Gentamicin concentration and acute kidney injury in term neonates treated for neonatal sepsis with gentamicin and ampicillin-cloxacillin combination.

Gentamicin is widely used to treat neonatal infections caused by both Gram-negative and Gram-positive bacteria, and the WHO recommends its use while monitoring serum creatinine and gentamicin concentrations to avoid drug-induced nephrotoxicity and ototoxicity. Yet in some resource-limited settings, the drug is used without monitoring. A population pharmacokinetics study involving term neonates with neonatal infection admitted to a neonatal unit. Participants were started on intravenous gentamicin 5 mg/kg once a day in combination with ampicilin-cloxacillin. Blood samples for serum gentamicin concentration were taken at 0.25, 0.5, 1, 2, 3, 5, 6, 8, 10, 12, 14, 16, 18, 20, 23, and 24 hours after the initial dose, each participant contributing two samples to the 24 hour sampling schedule. An additional sample for trough concentration was taken from each participant just before the third gentamicin dose while serum creatinine concentration was measured before and after treatment. Twenty-four participants were enrolled into the study and included in the final analysis. Mean (SD) peak and trough serum gentamicin concentrations were 16.66 (0.64) µg/mL and 3.28 (0.70) µg/mL, respectively. Gentamicin clearance (CL) was 0.40 mL min-1 kg-1 and volume of distribution (VD) was 0.31 L kg-1. Mean (SD) serum creatinine level after treatment was 209.7 (70.4) µmol/L compared to 103.3 (23.6) µmol/L before treatment [mean difference (106.4 ± 67.1; 95% confidence interval (CI): 78.1; 134.7 µmol/L; t (23) = 7.77; P < 0.001]. All participants fulfilled the Kidney Disease Improving Global Outcomes (KDIGO) criteria for acute kidney injury after treatment. Treatment of neonatal infection with antimicrobial regimen containing gentamicin, without renal function and gentamicin concentration monitoring, carries a significant risk for drug-induced acute kidney injury.

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.

Incidence and determinants of adverse events in individuals with HIV commencing Dolutegravir-based antiretroviral therapy in mainland Tanzania.

Tanzania adopted a Dolutegravir (DTG)-based regimen as first-line treatment in 2019 following the World Health Organization recommendation. Data on the DTG safety profile from sub-Saharan Africa including Tanzania are limited. We investigated the incidence of DTG-related adverse events (AEs) and associated factors among people living with HIV (PLHIV) initiated on a DTG regimen. A prospective cohort study was conducted from 25 Care and Treatment Clinics in mainland Tanzania. PLHIV aged 12 years and above who were initiated on a DTG-based regimen were actively followed up for three months. The Cox regression model was used to determine the predictors of occurrence of AEs over time. A p-value of 0.05 was considered statistically significant. From January 2020 to June 2022, a cohort of 935 participants who were both newly diagnosed and ART-experienced who transitioned to a DTG-based regimen was enrolled. Out of 935 participants, 59 (6.3%) reported a total of 62 AEs. The most frequently experienced AE was skin itching and rashes (15/62; 24.2%). DTG-associated neuropsychiatric AEs were less common and included headache (6 [9.6%]) and sleep disturbances (3 [4.8%]). The overall incidence of occurrence of the first AEs was 96.7 per 1000 person-months [95% C.I: 74.4-125.7] with the highest incidence observed among the elderly (≥ 60 years). Individuals on WHO HIV Clinical Stage 2 had a 2.7 significantly higher risk of developing AEs (adjusted hazard ratio = 2.73, 95% CI = 1.46-5.12, p = 0.017). We report a low incidence of grade I (mild) and grade II (moderate) DTG-associated AEs suggesting that the regimen is generally safe in the population. Continued monitoring of DTG safety in the population is recommended.

Trends of measles in Tanzania: A 5-year review of case-based surveillance data, 2018-2022.

OBJECTIVES: Tanzania observed a gradual increase in the number of measles cases since 2019 with a large outbreak recorded during 2022. This study describes the trend of measles in Tanzania over a 5-year period from 2018-2022. METHODS: This was a descriptive study conducted using routine measles case-based surveillance system including 195 councils of the United Republic of Tanzania. RESULTS: Between 2018 and 2022 there were 12,253 measles cases reported. Out of 10,691 (87.25%) samples tested by enzyme-linked immunosorbent assay, 903 (8.4%) were measles immunoglobulin M positive. The highest number of laboratory-confirmed measles cases was in 2022 (64.8%), followed by 2020 (13.8%), and 2019 (13.5%). Out of 1279 unvaccinated cases, 213 (16.7%) were laboratory-confirmed measles cases compared to 77/723 (10.6%) who were partially vaccinated and 71/1121 (6.3%) who were fully vaccinated (P < 0.001). Children aged between 1-4 years constituted the most confirmed measles cases after laboratory testing, followed by those aged 5-9 years. There was a notable increase in the number of laboratory-confirmed measles cases in children <1 year and 10-14 years during 2022 compared to previous years. The vaccination coverage of the first dose of measles-containing vaccine (MCV1) was maintained >90% since 2013 while MCV2 increased gradually reaching 88% in 2022. CONCLUSIONS: Accumulation of susceptible children to measles due to suboptimal measles vaccination coverage over the years has resulted in an increase in the number of laboratory-confirmed measles cases in Tanzania with more cases recorded during the COVID-19 pandemic. Strengthening surveillance, routine immunization, and targeted strategies are key to achieving the immunity levels required to interrupt measles outbreaks.

A Narrative Review of Recent Antibiotic Prescribing Practices in Ambulatory Care in Tanzania: Findings and Implications.

Background and objectives: There are concerns with the current prescribing practices of antibiotics in ambulatory care in Tanzania, including both the public and private sectors. These concerns need to be addressed as part of the national action plan (NAP) of Tanzania to reduce rising antimicrobial resistance (AMR) rates. Issues and concerns include high rates of prescribing of antibiotics for essentially self-limiting conditions. Consequently, there is a need to address this. As a result, the aims of this narrative review were to comprehensively summarize antibiotic utilization patterns particularly in ambulatory care and their rationale in Tanzania and to suggest ways forward to improve future prescribing practices. Materials and Methods: We undertook a narrative review of recently published studies and subsequently documented potential activities to improve future prescribing practices. Potential activities included instigating quality indicators and antimicrobial stewardship programs (ASPs). Results: Published studies have shown that antibiotics are being excessively prescribed in ambulatory care in Tanzania, in up to 95% to 96.3% of presenting cases depending on the sector. This is despite concerns with their appropriateness. High rates of antibiotic prescribing are not helped by variable adherence to current treatment guidelines. There have also been concerns with extensive prescribing of 'Watch' antibiotics in the private sector. Overall, the majority of antibiotics prescribed across the sectors, albeit inappropriately, were typically from the 'Access' group of antibiotics in the AWaRe (Access/Watch/Reserve) classification rather than 'Watch' antibiotics to limit AMR. The inappropriate prescribing of antibiotics in ambulatory care is linked to current knowledge regarding antibiotics, AMR, and ASPs among both prescribers and patients. Recommended activities for the future include improved education for all groups, the instigation of updated quality indicators, and the regular monitoring of prescribing practices against agreed-upon guidelines and indicators. Education for healthcare professionals on ASPs should start at undergraduate level and continue post qualification. Community advocacy on the rational use of antibiotics should also include social media activities to dispel misinformation. Conclusion: The quality of current prescribing practices of antibiotics in ambulatory care is sub-optimal in Tanzania. This needs to be urgently addressed.

Prevalence of blood stream infections and associated factors among febrile neutropenic cancer patients on chemotherapy at Ocean Road Cancer Institute, Tanzania.

BACKGROUND: Febrile Neutropenia (FN) caused by bacteria in cancer patients is associated with poor prognosis. The aim of this study was to determine the prevalence of FN and associated factors among cancer patients on chemotherapy at Ocean Road Cancer Institute (ORCI), Tanzania. METHODS: A cross-sectional study was conducted from June to September 2019. Study participants were conveniently recruited. A desk review of participants medical records was performed. Standard microbiological procedures used to culture and identify the bacterial isolates from the positive blood cultures of participants that presented with FN. Kirby-Bauer disc diffusion was used to perform the antibiotics susceptibility testing. SPSS version 20.0 and MS Excel were used in data entry and analysis. Chi-Square was used as a measure of association between various factors and neutropenia. P-value less than 0.05 was considered statistically significant. RESULTS: A total 213 participants were enrolled. Of these 76.1% were female. Most of the participants came from the Coast region. Majority of participants presented with breast Cancer (36.2%) and GIT (20.2%). The prevalence of FN and bacteremia was 5.6% and 35.3% respectively. Staphylococcus Aureus (60%) and Coagulase-Negative Staphylococci (40%) were the main isolates. Of the 6 isolates tested most were resistant to Co-Trimoxazole 4/6 (66.7%) and Doxycycline 3/6 (50%). FN was positively associated with chemotherapy regimen (P = 0.0001), platelets count (P = 0.0001) and use of G-CSF (P = 0.0001). CONCLUSION: The prevalence of FN among the cancer patients on chemotherapy in Tanzania is low but associated with drug-resistant bacteria.

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.

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.

Cardiometabolic syndrome in HIV-positive and HIV-negative patients at Zewditu Memorial Hospital, Addis Ababa, Ethiopia: a comparative cohort study.

Cardiometabolic syndrome (CMetS) has recently emerged as a serious public health concern, particularly for individuals living with chronic conditions. This study aimed to determine the incidence and prevalence of CMetS, as well as the risk factors linked with it, in HIV-positive and HIV-negative adult patients. Methods: A comparative cohort study was designed. The National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF) tools were used to determine the outcome variables. Association studies were done using logistic regression. Result: CMetS was found to have a greater point and period prevalence, and incidence estimation in HIV-negative than HIV+ patients using both the NCEP and the IDF tools. Using the NCEP tool, the risk of obesity was 44.1% [odds ratio (OR) = 0.559, 95% confidence interval (CI), (0.380-0.824); P = 0.003] lower in HIV+ than in HIV-negative participants. By contrast, no apparent difference was noted using the IDF tool. Similarly, hyperglycemia [OR = 0.651, 95% CI (0.457-0.926); P = 0.017], and hypertension [OR = 0.391, 95% CI (0.271-0.563); P < 0.001] were shown to be lower in HIV+ patients than HIV-negative patients by 34.9% and 60.9%, respectively. The study revealed significant variation in all biomarkers across the follow-up period in both HIV+ and HIV-negative participants, except for SBP. Conclusions: CMetS caused more overall disruption in HIV-negative people with chronic diseases than in HIV-positive people. All of the indicators used to assess the increased risk of CMetS were equally meaningful in HIV+ and HIV-negative subjects.

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.

Dyslipidemia and associated cardiovascular risk factors in HIV-positive and HIV-negative patients visiting ambulatory clinics: A hospital-based study.

Background: Dyslipidemia is a well-known risk factor for cardiovascular disease (CVD), accounting for more than half of all instances of coronary artery disease globally (CAD). Purpose: The purpose of this study was to determine lipid-related cardiovascular risks in HIV-positive and HIV-negative individuals by evaluating lipid profiles, ratios, and other related parameters. Methods: A hospital-based study was carried out from January 2019 to February 2021 in both HIV + and HIV- ambulatory patients. Results: High TG (p = .003), high TC (p = .025), and low HDL (p < .001) were all associated with a two-fold increased risk of CVD in people aged 45 and up. Due to higher TG (p < .001) and lower HDL (p < .001), males were found to have a higher risk of atherogenic dyslipidemia. A twofold increase in the likelihood of higher TG levels has been associated with smoking (p = .032) and alcohol intake (p = .022). A twofold increase in a high TC/HDL ratio and an elevated TG/HDL ratio was observed with an increase in waist-to-height ratio (p = .030) and a high level of FBS (126 mg/dl) and/or validated diabetes (p = .017), respectively. In HIV + participants, central obesity (p < .001), diabetes (p < .001), and high blood pressure (p < .001) were all less common than in HIV- participants. Conclusions: Dyslipidemia is linked to advanced age, male gender, diabetes, smoking, alcohol consumption, and increased waist circumference, all of which could lead to an increased risk of CVD, according to the study. The study also revealed that the risks are less common in HIV + people than in HIV-negative ambulatory patients.

Safety and Tolerability of Ivermectin and Albendazole Mass Drug Administration in Lymphatic Filariasis Endemic Communities of Tanzania: A Cohort Event Monitoring Study.

Ivermectin and albendazole (IA) combination preventive chemotherapy to all at-risk populations is deployed to eliminate lymphatic filariasis. Although safety monitoring is imperative, data from Sub-Saharan Africa is scarce. We conducted a large-scale active safety surveillance of adverse events (AEs) following IA mass drug administration (MDA) to identify the type, incidence, and associated risk factors in Tanzania. After recording sociodemographic, clinical, and medical histories, 9640 eligible residents received single-dose IA combination preventive chemotherapy. Treatment-associated AEs were actively monitored through house-to-house visits on day 1, day 2, and day 7 of MDA. Events reported before and after MDA were cross-checked and verified to identify MDA-associated AEs. 9288 participants (96.3%) completed the seven-day safety follow-up, of whom 442 reported 719 MDA-associated AEs. The incidence of experiencing one or more type of MDA-associated AE was 4.8% (95% CI = 4.3−5.2%); this being significantly higher among those with Pre-MDA clinical events than those without (8.5% versus 4.1%, p < 0.001). AEs were mild (83.8%), moderate (15.9%), and severe (0.3%), and most resolved within 72 h. The incidence of experiencing one, two, ≥ three types of AEs were 2.8%, 1.3%, and 0.6%, respectively. The most common AEs were headache (1.23%), drowsiness (1.15%), fever (1.12%), and dizziness (1.06%). A chronic illness, or clinical manifestation of lymphatic filariasis, or being female or pre-existing clinical symptoms were independent significant predictors of AEs. IA combination preventive chemotherapy is safe and tolerable, and associated AEs are mild-to-moderate and transient, with few severe AEs. Safety monitoring during MDA campaigns in individuals with underlying clinical conditions is recommended for timely detection and management of AEs.

The effect of sickle cell genotype on the pharmacokinetic properties of artemether-lumefantrine in Tanzanian children.

Since there are inconsistent data relating to the effect of haemoglobinopathies on disposition of artemisinin antimalarial combination therapy, and none in sickle cell trait (SCT) or sickle cell disease (SCD), the aim of this study was to characterize the pharmacokinetic properties of artemether-lumefantrine (ARM-LUM) in children with SCD/SCT. Thirty-eight Tanzanian children aged 5-10 years with normal (haemoglobin AA; n = 12), heterozygous (haemoglobin AS; n = 14) or homozygous (haemoglobin SS; n = 12) sickle genotypes received six ARM-LUM doses (1.7 mg/kg plus 10 mg/kg, respectively) over 3 days. Sparse venous and mixed-capillary dried blood spot (DBS) samples were taken over 42 days. Plasma and DBS ARM and LUM, and their active metabolites dihydroartemisinin (DHA) and desbutyl-lumefantrine (DBL), were assayed using validated liquid chromatography-mass spectrometry. Multi-compartmental pharmacokinetic models were developed using a population approach. Plasma but not DBS concentrations of ARM/DHA were assessable. The majority (85%) of the 15 measurable values were within 95% prediction intervals from a published population pharmacokinetic ARM/DHA model in Papua New Guinean children of similar age without SCD/SCT who had uncomplicated malaria, and there was no clear sickle genotype clustering. Plasma (n = 38) and corrected DBS (n = 222) LUM concentrations were analysed using a two-compartment model. The median [inter-quartile range] LUM AUC0-∞ was 607,296 [426,480-860,773] µg.h/L, within the range in published studies involving different populations, age-groups and malaria status. DBS and plasma DBL concentrations correlated poorly and were not modelled. These data support use of the conventional ARM-LUM treatment regimen for uncomplicated malaria in children with SCT/SCD.

Biomarkers and Prevalence of Cardiometabolic Syndrome Among People Living With HIV/AIDS, Addis Ababa, Ethiopia: A Hospital-Based Study.

BACKGROUND: While the fast extension of combination antiretroviral therapy (cART) has resulted in significant increases in life expectancy, disorders such as cardiometabolic syndrome (CMetS), which have received less attention, are becoming a major concern in HIV/AIDS patients (PLWHA). OBJECTIVES: The purpose of this research was to identify biomarkers and determine the prevalence of CMetS in PLWHA using the National Cholesterol Education Program (NCEP) and the International Diabetes Federation (IDF) tools. METHODS: Between January 2019 and February 2021, a hospital-based study of HIV-infected patients (n = 288) was conducted. The data were analyzed using binary logistic regression. To control the effect of confounders, independent variables with a P-value of <.20 in the bivariate logistic regression were incorporated into multivariate logistic regression. Statistical significance was defined as a 95% confidence interval and a P-value of less than .05. RESULTS: The risk of CMetS increased twofold as age increased each year (P = .009), 1.2 times as the age at which cART began increased (P = .015), and 6 times with 1 or more co-morbidities (P = .028), according to the NCEP tool. Furthermore, significant NCEP-CMetS correlations were produced by a rise in diastolic blood pressure (P < .001) and cART duration (P = .006). Male gender was 99.9% less likely to be related to CMetS using the IDF tool, and the risk of CMetS increased fourfold with each unit increase in waist circumference (P < .001). Triglycerides and blood type "A" have been found to have substantial relationships with CMetS using both techniques. CONCLUSION: According to the study, CMetS was found to be common in PLWHA. Age, time on cART, age when cART started, gender, co-morbidities, waist circumference, and diastolic blood pressure were all revealed to be significant predictors of CMetS. Triglycerides and blood type "A" were the only biomarkers found to be significant with CMetS using both the NCEP and IDF tools.

Lymphatic filariasis elimination status: Wuchereria bancrofti infections in human populations and factors contributing to continued transmission after seven rounds of mass drug administration in Masasi District, Tanzania.

BACKGROUND: Lymphatic filariasis (LF) affects more than 120 million people globally. In Tanzania, nearly six million people are estimated to live with clinical manifestations of the disease. The National LF control program was established in 2000 using Mass drug administration (MDA) of Ivermectin and Albendazole to individuals aged 5years and above. This study assessed the infection status in individuals aged 15 years and above who are eligible for participation in MDA. The level of compliance to MDA and the reasons for non-compliance to MDA were also assessed. METHODS: A community based cross-sectional study was conducted in two villages of Masasi District. A total of 590 participants aged 15 years and above were screened for the circulating filarial antigen (CFA) using the rapid diagnostic test. Night blood samples from CFA positive individuals were further analyzed for detection and quantification of Wuchereria bancrofti microfilaria (Mf) using the counting chamber technique. A pre-tested questionnaire was administered to collect information on compliance to MDA and the factors affecting continued transmission. Data were analyzed using SPSS Version 20. Chi-square test was used to compare the prevalence of CFA by gender and village where a P-value ≤0.05 was considered statistically significant. RESULTS: Out of 590 participants, 30 (5.1%) were positive for CFA and one (0.2%) was found positive for microfilaria of Wuchereria bancrofti. Compliance during the last round of MDA, in the year 2019 was 56% which is below the minimum coverage recommended by WHO. Absence from home during MDA and perceptions of being free from hydrocele or elephantiasis were the major reasons for non-compliance. CONCLUSION: There is a significant decline in LF transmission in Masasi District after seven rounds of MDA. However, the presence of individuals who are persistently non-compliant may delay elimination of LF in the District.

Knowledge of use of antibiotics among consumers in Tanzania.

BACKGROUND: Studies assessing consumers' knowledge of the rational use of antibiotics are essential to understand the knowledge gap before intervention strategies are instituted. OBJECTIVES: To assess the knowledge of rational use of antibiotics among consumers in Dar es Salaam, Tanzania. METHODS: A cross-sectional study assessing knowledge of rational use of antibiotics among 960 consumers was conducted in Dar es salaam in March 2021. Participants were consecutively enrolled from outpatient pharmacies in selected public and private hospitals and marketplaces in Ilala Municipality. Data were collected using the WHO-validated questions on knowledge of consumers of antibiotic uses. RESULTS: Overall, 196 (20.4%) and 503 (52.4%) participants demonstrated good knowledge of rational antibiotic use and conditions that can be treated with antibiotics, respectively. However, 678 (70.6%) responded that they stopped using antibiotics after dose completion, 515 (53.6%) would request the same antibiotic if it had helped to treat a similar condition in the past and 406 (42.3%) are willing to use the same antibiotic if a friend or family member used the medication previously to treat similar signs and symptoms. Besides, the following conditions were mentioned as being treatable with antibiotics: influenza (50.7%), sore throat (61.4%) and urinary tract infection (60.5%). CONCLUSIONS: The majority of the consumers had poor knowledge of the rational uses of antibiotics and a moderate proportion had good knowledge of the conditions that are treatable with antibiotics. Those with a high level of education and with health insurance had good knowledge of rational uses of antibiotics.

Predicting the risk of atherosclerotic cardiovascular disease among adults living with HIV/AIDS in Addis Ababa, Ethiopia: A hospital-based study.

BACKGROUND: Atherosclerotic Cardiovascular Disease (ASCVD) is an emerging problem among People living with HIV/AIDS (PLWHA). The current study aimed at determining the risk of ASCVD among PLWHA using the Pooled Cohort Equation (PCE) and the Framingham Risk score (FRS). METHODS: A hospital-based study was carried out from January 2019 to February 2020 in PLWHA. The prevalence of ASCVD risk was determined in individuals aged between 20 to 79 and 40 to 79 years using the FRS and PCE as appropriate. Chi-square, univariate and multivariate logistic regressions were employed for analysis. RESULTS: The prevalence of high-risk ASCVD for subjects aged 20 and above using both tools was 11.5 %. For those aged 40 to 79 years, PCE yielded an increased risk (28%) than FRS (17.7%). Using both tools; advanced age, male gender, smoking, and increased systolic blood pressure were associated with an increased risk of ASCVD. Younger age (adjusted odds ratio, AOR) 0.20, 95%CI: 0.004, 0.091; P< 0.001), lower systolic blood pressure (AOR 0.221, 95%CI: 0.074, 0.605 P< 0.004), and lower total cholesterol (AOR 0.270, 95%CI: 0.073, 0.997; p<0.049) were found to be independent predictors of reduced risk of ASCVD. Likewise, younger age (40 to 64 years), female gender, and lower systolic blood pressure were significantly associated with lower risk of ASCVD among patients aged 40 to 79 years using both PCE and FRS. CONCLUSIONS: A considerable number of PLWHA have been identified to be at risk for ASCVD. ASCVD risk was significantly associated with advanced age, male gender, higher blood pressure, and smoking using both FRS and PCE. These factors should therefore be taken into account for designing management strategies.

Effect of Pharmacogenetics Variations on Praziquantel Plasma Concentrations and Schistosomiasis Treatment Outcomes Among Infected School-Aged Children in Tanzania.

Studies on pharmacogenetics of praziquantel (PZQ) and its relevance on plasma drug concentrations and schistosomiasis treatment outcomes are lacking. We investigated the effect of pharmacogenetics variations of PZQ on plasma drug levels and schistosomiasis treatment outcomes among infected Tanzanian school-aged children. A total of 340 Schistosoma mansoni infected children were enrolled and treated with single-dose PZQ. Stool samples analysis was done by thick smear Kato-Katz technique, and treatment efficacy was assessed at 3-weeks post-treatment. Safety was assessed within 4 h after PZQ intake. Plasma samples were collected at 4 h post-dose, and PZQ and trans-4-OH-PZQ concentrations were quantified using UPLCMS/MS. Genotyping for CYP3A4*1B, CYP3A5 (*3, *6, *7), CYP2C19 (*2, *3, *17), and CYP2C9 (*2, *3) were done by Real-Time PCR. The median age (range) of the study participants was 12 years (7-17). There was a significant association of CYP2C19 genotypes with PZQ concentrations and its metabolic ratio (trans-4-OH-PZQ/PZQ). PZQ concentration was significantly higher among CYP2C19 (*2, *3) carriers than CYP2C19 *1/*1 and CYP2C19 *17 carriers (ultra-rapid metabolizers) (p = 0.04). The metabolic ratio was significantly higher among CYP2C19*17 carriers than CYP2C19 (*2, *3) carriers (p = 0.01). No significant effect of CYP3A4, CYP3A5, CYP2C19, and CYP2C9 genotypes on treatment efficacy or adverse events were observed. Baseline infection intensity and CYP3A5 genotype were significant predictors of treatment associated-adverse events. In conclusion, CYP2C19 genotype significantly affects plasma PZQ concentration and its metabolic ratio. For the first time, we report the importance of pharmacogenetic variation for the treatment of schistosomiasis, a neglected tropical disease.

Optimal single sampling time-point for monitoring of praziquantel exposure in children.

Praziquantel pharmacokinetics studies in schistosomiasis infected children are scarce partly due to the challenges/complexity of intensive blood sampling in the target population. This study was aimed to investigate the optimal single sampling time-point for monitoring praziquantel exposure. This was intensive pharmacokinetic study conducted among 32 Schistosoma mansoni infected children treated with an oral standard single-dose 40 mg/kg praziquantel. Plasma samples were collected at 0, 1, 2, 4, 6 and 8 h post-praziquantel administration. Quantification of praziquantel and its enantiomers (R- and S-praziquantel) concentrations was done by Liquid chromatography-tandem mass spectrometer (LC-MS/MS). The correlation between area under the plasma concentration-time curve from 0 to 8 h (AUC8) and plasma concentrations at each specific sampling time-point was determined by Pearson's correlation coefficient (r2). The median age (range) of the study population was 12.5 years (10-17). The study participants were 17 males and 15 females. Both total praziquantel and its enantiomers (R- and S-praziquantel) displayed a wide inter-individual pharmacokinetic variability. Regression analysis indicated that, plasma concentrations collected at 4 h post-dose had a significantly highest correlation with the AUC8 for both total praziquantel (r2 = 0.81, p < 0.001) and S-praziquantel (r2 = 0.84, p < 0.001) than any other sampling time-point; while for R-praziquantel, plasma concentrations collected at 6 h sampling time-point had a significantly highest correlation with the AUC8 (r2 = 0.79, p < 0.001) than any other sampling time-point. Four hours sampling time-point post-praziquantel administration is ideal optimal single sampling time-point for therapeutic monitoring of total praziquantel exposure while 6 h sampling time-point is suitable for monitoring of a pharmacologically active R-praziquantel enantiomer.

Effect of Dihydroartemisinin-Piperaquine on the Pharmacokinetics of Praziquantel for Treatment of Schistosoma mansoni Infection.

Praziquantel (PZQ) and dihydroartemisinin-piperaquine (DHP) combination recently showed superior effectiveness than PZQ alone to treat intestinal schistosomiasis. In this follow-up study, we investigated the effect of DHP co-administration on the pharmacokinetics of PZQ and its enantiomers among 64 Schistosoma mansoni infected children treated with PZQ alone (n = 32) or PZQ + DHP combination (n = 32). Plasma samples collected at 0, 1, 2, 4, 6, and 8 h post-dose were quantified using UPLCMS/MS. The geometric mean (GM) of AUCs for total PZQ, R-PZQ and S-PZQ were significantly higher among children who received PZQ + DHP than PZQ alone. The geometric mean ratio (GMR) and (90% CI) of AUC0-∞ for PZQ + DHP to PZQ for total PZQ, R-PZQ, and S-PZQ were 2.18 (1.27, 3.76), 3.98 (2.27, 7.0) and 1.86 (1.06, 3.28), respectively. The GMR and (90% CI) of AUC0-8 for total PZQ, R-PZQ, and S-PZQ were 1.73 (1.12, 2.69), 2.94 (1.75, 4.92), and 1.50 (0.97, 2.31), respectively. The GM of Cmax for total PZQ, R-PZQ and S-PZQ were significantly higher among those who received PZQ + DHP than PZQ alone. The GMR (90% CI) of Cmax of PZQ + DHP to PZQ for total PZQ, R-PZQ, and S-PZQ were 1.75 (1.15, 2.65), 3.08 (1.91, 4.96), and 1.50 (1.0, 2.25%), respectively. The 90% CI of the GMRs for both AUCs and Cmax for total PZQ, R-PZQ, and S-PZQ were outside the acceptable 0.80-1.25 range, indicating that the two treatment arms were not bioequivalent. DHP co-administration significantly increases systemic PZQ exposure, and this may contribute to increased effectiveness of PZQ + DHP combination therapy than PZQ alone to treat schistosomiasis.