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

Microbiological studies of cockroaches from three localities in Gaborone, Botswana

Cockroaches have become the most common pests in a majority of households in Gaborone, the capital city of Botswana Their presence has always raised safety concerns, especially as carriers of food-borne pathogens and food-spoilage organisms. To address the safety issues, bacteriological investigations were carried out on cockroaches trapped from the kitchens and toilets of three localities in Gaborone, households in Botswana. The bacterial, total spore forming, Bacillus cereus, coliforms and E. coli counts from the surfaces of cockroaches were estimated using bacteriological media. Aerobic and facultatively anaerobic bacteria from the fecal pellets were isolated and characterized. Specialized mediawere used for culturing pathogens. 67 %, 22.2 % and 28.6 % of the cockroaches trapped in the kitchen from Central/Broadhurst, Old Naledi and Tlokweng, respectively, had aerobic plate counts of > 106 CFU/cockroach. The cockroaches trapped from the toilets had higher counts than kitchens. Sporeformers were present in most samples though in lower numbers. However, Bacillus cereus was only found in some of the cockroaches at much lower numbers. As much as 70– 98.3% of the cockroaches had coliforms; but, E. coli was only found in 5–6.5% of the cockroaches at > 103 CFU/cockroach. 70 species of bacteria representing 37 genera were isolated from the surface and fecal pellets. Even though the majority of the bacteria that were isolated from the surfaces were Gram negative thosefrom the pellets were mostly Gram positive. The most common and abundant species belonged to Pseudomonas and Serratia, with members of the Enterobacteriaceae following. In the pellets, species of Bacillus were predominant, but, there were some members of Enterobacteriaceae. Pathogens like Salmonella, Shigella and B. cereus were isolated. Opportunistic pathogens like species of Pseudomonas, Klebsiella and Vibrio and food spoilage bacteria such as species of Enterobacter, Citrobacter, Escherichia, Erwinia, and Pseudomonas were also found. Proper care in disposal of food remnants and overall cleanliness at the householdsprevents cockroaches from foraging in the kitchen and toilet

Workforce Planning and Human Resource Development Strategies for Minnesota's Public Transportation Agencies

This study explored and examined possible causes of the workforce shortage in Minnesota’s transportation industry. Appropriate human resource strategies were proposed in response. Four interrelated approaches were undertaken: 1) a literature review, 2) a questionnaire, 3) audio interviews, and 4) integration of data to generate recommendations for Minnesota’s public transportation agencies. The findings showed a general level of agreement for a shortage of qualified individuals. Generational differences in the context of the transportation industry appeared to operate differently than in other sectors. Additional investigation will be needed to further examine whether differences in perceptions are more prominent at the industry or organizational level. When asked about recruitment strategies implemented by their agency, 17.4% of respondents reported that nothing was being done. The stated benefits of working for public agencies included job stability, set work hours for some positions, and work-life balance. Constraints of working in the public sector largely dealt with inflexible regulations, politics, and the complex barriers to new employee integration. Interviewees expressed overall satisfaction with their agency, but several noted problems that reflected bureaucratic policies. Standard pay scales, preferences for seniority, and lack of transparency for job roles were believed to be significant issues. In this report, we recommended a holistic approach to developing Minnesota’s public transportation industry through purposive change that focuses on existing opportunities related to the state’s and the nation’s changing demographics, as well as significant shifts related to the meaning and purpose of work

New synchronization method for <i>Plasmodium falciparum</i>

&lt;b&gt;Background&lt;/b&gt;: Plasmodium falciparum is usually asynchronous during in vitro culture. Although various synchronization methods are available, they are not able to narrow the range of ages of parasites. A newly developed method is described that allows synchronization of parasites to produce cultures with an age range as low as 30 minutes. &lt;b&gt;Methods&lt;/b&gt;: Trophozoites and schizonts are enriched using Plasmion. The enriched late stage parasites are immobilized as a monolayer onto plastic Petri dishes using concanavalin A. Uninfected erythrocytes are placed onto the monolayer for a limited time period, during which time schizonts on the monolayer rupture and the released merozoites invade the fresh erythrocytes. The overlay is then taken off into a culture flask, resulting in a highly synchronized population of parasites. &lt;b&gt;Results&lt;/b&gt;: Plasmion treatment results in a 10- to 13-fold enrichment of late stage parasites. The monolayer method results in highly synchronized cultures of parasites where invasion has occurred within a very limited time window, which can be as low as 30 minutes. The method is simple, requiring no specialized equipment and relatively cheap reagents. &lt;b&gt;Conclusions&lt;/b&gt;: The new method for parasite synchronization results in highly synchronized populations of parasites, which will be useful for studies of the parasite asexual cell cycle

Assessing the Effects of Mosquito Nets on Malaria Mortality Using a Space Time Model: A Case Study of Rufiji and Ifakara Health and Demographic Surveillance System Sites in Rural Tanzania.

Although malaria decline has been observed in most sub-Saharan African countries, the disease still represents a significant public health burden in Tanzania. There are contradictions on the effect of ownership of at least one mosquito net at household on malaria mortality. This study presents a Bayesian modelling framework for the analysis of the effect of ownership of at least one mosquito net at household on malaria mortality with environmental factors as confounder variables. The analysis used longitudinal data collected in Rufiji and Ifakara Health Demographic Surveillance System (HDSS) sites for the period of 1999-2011 and 2002-2012, respectively. Bayesian framework modelling approach using integrated nested laplace approximation (INLA) package in R software was used. The space time models were established to assess the effect of ownership of mosquito net on malaria mortality in 58 villages in the study area. The results show that an increase of 10 % in ownership of mosquito nets at village level had an average of 5.2 % decrease inall age malaria deaths (IRR = 0.948, 95 % CI = 0.917, 0.977) in Rufiji HDSS and 12.1 % decrease in all age malaria deaths (IRR = 0.879, 95 % CI = 0.806, 0.959) in Ifakara HDSS. In children under 5 years, results show an average of 5.4 % decrease of malaria deaths (IRR = 0.946, 95 % CI = 0.909, 0.982) in Rufiji HDSS and 10 % decrease of malaria deaths (IRR = 0.899, 95 % CI = 0.816, 0.995) in Ifakara HDSS. Model comparison show that model with spatial and temporal random effects was the best fitting model compared to other models without spatial and temporal, and with spatial-temporal interaction effects. This modelling framework is appropriate and provides useful approaches to understanding the effect of mosquito nets for targeting malaria control intervention. Furthermore, ownership of mosquito nets at household showed a significant impact on malaria mortality

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

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