed to multiple factors, continued promotion of the proper use of ITNs as well as community-based testing and treatment services, especially in remote areas, may lead to a further reduction of malaria cases in the province.
Article · Sep 2008 · Transactions of the Royal Society of Tropical Medicine and Hygiene