The pioneers of Vietnam's epidemiological transition: an ethnographic study of pregnant women's experiences of gestational diabetes.

BACKGROUND: Gestational diabetes mellitus (GDM) is an abnormal glucose metabolism diagnosed during pregnancy that can have serious adverse consequences for mother and child. GDM is an exceptional health condition, as its management serves not only as treatment but also as prevention, reducing the risk of future diabetes in mother and child. OBJECTIVES: This qualitative study aimed to explore how pregnant women experience and respond to GDM, focusing particularly on the role of the family environment in shaping women's experiences. METHODS: The research was carried out in Vietnam's Thái Bình province in April-May 2023. We conducted in-depth ethnographic interviews with 21 women with GDM, visiting them in their homes. Our theoretical starting point was phenomenological anthropology, and the data were analysed using a thematic analysis approach. RESULTS: At the centre of women's experiences was the contrast between GDM as a biomedical and a social condition. Whereas GDM was biomedically diagnosed and managed in the healthcare system, it was often deemed insignificant or non-existent by family members. This made GDM a biomedically present but socially absent health condition. This paradox posed challenges to women's GDM self-care, placing them in pioneering social positions. CONCLUSIONS: The biomedical presence yet social absence of GDM turned women into pioneers at biomedical, digital, epidemiological, and family frontiers. This article calls for appreciation of pregnant women's pioneering roles and for health systems action to involve women and families in the development of GDM policies and programmes at a time of sweeping global health changes.

Main findings: Vietnamese women's experiences of gestational diabetes were affected by social splits between clinic and home; between biomedical and family worlds.Added knowledge: Gestational diabetes places pregnant women in Northern Vietnam in pioneering roles on biomedical, digital, epidemiological, and family frontiers.Global health impact for policy and action: Pregnant women should be involved in the development of policies and programmes addressing gestational diabetes, with particular attention to the connections between clinical and family worlds.

Point-of-care glycated hemoglobin a1c testing for the identification of hyperglycemia severity among individuals with dual tuberculosis and diabetes mellitus in Tanzania.

Background: Poor glycemic control during tuberculosis (TB) treatment is challenging, as the optimum treatment strategy remains unclear. We assessed hyperglycemia severity using glycated hemoglobin (HbA1c) test and predictors of severe hyperglycemia at the time of TB diagnosis in three resources-diverse regions in Tanzania. Methods: This was a substudy from a large cohort study implemented in three regions of Tanzania. TB individuals with diabetes mellitus (DM) (prior history of DM or newly diagnosed DM) were assessed for hyperglycemic levels using HbA1c test and stratified as mild (<53 mmol/mol), moderate (≥53-<86 mmol/mol), and severe (≥86 mmo/mol). Results: From October 2019 to September 2020, 1344 confirmed TB individuals were screened for DM and 105 (7.8%) individuals had dual TB/DM and were assessed for glycemic levels. Of these, 69 (67.7%) had a prior history of DM and 26 (24.8%) were living with human immunodeficiency virus. Their mean age was 49.0 (±15.0) years and 56.2% were male. The majority (77.1%) had pulmonary TB, and 96.2% were newly diagnosed TB individuals. HbA1c test identified 41(39.0%), 37 (35.2%), and 27 (25.7%) individuals with severe, moderate, and mild the hyperglycaemia respectively. Female sex (odds ratio [OR]: 3.55, 95% confidence interval [CI]: 1.06-11.92, P = 0.040) and previous history of DM (OR: 3.71, 95% CI: 1.33-10.33, P = 0.013) were independent risk factors for severe hyperglycemic at the time of TB diagnosis. Conclusion: By integrating early HbA1c testing, a substantial proportion of individuals with severe hyperglycemia were identified. HbA1c testing can be recommended to identify and triage patients requiring personalized intensified DM management in resource-limited programmatic settings.

Implementing Innovative Approaches to Improve Health Care Delivery Systems for Integrating Communicable and Non-Communicable Diseases Using Tuberculosis and Diabetes as a Model in Tanzania.

Background: Many evidence-based health interventions, particularly in low-income settings, have failed to deliver the expected impact. We designed an Adaptive Diseases Control Expert Programme in Tanzania (ADEPT) to address systemic challenges in health care delivery and examined the feasibility, acceptability and effectiveness of the model using tuberculosis (TB) and diabetes mellitus (DM) as a prototype. Methods: This was an effectiveness-implementation hybrid type-3 design that was implemented in Dar es Salaam, Iringa and Kilimanjaro regions. The strategy included a stepwise training approach with web-based platforms adapting the Gibbs' reflective cycle. Health facilities with TB services were supplemented with DM diagnostics, including glycated haemoglobin A1c (HbA1c). The clinical audit was deployed as a measure of fidelity. Retrospective and cross-sectional designs were used to assess the fidelity, acceptability and feasibility of the model. Results: From 2019-2021, the clinical audit showed that ADEPT intervention health facilities more often identified median 8 (IQR 6-19) individuals with dual TB and DM, compared with control health facilities, median of 1 (IQR 0-3) (p = 0.02). Likewise, the clinical utility of HbA1c on intervention sites was 63% (IQR:35-75%) in TB/DM individuals compared to none in the control sites at all levels, whereas other components of the standard of clinical management of patients with dual TB and DM did not significantly differ. The health facilities showed no difference in screening for additional comorbidities such as hypertension and malnutrition. The stepwise training enrolled a total of 46 nurse officers and medical doctors/specialists for web-based training and 40 (87%) attended the workshop. Thirty-one (67%), 18 nurse officers and 13 medical doctors/specialists, implemented the second step of training others and yielded a total of 519 additional front-line health care workers trained: 371 nurses and 148 clinicians. Overall, the ADEPT model was scored as feasible by metrics applied to both front-line health care providers and health facilities. Conclusions: It was feasible to use a stepwise training and clinical audit to support the integration of TB and DM management and it was largely acceptable and effective in differing regions within Tanzania. When adapted in the Tanzania health system context, the model will likely improve quality of services.

Skeletal muscle fibre type and enzymatic activity in adult offspring following placental and peripheral malaria exposure in foetal life.

Background: Maternal malaria may restrict foetal growth. Impaired utero-placental blood flow due to malaria infection may cause hypoxia-induced altered skeletal muscle fibre type distribution in the offspring, which may contribute to insulin resistance and impaired glucose metabolism. This study assessed muscle fibre distribution 20 years after placental and/or peripheral in-utero malaria exposure compared to no exposure, i.e., PPM+, PM+, and M-, respectively. Methods: We traced 101 men and women offspring of mothers who participated in a malaria chemosuppression study in Muheza, Tanzania. Of 76 eligible participants, 50 individuals (29 men and 21 women) had skeletal muscle biopsy taken from m. vastus lateralis in the right leg. As previously reported, fasting and 30 min post-oral glucose challenge plasma glucose values were higher, and insulin secretion disposition index was lower, in the PPM+ group. Aerobic capacity (fitness) was estimated by an indirect VO2max test on a stationary bicycle. Muscle fibre sub-type (myosin heavy chain, MHC) distribution was analysed, as were muscle enzyme activities (citrate synthase (CS), 3-hydroxyacyl-CoA dehydrogenase, myophosphorylase, phosphofructokinase, lactate dehydrogenase, and creatine kinase activities. Between-group analyses were adjusted for MHC-I %. Results: No differences in aerobic capacity were found between groups. Despite subtle elevations of plasma glucose levels in the PPM+ group, there was no difference in MHC sub-types or muscle enzymatic activities between the malaria-exposed and non-exposed groups. Conclusion: The current study did not show differences in MHC towards glycolytic sub-types or enzymatic activity across the sub-groups. The results support the notion of the mild elevations of plasma glucose levels in people exposed to placental malaria in pregnancy being due to compromised pancreatic insulin secretion rather than insulin resistance.

Energy expenditure and intensity of ritual jumping-dancing in male Maasai.

OBJECTIVES: Traditional jumping-dance rituals performed by Maasai men involve prolonged physical exertion that may contribute significantly to overall physical activity level. We aimed to objectively quantify the metabolic intensity of jumping-dance activity and assess associations with habitual physical activity and cardiorespiratory fitness (CRF). METHODS: Twenty Maasai men (18-37 years) from rural Tanzania volunteered to participate in the study. Habitual physical activity was monitored using combined heart rate (HR) and movement sensing over 3 days, and jumping-dance engagement was self-reported. A 1-h jumping-dance session resembling a traditional ritual was organized, during which participants' vertical acceleration and HR were monitored. An incremental, submaximal 8-min step test was performed to calibrate HR to physical activity energy expenditure (PAEE) and assess CRF. RESULTS: Mean (range) habitual PAEE was 60 (37-116) kJ day-1 kg-1 , and CRF was 43 (32-54) mL O2 min-1 kg-1 . The jumping-dance activity was performed at an absolute HR of 122 (83-169) beats·min-1 , and PAEE of 283 (84-484) J min-1 kg-1 or 42 (18-75)% when expressed relative to CRF. The total PAEE for the session was 17 (range 5-29) kJ kg-1 , ~28% of the daily total. Self-reported engagement in habitual jumping-dance frequency was 3.8 (1-7) sessions/week, with a total duration of 2.1 (0.5-6.0) h/session. CONCLUSIONS: Intensity during traditional jumping-dance activity was moderate, but on average sevenfold higher than habitual physical activity. These rituals are common, and can make a substantial contribution to overall physical activity in Maasai men, and thus be promoted as a culture-specific activity to increase energy expenditure and maintain good health in this population.

Experiences and perceptions of participants on the pathway towards clinical management of dual tuberculosis and diabetes mellitus in Tanzania.

BACKGROUND: Diabetes mellitus (DM) is a common comorbidity among people with tuberculosis (TB). Despite the availability of guidelines on how to integrate dual TB/DM in Tanzania, the practice of integration at various healthcare levels is unclear. OBJECTIVE: To explore the participants' experiences and perceptions on the pathway towards clinical management of dual TB/DM. METHOD: The research was carried out in Dar es Salaam, Iringa, and Kilimanjaro regions between January and February 2020. A qualitative, in-depth interview approach was used to collect participants' experiences and perspectives on the acquisition of dual TB/DM services at various levels of healthcare facilities. The information gathered were coded and classified thematically. RESULTS: The participants' perception of TB services within the healthcare facilities was positive due to the support they received from the healthcare providers. On the other hand, participants reported difficulty receiving management in various health facilities for each condition in terms of access to dual TB/DM care and access to DM medication. This was viewed as a significant challenge for the participants with dual TB/DM. CONCLUSIONS: The current disjunction and disruption in healthcare for people with dual TB/DM makes it difficult to access services at various levels of health facilities. For optimal clinical management for people with dual TB/DM, patient-centered strategies and integrated approaches are urgently needed.

The choice of reference chart affects the strength of the association between malaria in pregnancy and small for gestational age: an individual participant data meta-analysis comparing the Intergrowth-21 with a Tanzanian birthweight chart.

BACKGROUND: The prevalence of small for gestational age (SGA) may vary depending on the chosen weight-for-gestational-age reference chart. An individual participant data meta-analysis was conducted to assess the implications of using a local reference (STOPPAM) instead of a universal reference (Intergrowth-21) on the association between malaria in pregnancy and SGA. METHODS: Individual participant data of 6,236 newborns were pooled from seven conveniently identified studies conducted in Tanzania and Malawi from 2003-2018 with data on malaria in pregnancy, birthweight, and ultrasound estimated gestational age. Mixed-effects regression models were used to compare the association between malaria in pregnancy and SGA when using the STOPPAM and the Intergrowth-21 references, respectively. RESULTS: The 10th percentile for birthweights-for-gestational age was lower for STOPPAM than for Intergrowth-21, leading to a prevalence of SGASTOPPAM of 14.2% and SGAIG21 of 18.0%, p < 0.001. The association between malaria in pregnancy and SGA was stronger for STOPPAM (adjusted odds ratio (aOR) 1.30 [1.09-1.56], p < 0.01) than for Intergrowth-21 (aOR 1.19 [1.00-1.40], p = 0.04), particularly among paucigravidae (SGASTOPPAM aOR 1.36 [1.09-1.71], p < 0.01 vs SGAIG21 aOR 1.21 [0.97-1.50], p = 0.08). CONCLUSIONS: The prevalence of SGA may be overestimated and the impact of malaria in pregnancy underestimated when using Intergrowth-21. Comparing local reference charts to global references when assessing and interpreting the impact of malaria in pregnancy may be appropriate.

Where can Tanzania health system integrate clinical management of patients with dual tuberculosis and diabetes mellitus? A cross-sectional survey at varying levels of health facilities.

Objective: To assess the current Tanzania health facilities readiness in integrating clinical management of dual Tuberculosis (TB) and Diabetes Mellitus (DM) by using the Service Availability and Readiness Assessment (SARA) manual of the World Health Organization prior to implementing an integrated service model. Study design: Cross-sectional study. Methods: A needs assessment survey was conducted at varying levels of health care facilities. The SARA manual evaluated the service delivery outcomes in terms of availability of guidelines, medicines and diagnostic equipment, training of healthcare workers in providing TB and DM care, and patient record review. Data were analyzed using Statistical Package for Social Science version 26. Results: Among 29 health facilities selected, three were regional referral hospitals, eight were district hospitals and eighteen were health centers. Baseline investigations revealed that GeneXpert MTB/RIF machines were present in 10 (34.5%) facilities, and glycated hemoglobin devices were present in two (6.9%) facilities, while all health facilities had a glucometer. The presence of an attending medical doctor in 19 (65.5%) facilities and the presence of operating biochemistry analyzers in 15 (51.7%) facilities were two mandatory variables used to assess readiness. Among the various guidelines observed, none of the facilities had the 2016 DM guidelines. Overall, 15 (51.7%) health facilities were ready to integrate dual TB and DM services. Conclusion: Integrative TB/DM screening and management activities can be achieved only if integration initiatives are prioritized at all levels of health facilities and among health policy makers in Tanzania. At least half of the health facilities were prepared to integrate the management of dual TB/DM. However, there is an urgent need to mobilize significant resources to improve the integration in these facilities, such as management guidelines and diagnostics..

Impact of early diagnosis of impaired glucose regulation in tuberculosis: Comparison of clinical outcomes in people with tuberculosis in Tanzania.

OBJECTIVE: Diabetes mellitus (DM) has been known to compromise tuberculosis (TB) treatment outcomes. Association data are limited for early hyperglycaemia detection and TB treatment outcomes. Thus, we assessed treatment outcomes including time to sputum conversion and death in TB participants with or without hyperglycaemia. METHODS: A prospective cohort study recruited TB participants receiving anti-TB treatment at health facilities in Tanzania between October 2019 and September 2020. Hyperglycaemia was defined as having pre-existing DM or pre-treatment random blood glucose of ≥7.8 mmol/L, in combination categorised as impaired glucose regulation (IGR). Those with IGR were further screened for hyperglycaemia severity using glycated haemoglobin. In case of unknown status, participants were tested for HIV. Time to death was determined at 6 months of TB treatment. RESULTS: Of 1344 participants, 187 (13.9%) had IGR, of whom 44 (23.5%) were HIV co-infected. Overall treatment success was 1206 (89.7%), and was similar among participants with or without IGR (p > 0.05). Time to death for participants with and without IGR was 18 versus 28 days (p = 0.870), respectively. Age ≥ 40 years (p = 0.038), bacteriological positive (p = 0.039), HIV (p = 0.009), or recurrent TB (p = 0.017) predicted death or treatment success during TB treatment in adjusted multivariable models. CONCLUSION: IGR did not influence clinical outcomes in TB patients with or without IGR in a programme of early IGR diagnosis and integration TB, HIV and DM care. Early detection and co-management of multi-morbidities among people diagnosed with TB may reduce likelihood of poor treatment outcomes in a programmatic setting.

Pre-pregnancy body mass index and gestational weight-gain predict maternal hemoglobin levels and are jointly associated with neonatal outcomes in a Mexican birth cohort.

Introduction: Introduction: there is scarce evidence of the effects of obesity and gestational weight- gain (GWG) on hemoglobin (Hb) levels in pregnancy. Little is known about the implications in offspring when pregnant mothers present with both at delivery. Aim: to identify if pre-pregnancy body mass index (BMI) and GWG are associated with Hb levels at pregnancy third trimester; and identify if the BMI status plus anemia at delivery could influence offspring anthropometry. Methods: in a sub-sample of pregnant women (n = 108) and their offspring (n = 63) from a Mexican birth cohort, information from medical files and questionnaires were used to obtain pre-pregnancy BMI (categorized as normal, overweight, and obese), GWG, and Hb during pregnancy; at delivery and postpartum anthropometric measures were obtained for offspring. Adjusted regression models predicted Hb levels according to pre-pregnancy BMI and GWG; offspring growth trajectories from birth to 3 months old were compared according to mother´s BMI status and anemia combinations at delivery. Results: pre-pregnancy normal (N), overweight (OV), and obesity (OB) were present in 48 %, 40 %, and 12 % of the participants, respectively. Anemia was detected in 22.8 % of the participants at third trimester. Hb levels in the third trimester were significantly lower in those with pre-pregnancy OB-BMI and excessive GWG (12.1 g/dL, 95 % CI: 10.7-13.5) compared to those with pre-pregnancy OB-BMI and insufficient GWG (13.3g/dL, 95 %CI: 11.9-14.8) (p = 0.04). At delivery, 11 % presented with OB-BMI and anemia. Women with OB-BMI and normal Hb levels had children with higher scores in Weight-for-Length-Z score and triceps skinfold. Conclusion: among OB women, excessive GWG was associated with having lower Hb levels in the third trimester. Newborns had higher scores in growth patterns related to adiposity from birth to 3 months old if mothers had normal Hb levels and OB.

Introducción: Introducción: existe escasa evidencia de los efectos de obesidad y ganancia de peso gestacional (GPG) y niveles de hemoglobina (Hb) durante el embarazo. Poco se conoce sobre las implicaciones en la descendencia cuando las embarazadas presentan ambos en el momento del parto. Objetivos: identificar si el índice de masa corporal (IMC) previo al embarazo y el GPG están asociados con los niveles de Hb en el tercer trimestre del embarazo; e identificar si el IMC más la anemia en el momento del parto podrían influir en la antropometría de la descendencia. Metodología: se utilizó información de expedientes médicos y cuestionarios para obtener el IMC antes del embarazo (categorizado como normal, con sobrepeso y obesidad), GPG y Hb durante el embarazo; en el momento del parto y posparto se obtuvieron medidas antropométricas para la descendencia de una submuestra de mujeres embarazadas (n = 108) y su descendencia (n = 63) de una cohorte mexicana. Los modelos de regresión ajustados predijeron los niveles de Hb según IMC y GPG antes del embarazo; se compararon las trayectorias de crecimiento de la descendencia desde el nacimiento hasta los 3 meses de edad según el estado de IMC de la madre y las combinaciones de anemia en el momento del parto. Resultados: peso preembarazo normal (N), sobrepeso (SP) y obesidad (OB) estuvieron presentes en 48 %, 40 % y 12 % de las participantes, respectivamente. Se diagnosticó anemia en el 22,8 % de las participantes en el tercer trimestre. Los niveles de Hb en el tercer trimestre fueron significativamente más bajos en aquellas con IMC-OB antes del embarazo y GPG excesivo (12,1 g/dL, IC del 95 %: 10,7-13,5) en comparación con aquellas con IMC-OB antes del embarazo y GPG insuficiente (13,3 g/dl, IC del 95 %: 11,9-14,8) (p = 0,04). Al momento del parto, el 11 % presentó OB-BMI y anemia. Las mujeres con OB-BMI y niveles normales de Hb tenían hijos con puntuaciones más altas en puntuación Z de peso para longitud y pliegue cutáneo del tríceps. Conclusión: la GPG excesiva entre las mujeres OB se asoció con niveles más bajos de Hb en el tercer trimestre. Los recién nacidos tenían puntajes más altos en los patrones de crecimiento relacionados con la adiposidad desde el nacimiento hasta los 3 meses de edad si las madres tenían niveles normales de Hb y OB.

Pre-pregnancy body mass index and gestational weight-gain predict maternal hemoglobin levels and are jointly associated with neonatal outcomes in a Mexican birth cohort / Índice de masa corporal y ganancia de peso durante el embarazo como predictores de niveles de hemoglobina materna y su asociación con desenlaces neonatales en una cohorte mexicana

Introduction: there is scarce evidence of the effects of obesity and gestational weight- gain (GWG) on hemoglobin (Hb) levels in pregnancy. Little is known about the implications in offspring when pregnant mothers present with both at delivery. Aim: to identify if pre-pregnancy body mass index (BMI) and GWG are associated with Hb levels at pregnancy third trimester; and identify if the BMI status plus anemia at delivery could influence offspring anthropometry. Methods: in a sub-sample of pregnant women (n = 108) and their offspring (n = 63) from a Mexican birth cohort, information from medical files and questionnaires were used to obtain pre-pregnancy BMI (categorized as normal, overweight, and obese), GWG, and Hb during pregnancy; at delivery and postpartum anthropometric measures were obtained for offspring. Adjusted regression models predicted Hb levels according to pre-pregnancy BMI and GWG; offspring growth trajectories from birth to 3 months old were compared according to mother´s BMI status and anemia combinations at delivery. Results: pre-pregnancy normal (N), overweight (OV), and obesity (OB) were present in 48 %, 40 %, and 12 % of the participants, respectively. Anemia was detected in 22.8 % of the participants at third trimester. Hb levels in the third trimester were significantly lower in those with pre-pregnancy OB-BMI and excessive GWG (12.1 g/dL, 95 % CI: 10.7-13.5) compared to those with pre-pregnancy OB-BMI and insufficient GWG (13.3g/dL, 95 %CI: 11.9-14.8) (p = 0.04). At delivery, 11 % presented with OB-BMI and anemia. Women with OB-BMI and normal Hb levels had children with higher scores in Weight-for-Length-Z score and triceps skinfold. Conclusion: among OB women, excessive GWG was associated with having lower Hb levels in the third trimester. Newborns had higher scores in growth patterns related to adiposity from birth to 3 months old if mothers had normal Hb levels and OB (AU)

Introducción: existe escasa evidencia de los efectos de obesidad y ganancia de peso gestacional (GPG) y niveles de hemoglobina (Hb) durante el embarazo. Poco se conoce sobre las implicaciones en la descendencia cuando las embarazadas presentan ambos en el momento del parto. Objetivos: identificar si el índice de masa corporal (IMC) previo al embarazo y el GPG están asociados con los niveles de Hb en el tercer trimestre del embarazo; e identificar si el IMC más la anemia en el momento del parto podrían influir en la antropometría de la descendencia. Metodología: se utilizó información de expedientes médicos y cuestionarios para obtener el IMC antes del embarazo (categorizado como normal, con sobrepeso y obesidad), GPG y Hb durante el embarazo; en el momento del parto y posparto se obtuvieron medidas antropométricas para la descendencia de una submuestra de mujeres embarazadas (n = 108) y su descendencia (n = 63) de una cohorte mexicana. Los modelos de regresión ajustados predijeron los niveles de Hb según IMC y GPG antes del embarazo; se compararon las trayectorias de crecimiento de la descendencia desde el nacimiento hasta los 3 meses de edad según el estado de IMC de la madre y las combinaciones de anemia en el momento del parto. Resultados: peso preembarazo normal (N), sobrepeso (SP) y obesidad (OB) estuvieron presentes en 48 %, 40 % y 12 % de las participantes, respectivamente. Se diagnosticó anemia en el 22,8 % de las participantes en el tercer trimestre. Los niveles de Hb en el tercer trimestre fueron significativamente más bajos en aquellas con IMC-OB antes del embarazo y GPG excesivo (12,1 g/dL, IC del 95 %: 10,7-13,5) en comparación con aquellas con IMC-OB antes del embarazo y GPG insuficiente (13,3 g/dl, IC del 95 %: 11,9-14,8) (p = 0,04). Al momento del parto, el 11 % presentó OB-BMI y anemia. Las mujeres con OB-BMI y niveles normales de Hb tenían hijos con puntuaciones más altas en puntuación Z de peso para longitud y pliegue cutáneo del tríceps (AU)

Influence of placental and peripheral malaria exposure in fetal life on cardiometabolic traits in adult offspring.

INTRODUCTION: Fetal malaria exposure may lead to intrauterine growth restriction and increase the risk of developing diabetes and cardiovascular diseases in adulthood. We investigated the extent to which fetal peripheral and placental malaria exposure impacts insulin sensitivity and secretion, body composition and cardiometabolic health 20 years after in utero malaria exposure. RESEARCH DESIGN AND METHODS: We traced 101 men and women in Muheza district, Tanga region whose mothers participated in a malaria chemosuppression during a pregnancy study in 1989-1992. All potential participants were screened for malaria, hepatitis B and HIV to ascertain study eligibility. Seventy-six individuals (44 men, 32 women) were included in this cohort study. The participants underwent a thorough clinical examination including anthropometric measurements, ultrasound scanning for abdominal fat distribution, blood pressure, 75 g oral glucose tolerance test, an intravenous glucose tolerance test followed by a hyperinsulinemic euglycemic clamp and a submaximal exercise test. RESULTS: Offspring exposed to placental malaria during pregnancy had significantly higher 30-minute plasma post-glucose load levels, but no significant difference in peripheral insulin resistance, insulin secretion or other cardiometabolic traits compared with non-exposed individuals. CONCLUSIONS: Using the state-of-the-art euglycemic clamp technique, we were unable to prove our a priori primary hypothesis of peripheral insulin resistance in young adult offspring of pregnancies affected by malaria. However, the subtle elevations of plasma glucose might represent an early risk marker for later development of type 2 diabetes if combined with aging and a more obesogenic living environment.

Directly measured aerobic fitness in male Maasai of Tanzania.

OBJECTIVES: The agro-pastoralist Maasai of East Africa are highly physically active, but their aerobic fitness has so far only been estimated using heart rate (HR) response to submaximal exercise and not directly measured. Thus, we aimed to measure aerobic fitness directly using respiratory gas analysis in a group of Maasai, and habitual physical activity energy expenditure (PAEE) as explanatory variable. METHODS: In total, 21 (10 rural, 11 semi-urban) of 30 volunteering Tanzanian Maasai men were eligible to participate. Respiratory gas exchange was measured during a graded exercise test until exhaustion on a stationary bicycle to determine aerobic fitness. Maximal effort criteria were at least two of the following (1) leveling off, (2) respiratory exchange ratio (RER) >1.10, and (3) maximum HR within 10 bpm of age-estimated maximum HR. Habitual PAEE was estimated using combined accelerometry and HR monitoring. Anthropometry, biochemistry, blood pressure, resting HR, and dietary intake information were collected for background information. RESULTS: Mean age was 43.2 (range 26-60) years, and hemoglobin was higher in the rural versus semi-urban Maasai (16.9 vs. 15.4 g/dl, p = .02). Mean aerobic fitness (34.4 vs. 33.3 mlO2 /min/kg, p = .79), and mean PAEE (58.5 vs. 52.9 kJ/day/kg, p = .64) were similar in rural and semi-urban Maasai, respectively. CONCLUSIONS: Aerobic fitness was low to moderate in male rural and semi-urban Maasai. This may be explained by relatively low PAEE in comparison to previous objectively measured activity levels in Maasai, which indicates recent lifestyle changes.

Protocol for establishing an Adaptive Diseases control Expert Programme in Tanzania (ADEPT) for integrating care of communicable and non-communicable diseases using tuberculosis and diabetes as a case study.

INTRODUCTION: Most sub-Saharan African countries endure a high burden of communicable infections but also face a rise of non-communicable diseases (NCDs). Interventions targeting particular epidemics are often executed within vertical programmes. We establish an Adaptive Diseases control Expert Programme in Tanzania (ADEPT) model with three domains; stepwise training approach, integration of communicable and NCDs and a learning system. The model aims to shift traditional vertical programmes to an adaptive diseases management approach through integrating communicable and NCDs using the tuberculosis (TB) and diabetes mellitus (DM) dual epidemic as a case study. We aim to describe the ADEPT protocol with underpinned implementation and operational research on TB/DM. METHODS AND ANALYSIS: The model implement a collaborative TB and DM services protocol as endorsed by WHO in Tanzania. Evaluation of the process and outcomes will follow the logic framework. A mixed research design with both qualitative and quantitative approaches will be used in applied research action. Anticipated implementation research outcomes include at the health facilities level for organising TB/DM services, pathways of patients with TB/DM seeking care in different health facilities, factors in service delivery that need deimplementation and the ADEPT model implementation feasibility, acceptability and fidelity. Expected operational research outcomes include additional identified patients with dual TB/DM, the prevalence of comorbidities like hypertension in patients with TB/DM and final treatment outcomes of TB/DM including treatment-related complications. Findings will inform the future policies and practices for integrating communicable and NCDs services. ETHICS AND DISSEMINATION: Ethical approval was granted by The National Research Health Ethical Committee (Ref-No. NIMR/HQ/R.8a/Vol.IX/2988) and the implementation endorsed by the government authorities. Findings will be proactively disseminated through multiple mechanisms including peer-reviewed journals, and engagement with various stakeholders' example in conferences and social media.

Reduced Birth Weight Caused by Sextuple Drug-Resistant Plasmodium falciparum Infection in Early Second Trimester.

Mutations in the Plasmodium falciparum genes Pfdhfr and Pfdhps, particularly the sextuple mutant haplotype threatens the antimalarial effectiveness of sulfadoxine-pyrimethamine (SP) as intermittent preventive treatment during pregnancy (IPTp). To explore the impact of sextuple mutant haplotype infections on outcome measures after provision of IPTp with SP, we monitored birth outcomes in women followed up from before conception or from the first trimester until delivery. Women infected with sextuple haplotypes, in the early second trimester specifically, delivered newborns with a lower birth weight compared with women who did not have malaria during pregnancy (difference, -267 g; 95% confidence interval, -454 to -59; P = .01) and women infected with less SP-resistant haplotypes (-461 g; -877 to -44; P = .03). Thus, sextuple haplotype infections seem to affect the effectiveness of SP for IPTp and directly affect birth outcome by lowering birth weight. Close monitoring and targeted malaria control during early pregnancy is therefore crucial to improving birth outcomes.

"If I Don't Eat Enough, I Won't Be Healthy". Women's Experiences with Gestational Diabetes Mellitus Treatment in Rural and Urban South India.

Gestational diabetes mellitus (GDM) is associated with a range of adverse pregnancy outcomes as well as increased risk of future type 2 diabetes and cardiovascular disease. In India, 10%-35% of pregnant women develop GDM. In this study, we investigated women's experiences with the dietary and pharmaceutical treatment for GDM in rural and urban Tamil Nadu, India. Semi-structured interviews were conducted with 19 women diagnosed with GDM. Data were analyzed using qualitative content analysis. Three overall aspects were discovered with several sub-aspects characterizing women's experiences: emotional challenges (fear and apprehension for the baby' health and struggling to accept a treatment seen as counterintuitive to being safe and healthy), interpersonal challenges (managing treatment in the near social relations and social support, and coordinating treatment with work and social life), and health system-related challenges (availability and cost of treatment, interaction with health care providers). Some aspects acted as barriers. However, social support and positive, high-quality interactions with health care providers could mitigate some of these barriers and facilitate the treatment process. Greater efforts at awareness creation in the social environment and systemic adjustments in care delivery targeting the individual, family, community and health system levels are needed in order to ensure that women with GDM have the opportunity to access treatment and are enabled and motivated to follow it as well.

An Individual Participant Data Population Pharmacokinetic Meta-analysis of Drug-Drug Interactions between Lumefantrine and Commonly Used Antiretroviral Treatment.

Treating malaria in HIV-coinfected individuals should consider potential drug-drug interactions. Artemether-lumefantrine is the most widely recommended treatment for uncomplicated malaria globally. Lumefantrine is metabolized by CYP3A4, an enzyme that commonly used antiretrovirals often induce or inhibit. A population pharmacokinetic meta-analysis was conducted using individual participant data from 10 studies with 6,100 lumefantrine concentrations from 793 nonpregnant adult participants (41% HIV-malaria-coinfected, 36% malaria-infected, 20% HIV-infected, and 3% healthy volunteers). Lumefantrine exposure increased 3.4-fold with coadministration of lopinavir-ritonavir-based antiretroviral therapy (ART), while it decreased by 47% with efavirenz-based ART and by 59% in the patients with rifampin-based antituberculosis treatment. Nevirapine- or dolutegravir-based ART and malaria or HIV infection were not associated with significant effects. Monte Carlo simulations showed that those on concomitant efavirenz or rifampin have 49% and 80% probability of day 7 concentrations <200 ng/ml, respectively, a threshold associated with an increased risk of treatment failure. The risk of achieving subtherapeutic concentrations increases with larger body weight. An extended 5-day and 6-day artemether-lumefantrine regimen is predicted to overcome these drug-drug interactions with efavirenz and rifampin, respectively.

Prevention of opportunistic non-communicable diseases.

As strategies targeting undernutrition and infections become increasingly successful in low- and middle-income countries (LMICs), a second challenge has appeared, namely premature onset of non-communicable diseases (NCDs). In LMICs, NCDs are often related to exposure to undernutrition and infections. As NCDs strike societies and individuals with impaired resistance or a deficient health (care) state, why not label such diseases 'opportunistic', in analogy with opportunistic infections attacking individuals with HIV? We propose the concept of opportunistic NCDs, hoping that fighting against infections, and for better maternal and child health, is becoming acknowledged as essential for the early prevention of NCDs.

FOETAL for NCD-FOetal Exposure and Epidemiological Transitions: the role of Anaemia in early Life for Non-Communicable Diseases in later life: a prospective preconception study in rural Tanzania.

PURPOSE: Low-income and middle-income countries such as Tanzania experience a high prevalence of non-communicable diseases (NCDs), including anaemia. Studying if and how anaemia affects growth, placenta development, epigenetic patterns and newborns' risk of NCDs may provide approaches to prevent NCDs. PARTICIPANTS: The FOETALforNCD (FOetal Exposure and Epidemiological Transitions: the role of Anaemia in early Life for Non-Communicable Diseases in later life) Study is a population-based preconception, pregnancy and birth cohort study (n=1415, n=538, n=427, respectively), conducted in a rural region of North-East Tanzania. All participants were recruited prior to conception or early in pregnancy and followed throughout pregnancy as well as at birth. Data collection included: maternal blood, screening for NCDs and malaria, ultrasound in each trimester, neonatal anthropometry at birth and at 1 month of age, cord blood, placental and cord biopsies for stereology and epigenetic analyses. FINDINGS TO DATE: At preconception, the average age, body mass index and blood pressure of the women were 28 years, 23 kg/m2 and 117/75 mm Hg, respectively. In total, 458 (36.7%) women had anaemia (haemoglobin Hb <12 g/dL) and 34 (3.6%) women were HIV-positive at preconception. During pregnancy 359 (66.7%) women had anaemia of which 85 (15.8%) women had moderate-to-severe anaemia (Hb ≤9 g/dL) and 33 (6.1%) women had severe anaemia (Hb ≤8 g/dL). In total, 185 (34.4%) women were diagnosed with malaria during pregnancy. FUTURE PLANS: The project will provide new knowledge on how health, even before conception, might modify the risk of developing NCDs and how to promote better health during pregnancy. The present project ended data collection 1 month after giving birth, but follow-up is continuing through regular monitoring of growth and development and health events according to the National Road Map Strategic Plan in Tanzania. This data will link fetal adverse event to childhood development, and depending on further grant allocation, through a life course follow-up.

Anemia in late pregnancy induces an adaptive response in fetoplacental vascularization.

INTRODUCTION: Anemia during pregnancy may compromise fetal and newborn's health, however, little is known about how and when the fetoplacental vascularization is most vulnerable to anemia. METHODS: Using systematic and isotropic uniform random sampling, placental samples were collected from 189 placentas in a cohort study of Tanzanian women whose hemoglobin concentration was measured throughout pregnancy. Fetoplacental vessels and villi were defined as exerting either a transport or diffusion function. The vascularization patterns for transport and diffusion vessels and villi were assessed by stereology. Blood vessel length, surface area and diffusion distance as well as placental villi volume were calculated. RESULTS: Anemia from a gestational age of 23 weeks was significantly associated with increased fetoplacental vascularization in vessels and villi compared to women who were non-anemic throughout pregnancy. Transport surface vessel area: 0.31 m2 [95% CI: 0.18-0.55], P = 0.01; Transport villi volume 19.8 cm3 [95% CI: 6.37-33.2], P = 0.004, Transport vessel diameter 7.23 µm [95% CI: 1.23-13.3], P = 0.02. Diffusion vessel surface: 3.23 m2 [95% CI: 1.55-4.91], P < 0.001 and diffusion villi volume: 29.8 cm3 [95% CI: 10.0-49.5], P = 0.003). Finally, all the measured transport vessel and villi significantly parameters and diffusion vessel surface, vessel diameter and diffusion distance were associated with birth weight. DISCUSSION: Increased fetoplacental vascularization related to anemia from a gestational age of 23 weeks in pregnancy together with the association between fetoplacental vascularity and birth weight suggest that the timing of anemia determines the effect on fetoplacental vascularization and underlines the clinical relevance for proper development of fetoplacental vasculature.