Medication exposure during pregnancy: a pilot pharmacovigilance system using health and demographic surveillance platform.

BACKGROUND: There is limited safety information on most drugs used during pregnancy. This is especially true for medication against tropical diseases because pharmacovigilance systems are not much developed in these settings. The aim of the present study was to demonstrate feasibility of using Health and Demographic Surveillance System (HDSS) as a platform to monitor drug safety in pregnancy. METHODS: Pregnant women with gestational age below 20 weeks were recruited from Reproductive and Child Health (RCH) clinics or from monthly house visits carried out for the HDSS. A structured questionnaire was used to interview pregnant women. Participants were followed on monthly basis to record any new drug used as well as pregnancy outcome. RESULTS: 1089 pregnant women were recruited; 994 (91.3%) completed the follow-up until delivery. 98% women reported to have taken at least one medication during pregnancy, mainly those used in antenatal programmes. Other most reported drugs were analgesics (24%), antibiotics (17%), and antimalarial (15%), excluding IPTp. Artemether-lumefantrine (AL) was the most used antimalarial for treating illness by nearly 3/4 compared to other groups of malaria drugs. Overall, antimalarial and antibiotic exposures in pregnancy were not significantly associated with adverse pregnancy outcome. Iron and folic acid supplementation were associated with decreased risk of miscarriage/stillbirth (OR 0.1; 0.08 - 0.3). CONCLUSION: Almost all women were exposed to medication during pregnancy. Exposure to iron and folic acid had a beneficial effect on pregnancy outcome. HDSS proved to be a useful platform to establish a reliable pharmacovigilance system in resource-limited countries. Widening drug safety information is essential to facilitate evidence based risk-benefit decision for treatment during pregnancy, a major challenge with newly marketed medicines

Status of Occupational Health and Safety and Related Challenges in Expanding Economy of Tanzania.

Occupational health and safety is related with economic activities undertaken in the country. As the economic activities grow and expand, occupational injuries and diseases are more likely to increase among workers in different sectors of economy such as agriculture, mining, transport, and manufacture. This may result in high occupational health and safety services demand, which might be difficult to meet by developing countries that are prioritizing economic expansion without regard to their impact on occupational health and safety. To describe the status of occupational health and safety in Tanzania and outline the challenges in provision of occupational health services under the state of an expanding economy. Tanzania's economy is growing steadily, with growth being driven by communications, transport, financial intermediation, construction, mining, agriculture, and manufacturing. Along with this growth, hazards emanating from work in all sectors of the economy have increased and varied. The workers exposed to these hazards suffer from illness and injuries and yet they are not provided with adequate occupational health services. Services are scanty and limited to a few enterprises that can afford it. Existing laws and regulations are not comprehensive enough to cover the entire population. Implementation of legislation is weak and does not protect the workers. Most Tanzanians are not covered by the occupational health and safety law and do not access occupational health services. Thus an occupational health and safety services strategy, backed by legislations and provided with the necessary resources (competent experts, financial and technological resources), is a necessity in Tanzania. The existing legal provisions require major modifications to meet international requirements and standards. OHS regulations and legislations need refocusing, revision, and strengthening to cover all working population. Capacities should be improved through training and research to enable enforcement. Finally the facilities and resources should be made available for OHS services to match with the growing economy

Levels and Correlates of Non-Adherence to WHO Recommended Inter-Birth Intervals in Rufiji, Tanzania.

Poorly spaced pregnancies have been documented worldwide to result in adverse maternal and child health outcomes. The World Health Organization (WHO) recommends a minimum inter-birth interval of 33 months between two consecutive live births in order to reduce the risk of adverse maternal and child health outcomes. However, birth spacing practices in many developing countries, including Tanzania, remain scantly addressed. METHODS: Longitudinal data collected in the Rufiji Health and Demographic Surveillance System (HDSS) from January 1999 to December 2010 were analyzed to investigate birth spacing practices among women of childbearing age. The outcome variable, non-adherence to the minimum inter-birth interval, constituted all inter-birth intervals <33 months long. Inter-birth intervals >=33 months long were considered to be adherent to the recommendation. Chi-Square was used as a test of association between non-adherence and each of the explanatory variables. Factors affecting non-adherence were identified using a multilevel logistic model. Data analysis was conducted using STATA (11) statistical software. RESULTS: A total of 15,373 inter-birth intervals were recorded from 8,980 women aged 15--49 years in Rufiji district over the follow-up period of 11 years. The median inter-birth interval was 33.4 months. Of the 15,373 inter-birth intervals, 48.4% were below the WHO recommended minimum length of 33 months between two live births. Non-adherence was associated with younger maternal age, low maternal education, multiple births of the preceding pregnancy, non-health facility delivery of the preceding birth, being an in-migrant resident, multi-parity and being married. CONCLUSION: Generally, one in every two inter-birth intervals among 15--49 year-old women in Rufiji district is poorly spaced, with significant variations by socio-demographic and behavioral characteristics of mothers and newborns. Maternal, newborn and child health services should be improved with a special emphasis on community- and health facility-based optimum birth spacing education in order to enhance health outcomes of mothers and their babies, especially in rural settings

Safety of Artemether-Lumefantrine Exposure in First Trimester of Pregnancy: An Observational Cohort.

There is limited data available regarding safety profile of artemisinins in early pregnancy. They are, therefore, not recommended by WHO as a first-line treatment for malaria in first trimester due to associated embryo-foetal toxicity in animal studies. The study assessed birth outcome among pregnant women inadvertently exposed to artemether-lumefantrine (AL) during first trimester in comparison to those of women exposed to other anti-malarial drugs or no drug at all during the same period of pregnancy. Pregnant women with gestational age <20 weeks were recruited from Maternal Health clinics or from monthly house visits (demographic surveillance), and followed prospectively until delivery. 2167 pregnant women were recruited and 1783 (82.3%) completed the study until delivery. 319 (17.9%) used anti-malarials in first trimester, of whom 172 (53.9%) used (AL), 78 (24.4%) quinine, 66 (20.7%) sulphadoxine-pyrimethamine (SP) and 11 (3.4%) amodiaquine. Quinine exposure in first trimester was associated with an increased risk of miscarriage/stillbirth (OR 2.5; 1.3-5.1) and premature birth (OR 2.6; 1.3-5.3) as opposed to AL with (OR 1.4; 0.8-2.5) for miscarriage/stillbirth and (OR 0.9; 0.5-1.8) for preterm birth. Congenital anomalies were identified in 4 exposure groups namely AL only (1/164[0.6%]), quinine only (1/70[1.4%]), SP (2/66[3.0%]), and non-anti-malarial exposure group (19/1464[1.3%]). Exposure to AL in first trimester was more common than to any other anti-malarial drugs. Quinine exposure was associated with adverse pregnancy outcomes which was not the case following other anti-malarial intake. Since AL and quinine were used according to their availability rather than to disease severity, it is likely that the effect observed was related to the drug and not to the disease itself. Even with this caveat, a change of policy from quinine to AL for the treatment of uncomplicated malaria during the whole pregnancy period could be already envisaged.\u

Adherence to Iron-Folic Acid Supplementation and Associated Factors among Pregnant Women in Kasulu Communities in North-Western Tanzania

This research article published by Hindawi, 2020Introduction. Pregnant women are at a high risk of anaemia, with iron-folate deficiency being the most common cause of anaemia among pregnant women. Despite the well-known importance of iron and folic acid supplementation (IFAS) during pregnancy, adherence to these supplements is relatively low and associated factors were not well identified in the study area. This study is aimed at investigating adherence to IFAS and associated factors among pregnant women in Kasulu district, north-western Tanzania. Methods. A health facility cross-sectional survey with a mixed-method approach was conducted in Kasulu district from March to April 2019. A structured questionnaire was given to 320 women with children aged 0-6 months to assess factors associated with adherence to IFAS among pregnant women. Data were entered into SPSS version 22.0 for analysis. Binary logistic regression was further employed to determine the factors associated with adherence to IFAS. Focus group discussions were done with 19 pregnant women and 15 mothers of children aged 0-6 months to obtain more clarifications on the factors associated with adherence to IFAS. Furthermore, in-depth interviews were done with six health care providers to explore their perceptions of IFAS. Results. Out of the 320 respondents of the survey, 20.3% (n = 65) adhered to IFAS. Factors associated with adherence to IFAS among pregnant women included time to start ANC (AOR = 3:72, 95% CI: 1.42, 9.79), knowledge of anaemia (AOR = 3:84, 95% CI: 1.335, 10.66), counseling on the importance of the iron-folic acid (AOR = 3:86, 95% CI: 1.42, 10.50), IFAS given during clinical visit (AOR = 15:72, 95% CI: 5.34, 46.31), number of meals consumed (AOR = 3:44, 95% CI: 1.28, 9.21), number of children (AOR = 3:462, 95% CI: 1.035, 11.58), and distance to health facility (AOR = 0:34, 95% CI: 0.131, 0.886). Qualitative findings revealed that delayed first ANC visit, lack of remainder for pregnant women to take IFAS, low awareness about the negative effects of anaemia, low of knowledge of IFAS and management of side effects, negative beliefs about the use of IFAS, and follow-up mechanism were major reasons for poor adherence. Conclusion. Adherence to iron-folic acid supplementation during pregnancy was low. Strengthening systems for creating reminding mechanism, raising community awareness through educational programs to pregnant women and health providers could improve adherence to IFAS

The gut microbiota: a major player in the toxicity of environmental pollutants?

Exposure to environmental chemicals has been linked to various health disorders, including obesity, type 2 diabetes, cancer and dysregulation of the immune and reproductive systems, whereas the gastrointestinal microbiota critically contributes to a variety of host metabolic and immune functions. We aimed to evaluate the bidirectional relationship between gut bacteria and environmental pollutants and to assess the toxicological relevance of the bacteria–xenobiotic interplay for the host. We examined studies using isolated bacteria, faecal or caecal suspensions—germ-free or antibiotic-treated animals—as well as animals reassociated with a microbiota exposed to environmental chemicals. The literature indicates that gut microbes have an extensive capacity to metabolise environmental chemicals that can be classified in five core enzymatic families (azoreductases, nitroreductases, β-glucuronidases, sulfatases and β-lyases) unequivocally involved in the metabolism of >30 environmental contaminants. There is clear evidence that bacteria-dependent metabolism of pollutants modulates the toxicity for the host. Conversely, environmental contaminants from various chemical families have been shown to alter the composition and/or the metabolic activity of the gastrointestinal bacteria, which may be an important factor contributing to shape an individual’s microbiotype. The physiological consequences of these alterations have not been studied in details but pollutant-induced alterations of the gut bacteria are likely to contribute to their toxicity. In conclusion, there is a body of evidence suggesting that gut microbiota are a major, yet underestimated element that must be considered to fully evaluate the toxicity of environmental contaminants

Rifapentine and isoniazid for prevention of tuberculosis in people with diabetes (PROTID): protocol for a randomised controlled trial.

BACKGROUND: Diabetes mellitus (DM) increases the risk of tuberculosis (TB) and will hamper global TB control due to the dramatic rise in type 2 DM in TB-endemic settings. In this trial, we will examine the efficacy and safety of TB preventive therapy against the development of TB disease in people with DM who have latent TB infection (LTBI), with a 12-week course of rifapentine and isoniazid (3HP). METHODS: The 'Prevention of tuberculosis in diabetes mellitus' (PROTID) consortium will randomise 3000 HIV-negative eligible adults with DM and LTBI, as evidenced by a positive tuberculin skin test or interferon gamma release assay, to 12 weeks of 3HP or placebo. Participants will be recruited through screening adult patients attending DM clinics at referral hospitals in Tanzania and Uganda. Patients with previous TB disease or treatment with a rifamycin medication or isoniazid (INH) in the previous 2 years will be excluded. The primary outcome is the occurrence of definite or probable TB disease; secondary outcome measures include adverse events, all-cause mortality and treatment completion. The primary efficacy analysis will be intention-to-treat; per-protocol analyses will also be carried out. We will estimate the ratio of TB incidence rates in intervention and control groups, adjusting for the study site using Poisson regression. Results will be reported as efficacy estimates (1-rate ratio). Cumulative incidence rates allowing for death as a competing risk will also be reported. Approximately 1000 LTBI-negative, HIV-negative participants will be enrolled consecutively into a parallel cohort study to compare the incidence of TB in people with DM who are LTBI negative vs positive. A number of sub-studies will be conducted among others to examine the prevalence of LTBI and active TB, estimate the population impact and cost-effectiveness of LTBI treatment in people living with DM in these African countries and address gaps in the prevention and therapeutic management of combined TB-DM. DISCUSSION: PROTID is anticipated to generate key evidence to guide decisions over the use of TB preventive treatment among people with DM as an important target group for better global TB control. TRIAL REGISTRATION: ClinicalTrials.gov NCT04600167 . Registered on 23 October 2020

High Resistance of Plasmodium falciparum to Sulphadoxine/Pyrimethamine in Northern Tanzania and the Emergence of dhps Resistance Mutation at Codon 581

BACKGROUND: Sulphadoxine-pyrimethamine (SP) a widely used treatment for uncomplicated malaria and recommended for intermittent preventive treatment of malaria in pregnancy, is being investigated for intermittent preventive treatment of malaria in infants (IPTi). High levels of drug resistance to SP have been reported from north-eastern Tanzania associated with mutations in parasite genes. This study compared the in vivo efficacy of SP in symptomatic 6-59 month children with uncomplicated malaria and in asymptomatic 2-10 month old infants. METHODOLOGY AND PRINCIPAL FINDINGS: An open label single arm (SP) standard 28 day in vivo WHO antimalarial efficacy protocol was used in 6 to 59 months old symptomatic children and a modified protocol used in 2 to 10 months old asymptomatic infants. Enrolment was stopped early (87 in the symptomatic and 25 in the asymptomatic studies) due to the high failure rate. Molecular markers were examined for recrudescence, re-infection and markers of drug resistance and a review of literature of studies looking for the 581G dhps mutation was carried out. In symptomatic children PCR-corrected early treatment failure was 38.8% (95% CI 26.8-50.8) and total failures by day 28 were 82.2% (95% CI 72.5-92.0). There was no significant difference in treatment failures between asymptomatic and symptomatic children. 96% of samples carried parasites with mutations at codons 51, 59 and 108 in the dhfr gene and 63% carried a double mutation at codons 437 and 540. 55% carried a third mutation with the addition of a mutation at codon 581 in the dhps gene. This triple: triple haplotype maybe associated with earlier treatment failure. CONCLUSION: In northern Tanzania SP is a failed drug for treatment and its utility for prophylaxis is doubtful. The study found a new combination of parasite mutations that maybe associated with increased and earlier failure. TRIAL REGISTRATION: ClinicalTrials.gov NCT00361114

Indicators of optimal diabetes care and burden of diabetes complications in Africa: a systematic review and meta-analysis.

OBJECTIVE: Contemporary data on the attainment of optimal diabetes treatment goals and the burden of diabetes complications in adult populations with type 2 diabetes in Africa are lacking. We aimed to document the current status of attainment of three key indicators of optimal diabetes care and the prevalence of five diabetes complications in adult African populations with type 2 diabetes. METHODS: We systematically searched Embase, PubMed and the Cochrane library for published studies from January 2000 to December 2020. Included studies reported any information on the proportion of attainment of optimal glycated haemoglobin (HbA1c), blood pressure (BP) and low-density lipoprotein cholesterol (LDLC) goals and/or prevalence of five diabetes complications (diabetic peripheral neuropathy, retinopathy, nephropathy, foot ulcers and peripheral arterial disease). Random effect model meta-analysis was performed to determine the pooled proportion of attainment of the three treatment goals and the prevalence of five diabetes complications. RESULTS: In total, 109 studies with a total of 63 890 participants (53.3% being females) were included in the meta-analysis. Most of the studies were conducted in Eastern African countries (n=44, 40.4%). The pooled proportion of attainment of an optimal HbA1c, BP and LDLC goal was 27% (95% CI 24 to 30, I2=94.7%), 38% (95% CI 30 to 46, I2=98.7%) and 42% (95% CI 32 to 52, I2=97.4%), respectively. The pooled prevalence of diabetic peripheral neuropathy, retinopathy, diabetic nephropathy, peripheral arterial disease and foot ulcers was 38% (95% CI 31 to 45, I2=98.2%), 32% (95% CI 28 to 36, I2=98%), 31% (95% CI 22 to 41, I2=99.3%), 19% (95% CI 12 to 25, I2=98.1%) and 11% (95% CI 9 to 14, I2=97.4%), respectively. CONCLUSION: Attainment of optimal diabetes treatment goals, especially HbA1c, in adult patients with type 2 diabetes in Africa remains a challenge. Diabetes complications, especially diabetic peripheral neuropathy and retinopathy, are highly prevalent in adult populations with type 2 diabetes in Africa