Thai-Myanmar Border Research Articles

A tool to improve competence in the management of emergency patients by rural clinic health workers: a pilot assessment on the Thai-Myanmar border.

BackgroundShoklo Malaria Research Unit has been providing health care in remote clinics on the Thai-Myanmar border to refugee and migrant populations since 1986 and 1995, respectively. Clinics are staffed by local health workers with a variety of training and experience. The need for a tool to improve the competence of local health workers in basic emergency assessment and management was recognised by medical faculty after observing the case mix seen at the clinic and reviewing the teaching programme that had been delivered in the past year (Jan-13 to March-14).AimsTo pilot the development and evaluation of a simple teaching tool to improve competence in the assessment and management of acutely unwell patients by local health workers that can be delivered onsite with minimal resources.MethodsA structured approach to common emergencies presenting to rural clinics and utilizing equipment available in the clinics was developed. A prospective repeated-measures observed structured clinical examination (OSCE) assessment design was used to score participants in their competence to assess and manage a scenario based ‘emergency patient’ at baseline, immediately post-course, and 8 weeks after the delivery of the teaching course. The assessment was conducted at 3 clinic sites and staff participation was voluntary. Participants filled out questionnaires on their confidence with different scenario based emergency patients.ResultsAll staff who underwent the baseline assessment failed to carry out the essential steps in initial emergency assessment and management of an unconscious patient scenario. Following delivery of the teaching session, all groups showed improved competence in both objective assessment and subjective confidence levels.ConclusionsStructured and practical teaching and learning with minimal theory in this resource limited setting had a positive short-term effect on the competence of individual staff to carry out an initial assessment and manage an acutely unwell patient. Health-worker confidence likewise improved. Workplace assessments are needed to determine if this type of skills training impacts upon mortality or near miss mortality patients at the clinic.Electronic supplementary materialThe online version of this article (doi:10.1186/s13031-015-0041-x) contains supplementary material, which is available to authorized users.

Prevalence of malaria and HIV coinfection and influence of HIV infection on malaria disease severity in population residing in malaria endemic area along the Thai–Myanmar border

The objective of the study is to investigate the prevalence of malaria and HIV coinfection and assess the effect of HIV coinfection on malaria disease severity in malaria patients from the endemic area of Thailand along the Thai–Myanmar border. Blood samples were collected from a total of 867 patients with malaria (all species and severity) who attended Mae Tao clinic for migrant workers, Tak Province during 2005–2007 (439 samples), 2008–2010 (273 samples), and 2011–2013 (155 samples). The average prevalence rate of malaria and HIV coinfected cases in this malaria endemic area of the country during the three periods was 1.85%. HIV coinfection was observed only in samples with mono-infection of Plasmodium falciparum or Plasmodium vivax, with similar proportions (0.81 vs. 1.04%). Patients’ admission parasite density, an indicator of disease severity, was significantly higher in cases with HIV coinfection observed during 2008–2010. Anemia was found at a significantly higher frequency in patients coinfected with malaria and HIV observed during 2005–2007 compared with those infected with malaria alone. No association was observed between malaria and HIV coinfection and gender, and infected malaria species during the three observation periods. Patients with malaria and HIV coinfection had a significantly lower hemoglobin level than those with malaria infection alone. In conclusion, the prevalence of malaria and HIV coinfection in population of the malaria endemic area along the Thai–Myanmar border is low. HIV coinfection tended to increase parasite density, an indicator of malaria disease severity.

Quality of intrapartum care by skilled birth attendants in a refugee clinic on the Thai-Myanmar border: a survey using WHO Safe Motherhood Needs Assessment

BackgroundIncreasing the number of women birthing with skilled birth attendants (SBAs) as one of the strategies to reduce maternal mortality and morbidity must be partnered with a minimum standard of care. This manuscript describes the quality of intrapartum care provided by SBAs in Mae La camp, a low resource, protracted refugee context on the Thai-Myanmar border.MethodsIn the obstetric department of Shoklo Malaria Research Unit (SMRU) the standardized WHO Safe Motherhood Needs Assessment tool was adapted to the setting and used: to assess the facility; interview SBAs; collect data from maternal records during a one year period (August 2007 – 2008); and observe practice during labour and childbirth.ResultsThe facility assessment recorded no ‘out of stock’ or ‘out of date’ drugs and supplies, equipment was in operating order and necessary infrastructure e.g. a stand-by emergency car, was present. Syphilis testing was not available. SBA interviews established that danger signs and symptoms were recognized except for sepsis and endometritis. All SBAs acknowledged receiving theoretical and ‘hands-on’ training and regularly attended deliveries. Scores for the essential elements of antenatal care from maternal records were high (>90%) e.g. providing supplements, recording risk factors as well as regular and correct partogram use. Observed good clinical practice included: presence of a support person; active management of third stage; post-partum monitoring; and immediate and correct neonatal care. Observed incorrect practice included: improper controlled cord traction; inadequate hand washing; an episiotomy rate in nulliparous women 49% (34/70) and low rates 30% (6/20) of newborn monitoring in the first hours following birth. Overall observed complications during labour and birth were low with post-partum haemorrhage being the most common in which case the SBAs followed the protocol but were slow to recognize severity and take action.ConclusionsIn the clinic of SMRU in Mae La refugee camp, SBAs were able to comply with evidence-based guidelines but support to improve quality of care in specific areas is required. The structure of the WHO Safe Motherhood Needs Assessment allowed significant insights into the quality of intrapartum care particularly through direct observation, identifying a clear pathway for quality improvement.Electronic supplementary materialThe online version of this article (doi:10.1186/s12884-015-0444-0) contains supplementary material, which is available to authorized users.

Subtype distribution of Blastocystis in Thai-Myanmar border, Thailand.

Blastocystis sp. is a common zoonotic intestinal protozoa which has been classified into 17 subtypes (STs). A cross-sectional study was conducted to determine the prevalence and subtype distribution of Blastocystis in villagers living on the Thai-Myanmar border, where the risk of parasitic infection is high. A total of 207 stool samples were collected and DNA was extracted. PCR and sequencing using primers targeting small-subunit ribosomal RNA (SSU rRNA) gene were performed. The prevalence of Blastocystis infection was 37.2% (77/207). ST3 (19.8%; 41/207) was the predominant subtype, followed by ST1 (11.6%; 24/207), ST2 (5.3%; 11/207), and ST4 (0.5%; 1/207). A phylogenetic tree was reconstructed using the maximum likelihood (ML) method based on the Hasegawa-Kishino-Yano + G + I model. The percentage of bootstrapped trees in which the associated taxa clustered together was relatively high. Some sequences of Blastocystis positive samples (TK18, 39, 46, 71, and 90) were closely related to animals (pig and cattle) indicating zoonotic risks. Therefore, proper health education in parasitic prevention for the villagers should be promoted to improve their personal hygiene. Further longitudinal studies are required to monitor the prevalence of parasitic infections after providing health education and to investigate Blastocystis ST in animals living in these villages.

Plasmodium vivax drug resistance genes; Pvmdr1 and Pvcrt-o polymorphisms in relation to chloroquine sensitivity from a malaria endemic area of Thailand.

The aim of the study was to explore the possible molecular markers of chloroquine resistance in Plasmodium vivax isolates in Thailand. A total of 30 P. vivax isolates were collected from a malaria endemic area along the Thai-Myanmar border in Mae Sot district of Thailand. Dried blood spot samples were collected for analysis of Pvmdr1 and Pvcrt-o polymorphisms. Blood samples (100 μl) were collected by finger-prick for in vitro chloroquine susceptibility testing by schizont maturation inhibition assay. Based on the cut-off IC50 of 100 nM, 19 (63.3%) isolates were classified as chloroquine resistant P. vivax isolates. Seven non-synonymous mutations and 2 synonymous were identified in Pvmdr1 gene. Y976F and F1076L mutations were detected in 7 (23.3%) and 16 isolates (53.3%), respectively. Analysis of Pvcrt-o gene revealed that all isolates were wild-type. Our results suggest that chloroquine resistance gene is now spreading in this area. Monitoring of chloroquine resistant molecular markers provide a useful tool for future control of P. vivax malaria.

Plasmodium falciparum genotype diversity in artemisinin derivatives treatment failure patients along the Thai-Myanmar border.

Genetic characteristics of Plasmodium falciparum may play a role in the treatment outcome of malaria infection. We have studied the association between diversity at the merozoite surface protein-1 (msp-1), msp-2, and glutamate-rich protein (glurp) loci and the treatment outcome of uncomplicated falciparum malaria patients along the Thai-Myanmar border who were treated with artemisinin derivatives combination therapy. P. falciparum isolates were collected prior to treatment from 3 groups of patients; 50 cases of treatment failures, 50 recrudescences, and 56 successful treatments. Genotyping of the 3 polymorphic markers was analyzed by nested PCR. The distribution of msp-1 alleles was significantly different among the 3 groups of patients but not the msp-2 and glurp alleles. The allelic frequencies of K1 and MAD20 alleles of msp1 gene were higher while RO33 allele was significantly lower in the successful treatment group. Treatment failure samples had a higher median number of alleles as compared to the successful treatment group. Specific genotypes of msp-1, msp-2, and glurp were significantly associated with the treatment outcomes. Three allelic size variants were significantly higher among the isolates from the treatment failure groups, i.e., K1270-290, 3D7610-630, G650-690, while 2 variants, K1150-170, and 3D7670-690 were significantly lower. In conclusion, the present study reports the differences in multiplicity of infection and distribution of specific alleles of msp-1, msp-2, and glurp genes in P. falciparum isolates obtained from treatment failure and successful treatment patients following artemisinin derivatives combination therapy.

Mutations in P. falciparum K13 propeller gene from Bangladesh: emerging resistance?

Bangladesh is a malaria hypo-endemic country sharing borders with India and Myanmar. ACT remains quite successful in Bangladesh. An increase of heritable artemisinin resistant malaria parasites on the Thai-Cambodia border and subsequently the Thai-Myanmar border is worrisome. K13 propeller gene (PF3D7_1343700 (PF13_0238) mutations have been linked to both in vitro artemisinin resistance and in vivo slow parasite clearance rates and therefore proposed as a marker of artemisinin resistance. We evaluated if mutations seen in Cambodia have emerged in Bangladesh where ACT use is now standard for over a decade. Samples were obtained from P. falciparum infected malaria patients from Upazila Health Complexes (UHC) of seven endemic districts of Bangladesh. These districts included Khagrachhari (Matiranga UHC), Rangamati (Rajsthali UHC), Cox’s Bazar (Ramu and Ukhia UHC), Bandarban (Lama UHC), Mymensingh (Haluaghat UHC), Netrokona (Durgapur and Kalmakanda UHC) and Moulvibazar (Srimongol and Kamalganj UHC). Out of 296 microscopically positive P. falciparum samples, 271(91.6%) were confirmed by both real-time PCR and nested PCR to have pure infection. Nested PCR of the K13 gene amplified 253 (93.4%) samples. After ClustalW alignment and Jalview analysis, we initially found three non-synonymous mutations (A578S, W470C, and Y604H) in Bangladeshi clinical isolates. The A578S mutation was confirmed and lies adjacent to the C580Y mutation, the major mutation observed in Cambodia, and based on computational modeling should have a significant effect on tertiary structure. We conclude that novel mutations that may confer artemisinin resistance are present in certain districts of Bangladesh.

Methylene blue inhibits the asexual development of vivax malaria parasites from a region of increasing chloroquine resistance.

Methylene blue, once discarded due to its unsettling yet mild side effects, has now found a renewed place in the pharmacopoeia of modern medicine. The continued spread of drug-resistant Plasmodium vivax and Plasmodium falciparum has also led to a recent re-examination of methylene blue's potent antimalarial properties. Here we examine the ex vivo susceptibility profile of Plasmodium spp. isolates to methylene blue; the isolates were from a region on the Thai-Myanmar border where there are increasing rates of failure when treating vivax malaria with chloroquine. To do this we used a newly developed ex vivo susceptibility assay utilizing flow cytometry and a portable flow cytometer with a near-UV laser. P. vivax (median methylene blue IC50 3.1 nM, IQR 1.7-4.3 nM) and P. falciparum (median methylene blue IC50 1.8 nM, IQR 1.6-2.3 nM) are susceptible to methylene blue treatment at physiologically relevant levels. Unfortunately, the addition of chloroquine to combination treatments with methylene blue significantly reduces the ex vivo effectiveness of this molecule. Our data support further efforts to employ methylene blue as a safe, low-cost antimalarial to treat drug-resistant malaria.

Genetic polymorphisms of candidate markers and in vitro susceptibility of Plasmodium falciparum isolates from Thai-Myanmar border in relation to clinical response to artesunate–mefloquine combination

The genetic polymorphisms of the candidate markers of antimalarial drug resistance pfcrt, pfmdr1, pfatp6, and pfmrp1 were investigated in relationship with in vitro susceptibility of Plasmodium falciparum isolates and clinical response following artesunate (AS)–mefloquine (MQ) combination in 21 and 27 samples obtained from patients with recrudescence and adequate clinical response, respectively. MQ (21.0 vs. 49.9nM) and AS (1.6 vs. 2.8nM) IC50 values (concentrations that inhibit parasite growth by 50%) were significantly higher in isolates collected from patients with recrudescence. Furthermore, a significantly higher MQ IC50 was found in isolates from patients with recrudescence that carried pfmrp1 mutations at amino acid residues 191Y, 437A, and 876V. For AS sensitivity, a significant association was also detected in isolates from patients with recrudescence that carried gene mutations at amino acid residues 437A and 876V. MQ IC50 of the isolates with recrudescence which carried ≥4 pfmdr1 gene copies was significantly higher than that carrying only one gene copy. In addition, a significantly higher proportion of isolates carrying one gene copy was detected in the group with adequate clinical response compared with recrudescence. Results from this limited sample size suggested the potential link between pfmdr1 gene copy number and pfmrp1 gene mutation, in vitro parasite susceptibility, and AS–MQ treatment response.

Quantifying low birth weight, preterm birth and small-for-gestational-age effects of malaria in pregnancy: a population cohort study.

BackgroundThe association between malaria during pregnancy and low birth weight (LBW) is well described. This manuscript aims to quantify the relative contribution of malaria to small-for-gestational-age (SGA) infants and preterm birth (PTB) in pregnancies accurately dated by ultrasound on the Thai-Myanmar border at the Shoklo Malaria Research Unit.Methods and FindingsFrom 2001 to 2010 in a population cohort of prospectively followed pregnancies, we analyzed all singleton newborns who were live born, normal, weighed in the first hour of life and with a gestational age (GA) between 28+0 and 41+6 weeks. Fractional polynomial regression was used to determine the mean birthweight and standard deviation as functions of GA. Risk differences and factors of LBW and SGA were studied across the range of GA for malaria and non-malaria pregnancies. From 10,264 newborns records, population centiles were created.Women were screened for malaria by microscopy a median of 22 [range 1–38] times and it was detected and treated in 12.6% (1,292) of pregnancies. Malaria was associated with LBW, PTB, and SGA compared to those without malaria. Nearly two-thirds of PTB were classified as LBW (68% (539/789)), most of which 83% (447/539) were not SGA. After GA 39 weeks, 5% (298/5,966) of non-LBW births were identified as SGA. Low body mass index, primigravida, hypertension, smoking and female sex of the newborn were also significantly and independently associated with LBW and SGA consistent with previous publications.ConclusionsTreated malaria in pregnancy was associated with an increased risk for LBW, PTB, and SGA, of which the latter are most important for infant survival. Using LBW as an endpoint without adjusting for GA incorrectly estimated the effects of malaria in pregnancy. Ultrasound should be used for dating pregnancies and birth weights should be expressed as a function (or adjusted for GA) of GA in future malaria in pregnancy studies.

Linking international clinical research with stateless populations to justice in global health.

BackgroundIn response to calls to expand the scope of research ethics to address justice in global health, recent scholarship has sought to clarify how external research actors from high-income countries might discharge their obligation to reduce health disparities between and within countries. An ethical framework—‘research for health justice’—was derived from a theory of justice (the health capability paradigm) and specifies how international clinical research might contribute to improved health and research capacity in host communities. This paper examines whether and how external funders, sponsors, and researchers can fulfill their obligations under the framework.MethodsCase study research was undertaken on the Shoklo Malaria Research Unit’s (SMRU) vivax malaria treatment trial, which was performed on the Thai-Myanmar border with Karen and Myanmar refugees and migrants. We conducted nineteen in-depth interviews with trial stakeholders, including investigators, trial participants, community advisory board members, and funder representatives; directly observed at trial sites over a five-week period; and collected trial-related documents for analysis.ResultsThe vivax malaria treatment trial drew attention to contextual features that, when present, rendered the ‘research for health justice’ framework’s guidance partially incomplete. These insights allowed us to extend the framework to consider external research actors’ obligations to stateless populations. Data analysis then showed that framework requirements are largely fulfilled in relation to the vivax malaria treatment trial by Wellcome Trust (funder), Oxford University (sponsor), and investigators. At the same time, this study demonstrates that it may be difficult for long-term collaborations to shift the focus of their research agendas in accordance with the changing burden of illness in their host communities and to build the independent research capacity of host populations when working with refugees and migrants. Obstructive factors included the research funding environment and staff turnover due to resettlement or migration.ConclusionsOur findings show that obligations for selecting research targets, research capacity strengthening, and post-trial benefits that link clinical trials to justice in global health can be upheld by external research actors from high-income countries when working with stateless populations in LMICs. However, meeting certain framework requirements for long-term collaborations may not be entirely feasible.

Low and stable rates of antenatal syphilis and HIV in migrant and refugee women on the Thai-Myanmar border: a descriptive study

Objective: The antenatal prevalence of syphilis and HIV/AIDS in migrants and refugees is poorly documented. The aim of this study was to audit the first year of routine syphilis screening in migrant and refugee women on the Thai Myanmar border.Methods: From August 2012 to July 2013, 3600 pregnant women were screened for HIV (ELISA) and syphilis (VDRL with TPHA confirmation) at clinics along the Thai-Myanmar border.Results: Seroprevalence for HIV 0.47% (95% CI 0.30-0.76) (17/3,599), and syphilis 0.39% (95% CI 0.23-0.65) (14/3,592), were low. Syphilis was significantly lower in refugees (0.07% 95% CI 0.01-0.38) (1/1,469), than in migrants (0.61% 95% CI 0.36-1.04) (13/2,123). The three active (VDRL≥1:8 and TPHA reactive) syphilis cases with VDRL titres of 1:32 were easy to counsel and treat. Women with low VDRL titres (>75% were < 1:8) and TPHA reactive results, in the absence of symptoms and both the woman and her husband having only one sexual partner in their lifetime, and the inability to determine the true cause of the positive results presented ethical difficulties for counsellors.Conclusion: As HIV and syphilis testing becomes available in more and more settings, the potential impact of false positive results should be considered, especially in populations with low prevalence for these diseases. This uncertainty must be considered in order to counsel patients and partners accurately and safely about the results of these tests, without exposing women to increased risk for abuse or abandonment. Our findings highlight the complexities of counselling patients about these tests and the global need for more conclusive syphilis testing strategies.

Gestational diabetes mellitus prevalence in Maela refugee camp on the Thai–Myanmar Border: a clinical report

Background Individuals in conflict-affected areas rarely get appropriate care for chronic or non-infectious diseases. The prevalence of gestational diabetes mellitus (GDM) is increasing worldwide, and new evidence shows conclusively that the negative effects of hyperglycemia occur even at mild glucose elevations and that these negative effects can be attenuated by treatment. Scientific literature on gestational diabetes in refugee camp settings is critically limited. Methods A 75 g 2-hour glucose tolerance test was administered to 228 women attending the antenatal care (ANC) clinic in Maela refugee camp on the Thai–Myanmar border. Prevalence of GDM was determined using the HAPO trial cut-offs [≥92 mg/dL (fasting),≥180 (1 hour), and≥153 (2 hour)] and the WHO criteria [≥126 mg/dL (fasting), and 140 mg/dL (2 hour)]. Results From July 2011 to March 2012, the prevalence of GDM was 10.1% [95% confidence interval (CI): 6.2–14.0] when the cut-off determined by the HAPO trial was applied. Applying the older WHO criteria yielded a prevalence of 6.6% (95% CI 3.3–9.8). Age, parity, and BMI emerged as characteristics that may be significantly associated with GDM in this population. Other risk factors that are commonly used in screening guidelines were not applicable in this diabetes-naïve population. Discussion The prevalence of GDM is lower in this population compared with other populations, but still complicates 10% of pregnancies. New evidence regarding gestational diabetes raises new dilemmas for healthcare providers in resource-poor settings. Efforts to identify and treat patients at risk for adverse outcomes need to be balanced with awareness of the risks and burdens associated with over diagnosis and unnecessary interventions. Screening approaches based on risk factors or using higher cut-off values may help minimize this burden and identify those most likely to benefit from intervention.

タイ北部国境地域における仏教僧による「開発」と宗教実践の再構築

タイ北部国境地域における仏教僧による「開発」と宗教実践の再構築

Household ecology and out-migration among ethnic Karen along the Thai-Myanmar border

Local migration in developing-world settings, particularly among rural populations, is an important yet understudied demographic process. Research on migration in such populations can help us test and inform anthropological and demographic theory. Furtherm

Two fatal cases of melioidosis on the Thai-Myanmar border.

Melioidosis is endemic in areas of Southeast Asia, however, there are no published reports from the Thai-Myanmar border. We report the first two documented cases of fatal melioidosis in this region. This is of great public health importance and highlights the need to both increase clinical awareness of melioidosis on the Thai-Myanmar border, and to assess the true burden of disease in the area through improved case detection and Burkholderia pseudomallei prevalence studies.

Distribution of pfmdr1 polymorphisms in Plasmodium falciparum isolated from Southern Thailand

BackgroundDrug resistance in Plasmodium falciparum is a major problem in malaria control especially along the Thai-Myanmar and Thai-Cambodia borders. To date, a few molecular markers have been identified for anti-malarial resistance in P. falciparum, including the P. falciparum chloroquine resistance transporter (pfcrt) and the P. falciparum multidrug resistance 1 (pfmdr1). However no information is available regarding the distribution pattern of these gene polymorphisms in the parasites from the Thai-Malaysia border. This study was conducted to compare the distribution pattern of the pfcrt and pfmdr1 polymorphisms in the parasites from the lower southern provinces, Thai-Malaysia border and the upper southern provinces, Thai-Myanmar border. In addition, in vitro sensitivities of anti-malarial drugs including chloroquine, mefloquine, quinine, and artesunate were determined.MethodsIn all, 492 P. falciparum-positive blood samples were collected from the lower southern provinces: Songkhla, Yala and Narathiwas. From the upper southern part of Thailand, Ranong and Chumphon, 66 samples were also collected. Polymorphisms of the pfcrt and the pfmdr1 gene were determined using PCR techniques. In vitro sensitivities of anti-malarial drugs were determined using radioisotopic method.ResultsAll parasites from both areas contained the pfcrt 76 T allele. The pfmdr1 86Y allele was significantly more common in the parasites isolated from the lower southern areas. In contrast, the pfmdr1 184F allele was predominant among the parasites from the upper southern areas especially Ranong. In addition, the parasites from Ranong contained higher copy numbers than the parasites from other provinces. All adapted parasite isolates exhibited CQ-resistant phenotype. Neither QN nor MQ resistance was detected in these isolates.ConclusionThe parasites from Thai-Malaysia border exhibited different resistant patterns compared to other areas along the international border of Thailand. This information will be useful for anti-malarial drug policy in Thailand.

Motivations and perceptions of community advisory boards in the ethics of medical research: the case of the Thai-Myanmar border

BackgroundCommunity engagement is increasingly promoted as a marker of good, ethical practice in the context of international collaborative research in low-income countries. There is, however, no widely agreed definition of community engagement or of approaches adopted. Justifications given for its use also vary. Community engagement is, for example, variously seen to be of value in: the development of more effective and appropriate consent processes; improved understanding of the aims and forms of research; higher recruitment rates; the identification of important ethical issues; the building of better relationships between the community and researchers; the obtaining of community permission to approach potential research participants; and, the provision of better health care. Despite these diverse and potentially competing claims made for the importance of community engagement, there is very little published evidence on effective models of engagement or their evaluation.MethodsIn this paper, drawing upon interviews with the members of a Community Advisory Board on the Thai-Myanmar border, we describe and critically reflect upon an approach to community engagement which was developed in the context of international collaborative research in the border region.Results and conclusionsDrawing on our analysis, we identify a number of considerations relevant to the development of an approach to evaluating community engagement in this complex research setting. The paper also identifies a range of important ways in which the Community Advisory Board is in practice understood by its members (and perhaps by community members beyond this) to have morally significant roles and responsibilities beyond those usually associated with the successful and appropriate conduct of research.

Four years’ monitoring of in vitro sensitivity and candidate molecular markers of resistance of Plasmodium falciparum to artesunate-mefloquine combination in the Thai-Myanmar border

BackgroundThe decline in efficacy of artesunate (AS) and mefloquine (MQ) is now the major concern in areas along the Thai-Cambodian and Thai-Myanmar borders.MethodsThe correlation between polymorphisms of pfatp6, pfcrt, pfmdr1 and pfmrp1 genes and in vitro sensitivity of Plasmodium falciparum isolates to the artemisinin-based combination therapy (ACT) components AS and MQ, including the previously used first-line anti-malarial drugs chloroquine (CQ) and quinine (QN) were investigated in a total of 119 P. falciparum isolates collected from patients with uncomplicated P. falciparum infection during 2006–2009.ResultsReduced in vitro parasite sensitivity to AS [median (95% CI) IC50 3.4 (3.1-3.7) nM] was found in 42% of the isolates, whereas resistance to MQ [median (95% CI) IC50 54.1 (46.8-61.4) nM] accounted for 58% of the isolates. Amplification of pfmdr1 gene was strongly associated with a decline in susceptibility of P. falciparum isolates to AS, MQ and QN. Significant difference in IC50 values of AS, MQ and QN was observed among isolates carrying one, two, three, and ≥ four gene copies [median (95% CI) AS IC50: 1.6 (1.3-1.9), 1.8 (1.1-2.5), 2.9 (2.1-3.7) and 3.1 (2.5-3.7) nM, respectively; MQ IC50: 19.2 (15.8-22.6), 37.8 (10.7-64.8), 55.3 (47.7-62.9) and 63.6 (49.2-78.0) nM, respectively; and QN IC50: 183.0 (139.9-226.4), 256.4 (83.7-249.1), 329.5 (206.6-425.5) and 420.0 (475.2-475.6) nM, respectively]. The prevalence of isolates which were resistant to QN was reduced from 21.4% during the period 2006–2007 to 6.3% during the period 2008–2009. Pfmdr1 86Y was found to be associated with increased susceptibility of the parasite to MQ and QN. Pfmdr1 1034C was associated with decreased susceptibility to QN. Pfmrp1 191Y and 1390I were associated with increased susceptibility to CQ and QN, respectively.ConclusionHigh prevalence of CQ and MQ-resistant P. falciparum isolates was observed during the four-year observation period (2006–2009). AS sensitivity was declined, while QN sensitivity was improved. Pfmdr1 and pfmrp1 appear to be the key genes that modulate multidrug resistance in P. falciparum.

Two fatal cases of melioidosis on the Thai-Myanmar border

Melioidosis is endemic in areas of Southeast Asia, however, there are no published reports from the Thai-Myanmar border. We report the first two cases of fatal melioidosis in this region. This is of great public health importance and highlights the need to increase clinical awareness of melioidosis on the Thai-Myanmar border and to assess the true burden of disease in the area through improved case detection and Burkholderia pseudomallei prevalence studies.