Improved Biorepository to Support Sickle Cell Disease Genomics and Clinical Research: A Practical Approach to Link Patient Data and Biospecimens from Muhimbili Sickle Cell Program, Tanzania.

In Africa, sickle cell disease phenotypes' genetic contributors remain understudied due to the dearth of databases that pair biospecimens with demographic and clinical details. The absence of biorepositories in these settings can exacerbate this issue. This article documents the physical verification process of biospecimens in the biorepository, connecting them to patient clinical and demographic data and aiding in the planning of future genomic and clinical research studies' experience from the Muhimbili Sickle Cell Program in Dar es Salaam, Tanzania. The biospecimen database was updated with the current biospecimen position following the physical verification and then mapping this information to its demographic and clinical data using demographic identifiers. The biorepository stored 74,079 biospecimens in three -80°C freezers, including 63,345 from 5159 patients enrolled in the cohort between 2004 and 2016. Patients were identified by a control (first visit), entry (when confirmed sickle cell homozygous), admission (when hospitalized), and follow-up numbers (subsequent visits). Of 63,345 biospecimens, follow-ups were 46,915 (74.06%), control 8067 (12.74%), admission 5517 (8.71%), and entry 2846 (4.49%). Of these registered patients, females were 2521 (48.87%) and males were 2638 (51.13%). The age distribution was 1-59 years, with those older than 18 years being 577 (11.18%) and children 4582 (88.82%) of registered patients. The notable findings during the process include a lack of automated biospecimen checks, laboratory information management system, and tubes with volume calibration; this caused the verification process to be tedious and manual. Biospecimens not linked to clinical and demographic data, date format inconsistencies, and lack of regular updating of a database on exhausted biospecimens and updates when biospecimens are moved between positions within freezers were other findings that were found. A well-organized biorepository plays a crucial role in answering future research questions. Enforcing standard operating procedures and quality control will ensure that laboratory users adhere to the best biospecimen management procedures.

High viral suppression and detection of dolutegravir-resistance associated mutations in treatment-experienced Tanzanian adults living with HIV-1 in Dar es Salaam.

To curb HIV infection rate in Tanzania, antiretroviral therapy (ART) has been scaled up since 2006, and in 2019, the country shifted to regimen including dolutegravir as a default first line. We assessed the success of ART and the contribution of HIV drug resistance (HIVDR) to unsuppressed viral loads. Between February and May 2023 a cross-sectional survey with random sampling was conducted in the six clinics in an urban cohort in Dar es Salaam. Patients with unsuppresed viral loads (local criteria viral load (VL) ≥ 1000 copies/mL) were tested for HIVDR mutations using the WHO adapted protocol for plasma samples. Mutations were interpreted using the Stanford HIVDR database. In total 600 individuals participated in this survey, the majority were female (76.83%), mean age ([Formula: see text] standard deviation) was 44.0 ([Formula: see text] 11.6) years. The median duration on ART (interquartile range) was 6.5 (3.9-10.2) years. Approximately 99% were receiving tenofovir + lamivudine + dolutegravir as a fixed dose combination. VL testing was successful in 99.67% (598/600) of survey patients and only 33 had VL ≥ 1000 copies/mL, resulting in a viral suppression level of 94.48% (565/598, 95% CI 92.34-96.17%). For 23 samples, protease and reverse transcriptase (RT) genotyping were successful, with 13 sequences containing RT inhibitor surveillance drug resistance mutations (SDRMs) (56.5%). No SDRM against protease inhibitors were detected. Thirty samples were successfully genotyped for integrase with 3 sequences (10.08%) containing integrase strand transfer inhibitor (INSTI) SDRMs. In samples successfully genotyped in the three genetic regions, 68.18% (16/22) had a genotypic susceptibility score (GSS) ≥ 2.5 for the concurrent regimen, implying factors beyond drug resistance caused the unsuppressed viral load. For five patients, GSS indicated that HIVDR may have caused the unsuppressed viral load. All three patients with INSTI resistance mutations were highly resistant to dolutegravir and accumulated nucleoside and non-nucleoside RT inhibitor HIVDR mutations. Although in this cohort the last 95 UNAIDS target was almost achieved, HIVDR mutations, including INSTIs resistance mutations were detected in HIV-positive individuals taking ART for at least one year. We recommend the design and implementation of high-impact interventions to prevent the increase of HIVDR, failure of dolutegravir and address the non-resistance factors in the study area.

Prevalence of urinary tract infection and antimicrobial resistance patterns of uropathogens with biofilm forming capacity among outpatients in morogoro, Tanzania: a cross-sectional study.

INTRODUCTION: Urinary tract infection (UTI) is the second most common infectious disease affecting more than 150 million people globally annually. Uropathogenic E. coli (UPEC), the predominant cause of UTI, can occur as a biofilm associated with antimicrobial resistance (AMR). There is a data gap on global AMR patterns from low-income settings, including Tanzania. Data on antimicrobial susceptibility patterns in relation to biofilm formation will help in the proper selection of antibiotics and the fight against AMR. METHODS: This analytical cross-sectional study was conducted among consecutively selected outpatients (n = 344) from January to May 2022 at Morogoro Regional Referal Hospital. Mid-stream urine samples were collected aseptically from symptomatic patients. A significant UTI was defined when more than 105 colonies/ml of urine were recorded. Kirby Bauer's disc diffusion method was used for antibiotics susceptibility patterns and a Congo Red Agar method was used to determine biofilm formation. Two-sided χ2 test or Fisher's exact test, Cohen's kappa coefficient and logistic regression were used for data analysis. A p-value < 0.05 was considered statistically significant. RESULTS: The prevalence of UTIs was 41% (141/344) and elders (>=60 years) had five times higher odds of having UTI as compared to adolescents (p < 0.001). E. coli was the most predominant bacteria (47%; 66/141), which displayed moderate susceptibility against ciprofloxacin (59.1%) and nitrofurantoin (57.6%). A total of 72 (51%) of all isolated bacteria were multi-drug resistant. All isolated bacteria demonstrated high resistance (> 85%) against ampicillin and co-trimoxazole. In this study, 51.5% (34/66) were biofilm-forming E. coli and demonstrated relatively higher antibiotic resistance as compared to non-biofilm forming bacteria (p < 0.05). CONCLUSION: We report high antibiotic resistance against commonly used antibiotics. Slightly more than half of the isolated bacteria were biofilm forming E. coli. A need to strengthen stewardship programs is urgently advocated.

Impact of differentiated service delivery models on retention in HIV care and viral suppression among people living with HIV in sub-Saharan Africa: A systematic review and meta-analysis of randomised controlled trials.

Differentiated service delivery (DSD) models, such as adherence clubs (ACs), are client-centred approaches where clinically stable people living with HIV (PLHIV) meet to receive various services, including psychosocial support, brief symptoms screening, and refills of antiretroviral medications, among others. We conducted a review to assess the impact of DSD models, including ACs, on sustaining retention in care (RC) and achieving viral suppression (VS) among PLHIV in sub-Saharan Africa. The review protocol was registered in PROSPERO (CRD42023418988). We searched the literature from PubMed, Scopus, Web of Science, Embase and Google Scholar from their inception through May 2023. Eligible randomised controlled trials of adherence clubs were reviewed to assess impact on retention and viral suppression. Random effect models were used to estimate the risk ratios (RR) and 95% confidence intervals (CI). The literature search yielded a total of 1596 records of which 16 randomised clinical trials were determined to be eligible. The trials were conducted in diverse populations among adults and children with a total of 13,886 participants. The RR between any DSD models and standard of care (SoC) was 1.09 (95% CI: 1.08-1.11, I2 : 0%, p: <0.96) and 1.01 (95% CI: 1.00-1.02, I2 : 0%, p: <0.85) for RC and VS, respectively. The RR between ACs and SoC was 1.01 (95% CI: 0.96-1.07, I2 : 84%, p: <0.01) and 1.02 (95% CI: 0.98-1.07, I2 : 77%, p: <0.01) for RC and VS, respectively. DSD models, including ACs, show comparable effectiveness to SoC in maintaining care and achieving viral suppression for stable PLHIV. To maximise adoption, an implementation science approach is crucial for designing effective strategies and overcoming challenges.

Infrastructure for bioinformatics applications in Tanzania: Lessons from the Sickle Cell Programme.

Sickle cell disease (SCD) is a common genetic disorder in Africa. Some ongoing work in SCD research includes the analysis and comparisons of variation in phenotypic presentations and disease outcomes with the genotypic signatures. This has contributed to the observed growth of molecular and genetic data in SCD. However, while the "omics" data continues to pile, the capacity to interpret and turn the genetic findings into clinical practice is still underdeveloped, especially in the developing region. Building bioinformatics infrastructure and capacity in the region is key to bridging the gap. This paper seeks to illustrate how the Sickle Cell Programme (SCP) at the Muhimbili University of Health and Allied Sciences (MUHAS) in Tanzania, modeled the integration of infrastructure for bioinformatics and clinical research while running day-to-day clinical care for SCD in Tanzania.

Comparison of knowledge, attitude, practice and predictors of self-medication with antibiotics among medical and non-medical students in Tanzania.

Introduction: Self-medication with antibiotics (SMA) is a widespread problem in developing nations, including Tanzania. Methods: This study compared knowledge, attitudes, practices, and factors influencing antibiotic SMA among medical and non-medical students. Results: The prevalence of SMA among medical students was 49.1% and 59.2% among non-medical students, respectively. The mean knowledge score of medical students (6.4) was significantly higher (p-value <0.001) than that of non-medical students (5.6). The main factors influencing SMA practices were the availability of antibiotics without a prescription, easy access to pharmacies, and a lack of knowledge about the risks of SMA. This experience was pivotal in influencing medical students to take antibiotics, with a substantial proportion of 67.5% as opposed to 59.4% of non-medical students. Medical students were 1.6 times more likely to self-medicate with antibiotics than non-medical students (Adjusted Odds Ratio (AOR): 1.6; 95% Confidence Interval (CI): 1.2-2.3, p-value = 0.004). Age was also associated with self-medication, with an AOR of 1.1 (95% CI: 1.04-1.2, p-value = 0.006) per year increase in age. Additionally, attitude was associated with self-medication, with an AOR of 1.05 (95% CI: 1.04-1.1, p-value = 0.001) per unit increase in attitude score. Discussion: No significant associations were found between sex, marital status, having children, year of study, knowledge score, and self-medication with antibiotics. This study emphasizes the importance of educational interventions and public awareness campaigns to promote antimicrobial stewardship, appropriate antibiotic use, and preventing pharmacies from dispensing antibiotics without a prescription.

Adherence to Antiretroviral Therapy Among HIV-Infected Clients Attending Opioid Treatment Program Clinics in Dar es Salaam, Tanzania.

Background Adherence to antiretroviral therapy (ART) among key populations like human immunodeficiency virus (HIV)-positive People Who Inject Drugs (PWID) could be challenging, especially in low and middle-income countries (LMICs). Therefore we conducted this study to assess the adherence to ART among HIV-positive PWID attending three methadone clinics in Dar es Salaam, Tanzania. Methods A cross-sectional study was conducted at three methadone clinics in Dar es Salaam, Tanzania. Adherence to ART was measured by using pharmacy refill and patient self-report methods. Bivariate and multivariable logistic regression was performed to determine the association between dependent and independent variables. A p-value of less than 0.05 was considered to be statistically significant. Results Of the 180 participants, 97.2% recorded good adherence to ART as per the pharmacy refill method. However, only 66.1% of the PWID were found to adhere to ART based on the patient self-report method. Upon associating the self-report method with a viral load of >1000 copies/mL, participants were 3.37 times more likely to have missed their ART dose at least once in the last three days before their refill visit compared to those with a viral load of <1000 copies/mL [Adjusted Odds ratio; 3.37, 95% Confidence Interval (95% CI); 1.35 - 8.45, p = 0.009]. Conclusion The adherence to ART among HIV-infected PWID attending methadone clinics was high based on the pharmacy refill method but relatively much lower based on the patient self-report method. There was a strong correlation between viral load and the level of adherence measured by the patient self-report method.

Magnitude of Extended-Spectrum Beta-Lactamase-Producing Gram-Negative and Beta-Lactamase-Producing Gram-Positive Pathogens Isolated from Patients in Dar es Salaam, Tanzania: A Cross-Sectional Study.

Background The worldwide emergence of antibiotic-resistant bacteria threatens to overshadow the dramatic advances in medical sciences since the discovery of antibiotics. Antibiotic resistance has rendered some antibiotics obsolete, creating a reliance on synthetic drugs. In some instances, bacteria can be resistant to all antibiotics. The problem of antibiotic resistance is eminent in resource-limited countries like Tanzania, where systematic surveillance and routine susceptibility tests are rarely conducted. Therefore, this study aimed to investigate the magnitude of beta-lactamase-producing Gram-positive pathogens and Enterobacteriaceae with extended-spectrum beta-lactamase (ESBL) in Dar es Salaam, Tanzania. Methodology This multi-site cross-sectional study involved three private hospitals in Dar es Salaam, Tanzania. The study was conducted between July and September 2008. Bacterial isolates were collected, identified, and subjected to antibiotic-sensitivity testing against cephalosporins, including ceftriaxone, cefuroxime and cefotaxime, and clavulanic acid, which are antibiotics readily available on the Tanzanian market at the time of the study. The microdilution method was employed to determine beta-lactamase and ESBL production per the Clinical Laboratory and Standards Institute (CLSI) protocol. Cephalosporins, including ceftriaxone, cefuroxime and cefotaxime, the beta-lactamase inhibitor, and clavulanic acid, were serially diluted with concentrations ranging from 0.011 mg/ml to 200 mg/ml. Each of these antibiotics was subjected to sensitivity tests by determining the minimum inhibitory concentrations (MIC) of the clinical isolates of bacteria using a 96-well microdilution plate. Five microliters of bacterial suspension were inoculated into each well-containing 120µl of sterile Mueller-Hinton broth before incubation overnight. Results A total of 111 bacterial isolates were tested. Of the 111 tested bacterial isolates, 85 (76.6%) and 26 (23.4%) were Gram-negative and Gram-positive bacteria, respectively. Fifty-six clinical isolates (50.4%) were Escherichia coli, and 13 Salmonella species (11.7%) were among the Gram-negative isolates. On the other hand, 15 (13.5%) and 11 (9.9%) Gram-positive bacteria were Staphylococcus aureus and Streptococcus species, respectively, of all isolates. The majority of these clinical isolates, 71 (64.0%), were obtained from mid-stream urine, while the remaining were from stool, vaginal secretions, blood, pus, catheter sip, and urethra. A high proportion of tested Gram-negative bacteria, 58 (68.2%), were identified as ESBL producers, and 16 (61.5%) of the Gram-positive bacteria were identified as beta-lactamase producers. Cefuroxime was the least effective, exhibiting the largest MIC (18.47 ± 22.6 mg/ml) compared to clavulanic acid alone (5.28 ± 8.0 mg/ml) and clavulanic acid-cefuroxime (5.0± 12.32 mg/ml). Of all isolates, 78.2% were sensitive to chloramphenicol. Only five isolates had MIC larger than 32.23 mg/ml as opposed to cefotaxime and ampicillin, which had more isolates in that similar MIC range. Conclusion There is a high proportion of beta-lactamase, particularly ESBL-producing pathogens, in Dar es Salaam, Tanzania. Therefore, regular detection of beta-lactamase and ESBL production may help detect resistance to beta-lactam antibiotics.

Isolation Frequency of Fluconazole-Resistant Candida Species From Cockroaches: A Cross-Sectional Study From a National Hospital in Dar es Salaam, Tanzania.

BACKGROUND: Cockroaches are common pests in homes and hospitals. They cause allergic reactions in some individuals and are potential vectors for various infectious pathogens. The study investigated the extent to which hospital cockroaches act as vectors and reservoirs of medically important fungal pathogens on their external surfaces. METHODS: Cockroaches were captured from the selected hospital locations including the burn unit, adult surgical wards, pediatric oncology wards, intern hostel kitchen, and the central kitchen of a national referral teaching hospital in Tanzania. Normal saline washings from the external surface of cockroaches were cultured on standard mycological media to facilitate isolation and identification of medically important molds and yeasts. The susceptibility of Candida species isolates to fluconazole was tested using the Clinical and Laboratory Standards Institute (CLSI) M27-A3 microdilution method. RESULTS: A total of 69 cockroaches were captured from various hospital sites between February and April 2017. All cockroaches captured were shown to carry medically important fungi. A total of 956 medically important fungi were isolated; 554 (57.9%) were of Candida species, 222 (23.2%) were of Aspergillus species, 30 (3.1%) were of​​​​​​​ Cladosporium species, 17 (1.8%) were of​​​​​​​ Rhizopus species, 11 (1.2%) were of​​​​​​​ Geotrichum species, nine (0.9%) were of​​​​​​​ Penicillium species, seven (0.7%) were of​​​​​​​ Alternaria species, six (0.6%) were of​​​​​​​ Fusarium species, three (0.3%) were of​​​​​​​ Mucor species, and 97 (10.1%) were of other species. Of the Aspergillus species, Aspergillus fumigatus (111, 50.0%) was the most commonly isolated, followed by Aspergillus niger (35, 15.8%) among the Aspergillus isolates. Out of the 103 selected isolates, 18 (17.5%) of the Candida isolates normally not intrinsically resistant to fluconazole demonstrated resistance to this drug. Resistance was most frequently found in Candida parapsilosis (3, 30%), Candida pseudotropicalis (10, 23.8%), and Candida glabrata (2, 18.2%). The isolates with the least proportion of resistance to fluconazole were Candida albicans (2, 6.3%). CONCLUSION: Cockroaches from this hospital may act as reservoirs of medically important opportunistic fungi exhibiting resistance to fluconazole.

Adherence to Antiretroviral Therapy by Medication Possession Ratio and Virological Suppression among Adolescents and Young Adults Living with HIV in Dar es Salaam, Tanzania.

Background: Adherence to antiretroviral therapy (ART) is a strong determinant of virological suppression. We aimed to determine the magnitude of adherence as measured by medication possession ratio (MPR) and virological suppression with its predictors among adolescents and young adults (AYA) living with HIV on ART in Tanzania. Methods: This retrospective cohort study was conducted using archived data from HIV care and treatment centers in Dar es Salaam, Tanzania between 2015 and 2019. The logistic regression model assessed predictors for adherence and virological suppression. Results: Data of 5750 AYA living with HIV were analysed. The majority were females: 4748 (82.6%). About 63% had good adherence with MPR ≥ 85% at one year post ART initiation. Independent predictors of ART adherence were male sex (aOR = 1.3, 95% CI 1.1−1.5), CD4 > 500 cells/mm3 (aOR = 0.7, 95% CI: 0.6−0.9), WHO stage III (aOR = 1.6, 95% CI 1.3−1.9), enrollment in 2019 (aOR = 1.5, 95% CI 1.2−1.9), and virological suppression (aOR = 2.0, 95% CI 1.6−2.9). Using an Efavirenz- and a Nevirapine-based combination was associated with reduced odds of ART adherence (aOR = 0.3, 95% CI 0.1−0.8) and (aOR = 0.2, 95% CI 0.1−0.6), respectively. Predictors of virological suppression were MPR ≥ 85% (aOR = 2.0, 95% CI 1.6−2.4); CD4 > 500 cells/mm3 (aOR = 2.4, 95% CI 1.7−3.4), and once-daily dosing (aOR = 2.0, 95% CI 1.3−2.5). Conclusion: Adherence to ART among AYA living with HIV is suboptimal. Sex, year of enrollment, ART drug combination used, and immunological status at ART initiation are important predictors of adherence to ART and virological suppression.

Microbiological Quality of Selected Local and Imported Non-Sterile Pharmaceutical Products in Dar es Salaam, Tanzania.

Background: Pathogenic and non-pathogenic microbial contaminants can cause physical-chemical alterations of pharmaceuticals and medicine-related infections. This study aimed to examine the microbiological quality of selected local and imported non-sterile pharmaceutical products in the Dar es Salaam market and the antibiogram of the isolated microorganisms. Methods: Samples were collected between April and June 2021 and analysed for microbial content as per the harmonised methods of the European Pharmacopoeia (EP). Antibiotic susceptibility of the microbial isolates was studied using Kirby-Bauer disc diffusion method. Results: Fifty percent (50%) of the samples failed both bacterial and fungal enumeration tests. In this study, local products recorded lower microbial counts than imported products. Major bacterial contaminants isolated were P. aeruginosa (45.5%), S. epidermidis, (45.5%) and K. pneumoniae, while major fungal contaminants were A. flavus (58.3%), followed by A. fumigatus (25%) and Penicillium spp (16.7%). The isolated bacterial contaminants recorded high resistance levels to commonly used antibiotics. Conclusion: The tested products were contaminated with microorganisms at different levels, most of them exceeding the maximum acceptable colony counts. Syrups or suspensions were more contaminated than tablets and capsules. The isolated bacterial contaminants were highly resistant to commonly used antibiotics. Recommendations: We recommend that pharmaceutical manufacturers abide by good manufacturing, distribution and storage practices to limit contamination and cross-contamination of products. Responsible drug regulatory authorities should heighten the frequency of inspection of manufacturing facilities and regularly conduct post-marketing surveillance (PMS) of registered products to assess continued conformity to GMP guidelines. Future studies should involve samples collected directly from manufacturing sites.

Exploring the mechanisms behind HIV drug resistance in sub-Saharan Africa: conceptual mapping of a complex adaptive system based on multi-disciplinary expert insights.

BACKGROUND: HIV drug resistance (HIVDR) continues to threaten the effectiveness of worldwide antiretroviral therapy (ART). Emergence and transmission of HIVDR are driven by several interconnected factors. Though much has been done to uncover factors influencing HIVDR, overall interconnectedness between these factors remains unclear and African policy makers encounter difficulties setting priorities combating HIVDR. By viewing HIVDR as a complex adaptive system, through the eyes of multi-disciplinary HIVDR experts, we aimed to make a first attempt to linking different influencing factors and gaining a deeper understanding of the complexity of the system. METHODS: We designed a detailed systems map of factors influencing HIVDR based on semi-structured interviews with 15 international HIVDR experts from or with experience in sub-Saharan Africa, from different disciplinary backgrounds and affiliated with different types of institutions. The resulting detailed system map was conceptualized into three main HIVDR feedback loops and further strengthened with literature evidence. RESULTS: Factors influencing HIVDR in sub-Saharan Africa and their interactions were sorted in five categories: biology, individual, social context, healthcare system and 'overarching'. We identified three causal loops cross-cutting these layers, which relate to three interconnected subsystems of mechanisms influencing HIVDR. The 'adherence motivation' subsystem concerns the interplay of factors influencing people living with HIV to alternate between adherence and non-adherence. The 'healthcare burden' subsystem is a reinforcing loop leading to an increase in HIVDR at local population level. The 'ART overreliance' subsystem is a balancing feedback loop leading to complacency among program managers when there is overreliance on ART with a perceived low risk to drug resistance. The three subsystems are interconnected at different levels. CONCLUSIONS: Interconnectedness of the three subsystems underlines the need to act on the entire system of factors surrounding HIVDR in sub-Saharan Africa in order to target interventions and to prevent unwanted effects on other parts of the system. The three theories that emerged while studying HIVDR as a complex adaptive system form a starting point for further qualitative and quantitative investigation.

Factors Associated with HIV Drug Resistance in Dar es Salaam, Tanzania: Analysis of a Complex Adaptive System.

HIV drug resistance (HIVDR) is a complex problem with multiple interconnected and context dependent causes. Although the factors influencing HIVDR are known and well-studied, HIVDR remains a threat to the effectiveness of antiretroviral therapy. To understand the complexity of HIVDR, a comprehensive, systems approach is needed. Therefore, a local systems map was developed integrating all reported factors influencing HIVDR in the Dar es Salaam Urban Cohort Study area in Tanzania. The map was designed based on semi-structured interviews and workshops with people living with HIV and local actors who encounter people living with HIV during their daily activities. We visualized the feedback loops driving HIVDR, compared the local map with a systems map for Sub-Saharan Africa, previously constructed from interviews with international HIVDR experts, and suggest potential interventions to prevent HIVDR. We found several interconnected balancing and reinforcing feedback loops related to poverty, stigmatization, status disclosure, self-esteem, knowledge about HIVDR and healthcare system workload, among others, and identified three potential leverage points. Insights from this local systems map were complementary to the insights from the Sub-Saharan systems map showing that both viewpoints are needed to fully understand the system. This study provides a strong baseline for quantitative modelling, and for the identification of context-dependent, complexity-informed leverage points.

Utilization of Pneumococcal Vaccine and Penicillin Prophylaxis in Sickle Cell Disease in Three African Countries: Assessment among Healthcare Providers in SickleInAfrica.

Sickle cell disease is a genetic disease with a predisposition to infections caused by encapsulated organisms, especially Streptococcus pneumoniae. Pneumococcal vaccines and prophylactic penicillin have reduced the rate of this infection and mortality in sickle cell disease. However, implementation of these interventions is limited in Africa. The objectives of the study were to assess health care providers' behaviors with the implementation of pneumococcal vaccination and penicillin prophylaxis and to identify barriers to their use. A 25-item online questionnaire was administered through SickleinAfrica: a network of researchers, and healthcare providers, in Ghana, Nigeria, and Tanzania, working to improve health outcomes of sickle cell disease in Africa. Data was collected and managed using the Research Electronic Data Capture (REDCap), tools and data analysis was done using STATA version 13 and R statistical software. Eighty-two medical practitioners responded to the questionnaire. Only 54.0 and 48.7% of respondents indicated the availability of published guidelines on sickle cell disease management and pneumococcal vaccine use, respectively, at their facilities. The majority (54.0%) perceived that the vaccines are effective but over 20.0% were uncertain of their usefulness. All respondents from Ghana and Tanzania affirmed the availability of guidelines for penicillin prophylaxis in contrast to 44.1% in Nigeria. Eighty-five percent of respondents affirmed the need for penicillin prophylaxis but 15.0% had a contrary opinion for reasons including the rarity of isolation of Streptococcus pneumoniae in African studies, and therefore, the uncertainty of its benefit. Lack of published guidelines on the management of sickle cell disease and doubts about the necessity of prophylactic measures are potential barriers to the implementation of effective interventions.

Patterns and patient factors associated with loss to follow-up in the Muhimbili sickle cell cohort, Tanzania.

BACKGROUND: Monitoring patient's clinical attendance is a crucial means of improving retention in care and treatment programmes. Sickle cell patients' outcomes are improved by participation in comprehensive care programmes, but these benefits cannot be achieved when patients are lost from clinical care. In this study, patients are defined as loss to follow-up when they did not attend clinic for more than 9 months. Precise information on the retention rate and characteristics of those who are not following their clinic appointments is needed to enable the implementation of interventions that will be effective in increasing the retention to care. METHOD: This was a retrospective study involving sickle cell patients registered in the Muhimbili Sickle Cohort in Tanzania. Descriptive and survival analysis techniques both non-parametric methods (Kaplan-Meier estimator and Log-rank test) and semi-parametric method (Cox's proportional hazard model), were used. A p-value of 0.05 was considered significant to make an inference from the analysis. RESULTS: A total of 5476 patients were registered in the cohort from 2004 to 2016. Of these, 3350 (58.13%) were actively participating in clinics, while 2126 (41.87%) were inactive, of which 1927 (35.19%) were loss to follow-up. We used data from 2004 to 2014 because between 2015 and 2016, patients were referred to other government hospitals. From the survival analysis results, pediatric (HR: 14.29,95% CI: 11.0071-18.5768, p <  0.001) and children between 5 and 17 years [HR:2.61,95% CI:2.2324-3.0705, p <  0.001] patients were more likely to be loss to follow-up than the adult (18 and above years) patients. It was found that patients with above averages for hematocrit (HR: 2.38, 95% CI: 1.0076-1.0404, p = 0.0039) or mean cell volume (HR: 4.28, (95% CI: 1.0260-1.0598, p < 0.001) were more likely to be loss to follow-up than their counterparts. CONCLUSION: Loss to follow-up is evident in the cohort of patients in long term comprehensive care. It is, therefore, necessary to design interventions that improve patients' retention. Suggested solutions include refresher training for health care workers and those responsible for patient follow-up on techniques for retaining patients and comprehensive transition programs to prepare patients who are moving from pediatric to adult clinics.

Assessment of Implementation of Antimicrobial Resistance Surveillance and Antimicrobial Stewardship Programs in Tanzanian Health Facilities a Year After Launch of the National Action Plan.

Introduction: Antimicrobial resistance (AMR) is a current global health threat and a challenge to the treatment of infectious diseases. The WHO advocates a strategy of antibiotic stewardship programs (ASP) in optimizing antimicrobial use in hospitals. This study aimed at assessing the existence of AMR surveillance and ASP implementation in health facilities in Tanzania in the year following the launch of the National Action Plan (NAP). Methodology: From December 2017 through July 2018, a descriptive cross-sectional study was conducted using a structured questionnaire administered online. A total of 199 health facilities in Tanzania mainland whose contacts was obtained from the Ministry of Health Community Development Gender Elderly and Children (MoHCDGEC) were reached by phone and thereafter, a survey was sent via text or e-mail to focal persons in the corresponding facilities. Results: Only 39 (32.5%) responses from contacted facilities were received and analyzed. Thirty (76.9%) of the facilities were government-owned. Of the 39 respondents surveyed, 13 (35.9%) declared to have implemented some sort of coordinated ASP to promote the rational use of antimicrobials at their facilities. The respondents reported the presence of guidelines for the implementation of ASP at variable proportions, whereas the presence of a committee for Infection Prevention and Control was reported by 27 (69.2%). Twenty-four (61.5%) had a Medical and Therapeutic Committee. Although all 39 (100%) respondents were aware of the presence of AMR in Tanzania, only 26 (66.7%) were aware of the presence of the Tanzanian NAP for AMR. Hospital antibiotic policy document was present in 6 (15.4%) facilities. Only 7 (17.9%) facilities conducted prescription auditing; 9 (23.1%) had a hospital formulary; 14 (35.9%) had standard hospital prescription. 9 (23.1%) had software for data storage about AMR. Only 7 (17.9%) facilities conducted microorganisms' susceptibility tests and kept the record of the microorganism susceptibility testing. Conclusion: Our study found the existence of AMR surveillance activities and ASP implementation in Tanzania, albeit at a low level. The implementation was inconsistent across the surveyed facilities. These data have identified areas of improvement in addressing AMR in Tanzania through the NAP.

White Matter Integrity in Tanzanian Children With Sickle Cell Anemia: A Diffusion Tensor Imaging Study.

Background and Purpose- Widespread reductions in white matter integrity are associated with cognitive dysfunction in sickle cell anemia. Silent cerebral infarction (SCI), vasculopathy (VSC), and low hemoglobin concentration (Hb) are implicated; we aimed to determine independent contributions to microstructural white matter injury and whether white matter integrity differs across arterial territories. Methods- Sixty two children with sickle cell anemia aged 6 to 19 years were prospectively studied at Muhimbili National Hospital, Tanzania. SCI± and VSC± were identified on magnetic resonance imaging (MRI)/magnetic resonance angiography (MRA) scans by 2 neuroradiologists. Tract-based spatial statistics tested for voxel-wise differences in diffusion tensor imaging metrics (ie, fractional anisotropy, mean diffusivity, radial diffusivity, and axial diffusivity) between SCI± and VSC± groups, with correlations between diffusion tensor imaging metrics and Hb. In tract-based spatial statistics analyses, potentially mediating factors (ie, age, sex, as well as Hb, SCI, and/or vasculopathy) were covariates. Differences in mean diffusion tensor imaging metrics across regions of interest in arterial territories were explored. Results- Compared with SCI- patients (n=45), SCI+ patients (n=17) exhibited increased radial diffusivity in multiple regions; negative relationships were observed between mean diffusivity, axial diffusivity, and Hb (P<0.005). Compared with VSC- patients (n=49), mild (n=6) or moderate (n=7) VSC+ patients exhibited reduced fractional anisotropy in widespread regions (P<0.05) including the anterior longitudinal fasciculi, corpus callosum, internal capsule, corona radiata, and corticospinal tracts. Overall, the posterior cerebral arterial territory had higher mean mean diffusivity and mean radial diffusivity than the anterior and middle cerebral arterial territories, although no patient had vasculopathy in this area. There was an interaction between territory and vasculopathy. Conclusions- SCI, vasculopathy, and Hb are independent risk factors, and thus treatment targets, for diffuse white matter injury in patients with sickle cell anemia. Exacerbation of hemodynamic stress may play a role.

Cerebral Infarcts and Vasculopathy in Tanzanian Children With Sickle Cell Anemia.

BACKGROUND: Cerebral infarcts and vasculopathy in neurologically asymptomatic children with sickle cell anemia (SCA) have received little attention in African settings. This study aimed to establish the prevalence of silent cerebral infarcts (SCI) and vasculopathy and determine associations with exposure to chronic hemolysis, anemia, and hypoxia. METHODS: We prospectively studied 224 children with SCA with transcranial Doppler (TCD), and magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA). Regressions were undertaken with contemporaneous hemoglobin, reticulocyte count, mean prior hemoglobin, oxygen content, reticulocyte count, and indirect bilirubin. RESULTS: Prevalence of SCI was 27% (61 of 224); cerebral blood flow velocity was abnormal (>200 cm/s) in three and conditional (>170<200 cm/s) in one. Vasculopathy grades 2 (stenosis) and 3 (occlusion) occurred in 16 (7%) and two (1%), respectively; none had grade 4 (moyamoya). SCI was associated with vasculopathy on MRA (odds ratio 2.68; 95% confidence intervals [95% CI] 1.32 to 5.46; P = 0.007) and mean prior indirect bilirubin (odds ratio 1.02, 95% CI 1.00 to 1.03, P = 0.024; n = 83) but not age, sex, non-normal TCD, or contemporaneous hemoglobin. Vasculopathy was associated with mean prior values for hemoglobin (odds ratio 0.33, 95% CI 0.16 to 0.69, P = 0.003; n = 87), oxygen content (odds ratio 0.43, 95% CI 0.25 to 0.74, P = 0.003), reticulocytes (odds ratio 1.20, 95% CI 1.01-1.42, P = 0.041; n = 77), and indirect bilirubin (odds ratio 1.02, 95% CI 1.01 to 1.04, P = 0.009). CONCLUSIONS: SCI and vasculopathy on MRA are common in neurologically asymptomatic children with SCA living in Africa, even when TCD is normal. Children with vasculopathy on MRA are at increased risk of SCI. Longitudinal exposure to anemia, hypoxia, and hemolysis appear to be risk factors for vasculopathy.

Effects of lemon decoction on malaria parasite clearance and selected hematological parameters in Plasmodium berghei ANKA infected mice.

BACKGROUND: Citrus plants particularly lemon (Citrus limon L.) concoctions are ethno-medically used for treatment of infectious diseases including malaria. Therefore, we set an experiment to investigate the effects of lemon decoction in mice infected with Plasmodium berghei ANKA parasites. METHODS: Antimalarial activity was determined using Rane's curative test on 25 Theiler's albino mice. Twenty mice were each injected with 2 × 107 infected red blood cells (iRBCs). The mice were divided into four groups, consisting of five mice per group. Each group received an oral dose of either 5% carboxymethyl cellulose/placebo (negative infected control), lemon decoction (Citrus limon [CILI extract]) alone or a combination of artemether/lumefantrine (A/LU, 28 mg/kg) and CILI extract and A/LU alone. A fifth group of mice consisted of uninfected mice as parasite-negative control. RESULTS: Within 72 hours after initiation of treatment, the mean percentage parasitemia ± standard deviation of the CILI extract group (24.2% ± 9.83%) was lower compared to placebo group (40.0% ± 14.78%), p = 0.037. CILI extract group was found to have an increased survival rate (11 days ± 1.6 days) as compared to placebo group (8.6 days ± 3.4 days), p = 0.226. Mice in the combination group (A/LU + CILI extract) had the highest mean counts in terms of hemato-immunological parameters, whereas those in the CILI extract alone had the lowest hematocrit levels. The study also found that mice that received a combination of CILI extract and A/LU exhibited a decreased lag time with regards to time required to clear 99% of parasites (58.8 h vs. 64.2 h, p = 0.681) as compared to the A/LU alone group. CONCLUSION: Lemon decoction demonstrated antimalarial activity in mice infected with P. berghei ANKA through parasites suppression by 39% as compared to those received placebo. However, when used alone, lemons did not suffice as a cure but in combination with standard antimalarials, lemons promoted early parasite clearance with an improved hematological parameters.