Pharmacokinetics of piperaquine and its association with intermittent malaria preventive therapy outcomes during pregnancy.

BACKGROUND: Dihydroartemisinin-piperaquine (DHP) recently showed superior effectiveness over sulfadoxine-pyrimethamine for malaria intermittent preventive treatment in pregnancy (IPTp). We investigated day 7 piperaquine pharmacokinetics and its therapeutic efficacy in preventing malaria during pregnancy. METHODS: Malaria-free (mRDT) pregnant women (n = 400) who received monthly IPTp-DHP were enrolled and followed till delivery. Day 7 Plasma piperaquine concentrations were determined after each IPTp dose using UPLC/MS/MS. IPTp outcomes (symptomatic malaria and parasitemia during pregnancy, placental malaria, and maternal malaria at delivery) were monitored. Linear mixed model and Cox regression were used to assess predictors of day 7 piperaquine concentration and treatment outcome, respectively. RESULTS: The incidences of symptomatic malaria and parasitemia during pregnancy per 100 person-year at risk were 2 and 33, respectively. The prevalence of histopathologically confirmed placental malaria and maternal malaria at delivery were 3% and 9.8%, respectively. Repeated monthly IPTp-DHP resulted in significantly increased day 7 plasma piperaquine concentration (p < 0.001). Following the 1st, 2nd, and 3rd monthly IPTp-DHP doses, the proportions of women with day 7 piperaquine concentration below the therapeutic threshold (< 30 ng/mL) were 6.1%, 4.1% and 3.6%, respectively. Factors such as maternal age, body weight and trimester were not significant predictors of day 7 piperaquine concentration. However, having a low day 7 piperaquine plasma concentration (< 30 ng/mL) was significantly associated with a higher risk of parasitemia during pregnancy (p = 0.004). CONCLUSION: Lower day 7 piperaquine plasma concentration is a risk factor for parasitemia during pregnancy. Single plasma sampling at day 7 can be used to monitor piperaquine effectiveness during IPTp-DHP. TRIAL REGISTRATION: Registered 09/12/2016, PACTR201612001901313.

Efficacy of ivermectin and albendazole combination in suppressing transmission of lymphatic filariasis following mass administration in Tanzania: a prospective cohort study.

BACKGROUND: Preventive chemotherapy with ivermectin and albendazole (IA) in mass drug administration (MDA) programs for all at-risk populations is the core public health intervention to eliminate lymphatic filariasis (LF). Achieving this goal depends on drug effectiveness in reducing parasite reservoirs in the community to halt transmission. We assessed the efficacy of ivermectin and albendazole in clearing microfilariae and circulating filarial antigens (CFA) following MDA. METHODS: This community-based prospective study was conducted in Mkinga district, Tanga region, Tanzania, from November 2018 to June 2019. A total of 4115 MDA-eligible individuals were screened for CFA using Filarial test strips. CFA positives were re-examined for microfilariae by microscopy. CFA and microfilariae positive individuals were enrolled and received IA through MDA campaign. The status of microfilariae and CFA was monitored before MDA, and on day 7 and six-month following MDA. The primary efficacy outcomes were the clearance rates of microfilariae on day 7 and six-months, and CFA at 6 months of post-MDA. The McNemar test assessed the proportions of microfilariae positive pre- and post-MDA, while Chi-square tests were utilized to examine factors associated with CFA status six months post-MDA. RESULTS: Out of 4115 individuals screened, 239 (5.8%) tested positive for CFA, of whom 11 (4.6%) were also positive for microfilariae. Out of the ten microfilariae-positive individuals available for follow-up on day 7, nine tested negative, yielding a microfilariae clearance rate of 90% [95% confidence interval (CI): 59.6-98.2%]. Participants who tested negative for microfilariae on day 7 remained free of microfilariae six months after MDA. However, those who did not clear microfilariae on day-7 remained positive six-months post-MDA. The McNemar test revealed a significant improvement in microfilariae clearance on day 7 following MDA (P = 0.02). Out of 183 CFA-positive individuals who were available at 6-month follow-up, 160 (87.4%) remained CFA positive, while 23 became CFA negative. The CFA clearance rate at 6 months post-MDA was 12.6% (95% CI: 8.5-8.5%). There was no significant association of variability in ivermectin plasma exposure, measured by maximum concentration or area under the curve, and the clearance status of microfilariae or CFA post-MDA. CONCLUSIONS: Preventive chemotherapy with IA effectively clears microfilariae within a week. However, it is less effective in clearing CFA at six months of post-MDA. The low clearance rate for filarial antigenemia underscores the need for alternative drug combinations and additional preventive measures to achieve LF elimination by 2030.

Characterization of Non-Ischemic Dilated Cardiomyopathy in a Native Tanzanian Cohort: MOYO Study.

Background: Non-ischemic dilated cardiomyopathy (NIDCM) is a common cause of heart failure with progressive tendency. The disease occurs in one in every 2,500 individuals in the developed world, with high morbidity and mortality. However, detailed data on the role of NIDCM in heart failure in Tanzania is lacking. Aim: To characterize NIDCM in a Tanzanian cohort with respect to demographics, clinical profile, imaging findings and management. Methods: Characterization of non-ischemic dilated cardioMyOpathY in a native Tanzanian cOhort (MOYO) is a prospective cohort study of NIDCM patients seen at the Jakaya Kikwete Cardiac Institute. Patients aged ≥18 years with a clinical diagnosis of heart failure, an ejection fraction of ≤45% on echocardiography and no evidence of ischemia were enrolled. Clinical data, echocardiography, electrocardiography (ECG), coronary angiography and stress ECG information were collected from February 2020 to March 2022. Results: Of 402 patients, n = 220 (54.7%) were males with a median (IQR) age of 55.0 (41.0, 66.0) years. Causes of NIDCM were presumably hypertensive n = 218 (54.2%), idiopathic n = 116 (28.9%), PPCM n = 45 (11.2%), alcoholic n = 10 (2.5%) and other causes n = 13 (3.2%). The most common presenting symptoms were dyspnea n = 342 (85.1%), with the majority of patients presenting with New York Heart Association (NYHA) Class III n = 195 (48.5%). The mean (SD) left ventricular ejection fraction (LVEF) was 29.4% (±7.7), and severe systolic dysfunction (LVEF <30%) was common n = 208 (51.7%). Compared with other forms of DCM, idiopathic DCM patients were significantly younger, had more advanced NYHA class (p < 0.001) and presented more often with left bundle branch block on ECG (p = 0.0042). There was suboptimal use of novel guidelines recommended medications ARNI n = 10 (2.5%) and SGLT2 2-inhibitors n = 2 (0.5%). Conclusions: In our Tanzanian cohort, the majority of patients with NIDCM have an identified underlying cause, and they present at late stages of the disease. Patients with idiopathic DCM are younger with more severe disease compared to other forms of NIDCM.

National Non-Communicable Diseases Conferences- A Platform to Inform Policies and Practices in Tanzania.

Background: Non-communicable diseases (NCDs) arise from diverse risk factors with differences in the contexts and variabilities in regions and countries. Addressing such a complex challenge requires local evidence. Tanzania has been convening stakeholders every year to disseminate and discuss scientific evidence, policies, and implementation gaps, to inform policy makers in NCDs responses. This paper documents these dissemination efforts and how they have influenced NCDs response and landscape in Tanzania and the region. Methods: Desk review was conducted through available MOH and conference organizers' documents. It had both quantitative and qualitative data. The review included reports of the four NCDs conferences, conference organization, and conduct processes. In addition, themes of the conferences, submitted abstracts, and presentations were reviewed. Narrative synthesis was conducted to address the objectives. Recommendations emanated from the conference and policy uptake were reviewed and discussed to determine the impact of the dissemination. Findings: Since 2019, four theme-specific conferences were organized. This report includes evidence from four conferences. The conferences convened researchers and scientists from research and training institutions, implementers, government agencies, and legislators in Tanzania and other countries within and outside Africa. Four hundred and thirty-five abstracts were presented covering 14 sub-themes on health system improvements, financing, governance, prevention intervention, and the role of innovation and technology. The conferences have had a positive effect on governments' response to NCDs, including health care financing, NCDs research agenda, and universal health coverage. Conclusion: The National NCDs conferences have provided suitable platforms where stakeholders can share, discuss, and recommend vital strategies for addressing the burden of NCDs through informing policies and practices. Ensuring the engagement of the right stakeholders, as well as the uptake and utilization of the recommendations from these platforms, remains crucial for addressing the observed epidemiological transition in Tanzania and other countries with similar contexts.

Establishment of clinical pharmacy services: evidence-based information from stakeholders.

High morbidity and mortality related to the use of drugs resulted in demand for clinical pharmacy services (CPS) globally. In developed countries, the evolution of pharmacists' role in direct patient care started in the 1960s. The participation of pharmacists in CPS has resulted in positive clinical, economic, and humanistic outcomes. In developing countries, efforts have started to ensure pharmacists are engaged in the provision of CPS. However, the efforts are hampered by poorly defined pharmacist career paths, financial constraints, and a lack of political willingness. In Tanzania, efforts started in 2008, in which CPS was introduced into the Bachelor of Pharmacy curriculum, followed by the initiation of a postgraduate program on hospital and clinical pharmacy in 2013. A regulation was released by the Tanzania Ministry of Health in 2020 to enforce pharmacists' engagement in providing CPS. In 2021, a project was launched in the country, aiming to strengthen the provision of CPS in public and faith-based hospitals by training on-job pharmacists. The project was implemented in phases, including stakeholders' engagement, baseline survey, training, and supportive supervision of the trained pharmacists. Therefore, this commentary aims to share what we experienced during project implementation, the achievements, challenges, and key lessons learned.

Comparison between interventional versus medical therapy in patients with rheumatic mitral valve stenosis in Tanzania.

BACKGROUND: Rheumatic heart disease remains the most common cardiovascular disease in children and young adults. The outcome of interventional versus medical therapy on the long term is not fully elucidated yet. This study provides contemporary data on the clinical profile, treatment and follow up of patients with rheumatic mitral stenosis (MS) in Tanzania. METHODS: Patients' medical information, investigations and treatment data were recorded in this prospective cohort study. They were followed up for 6-24 months to determine the long-term outcome. Interventional therapy was defined as a combination of surgery and percutaneous balloon mitral valvuloplasty. Kaplan-Meier curves and Cox proportional hazards model were used in analyses. p-Value < 0.05 was considered statistically significant. RESULTS: We enrolled 290 consecutive patients. Interventions were done in half of the patients. Median follow up was 23.5 months. Mortality was higher in the medical than interventional treatment (10.4% vs. 4%, log-rank p = 0.001). Median age was 36 years, females (68.3%) and low income (55.5%). Multivalvular disease was found in 116 (40%) patients, atrial fibrillation (31.4%), stroke/transient ischaemic attack (18.9%) and heart failure class III-IV (44.1%). Median (IQR) duration of disease was 3 (4) years, secondary prophylaxis (27.7%) and oral anticoagulants use (62.3%). In multivariable analysis, the risk of death among patients on medical was 3.07 times higher than those on interventional treatment (crude HR 3.07, 95% CI 1.43-6.56, p = 0.004), 2.44 times higher among patients with arrhythmias versus without arrhythmias (crude HR 2.44, 95% CI 1.19-4.49, p = 0.015) and 2.13 times higher among patients with multivalvular than single valve disease (crude HR 2.13, 95% CI 1.09-4.16, p = 0.026). CONCLUSIONS: Intervention is carrying low mortality compared to medical treatment. Arrhythmias and multivalvular disease are associated with a high mortality. Rheumatic MS is more prevalent in young people, females and individuals with low income. There is a late hospital presentation and a low use of both secondary prophylactic antibiotics and anticoagulants.

Non-communicable Diseases Week: Best Practices in Addressing the NCDs Burden from Tanzania.

Background: Five million people die every year from non-communicable diseases (NCDs) globally. In Tanzania, more than two-thirds of deaths are NCD-related. The country is investing in preventive and advocacy activities as well as interventions to reduce the burden. Of particular interest, the Ministry of Health (MoH) commemorates NCDs' week using a multisectoral and multi-stakeholders' approach. This paper highlights activities conducted during NCDs week with the aim of sharing lessons for other countries with similar context and burdens. Methods: A thorough review of official reports and the national strategic plans for NCDs was done including the 2020 and 2021 National NCDs' week reports, the National Strategic Plan for NCDs 2015-2020, and the National NCDs agenda. Findings: NCDs week is commemorated annually throughout the country involving the five key activities. First, community awareness and participation are encouraged through media engagement and community-based preventive and advocacy activities. Second, physical activities and sports festivals are implemented with a focus on developing and renovating infrastructures for sports and recreation. Third, health education is provided in schools to promote healthy behaviors for secondary school adolescents in transition to adulthood. Fourth, health service provision and exhibitions are conducted involving screening for hypertension, diabetes, obesity, alcohol use, and physical activities. The targeted screening of NCDs identified 10% of individuals with at least one NCD in 2020. In 2021, a third of all screened individuals were newly diagnosed with hypertension, and 3% were found to have raised blood glucose levels. Fifth, the national NCDs scientific conferences conducted within the NCDs week provide an avenue for stakeholders to discuss scientific evidence related to NCDs and recommend strategies to mitigate NCDs burden. Conclusion: The initiation of NCDs week has been a cornerstone in advocating for NCDs control and prevention in the country. It has created awareness on NCDs, encourage healthy lifestyles and regular screening for NCDs. The multi-stakeholder and multi-sectoral approaches have made the implementation of the mentioned activities feasible and impactful. This has set an example for the united efforts toward NCD control and prevention at national, regional, and global platforms while considering contextual factors during adoption and implementation.

Mitigating the Rising Burden of Non-Communicable Diseases through Locally Generated Evidence-Lessons from Tanzania.

Background: The burden of Non-Communicable Diseases (NCDs) is rapidly increasing globally, and low- and middle-income countries (LMICs) bear the brunt of it. Tanzania is no exception. Addressing the rising burden of NCDs in this context calls for renewed efforts and commitment by various stakeholders. This paper highlights local initiatives and strategies to combat NCDs in Tanzania and provides lessons for countries with similar contexts. Methods: We reviewed published and grey literature and conducted policy analysis on NCDs in Tanzania to examine the burden of NCDs and the national response addressing it. The documents included National NCD strategic plans, NCD research agenda, and reports from the World Diabetes Foundation and the World Health Organization. Moreover, a scoping review of ongoing NCD activities and programs in other countries was also conducted to supplement the evidence gathered. Results: The rising burden of NCDs as a result of the epidemiological transition in Tanzania called for the launching of a dedicated National NCD Control and Prevention Program. The Ministry of Health collaborates with local, national, and international partners on NCD prevention and curative strategies. This led to the development of important guidelines and policies on NCDs, including strengthening the capacity of health facilities and healthcare workers, increased community engagement and awareness of NCDs, and increased advocacy for more resources in NCD initiatives. Strong governmental commitment has been vital; this is demonstrated by a renewed commitment to the fight through national NCD week and related advocacy activities conducted annually. To ensure multi-stakeholders' engagement and political commitment, all these activities are coordinated at the Prime Minister's office and provide strong lessons for countries with contexts similar to Tanzania. Conclusion: Multi-stakeholders' engagement, innovative approaches, and coordinated governmental efforts to address NCDs have shone a light on addressing the burden of NCDs and may be sustainable if aligned with locally available resources. Such initiatives are recommended for adoption by other nations to address the burdens of NCDs.

Population pharmacokinetics of ivermectin after mass drug administration in lymphatic filariasis endemic communities of Tanzania.

Ivermectin (IVM) is a drug of choice used with albendazole for mass drug administration (MDA) to halt transmission of lymphatic filariasis. We investigated IVM pharmacokinetic (PK) variability for its dose optimization during MDA. PK samples were collected at 0, 2, 4, and 6 h from individuals weighing greater than 15 kg (n = 468) receiving IVM (3-, 6-, 9-, or 12 mg) and ALB (400 mg) during an MDA campaign in Tanzania. Individual characteristics, including demographics, laboratory/clinical parameters, and pharmacogenetic variations were assessed. IVM plasma concentrations were quantified by liquid-chromatography tandem mass spectrometry and analyzed using population-(PopPK) modeling. A two-compartment model with transit absorption kinetics, and allometrically scaled oral clearance (CL/F) and central volume (Vc /F) was adapted. Fitting of the model to the data identified 48% higher bioavailability for the 3 mg dose compared to higher doses and identified a subpopulation with 97% higher mean transit time (MTT). The final estimates for CL/F, Vc /F, intercompartment clearance, peripheral volume, MTT, and absorption rate constant for a 70 kg person (on dose other than 3 mg) were 7.7 L/h, 147 L, 20.4 L/h, 207 L, 1.5 h, and 0.71/h, respectively. Monte-Carlo simulations indicated that weight-based dosing provides comparable exposure across weight bands, but height-based dosing with capping IVM dose at 12 mg for individuals with height greater than 160 cm underdoses those weighing greater than 70 kg. Variability in IVM PKs is partly explained by body weight and dose. The established PopPK model can be used for IVM dose optimization. Height-based pole dosing results in varying IVM exposure in different weight bands, hence using weighing scales for IVM dosing during MDA is recommended.

Health related quality of life of patients following mechanical valve replacement surgery for rheumatic mitral stenosis in Tanzania.

BACKGROUND: The assessment of outcomes of interventions based on the patient's perspective using patient-reported outcome measures (PROMs) has been increasingly highlighted in clinical practice. However, health related quality of life (HRQoL), one of the common constructs measured by PROMs remain unknown among patients after heart valve replacement (HVR) in Tanzania. OBJECTIVES: To assess the HRQoL amongst patients operated on for rheumatic mitral stenosis at Jakaya Kikwete Cardiac Institute (JKCI). METHODS: A prospective study of patients operated on due to rheumatic mitral stenosis at JKCI from January 2020 to April 2021 was undertaken. The HRQoL was assessed by using the MacNew questionnaire, addressing three domains (physical, emotional, and social function); the score ranges from 0 to 7. We categorized HRQoL as low (mean score ≤ 4.9), moderate (5-6) and high (> 6). We analysed several sociodemographic and clinical variables for HRQoL. RESULTS: Out of 54 patients, there were 34 females and 20 males. Their mean (± SD) age was 37.98 (± 12.58) years. The reliability of translated Kiswahili version of MacNew was good. The mean (± SD) global scores were 3.47 ± 0.59, 4.88 ± 0.71 and 6.14 ± 0.50 preoperatively, at 3 months and 6 months respectively (p-values < 0.001 preoperatively vs. 3 months, preoperatively vs. 6 months and at 3 months vs. 6 months). The median of individual mean difference HRQoL score pre-operatively and at 6 months was 2.67. The preoperative and 6 months mean difference HRQoL scores were higher among patients with vs. without atrial fibrillation (2.95 ± 0.59 vs. 2.45 ± 0.53, p = 0.003) and those on anticoagulants (preoperatively) vs. not on anticoagulants (3.14 ± 0.58 vs. 2.57 ± 0.57, 0.009). The mean difference HRQoL scores were similar for sociodemographic and other clinical parameters, including those with stroke vs. without stroke. CONCLUSION: Six months after HVR the overall MacNew HRQoL scores improved markedly. This improvement in HRQoL was regardless of the presence of comorbidities (e.g. stroke and atrial fibrillation) which underscores the importance of considering valvular surgery if they fit the criteria. Clinicians and researchers in low-resource settings should collaborate to promote the utilization of PROMs in the routine care of patients.

Effectiveness of antenatal dexamethasone in reducing respiratory distress syndrome and mortality in preterm neonates: a nested case control study.

BACKGROUND: Respiratory distress syndrome (RDS) is a significant cause of preterm neonatal morbidity and mortality globally. Measures like the use of antenatal corticosteroids (ACS) and immediate resuscitation of the newborn after birth are taken to abate preterm related complications. Most studies that evidenced the benefit of ACS were done in high resource settings. Therefore, this study was conducted to assess the effectiveness of ACS in reducing RDS and neonatal mortality in preterm neonates in resource-limited settings. METHODS: A three months prospective nested case-control study (1:2 unmatched) was conducted at Muhimbili National Hospital and Amana regional referral hospital in Dar es salaam, Tanzania. Neonates delivered at 28 to 34 gestational weeks were enrolled and followed up until discharge. Data analysis was done using the statistical package of social sciences version 23. Logistic regression analysis was used to determine the effect of ACS on the RDS and mortality in the cohort, controlling for important maternal and neonatal variables. All tests were considered statistically significant at p < 0.05. RESULTS: Out of 330 preterm neonates enrolled, 110 were cases and 220 were controls. The median gestational age at delivery was 30 weeks and 6 days (IQR 4.68) among cases and 33 weeks (IQR 3) among controls. One-minute APGAR score of < 7 (AOR: 3.11; 95% CI 1.54-6.30), and neonatal birth weight (AOR: 0.998; 95% CI 0.997-0.999) were significantly associated with RDS. No significant association was observed between ACS exposure and RDS occurrence (AOR: 1.65; 95% CI 0.86 - 3.15). The overall mortality rate was 9 per 1000 neonates. Neonatal mortality occurred only among cases whereby, a unit increase in gestational age was associated with a 30% reduction in neonatal mortality (Adjusted hazard ratio, AHR: 0.70, 95% CI: 0.5-0.92, p = 0.011). CONCLUSION: Decrease in gestational age, one minute APGAR score of < 7 and decreasing birth weight were associated with RDS among preterm neonates. ACS was not associated with reduced RDS occurrence and neonatal mortality rates. Moreover, increase in gestation age was the only factor found to be protective against preterm neonatal mortality.

Barriers and facilitators of integration of pharmacists in the provision of clinical pharmacy services in Tanzania.

BACKGROUND: Collaboration between medical doctors and nurses in the provision of healthcare services has been there for decades. The concept of clinical pharmacy services as a main goal for pharmacy practice is relatively new and is yielding more positive results for healthcare providers (HCPs), patients, and the health system. This study assessed barriers and facilitators toward the integration of pharmacists in the provision of CPS in Tanzania. METHODS: A qualitative study was conducted in five tertiary hospitals representing Tanzania mainland. Ten (10) focus group discussions (FGDs) with 83 HCPs and 14 in-depth interviews (IDIs) with hospital administrators in referral hospitals were conducted between August and September 2021. The experienced qualitative researchers moderated the IDIs and FGDs, and all discussions were audio-recorded. Finally, the audios were transcribed verbatim, and analysis was done using a thematic approach. RESULTS: Limited skills, lack of confidence, poor communication, inferiority, and superiority behaviors among HCPs were among the mentioned barriers. Shortage of pharmacists, lack of in-job training, standard operating procedures (SOPs), and guidelines were also mentioned. The study noted the high acceptability of CPS by other HCPs, the positive perception of pharmacists, and the recognition of CPS by the Tanzania Pharmacy Act and regulation. CONCLUSION: The facilitators and barriers to the integration of pharmacists in the provision of CPS lie at the individual, health facility, and health system levels. Therefore, the study recommends in-job pharmacists training, fostering teamwork among HCPs, and development of CPS SoPs, and guidelines.

Sub-clinical rheumatic heart disease (RHD) detected by hand-held echocardiogram in children participating in a school-based RHD prevention program in Tanzania.

BACKGROUND: Rheumatic Heart Disease (RHD) continues to cause suffering and premature deaths in many sub-Saharan Africa (SSA) countries, where the disease is still endemic. RHD is largely preventable and determining its community burden is an important critical step in any RHD prevention program. METHODS: We conducted a cross-sectional study of 5-16 years old pupils from 11 primary schools participating in an RHD prevention program in 4 districts in Tanzania, between 2018 and 2019. At the school, all children were invited to participate after receiving consent from their parents/guardians. Participating children filled a questionnaire and were auscultated for cardiac murmurs. Echocardiographic screening was done by two experienced cardiologists, using a hand-held machine (V-Scan, GE®). All positive screening tests were stored for further examination by the same two cardiologists to reach to a consensus of definite, borderline or no RHD, using a modified World Heart Federation (WHF) criterion. RESULTS: Of the 6895 children invited, 4738 (68.7%) were screened and 4436 (64.3%) had complete data. The mean (SD) age was 10.04 (2.43) years, and 2422 (54.6%) were girls. Fifty three (1.2%) children were found to have a murmur. The proportion of children with trace or mild valvular regurgitation, sub-valvular/chordal thickening and valvular thickening/deformity were 8.3%, 1.3%, and 1.0%, respectively. Sub-clinical RHD was found in 95 children (59 definite and 36 borderline), giving a prevalence of 2.1%, [95% CI 1.7% - 2.6%]. Sub-clinical RHD was independently associated with female sex (aOR 1.83, 95% CI 1.18-2.85, p = 0.007), older age groups (aOR 1.73, 95% CI 1.10-2.72, p = 0.018 for age group 11-14 years; and aOR 3.02 95% CI 1.01-9.05, p = 0.048 for age group 15-16 years), as well as presence of a cardiac murmur, aOR 5.63 95% CI 2.31-13.69, p < 0.0001. None of the studied socio- or economic factors was associated with the presence of sub-clinical RHD in this study. CONCLUSION: The prevalence of sub-clinical RHD among primary school children in Tanzania is 2.1%, similar to previous reports in SSA. Efforts to prevent and control RHD in our communities are highly warranted.

Characteristics and immediate outcomes of patients who underwent percutaneous balloon mitral valvuloplasty at the Jakaya Kikwete Cardiac Institute, Tanzania.

BACKGROUND: For rheumatic mitral stenosis (MS), a multidisciplinary evaluation is mandatory to determine the optimal treatment: medical, percutaneous balloon mitral valvuloplasty (PBMV) or valve surgery. Clinical and imaging evaluations are essential for procedural risk assessment and outcomes. PBMV interventions are increasingly available in Africa and are feasible options for selected candidates. Enhancing PBMV training/skills transfer across most of African countries is possible. OBJECTIVES: The aim of this study was to provide insight into the clinical practice of patients with rheumatic MS evaluated for PBMV in a Tanzanian teaching hospital and to define the role of imaging, and evaluate the heart team and training/skills transfer in PBMV interventions. METHODS: From August 2019 to May 2022, 290 patients with rheumatic MS were recruited consecutively in the Tanzania Mitral Stenosis study. In total, 43 (14.8%) patients were initially evaluated for eligibility for PBMV by a heart team. We carried out the clinical assessment, laboratory investigations, transthoracic/oesophageal echocardiography (TTE/TEE) and electrocardiography. RESULTS: The median age was 31 years (range 11-68), and two-thirds of the patients were female (four diagnosed during pregnancy). Two patients had symptomatic MS at six and eight years. Nine patients had atrial fibrillation with left atrial thrombus in three, and two were detected by TEE. Nine patients in normal sinus rhythm had spontaneous echo contrast. The mean Wilkins score was 8.6 (range 8-12). With re-evaluation by the local and visiting team, 17 patients were found to have unfavourable characteristics: Bi-commissural calcification (four), ≥ grade 2/4 mitral regurgitation (six), high scores and left atrial thrombus (three), left atrial thrombus (two), and severe pulmonary hypertension (two). Three patients died before the planned PBMV. Eleven patients were on a waiting list. We performed PBMV in 12 patients, with success in 10 of these, and good short-term outcomes [mean pre-PBMV (16.03 ± 5.52 mmHg) and post-PBMV gradients (3.08 ± 0.44 mmHg, p < 0.001)]. There were no complications. CONCLUSIONS: PBMV had good outcomes for selected candidates. TEE is mandatory in pre-PBMV screening and for procedural guidance. In our cohort, patients with Wilkins score of up to 11 underwent successful PBMV. We encourage PBMV skills expansion in low- and middle-income countries, concentrating on expertise centres.

Pregnancy Increases CYP3A Enzymes Activity as Measured by the 4ß-Hydroxycholesterol/Cholesterol Ratio.

Changes in cortisol and other hormones during pregnancy may alter CYP3A enzymes activity, but data from sub-Saharan Africa are sparse. We investigated the effect of pregnancy and CYP3A5 genotypes on CYP3A enzymes activity using the plasma 4ß-hydroxycholesterol (4ß-OHC)/cholesterol (Chol) ratio, a known endogenous biomarker. Tanzanian pregnant women (n = 110) and non-pregnant women (n = 59) controls were enrolled. Plasma 4ß-OHC and Chol were determined in the second and third trimesters for pregnant women and once for non-pregnant women using gas chromatography−mass spectrometry. Genotyping for CYP3A5 (*3, *6, *7) was performed. Wilcoxon Signed-Rank Test and Mann−Whitney U test were used to compare the median 4ß-OHC/Chol ratio between trimesters in pregnant women and between pregnant and non-pregnant women. Repeated-measure ANOVA was used to evaluate the effect of the CYP3A5 genotypes on the 4ß-OHC/Chol ratio in pregnant women. No significant effect of the pregnancy status or the CYP3A5 genotype on the cholesterol level was observed. The plasma 4ß-OHC/Chol ratio significantly increased by 7.3% from the second trimester to the third trimester (p = 0.02). Pregnant women had a significantly higher mean 4ß-OHC/Chol ratio than non-pregnant women, (p < 0.001). In non-pregnant women, the mean 4ß-OHC/Chol ratio was significantly lower in carriers of defective CYP3A5 alleles (*3, *6 or *7) as compared to women with the CYP3A5*1/*1 genotypes (p = 0.002). Pregnancy increases CYP3A enzymes activity in a gestational-stage manner. The CYP3A5 genotype predicts CYP3A enzymes activity in the black Tanzanian population, but not during pregnancy-mediated CYP3A enzyme induction.

Barriers and Facilitators of Availability of Hydroxyurea for Sickle Cell Disease in Tanzania; A Qualitative Study of Pharmaceutical Manufacturers, Importers, and Regulators.

Despite three decades of proven safety and effectiveness of hydroxyurea in modifying sickle cell disease (SCD), its accessibility is limited in Sub-Saharan Africa, which shares 75% of the world's SCD burden. Therefore, it is time to explore the barriers and facilitators for manufacturing and importation of hydroxyurea for SCD in Tanzania. This was qualitative research that employed a case study approach. Purposive sampling followed by an in-depth interview (IDI) using a semi-structured questionnaire aspired by data saturation enabled us to gather data from 10 participants. The study participants were people with more than three years of experience in pharmaceuticals importation, manufacturing, and regulation. The audio-recorded data were verbatim transcribed and analyzed using thematic analysis. Two themes were generated. The first comprised barriers for importation and manufacturing of hydroxyurea with sub-themes such as inadequate awareness of SCD and hydroxyurea, limited market, and investment viability. The second comprised opportunities for importation and manufacturing of hydroxyurea with sub-themes such as awareness of activities performed by medicines regulatory authority and basic knowledge on SCD and hydroxyurea. Inadequate understanding of SCD, hydroxyurea, and orphan drug regulation are major issues that aggravate the concern for limited market and investment viability. Existing opportunities are a starting point towards increasing the availability of hydroxyurea.

Nasopharyngeal Carriage and Antibiogram of Pneumococcal and Other Bacterial Pathogens from Children with Sickle Cell Disease in Tanzania.

Background: Bacterial infections contribute significantly to morbidity and mortality in sickle cell disease (SCD) patients, particularly children under five years of age. In Tanzania, prophylaxis against pneumococcal infection among children with SCD advocates the use of both oral penicillin V (PV) and pneumococcal vaccines (PNV). Therefore, this study aimed to investigate nasopharyngeal carriage and antibiogram of Streptococcal pneumoniae (S. pneumoniae) and Staphylococcus aureus (S. aureus) in children with SCD in Tanzania. Methods: This cross-sectional study was undertaken at the two Sickle Pan-African Research Consortium (SPARCO) study sites in Dar es salaam, Tanzania. The study was conducted for six months and enrolled children with SCD between the ages of 6 to 59-months. A semi-structured questionnaire was used to collect patient data. Nasopharyngeal swabs were collected from all participants and cultured for Streptococcal pneumoniae and other bacterial isolates. Antimicrobial susceptibility tests of the isolates were done using the disc diffusion method. Results: Out of 204 participants, the overall prevalence of bacterial carriage was 53.4%, with S. aureus (23.5%), coagulase-negative Staphylococci (CoNS) (23%) and S. pneumoniae (7.8%) being commonly isolated. In antibiotic susceptibility testing, S. aureus isolates were most resistant to penicillin (81.8%), whereas 81.3% of S. pneumoniae isolates were resistant to co-trimoxazole. The least antimicrobial resistance was observed for chloramphenicol for both S. aureus and S. pneumoniae isolates (6.3% versus 0%). The proportion of multi-drug resistance (MDR) was 66.7% for S. aureus isolates and 25% for S. pneumoniae isolates. Conclusion: There are substantially high nasopharyngeal carriage pathogenic bacteria in children with SCD in Dar es Salaam, Tanzania. The presence of MDR strains to the commonly used antibiotics suggests the need to reconsider optimizing antimicrobial prophylaxis in children with SCD and advocacy on pneumococcal vaccines.

Adherence, Effectiveness and Safety of Dolutegravir Based Antiretroviral Regimens among HIV Infected Children and Adolescents in Tanzania.

Objectives:This study aimed at assessing adherence, effectiveness, and safety of DTG-based HAART regimens among HIV-infected children and adolescents in Tanzania. Methods: This was a single-center prospective cohort study, conducted at the pediatric HIV Clinic in Mbeya, Tanzania. A binary logistic regression model was used to determine predictors of undetectable viral load at week 24. The results were significant when P-value was <0.05. Results: A total of 200 patients were enrolled with the majority (85.5%) being treatment experienced. High adherence levels (71%) were observed using the pharmacy refill method. At week 24, the overall proportion of patients with undetectable viral load was 70.2%. The predictors of undetectable viral load were age, World Health Organization (WHO) clinical stage, baseline VL and adherence to pharmacy refill. Conclusion: The majority of patients attained undetectable viral load 6 months after using DTG based regimen. DTG-based regimens were generally safe with few ADEs reported.

Newborn Screening for Critical Congenital Heart Disease in a Low-Resource Setting; Research Protocol and Preliminary Results of the Tanzania Pulse Oximetry Study.

Background: Critical Congenital Heart Disease (CCHD) is the leading cause of early new-born mortality. Its early detection and intervention is crucial for the survival of affected new-born. Pulse Oximetry (POX) has shown to be one of the feasible, accurate and cost-effective tools in screening CCHD in developed nations, it is yet to be practiced and established as standard of care in a low-resource setting. Objectives: This paper reports on the research protocol and preliminary results of an ongoing study regarding the performance of POX in detecting CCHD in new-borns in a low resource setting. Secondary objectives include investigating the burdens of CCHD and outcome at 12 months of age. Methods: The Tanzanian Pulse Oximetry Study (TPOXS) is a prospective cohort study which plans to enrol 30,000 mothers and new-borns delivered at two referral hospitals in Tanzania. New-borns are offered POX test 12 hours after birth, those positively undergoes echocardiography examinations. Confirmed with CCHD are placed under observation for up to first birthday. Results: During a 5-months pilot period, a total of 1,592 infants at the Muhimbili National Hospital, received POX test .65% of them were post-caesarean section and 52% being male. Most babies delivered through Spontaneous Vertex Delivery (SVD) were promptly discharge and did not get screened. The detection-rate of CCHD was 2.5 per 1,000 live births (at 95% confidence interval [CI] 0.9 to 6.7 per 1000 live birth); with a POX false positive rate of 0.6%. Seven false-positive infants out of 10 were found to carry significant other neonatal conditions, including persistent pulmonary hypertension of the new-born, transient tachypnoeic and neonatal sepsis. Conclusion: This paper provides the protocol of the ongoing TPOXS with the preliminary results showing prevalence matching closely the global data. It shows acceptability of POX screening for CCHD in a well-prepared low resource setting. Highlight: This study addresses the utilization of pulse oximeter in detecting critical congenital heart disease (CCHD) in a low-resource setting (such as sub-Saharan African countries).