Longer exposure to a new refugee food ration is associated with reduced prevalence of small for gestational age: results from 2 cross-sectional surveys on the Thailand-Myanmar border.

Background: Despite the high risk of compromised nutrition, evidence of the effect of refugee rations on fetal growth is limited. A new ration containing micronutrient-fortified flour without increased caloric content of the general food basket was introduced to the Maela refugee camp in Thailand, July 2004. Objective: The effect of the length of gestational exposure of the new ration on fetal growth was compared with birth outcomes [small for gestational age (SGA), preterm birth (PTB)]. Design: In an observational study in 987 newborns from 1048 prospectively followed antenatal clinic (ANC) attendees enrolled in 2 cross-sectional surveys, exposure was categorized in 2004 according to gestation at the time of commencing the new ration and in 2006 as comprehensive (preconception and pregnancy). In both surveys, the pregnancy-specific ration and vitamin supplements were routine. Results: In 2004, the proportions of SGA decreased with longer exposure to the new ration: no exposure during pregnancy (27.7%; n = 13 of 47) and exposure in the third (27.6%; n = 37 of 134), second (18.6%; n = 35 of 188), and first (19.4%; n = 6 of 31) trimesters, respectively (adjusted P-trend = 0.046). In 2006, the new ration was available to all women and there was no significant additional impact of the pregnancy-specific ration and vitamin supplements. Between 2004 and 2006, SGA decreased from 28.9% (13 of 45) to 17.3% (69 of 398) (adjusted P = 0.050), a reduction of 40.1% (95% CI: 34.7%, 45.9%); there was also a decrease in the percentage of underweight women on admission to the ANC (38.2%; 95% CI: 31.4%, 45.5%). PTB rates were low and not significantly different with exposure to the new ration. Conclusions: In 2004, the earlier in gestation in which the new ration was available the greater the effect on fetal growth as shown by a reduced prevalence of SGA. In 2006, additional benefits to fetal growth from the pregnancy-specific ration and vitamin supplements beyond those of the preconception ration were not observed. Good nutrition in pregnancy remains an important challenge for refugee populations. This trial was registered at http://drks-neu.uniklinik-freiburg.de/drks_web/ as DRKS00007736

Enantiospecific pharmacokinetics and drug-drug interactions of primaquine and blood-stage antimalarial drugs

Objectives Characterization of the pharmacokinetic properties of the enantiomers of primaquine and carboxyprimaquine following administration of racemic primaquine given alone and in combination with commonly used antimalarial drugs. Methods Enantiomeric pharmacokinetics were evaluated in 49 healthy adult volunteers enrolled in three randomized cross-over studies in which a single dose of primaquine was given alone and then, after a suitable washout period, in combination with chloroquine, dihydroartemisinin/piperaquine or pyronaridine/artesunate. Non-linear mixed-effects modelling was used to characterize pharmacokinetics and assess the impact of drug–drug interactions. Results The volume of distribution of racemic primaquine was decreased by a median (95% CI) of 22.0% (2.24%–39.9%), 24.0% (15.0%–31.5%) and 25.7% (20.3%–31.1%) when co-administered with chloroquine, dihydroartemisinin/piperaquine and pyronaridine/artesunate, respectively. The oral clearance of primaquine was decreased by a median of 19.1% (14.5%–22.8%) when co-administered with pyronaridine/artesunate. These interactions were enantiospecific with a relatively higher effect on (+)-S-primaquine than on (−)-R-primaquine. No drug–drug interaction effects were seen on the pharmacokinetics of either carboxyprimaquine enantiomer. Conclusions Population pharmacokinetic models characterizing the enantiospecific properties of primaquine were developed successfully. Exposure to primaquine, particularly to the (+)-S-primaquine but not the carboxy metabolites, increased by up to 30% when co-administered with commonly used antimalarial drugs. A better mechanistic understanding of primaquine metabolism is required for assessment of its efficacy and haematological toxicity in humans

Challenges arising when seeking broad consent for health research data sharing: a qualitative study of perspectives in Thailand

Background Research funders, regulatory agencies, and journals are increasingly expecting that individual-level data from health research will be shared. Broad consent to such sharing is considered appropriate, feasible and acceptable in low- and middle-income settings, but to date limited empirical research has been conducted to inform the design of such processes. We examined stakeholder perspectives about how best to seek broad consent to sharing data from the Mahidol Oxford Tropical Medicine Research Unit, which implemented a data sharing policy and broad consent to data sharing in January 2016. Methods Between February and August 2017 qualitative data were collected at two sites, Bangkok and the Thai-Myanmar border town of Mae Sot. We conducted eighteen semi-structured interviews. We also conducted four focus group discussions with a total of nineteen people. Descriptive and thematic coding informed analysis of aspects of data sharing that are considered most important to inform participants about, and the best ways to explain complex and abstract topics relating to data sharing. Results The findings demonstrated that clinical trial participants prioritise information about the potential benefits and harms of data sharing. Stakeholders made multiple suggestions for clarifying information provided about data sharing on such topics. There was significant variation amongst stakeholders’ perspectives about how much information should be provided about data sharing, and it was clear that effective information provision should be responsive to the study, the study population, the individual research participant and the research context. Conclusions Effectively communicating about data sharing with research participants is challenging in practice, highlighting the importance of robust and effective data sharing governance in this context. Broad consent should incorporate effective and efficient explanations of data sharing to promote informed decision-making, without impeding research participants’ understandings of key aspects of the research from which data will be shared. Further work is required to refine both the development of core information about data sharing to be provided to all research participants, and appropriate solutions for context specific-challenges arising when explaining data sharing

Correction: Yuhana et al. Rickettsial infections are neglected causes of acute febrile illness in Teluk Intan, Peninsular Malaysia. Trop. Med. Infect. Dis. 2022, 7, 77

The authors wish to make the following correction to this paper [...]

Diagnostic performances of the fluorescent spot test for G6PD deficiency in newborns along the Thailand-Myanmar border: A cohort study

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an inherited enzymatic disorder associated with severe neonatal hyperbilirubinemia and acute haemolysis after exposure to certain drugs or infections. The disorder can be diagnosed phenotypically with a fluorescent spot test (FST), which is a simple test that requires training and basic laboratory equipment. This study aimed to assess the diagnostic performances of the FST used on umbilical cord blood by locally-trained staff and to compare test results of the neonates at birth with the results after one month of age. Methods: We conducted a cohort study on newborns at the Shoklo Malaria Research Unit, along the Thai-Myanmar border between January 2015 and May 2016. The FST was performed at birth on the umbilical cord blood by locally-trained staff and quality controlled by specialised technicians at the central laboratory. The FST was repeated after one month of age. Genotyping for common local G6PD mutations was carried out for all discrepant results. Results: FST was performed on 1521 umbilical cord blood samples. Quality control and genotyping revealed 10 misdiagnoses. After quality control, 10.7% of the males (84/786) and 1.2% of the females (9/735) were phenotypically G6PD deficient at birth. The FST repeated at one month of age or later diagnosed 8 additional G6PD deficient infants who were phenotypically normal at birth. Conclusions: This study shows the short-comings of the G6PD FST in neonatal routine screening and highlights the importance of training and quality control. A more conservative interpretation of the FST in male newborns could increase the diagnostic performances. Quantitative point-of-care tests might show higher sensitivity and specificity for diagnosis of G6PD deficiency on umbilical cord blood and should be investigated

Sequential open-label study of the safety, tolerability, and pharmacokinetic interactions between dihydroartemisinin-piperaquine and mefloquine in healthy Thai adults

Artemisinin-based combination therapies (ACTs) have contributed substantially to the global decline in Plasmodium falciparum morbidity and mortality, but resistance to artemisinins and their partner drugs is increasing in Southeast Asia, threatening malaria control. New antimalarial compounds will not be generally available soon. Combining three existing antimalarials in the form of triple ACTs, including dihydroartemisinin (DHA)-piperaquine mefloquine, is a potential treatment option for multidrug-resistant Plasmodium falciparum malaria. In a sequential openlabel study, healthy Thai volunteers were treated with DHA-piperaquine (120 to 960 mg), mefloquine (500 mg), and DHA-piperaquine mefloquine (120 to 960 mg 500 mg), and serial symptom questionnaires, biochemistry, full blood counts, pharmacokinetic profiles, and electrocardiographic measurements were performed. Fifteen healthy subjects were enrolled. There was no difference in the incidence or severity of adverse events between the three treatment arms. The slight prolongation in QTc (QT interval corrected for heart rate) associated with DHA-piperaquine administration did not increase after administration of DHA-piperaquine mefloquine. The addition of mefloquine had no significant effect on the pharmacokinetic properties of piperaquine. However, coadministration of mefloquine significantly reduced the exposures to dihydroartemisinin for area under the concentration-time curve (22.6%; 90% confidence interval [CI], 33.1, 10.4; P = 0.0039) and maximum concentration of drug in serum (29.0%; 90% CI, 40.6, 15.1; P = 0.0079). Mefloquine can be added safely to dihydroartemisinin-piperaquine in malaria treatment. (This study has been registered at ClinicalTrials.gov under identifier NCT02324738.

High hepatitis B seroprevalence and risk factors for infection in pregnant women on the Thailand-Myanmar border

Introduction: Infection from Hepatitis B primarily results from peri-partum vertical transmission and the risk increases in the presence of hepatitis B e antigen. We aimed to evaluate a new screening program for hepatitis B in pregnant women as a component of antenatal services in a marginalized population. Methodology: Counseling and screening for hepatitis B screening was offered to all women at the first visit, at Shoklo Malaria Research Unit (SMRU) antenatal clinics on the Thai-Myanmar border. Point-of-care rapid diagnostic tests (RDT) were used throughout the period of evaluation. A certified Thai Public Health laboratory at Mae Sot Hospital verified RDT positive cases using enzyme-linked immunosorbent assay (ELISA) for HBsAb and HBeAg. Risk factors for hepatitis B were identified by data linkage to antenatal care records. Results: There were 523 (8.5%) RDT positive for HBsAg among 6158 women tested (Aug-2012 to April-2014). Of these 373 (96.9%) of 385 sent for confirmation were positive by ELISA i.e. RDT false positive rate of 3.1% (95% CI 1.7- 5.4). The overall confirmed HbsAg prevalence was 8.3% (511/6158) (95% CI 7.6-9.0). HBeAg prevalence was 32.7% (114/350) (95% CI 27.9-37.7) of cases tested. Risk factors for HBsAg positivity included age > 25 years (OR 1.24, CI 1.03-1.49, p 0.021) and Karen heritage (OR 1.73, CI 1.39-2.15, p < 0.01). Conclusions: High hepatitis B seroprevalence amongst migrants and refugees accessing SMRU antenatal services likely reflects that of Kayin State, Myanmar, and perinatal prevention programs are required. False positive cases with HBsAg RDT complicate what is theoretically a straightforward screening

Epidemiology of Plasmodium vivax malaria infection in Nepal

Malaria is endemic in the southern plain of Nepal which shares a porous border with India. More than 80% cases of malaria in Nepal are caused by Plasmodium vivax. The main objective of this study was to review the epidemiology of P. vivax malaria infections as recorded by the national malaria control program of Nepal between 1963 and 2016. National malaria data were retrieved from the National Malaria program in the Ministry of Health, Government of Nepal. The epidemiological trends and malariometric indicators were analyzed. Vivax malaria has predominated over falciparum malaria in the past 53 years, with P. vivax malaria comprising 70-95% of the annual malaria infections. In 1985, a malaria epidemic occurred with 42,321 cases (82% P. vivax and 17% Plasmodium falciparum). Nepal had experienced further outbreaks of malaria in 1991 and 2002. Plasmodium falciparum cases increased from 2005 to 2010 but since then declined. Analyzing the overall trend between 2002 (12,786 cases) until 2016 (1,009 cases) shows a case reduction by 92%. The proportion of imported malaria cases has increased from 18% of cases in 2001 to 50% in 2016. The current trends of malariometric indices indicate that Nepal is making a significant progress toward achieving the goal of malaria elimination by 2025. Most of the cases are caused by P. vivax with imported malaria comprising an increasing proportion of cases. The malaria control program in Nepal needs to counter importation of malaria at high risk areas with collaborative cross border malaria control activities

Safety, pharmacokinetics, and mosquito‐lethal effects of ivermectin in combination with dihydroartemisinin‐piperaquine and primaquine in healthy adult Thai subjects

Mass administration of antimalarial drugs and ivermectin are being considered as potential accelerators of malaria elimination. The safety, tolerability, pharmacokinetics and mosquito-lethal effects of combinations of ivermectin, dihydroartemisinin-piperaquine, and primaquine were evaluated. Co-administration of ivermectin and dihydroartemisinin-piperaquine, resulted in increased ivermectin concentrations with corresponding increases in mosquito-lethal effect across all subjects. Exposure to piperaquine was also increased when co-administered with ivermectin, but electrocardiograph QT-interval prolongation was not increased. One subject had transiently impaired liver function. Ivermectin mosquito-lethal effect was greater than predicted previously against the major Southeast Asian malaria vectors. Both Anopheles dirus and Anopheles minimus mosquito mortality was increased substantially (20-fold and 35-fold increase, respectively) when feeding on volunteer blood after ivermectin administration compared to in vitro ivermectin-spiked blood. This suggests the presence of ivermectin metabolites that impart mosquito-lethal effects. Further studies of this combined approach to accelerate malaria elimination are warranted

Maternal hepatitis B infection burden, comorbidity and pregnancy outcome in a low-income population on the Myanmar-Thailand border: A retrospective cohort study

Objectives:Hepatitis B virus (HBV) was believed to have minimal impact on pregnancy outcomes apart from the risk of perinatal transmission. In more recent years, there have been reports of adverse associations, most consistently preterm birth (PTB), but this is in the context of high rates of caesarean section. The aim of this study was to explore the association of HBV on pregnancy outcomes in marginalized, low-income populations on the Myanmar-Thailand border. Methods:HBsAg positive (+) point of care rapid detection tests results were confirmed by immunoassays. Women with a confirmed HBsAg status, HIV- and syphilis-negative at first antenatal care screening, singleton fetus and known pregnancy outcome (Aug-2012 to Dec-2016) were included. Logistic regression analysis was used to evaluate associations between HBV group (controls HBsAg negative, HBsAg+/HBeAg-, or HBsAg+/HBeAg+) and pregnancy outcome and comorbidity. Results:Most women were tested, 15,046/15,114 (99.6%) for HBV. The inclusion criteria were not met for 4,089/15,046 (27.2%) women due mainly to unavailability of pregnancy outcome and nonconfirmation of HBsAg+. In evaluable women 687/11,025 (6.2%) were HBsAg+, with 476/11,025 (4.3%) HBsAg+/HBeAg- and 211/11,025 (1.9%) were HBsAg+/HBeAg+. The caesarean section rate was low at 522/8,963 (5.8%). No significant associations were observed between pregnancy comorbidities or adverse pregnancy outcomes and HBV status. Conclusions:The results highlight the disease burden of HBV in women on the Myanmar-Thailand border and support original reports of a lack of significant associations with HBsAg+ irrespective of HBeAg status, for comorbidity, and pregnancy outcomes in deliveries supervised by skilled birth attendants