Social Transfers for Exclusive Breastfeeding (STEB) Intervention in Lao People's Democratic Republic: Protocol for a Randomized Controlled Trial.

BACKGROUND: Children in Lao People's Democratic Republic (Lao PDR) receive suboptimal nutrition because of low breastfeeding rates, undermining their developmental potential. While major public health campaigns have attempted to increase breastfeeding rates, they have been largely unsuccessful. One explanation for these unsuccessful interventions is the economic and financial constraints faced by mothers. A potential solution for alleviating these pressures is providing social transfers to support breastfeeding; defined as a cash or in-kind transfer. Capitalizing on key strategies used in previous social transfer programs, we will assess the effectiveness of social transfer intervention for increasing exclusive breastfeeding rates in Vientiane, Lao PDR. OBJECTIVE: This study aims to conduct a randomized controlled trial (RCT) designed to assess whether social transfers can increase exclusive breastfeeding rates in Vientiane Capital, Lao PDR. METHODS: A prospective, parallel cluster-RCT was conducted among 300 mothers who recently gave birth and initiated breastfeeding. Enrolling 100 participants for each intervention arm provided us with 80% power to detect an increase in exclusive breastfeeding from the anticipated 21% in the control arm to 40% in either of the 2 intervention arms. Mother-infant dyads were enrolled at approximately 1 month post partum. Follow-up visits will occur at 6 months, 1 year, 2 years, and 3 years post partum; with the ambition to extend the follow-up period. Mother-infant dyads were enrolled between August 2022 and April 2023 with follow-up until 3 years post partum (2026). A local study team comprised of 2 nurses and 2 laboratory technicians is responsible for enrollment and follow-up of participants. Participants were randomly assigned to one of three groups during the baseline, 1-month visit: (1) control group, no social transfer; (2) intervention group 1, an unconditional social transfer at 6 months post partum; and (3) intervention group 2, a social transfer at 6 months post partum conditional upon mothers exclusively breastfeeding. All groups received educational materials supporting mothers to exclusively breastfeed. The primary end point will be exclusive breastfeeding at 6 months post partum. Secondary end points will include exclusive and complementary breastfeeding duration, childhood wasting and stunting, child growth, maternal and infant stress, predictors of early breastfeeding cessation, intestinal inflammation, anemia, maternal weight loss, maternal blood pressure, maternal anxiety, and GRIT personality score. Questionnaires and physical examinations were used to collect information. RESULTS: As of November 2023, the study has enrolled 300 participants. Study participation is ongoing until December 2026 at minimum. Over the study lifetime, 93% have completed all visits. CONCLUSIONS: We see potential for a long-term program that may be implemented in other low- or lower-middle-income countries with only minor modifications. The RCT will be used as a basis for observational studies and to investigate the impact of human milk on child fecal microbiota and growth. TRIAL REGISTRATION: ClinicalTrials.gov NCT05665049; https://clinicaltrials.gov/study/NCT05665049. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54768.

Current advances in serological and molecular diagnosis of Schistosoma mekongi infection.

Schistosomiasis, a neglected tropical disease, caused by blood flukes belonging to the genus Schistosoma; it persists as a public health problem in selected regions throughout Africa, South America, and Asia. Schistosoma mekongi, a zoonotic schistosome species endemic to the Mekong River in Laos and Cambodia, is one of the significant causes of human schistosomiasis along with S. japonicum, S. mansoni, S. haematobium and S. intercalatum. Since its discovery, S. mekongi infection has been highly prevalent in communities along the Mekong River. Although surveillance and control measures have shown success in recent years, more robust diagnostic tools are still needed to establish more efficient control and prevention strategies to achieve and sustain an elimination status. Diagnosis of S. mekongi infection still relies on copro-parasitological techniques, commonly made by Kato-Katz stool examination. Serological techniques such as enzyme-linked immunosorbent assay (ELISA) may also be applicable but in a limited setting. Targeted molecular and serological tools specific to the species, on the other hand, have been limited. This is due, in part, to the limited research and studies on the molecular biology of S. mekongi since genome information of this species has not yet been released. In this review, current advances, and gaps and limitations in the molecular and immunological diagnosis of S. mekongi are discussed.

Egg excretion patterns of soil-transmitted helminth infections in humans following albendazole-ivermectin and albendazole treatment.

BACKGROUND: Control efforts of soil-transmitted helminthiases rely primarily on large scale administration of anthelminthic drugs. The assessment of drug efficacies and understanding of drug behavior is pivotal to the evaluation of treatment successes, both in preventive chemo-therapy programs as well as in research of novel treatment options. The current WHO guidelines recommend an interval of 14-21 days between the treatment and follow-up, yet no in-depth analysis of egg excretion patterns of Trichuris trichiura after treatment has been conducted to date. METHODS: Within the framework of a multi-country trial to assess the efficacy and safety of albendazole-ivermectin combination therapy vs albendazole monotherapy against T. trichiura infections, we conducted a study collecting daily stool samples over the period of 28 days post-treatment in 87 participants in Pak Khan, Lao PDR. Egg counts were derived by duplicate Kato-Katz on-site for T. trichiura, hookworm and Ascaris lumbricoides and stool sample aliquots were subsequently analyzed by qPCR for the detection of T. trichiura infections. Sensitivity and specificity was calculated for each day separately using data derived by Kato-Katz to determine the optimal timepoint at which to assess drug efficacy. RESULTS: Egg excretion patterns varied across treatment arms. For T. trichiura, only the albendazole-ivermectin treatment led to a considerable reduction in mean egg counts, whereas both treatments reduced hookworm egg counts and A. lumbricoides were cleared in all participants after day 7. For T. trichiura, we found sensitivity to be highest at days 18 and 22 when using egg counts as outcome and days 19 and 24 when using qPCR. Specificity was high (>0.9) from day 14 onwards. For hookworm, the highest sensitivity and specificity were found at days 17 and 25, respectively. CONCLUSIONS: Based on our study, the ideal time period to assess drug efficacy for soil-transmitted helminth infections would be between day 18 and 24. The current WHO recommendation of 14 to 21 days is likely to yield acceptable outcome measures for soil-transmitted helminth infections. TRIAL REGISTRATION: NCT03527732.

Steatotic liver disease among lean and non-lean individuals in Southern Lao PDR: a cross-sectional study of risk factors.

BACKGROUND: Steatotic liver disease (SLD) prevalence is rising worldwide, linked to insulin resistance and obesity. SLD prevalence can surpass 10% even among those with normal weight. In Lao People's Democratic Republic (Lao PDR), where Opisthorchis viverrini (OV) trematode infection and type 2 diabetes mellitus (T2DM) are common, infection related liver morbidity such as cholangiocarcinoma (CCA) is high, but data on SLD prevalence is lacking. The objective of this study was to estimate the prevalence and explore determinants of SLD in rural southern Lao PDR for lean and non-lean populations. METHOD: A cross-sectional community-based study assessed SLD prevalence using abdominal ultrasonography (US). Factors investigated for association with SLD were identified by interview, serological tests (Hepatitis B surface antigen (HBsAg); lipids and HbA1c), anthropometrical measurements, and parasitological assessments (OV infection). Uni- and multivariable logistic regression analyses with SLD as endpoint were conducted separately for lean (body mass index (BMI) <23.0 kg/m2) and non-lean (BMI ≥ 23.0 kg/m2) participants. RESULT: 2,826 participants were included. SLD prevalence was 27.1% (95% confidence interval (95% CI) 24.0%-30.4%), higher among non-lean (39.8%) than lean individuals (17.4%). Lean individuals with OV infection had a statistically significant association with lower odds of SLD (adjusted odds ratio (aOR) 0.49, 95% CI 0.33 - 0.73). T2DM showed a significant positive association with SLD in both lean (aOR 3.58, 95% CI 2.28 - 5.63) and non-lean individuals (aOR 3.31, 95% CI 2.31 - 4.74) while dyslipidemia was significantly associated only in the non-lean group (aOR 1.83, 95% CI 1.09 - 3.07). Females participants exhibited elevated odds of SLD in both lean (aOR 1.43, 95% CI 1.02 - 2.01) and non-lean SLD (aOR 1.50, 95% CI 1.12 - 2.01). CONCLUSION: SLD prevalence is notably high among Laotian adults in rural areas, particularly in females and in non-lean individuals. Lean individuals with OV infection exhibited lower SLD prevalence. SLD was more prevalent in individuals with T2DM, independent of BMI. SLD adds to the burden of infection-related liver morbidity in Lao PDR.

Natural variables separate the endemic areas of Clonorchis sinensis and Opisthorchis viverrini along a continuous, straight zone in Southeast Asia.

BACKGROUND: Clonorchiasis and opisthorchiasis, caused by the liver flukes Clonorchis sinensis and Opisthorchis viverrini respectively, represent significant neglected tropical diseases (NTDs) in Asia. The co-existence of these pathogens in overlapping regions complicates effective disease control strategies. This study aimed to clarify the distribution and interaction of these diseases within Southeast Asia. METHODS: We systematically collated occurrence records of human clonorchiasis (n = 1809) and opisthorchiasis (n = 731) across the Southeast Asia countries. Utilizing species distribution models incorporating environmental and climatic data, coupled machine learning algorithms with boosted regression trees, we predicted and distinguished endemic areas for each fluke species. Machine learning techniques, including geospatial analysis, were employed to delineate the boundaries between these flukes. RESULTS: Our analysis revealed that the endemic range of C. sinensis and O. viverrini in Southeast Asia primarily spans across part of China, Vietnam, Thailand, Laos, and Cambodia. During the period from 2000 to 2018, we identified C. sinensis infections in 84 distinct locations, predominantly in southern China (Guangxi Zhuang Autonomous Region) and northern Vietnam. In a stark contrast, O. viverrini was more widely distributed, with infections documented in 721 locations across Thailand, Laos, Cambodia, and Vietnam. Critical environmental determinants were quantitatively analyzed, revealing annual mean temperatures ranging between 14 and 20 °C in clonorchiasis-endemic areas and 24-30 °C in opisthorchiasis regions (P < 0.05). The machine learning model effectively mapped a distinct demarcation zone, demonstrating a clear separation between the endemic areas of these two liver flukes with AUC from 0.9 to1. The study in Vietnam delineates the coexistence and geographical boundaries of C. sinensis and O. viverrini, revealing distinct endemic zones and a transitional area where both liver fluke species overlap. CONCLUSIONS: Our findings highlight the critical role of specific climatic and environmental factors in influencing the geographical distribution of C. sinensis and O. viverrini. This spatial delineation offers valuable insights for integrated surveillance and control strategies, particularly in regions with sympatric transmission. The results underscore the need for tailored interventions, considering regional epidemiological variations. Future collaborations integrating eco-epidemiology, molecular epidemiology, and parasitology are essential to further elucidate the complex interplay of liver fluke distributions in Asia.

A Predictive Model for Thiamine Responsive Disorders Among Infants and Young Children: Results from a Prospective Cohort Study in Lao People's Democratic Republic.

OBJECTIVE: To develop a predictive model for thiamine responsive disorders (TRDs) among infants and young children hospitalized with signs or symptoms suggestive of thiamine deficiency disorders (TDDs) based on response to therapeutic thiamine in a high-risk setting. STUDY DESIGN: Children aged 21 days to <18 months hospitalized with signs or symptoms suggestive of TDD in northern Lao People's Democratic Republic were treated with parenteral thiamine (100 mg daily) for ≥3 days in addition to routine care. Physical examinations and recovery assessments were conducted frequently for 72 hours after thiamine was initiated. Individual case reports were independently reviewed by three pediatricians who assigned a TRD status (TRD or non-TRD), which served as the dependent variable in logistic regression models to identify predictors of TRD. Model performance was quantified by empirical area under the receiver operating characteristic curve. RESULTS: A total of 449 children (median [Q1, Q3] 2.9 [1.7, 5.7] months old; 70.3% exclusively/predominantly breastfed) were enrolled; 60.8% had a TRD. Among 52 candidate variables, those most predictive of TRD were exclusive/predominant breastfeeding, hoarse voice/loss of voice, cyanosis, no eye contact, and no diarrhea in the previous 2 weeks. The area under the receiver operating characteristic curve (95% CI) was 0.82 (0.78, 0.86). CONCLUSIONS: In this study, the majority of children with signs or symptoms of TDD responded favorably to thiamine. While five specific features were predictive of TRD, the high prevalence of TRD suggests that thiamine should be administered to all infants and children presenting with any signs or symptoms consistent with TDD in similar high-risk settings. The usefulness of the predictive model in other contexts warrants further exploration and refinement. TRIAL REGISTRATION: Clinicaltrials.gov NCT03626337.

Modeling the persistence of Opisthorchis viverrini worm burden after mass-drug administration and education campaigns with systematic adherence.

Opisthorchis viverrini is a parasitic liver fluke contracted by consumption of raw fish, which affects over 10 million people in Southeast Asia despite sustained control efforts. Chronic infections are a risk factor for the often fatal bile duct cancer, cholangiocarcinoma. Previous modeling predicted rapid elimination of O. viverrini following yearly mass drug administration (MDA) campaigns. However, field data collected in affected populations shows persistence of infection, including heavy worm burden, after many years of repeated interventions. A plausible explanation for this observation is systematic adherence of individuals in health campaigns, such as MDA and education, with some individuals consistently missing treatment. We developed an agent-based model of O. viverrini which allows us to introduce various heterogeneities including systematic adherence to MDA and education campaigns at the individual level. We validate the agent-based model by comparing it to a previously published population-based model. We estimate the degree of systematic adherence to MDA and education campaigns indirectly, using epidemiological data collected in Lao PDR before and after 5 years of repeated MDA, education and sanitation improvement campaigns. We predict the impact of interventions deployed singly and in combination, with and without the estimated systematic adherence. We show how systematic adherence can substantially increase the time required to achieve reductions in worm burden. However, we predict that yearly MDA campaigns alone can result in a strong reduction of moderate and heavy worm burden, even under systematic adherence. We predict latrines and education campaigns to be particularly important for the reduction in overall prevalence, and therefore, ultimately, elimination. Our findings show how systematic adherence can explain the observed persistence of worm burden; while emphasizing the benefit of interventions for the entire population, even under systematic adherence. At the same time, the results highlight the substantial opportunity to further reduce worm burden if patterns of systematic adherence can be overcome.

Efficacy and safety of moxidectin compared with ivermectin against Strongyloides stercoralis infection in adults in Laos and Cambodia: a randomised, double-blind, non-inferiority, phase 2b/3 trial.

BACKGROUND: Infection with the soil-transmitted helminth Strongyloides stercoralis affects up to 600 million people globally, most of whom live in rural areas with poor sanitation. If untreated, infection leads to long-lasting morbidity and might even be life-threatening. Moxidectin might be a promising alternative to ivermectin, the only currently recommended single-dose treatment. We aimed to assess whether moxidectin is non-inferior in terms of efficacy and safety compared with ivermectin. METHODS: In this randomised, double-blind, parallel-group, non-inferiority, phase 2b/3 trial in communities in Laos and Cambodia, adults aged 18-65 years were screened for the presence of S stercoralis larvae in their stool via sextuplicate quantitative Baermann assays. Using computer-generated group allocation (block randomisation stratified by infection intensity), parasitologically (two or more positive Baermann assays) and clinically eligible participants were randomly assigned (1:1) to receive single oral doses of either moxidectin (8 mg) and ivermectin-matched placebo, or ivermectin (200 µg/kg bodyweight) and moxidectin-matched placebo. The primary endpoint was cure rate assessed at 14-21 days after treatment, using the available-case population analysed according to intention-to-treat principles. Moxidectin was considered non-inferior to ivermectin if the lower limit of the two-sided 95% CI of the difference was greater than the non-inferiority margin of -10 percentage points. Safety endpoints were assessed before treatment, and at 2-3 h, 24 h, and 14-21 days after treatment. This trial is registered at ClinicalTrials.gov, NCT04056325 and NCT04848688. FINDINGS: Between Dec 6, 2020, and May 21, 2022, 4291 participants were screened, 726 of whom were enrolled and randomly assigned to moxidectin (n=363) or ivermectin (n=363). For the participants with primary outcome data, we observed a cure rate of 93·6% (95% CI 90·5 to 96·0; 324 of 346 participants) in the moxidectin group and 95·7% (93·0 to 97·6; 335 of 350 participants) in the ivermectin group, resulting in a between-group difference of -2·1 percentage points (95% CI -5·5 to 1·3). The most common adverse events were abdominal pain (32 [9%] of 363 with moxidectin vs 34 [9%] of 363 with ivermectin) and headache (25 [7%] vs 30 [8%]), which were predominantly mild and transient. INTERPRETATION: Moxidectin was non-inferior to ivermectin in terms of efficacy in the treatment of strongyloidiasis. Additionally, both drugs had a similar safety profile. The fixed dose and lower cost of moxidectin compared with ivermectin make it a valuable alternative for people with strongyloidiasis. FUNDING: Swiss National Science Foundation.

Developing an infection prevention and control intervention to reduce hospital-acquired infections in Cambodia and Lao People's Democratic Republic: the HAI-PC study protocol.

Background: Hospital-acquired infections (HAIs) are significant public health issues, especially in low-and middle-income countries (LMICs). Hand hygiene and low-level disinfection of equipment practices among healthcare workers are some of the essential measures to reduce HAIs. Various infection prevention and control (IPC) interventions to reduce HAI incidence have been developed. However, effective interventions have not been well developed in the LMICs context. Therefore, this protocol aims to develop, pilot, and assess the feasibility and acceptability of an IPC intervention in Cambodia and the Lao People's Democratic Republic. Methods: This study will consist of four phases guided by the Medical Research Council (MRC) Framework. Three hospitals will be purposely selected - each from the district, provincial, and national levels - in each country. The gap analysis will be conducted in Phase 1 to explore IPC practices among healthcare workers at each hospital through desk reviews, direct observation of hand hygiene and low-level disinfection of equipment practices, in-depth interviews with healthcare workers, and key informant interviews with stakeholders. In Phase 2, an IPC intervention will be developed based on the results of Phase 1 and interventions selected from a systematic literature review of IPC interventions in LMICs. In Phase 3, the developed intervention will be piloted in the hospitals chosen in Phase 1. In Phase 4, the feasibility and acceptability of the developed intervention will be assessed among healthcare workers and representatives at the selected hospitals. National consultative workshops in both countries will be conducted to validate the developed intervention with the national technical working groups. Discussion: The MRC Framework will be employed to develop and evaluate an intervention to reduce HAIs in two LMICs. This theoretical framework will be used to explore the factors influencing hand hygiene compliance among healthcare workers. The gap analysis results will allow us to develop a comprehensive IPC intervention to reduce HAI incidence in Cambodia and Lao People's Democratic Republic. Findings from this protocol will feed into promising IPC interventions to reduce HAI incidence in other resource-limited settings. Clinical trial registration: ClinicalTrial.Gov, identifier NCT05547373.

Low Prevalence of Schistosoma mekongi Infection and High Prevalence of Other Helminth Infections among Domestic Animals in Southern Lao People's Democratic Republic.

The prevalence of Schistosoma mekongi in humans in the Lao People's Democratic Republic (Lao PDR) has been relatively well monitored and has decreased due to effective interventions such as preventative chemotherapy with mass drug administration of praziquantel and community awareness programs. However, the prevalence among potential domestic reservoir animals remains broadly unclear, except for a few villages in the endemic area. Therefore, we conducted S. mekongi surveys for the domestic animals that had contact with Mekong River water. We conducted a cross-sectional study of the domestic animals in the seven sentinel villages in the Khong and Mounlapamok Districts of Champasak Province in southern Lao PDR in 2018 by random sampling with a statistically reliable sample size. Stool samples of the five predominant domestic animal species, cattle (n = 160), pig (n = 154), buffalo (n = 149), dog (n = 143), and goat (n = 85), were collected and examined using parasitological FECT method and the LAMP technique. The microscopic analysis did not detect any eggs of S. mekongi in the stool samples of any animal species. However, S. mekongi DNA was detected by the LAMP test in dog stool samples (0.7%; 1/143). On the other hand, the prevalence of other helminths was quite high and heterogeneous among animal species and sentinel sites by the microscopic analysis. These findings suggested that an intervention for S. mekongi infection should focus solely on human populations. However, periodic surveillance for S. mekongi infection among dogs should be conducted to monitor a possible resurgence of S. mekongi infection in the domestic animal population.

Intestinal helminth infections and associated risk factors among adults in the Lao People's Democratic Republic.

BACKGROUND: Helminthiases are highly endemic in Southeast Asia, including the Lao People's Democratic Republic (Lao PDR). This study aimed to assess the current intestinal helminth infections and the associated risk factors among adults across the Lao PDR. METHODS: A cross-sectional survey was conducted in 165 villages across 17 provinces and the Vientiane Capital, Lao PDR. A multi-stage sampling method was employed to select the adult study participants (≥ 18 years). Data collection included (1) interview of the study participants, (2) physical measurements, and (3) a five gram of stool sample from each study participant was collected and preserved in 10% formalin solution for intestinal helminth detection using formalin-ether concentration technique (FECT). Descriptive analysis was used to describe the socio-demographic characteristics of study participants and the prevalence of intestinal helminth infections. Logistic regressions were applied to test the association between intestinal helminth infection and individual risk factors. A P-value below 0.05 was considered statistically significant. RESULTS: A total of 2800 study participants were enrolled. Their average age was 46.0 years; 57.8% were female. Overall, 30.9%, 8.6% and 1.5% of study participants were infected with one, two, or three different intestinal helminth species, respectively. Among the study participants 21.6% were infected with hookworm, 18.8% with Opisthorchis viverrini-like (Ov-like) infection, 4.8% with Strongyloides stercoralis, 2.3% with Ascaris lumbricoides, 1.5% with Trichuris trichiura, and 3.3% with Taenia spp. Ov-like infection was of high prevalence in the southern (28.8%) and central (21.3%) provinces, while hookworm (26.3%), A. lumbricoides (7.3%), T. trichiura (3.1%), and Taenia spp. (4.2%) were prevalent in the northern provinces. Risk analysis showed that men were more likely to be infected with hookworm [adjusted odds ratio (aOR) = 1.2, P = 0.019]. The Lao-Tai ethnic group had a 5.2-times (P < 0.001) higher chance of having Ov-like infection than the minorities. Possession of toilet facility at home was associated with reduced odds for Ov-like (aOR = 0.4, P < 0.001) and hookworm (aOR = 0.6, P < 0.001) infections. CONCLUSIONS: Our study provides a nationwide update of the intestinal helminth prevalence among adults in Lao PDR. To the best of our knowledge, this is the first Lao nationwide survey on intestinal helminth infections and risk factors in adults. It provides crucial information for national control programs for intestinal helminth infections in Lao PDR.

Dynamics and consequences of nutrition-related microbial dysbiosis in early life: study protocol of the VITERBI GUT project.

Introduction: Early life under- and overnutrition (jointly termed malnutrition) is increasingly recognized as an important risk factor for adult obesity and metabolic syndrome, a diet-related cluster of conditions including high blood sugar, fat and cholesterol. Nevertheless, the exact factors linking early life malnutrition with metabolic syndrome remain poorly characterized. We hypothesize that the microbiota plays a crucial role in this trajectory and that the pathophysiological mechanisms underlying under- and overnutrition are, to some extent, shared. We further hypothesize that a "dysbiotic seed microbiota" is transmitted to children during the birth process, altering the children's microbiota composition and metabolic health. The overall objective of this project is to understand the precise causes and biological mechanisms linking prenatal or early life under- or overnutrition with the predisposition to develop overnutrition and/or metabolic disease in later life, as well as to investigate the possibility of a dysbiotic seed microbiota inheritance in the context of maternal malnutrition. Methods/design: VITERBI GUT is a prospective birth cohort allowing to study the link between early life malnutrition, the microbiota and metabolic health. VITERBI GUT will include 100 undernourished, 100 normally nourished and 100 overnourished pregnant women living in Vientiane, Lao People's Democratic Republic (PDR). Women will be recruited during their third trimester of pregnancy and followed with their child until its second birthday. Anthropometric, clinical, metabolic and nutritional data are collected from both the mother and the child. The microbiota composition of maternal and child's fecal and oral samples as well as maternal vaginal and breast milk samples will be determined using amplicon and shotgun metagenomic sequencing. Epigenetic modifications and lipid profiles will be assessed in the child's blood at 2 years of age. We will investigate for possible associations between metabolic health, epigenetics, and microbial changes. Discussion: We expect the VITERBI GUT project to contribute to the emerging literature linking the early life microbiota, epigenetic changes and growth/metabolic health. We also expect this project to give new (molecular) insights into the mechanisms linking malnutrition-induced early life dysbiosis and metabolic health in later life, opening new avenues for microbiota-engineering using microbiota-targeted interventions.

Low seroprotection against diphtheria and tetanus in Lao adolescents.

OBJECTIVES: There is currently no booster diphtheria or tetanus vaccine for Lao children before adolescence, despite international recommendations. We investigated seroprotection against diphtheria and tetanus among Lao adolescents. METHODS: Seven hundred seventy-nine serum samples were tested for anti-diphtheria and anti-tetanus antibodies. RESULTS: Overall, 25.8% of the adolescents had antibody titers corresponding to protection against diphtheria and 30.9% to sufficient immunity against tetanus. Female participants >16 years were more likely to be protected against diphtheria (p < 0.001) and tetanus (p < 0.029). CONCLUSION: Low protection against diphtheria and tetanus, possibly due to low vaccination coverage or antibody waning, suggests booster doses are warranted before adolescence.

A general framework to support cost-efficient fecal egg count methods and study design choices for large-scale STH deworming programs-monitoring of therapeutic drug efficacy as a case study.

BACKGROUND: Soil-transmitted helminth (STH) control programs currently lack evidence-based recommendations for cost-efficient survey designs for monitoring and evaluation. Here, we present a framework to provide evidence-based recommendations, using a case study of therapeutic drug efficacy monitoring based on the examination of helminth eggs in stool. METHODS: We performed an in-depth analysis of the operational costs to process one stool sample for three diagnostic methods (Kato-Katz, Mini-FLOTAC and FECPAKG2). Next, we performed simulations to determine the probability of detecting a truly reduced therapeutic efficacy for different scenarios of STH species (Ascaris lumbricoides, Trichuris trichiura and hookworms), pre-treatment infection levels, survey design (screen and select (SS); screen, select and retest (SSR) and no selection (NS)) and number of subjects enrolled (100-5,000). Finally, we integrated the outcome of the cost assessment into the simulation study to estimate the total survey costs and determined the most cost-efficient survey design. PRINCIPAL FINDINGS: Kato-Katz allowed for both the highest sample throughput and the lowest cost per test, while FECPAKG2 required both the most laboratory time and was the most expensive. Counting of eggs accounted for 23% (FECPAKG2) or ≥80% (Kato-Katz and Mini-FLOTAC) of the total time-to-result. NS survey designs in combination with Kato-Katz were the most cost-efficient to assess therapeutic drug efficacy in all scenarios of STH species and endemicity. CONCLUSIONS/SIGNIFICANCE: We confirm that Kato-Katz is the fecal egg counting method of choice for monitoring therapeutic drug efficacy, but that the survey design currently recommended by WHO (SS) should be updated. Our generic framework, which captures laboratory time and material costs, can be used to further support cost-efficient choices for other important surveys informing STH control programs. In addition, it can be used to explore the value of alternative diagnostic techniques, like automated egg counting, which may further reduce operational costs. TRIAL REGISTRATION: ClinicalTrials.gov NCT03465488.

Gender in public health research: Reflections on design and process across four research projects in low-and middle-income countries.

A growing body of work clearly documents the gendered inequalities in health. The COVID-19 pandemic further exposed these deep inequities: men appear to be more vulnerable to poorer outcomes, but most of the global health workforce is female who are at increased risk of exposure to hospital infection. However, researchers often fail to adequately embed gender as part of the public health research. This paper reports findings from a synthesis exercise that identified some of the challenges of integrating gender in the design and processes of research studies in four projects conducted in six low- and middle-income countries. Through a collective retrospective meta-synthesis process with researchers from each project, we identified two main themes; (i) we deep dive on two of the structural pillars of conducting public health research (design and process) and (ii) we describe some of the underlying opportunities and resistances to the integration of a gender perspective in these research projects. In conclusion, we suggest that public health funding bodies require researchers to integrate gender in public health research from early on as part of the design and to conduct gendered analysis, as part of the overall drive towards more equitable health systems delivery.

Diagnosis of helminths depends on worm fecundity and the distribution of parasites within hosts.

Helminth transmission and morbidity are dependent on the number of mature parasites within a host; however, observing adult worms is impossible for many natural infections. An outstanding challenge is therefore relating routine diagnostics, such as faecal egg counts, to the underlying worm burden. This relationship is complicated by density-dependent fecundity (egg output per worm reduces due to crowding at high burdens) and the skewed distribution of parasites (majority of helminths aggregated in a small fraction of hosts). We address these questions for the carcinogenic liver fluke Opisthorchis viverrini, which infects approximately 10 million people across Southeast Asia, by analysing five epidemiological surveys (n = 641) where adult flukes were recovered. Using a mechanistic model, we show that parasite fecundity varies between populations, with surveys from Thailand and Laos demonstrating distinct patterns of egg output and density-dependence. As the probability of observing faecal eggs increases with the number of mature parasites within a host, we quantify diagnostic sensitivity as a function of the worm burden and find that greater than 50% of cases are misdiagnosed as false negative in communities close to elimination. Finally, we demonstrate that the relationship between observed prevalence from routine diagnostics and true prevalence is nonlinear and strongly influenced by parasite aggregation.

Assessment of cognitive function among adults aged ≥ 60 years using the Revised Hasegawa Dementia Scale: cross-sectional study, Lao People's Democratic Republic.

BACKGROUND: Rapid population ageing remains an important concern for health, social and economics systems; thus, a broader assessment of cognitive decline among adults aged ≥ 60 years is essential. It is important to regularly collect reliable data through validated and affordable methods from people living in different areas and in different circumstances to better understand the significance of this health problem. This study aimed to identify the prevalence of cognitive impairment and the related risk factors by reassessing the scoring of the Revised Hasegawa Dementia Scale among older adults in the Lao People's Democratic Republic. METHODS: A community-based cross-sectional investigation was conducted in rural and urban settings in six districts of three provinces in the country from January to July 2020. In total, 2206 individuals aged 60-98 years (1110 men and 1096 women) were interviewed in person using a pretested Lao version of the Revised Hasegawa Dementia Scale and the WHO STEPwise approach to noncommunicable disease (NCD) risk factor surveillance (the STEPS survey tool). The adjusted odds ratios (AORs) and 95% confidence intervals (95% CIs) were estimated using a logistic model. RESULTS: The study found that 49.3% (1088/2206) of respondents (39.7% [441/1110] of men and 59.0% [647/1096] of women) had scores associated with some level of cognitive impairment. In addition to age, the following factors were significantly associated with cognitive impairment: having no formal education (AOR = 9.5; 95% CI: 5.4 to 16.8, relative to those with a university education), living in the northern region of the country (AOR = 1.4; 95% CI: 1.1 to 1.9, relative to living in the central region), living in a rural area (AOR = 1.5; 95% CI: 1.2 to 1.8), needing assistance with self-care (AOR = 1.8; 95% CI: 1.2 to 2.7) and being underweight (AOR = 1.5; 95% CI: 1.1 to 2.2). Factors associated with no cognitive impairment among older adults include engaging in moderate-intensity physical activity lasting for 10 minutes and up to 1 hour (AOR = 0.6; 95% CI: 0.5 to 0.8) and for > 1 hour (AOR = 0.6; 95% CI: 0.4 to 0.8). CONCLUSIONS: Using the Lao version of the Revised Hasegawa Dementia Scale, this study found that more than half of adults aged ≥ 60 years had cognitive impairment, and this impairment was associated with several risk factors. The limitations of this study may include possible overdetection due to the cutoff point for the assessment of cognitive decline used in the Revised Hasegawa Dementia Scale, given that the participants were not familiar with the instrument. However, the study results can be used to help inform health policy in the Lao People's Democratic Republic regarding the urgent need for a routine data collection system and for providing an environment that addresses and reduces the identified risk factors for cognitive decline to mitigate their impact.

Performance of a rapid immuno-chromatographic test (Schistosoma ICT IgG-IgM) for detecting Schistosoma-specific antibodies in sera of endemic and non-endemic populations.

BACKGROUND: Schistosomiasis, an acute and chronic parasitic disease caused by human pathogenic Schistosoma species, is a neglected tropical disease affecting more than 220 million people worldwide. For diagnosis of schistosomiasis, stool and urine microscopy for egg detection is still the recommended method, however sensitivity of these methods is limited. Therefore, other methods like molecular detection of DNA in stool, detection of circulating cathodic antigen in urine or circulating anodic antigen in urine and serum, as well as serological tests have gained more attention. This study examines the sensitivity and specificity of a rapid diagnostic test based on immunochromatography (Schistosoma ICT IgG-IgM, LD Bio, Lyon, France) for simultaneous detection of specific IgG and IgM antibodies in serum, against Schistosoma spp. in endemic and non-endemic populations. METHODOLOGY/PRINCIPAL FINDINGS: Frozen banked serum samples from patients with confirmed schistosomiasis, patients with other helminth infections, patients with seropositive rheumatoid arthritis and healthy blood donors were used to assess the sensitivity and the specificity of the Schistosoma ICT IgG-IgM rapid diagnostic test. The test showed a sensitivity of 100% in patients with parasitologically confirmed schistosomiasis, irrespective of the species (S. mansoni, S. haematobium, S. japonicum, S. mekongi). In healthy blood donors and patients with rheumatoid factor positive rheumatoid arthritis from Europe, specificity was 100%. However, in serum samples of patients with other tissue invasive helminth infections, the test showed some cross-reactivity, resulting in a specificity of 85%. CONCLUSION/SIGNIFICANCE: With its high sensitivity, the Schistosoma ICT IgG-IgM rapid diagnostic test is a suitable screening test for detection of Schistosoma specific antibodies, including S. mekongi. However, in populations with a high prevalence of co-infection with other tissue invasive helminths, positive results should be confirmed with other diagnostic assays due to the test's imperfect specificity.

Susceptibility to Vaccine-Preventable Diseases in Four Districts of Xaysomboun Province, Lao People's Democratic Republic.

Xaysomboun province has some of the lowest health indicators in Lao People's Democratic Republic (PDR). This cross-sectional study aimed to determine the vaccination, susceptibility and exposure status of the population to hepatitis B virus (HBV), measles, rubella, and tetanus. Participants aged 5 years and older were randomly selected from four districts. From each enrolled participant, demographic data and 5 mL of blood sample were taken. HBV surface antigen (HBsAg) and antibodies against HBV, measles, rubella, and tetanus were detected by ELISA. A total of 363 participants (age 5 to 80 years) were included. HBV exposure, as determined by anti-HBV core (anti-HBc) antibodies, was 56.2% overall, and was significantly higher among those aged ≥21 years (78.1%). HBsAg was detected in 9.4% overall and increased to 20% in ages 31-40 years. Only 13.8% of participants had serology indicative of vaccination (anti-HBs positive, anti-HBc negative). Seroprotection against measles was 74.6% overall but only 41.7% in children aged 5-10 years. Anti-rubella IgG was 94.2% overall and high in all age groups. Tetanus seroprevalence was only 47.4% overall but significantly higher in females aged 31-40 (75.6%). We suggest strengthening of routine and booster HBV, measles, and tetanus vaccine coverage in Xaysomboun province.