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Nathanael Sirili,1 Doreen Mloka,2 Lilian Mselle,3 Rodrick Kisenge,4 Erasto Mbugi,5 Dennis Russa,6 Obadia Nyongole,7 Stephen E Mshana,8 Rose Laisser,9 Kien Mteta,10 Levina Msuya,11 Eligius Lyamuya,12 Judith Martin-Holland,13 Gideon Kwesigabo,14 Ephata Kaaya15 1Department of Development Studies, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; 2Department of Pharmaceutical Microbiology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; 3Department of Clinical Nursing, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; 4Department of Pediatrics, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; 5Department of Biochemistry, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; 6Department of Anatomy, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; 7Department of Surgery, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; 8Department of Microbiology and Immunology, Catholic University of Health and Allied Sciences, Mwanza, Tanzania; 9Archbishop Anthony Mayalla School of Nursing, Catholic University of Health and Allied Sciences, Mwanza, Tanzania; 10Department of Surgery, Kilimanjaro Christian Medical University College, Moshi, Tanzania; 11Department of Paediatrics and Child Health, Kilimanjaro Christian Medical University College, Moshi, Tanzania; 12Department of Microbiology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; 13Department of Physiological Nursing, University of San Francisco California, San Francisco, CA, USA; 14Department of Epidemiology and Biostatistics, Muhimbili University of Health and Allied Sciences, Dar Es Salaam, Tanzania; 15Department of Pathology, Kilimanjaro Christian Medical University College, Moshi, TanzaniaCorrespondence: Nathanael Sirili, Email drnsirili@gmail.comBackground: In 2012, the Muhimbili University of Health and Allied Sciences (MUHAS) embarked on structured competency-based curricula (CBC) for its programmes. Other health profession training institutions continued with their traditional way of teaching and thus causing variability in the competencies of the graduates. We aimed to analyze the experiences of different stakeholders on the implementation of CBC specifically on biomedical sciences by MUHAS to inform the development of harmonized competency-based curricula in three health professional training institutions in Tanzania.Methods: We adopted an exploratory case study to analyse the implementation of CBC in programmes of Medicine and Nursing involving MUHAS graduates, immediate supervisors at the employment sites, faculty, and continuing students at MUHAS. Kiswahili guides were used to conduct the in-depth interviews (IDIs) and focus group discussions (FGDs). Qualitative content analysis was adopted for analysis.Results: From the 38 IDIs and 15 FGDs, four categories of human resources teaching and learning environment; curriculum content; and support systems emerged. Human resources were attributed to the shortage of an adequate number of faculty and teaching skills variation. The curriculum content category was linked to the redundancy of courses or topics, poor sequencing of some topics or courses, and limited time for teaching some essential courses or topics. Training and practice area mismatch, accommodation to students, teaching space, and library were the sub-categories linked to teaching and learning environment. Lastly, support systems related to teaching methods and opportunities for improving teaching and learning were revealed.Conclusion: The findings of this study highlight the challenges and opportunities for the implementation of CBC. The solutions to the revealed challenges are beyond the training institutions’ capacity. The latter call for multi-stakeholder engagement including those from the public and private sectors in health, higher education and finance for common and sustainable solutions.Keywords: competency-based curricula, biomedical sciences, teaching pedagogy, health training institutions, harmonized training, Tanzania

To determine the levels and patterns of resistance to first- and second-line anti-tuberculosis (TB) drugs among new and previously treated sputum smear positive pulmonary TB (PTB) patients.We conducted a nationally representative cross-sectional facility-based survey in June 2017-July 2018 involving 45 clusters selected based on probability proportional to size. The survey aimed to determine the prevalence of anti-TB drug resistance and associated risk factors among smear positive PTB patients in Tanzania. Sputum samples were examined using smear microscopy, Xpert MTB/RIF, culture and drug susceptibility testing (DST). Logistic regression was used to account for missing data and sampling design effects on the estimates and their standard errors.We enrolled 1557 TB patients, including 1408 (90.4%) newly diagnosed and 149 (9.6%) previously treated patients. The prevalence of multidrug-resistant TB (MDR-TB) was 0.85% [95% confidence interval (CI): 0.4-1.3] among new cases and 4.6% (95% CI: 1.1-8.2) among previously treated cases. The prevalence of Mycobacterium tuberculosis strains resistant to any of the four first-line anti-TB drugs (isoniazid, rifampicin, streptomycin and ethambutol) was 1.7% among new TB patients and 6.5% among those previously treated. Drug resistance to all first-line drugs was similar (0.1%) in new and previously treated patients. None of the isolates displayed poly-resistance or extensively drug-resistant TB (XDR-TB). The only risk factor for MDR-TB was history of previous TB treatment (odds ratio = 5.7, 95% CI: 1.9-17.2).The burden of MDR-TB in the country was relatively low with no evidence of XDR-TB. Given the overall small number of MDR-TB cases in this survey, it will be beneficial focusing efforts on intensified case detection including universal DST.

Background: Surgical Site Infection (SSI) is one of the major hospital acquired infections, highly associated with prolonged hospitalisation, morbidity and mortality. In open urological surgeries, little is known on magnitude and factors associated with development of SSI. Methods and Materials: The intervention was a cross-sectional prospective observational study performed between August 2015 and March 2016 at Muhimbili National hospital (MNH), Dar es Salaam, Tanzania. Patients who underwent open urological surgery at MNH during the study period and met inclusion criteria were consecutively enrolled, and followed up for 30 days. Patients´ and operative characteristics were recorded using standard structured questionnaires. Wound/ pus swabs were collected from patients with clinical evidence of SSI for bacteriological processing. Data analysis was performed using SPSS version 20. Results: Of 182 patients who underwent open urological surgery, 22% (40/182) developed SSI. Pre-operative urinary tract infection (aOR 9.73, 95%CI 3.93-24.09, p

James Samwel Mundamshimu,1 Kija Malale,1 Benson R Kidenya,1 Daniel W Gunda,1 Logious Bwemelo,1,* Mwakile Mwashiuya,1,* Salhida Shamnte Omar,1,* Neema Mlowe,1,* Magwa Kiyumbi,1 James S Ngocho,2,3 Emmanuel Balandya,4 Bruno Sunguya,4 Stephen E Mshana,1 Kien Mteta,2 John Bartlett,5,6 Eligius Lyamuya,4 Blandina Theophil Mmbaga,2,3 Samuel Kalluvya1 1Catholic University of Health and Allied Sciences, Mwanza, Tanzania; 2Kilimanjaro Christian Medical University College, Moshi, Tanzania; 3Kilimanjaro Clinical Research Institute, Moshi, Tanzania; 4Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; 5Kilimanjaro Christian Medical University College, Mosh, Tanzania; 6Duke Global Health Institute, Duke University Medical Center, Durham, NC, USA*These authors contributed equally to this workCorrespondence: James Samwel Mundamshimu, Tel +255746999249, Email jamessamwel913@yahoo.comBackground: Introduction and expansion of antiretroviral therapy (ART) have turned the tide of HIV pandemic, thus helping people living with HIV (PLHIV) achieve viral suppression. This success may need to be complemented by intensified adherence counseling (IAC) to improve adherence to treatment. However, some PLHIV still face higher than acceptable viral loads despite being on treatment.Purpose: We investigated the factors associated with the failure to suppress HIV viral load after three months of IAC sessions.Patients and Methods: This cross-sectional study analyzed secondary data from PLHIV-attended care and treatment clinics in Mwanza between January 2018 and December 2019 who had unsuppressed VL after being on ART for at least six months. We identified PLHIV in first-line ART with viral load evaluation before receiving IAC and had viral load results done at 90 days after IAC. We conducted descriptive statistics to examine the magnitude of viral suppression. Wilcoxon signed-rank test used to compare the median viral load before and after IAC sessions, and logistic regressions predicted the factors associated with failure.Results: This study included 212 subjects. After intervention, most participants 85.9% (182) had significantly improved adherence compared to baseline. More than half 75.5% (160) of the participants had viral suppression after the intervention. Participants aged 18– 25 years (AOR = 5.6, 95% CI, 1.1– 29.6), unstable client during ART initiation (AOR = 0.3, 95% CI, 0.13– 0.62), and poor adherence to ART (AOR = 4, 95% CI, 1.3– 12.3) remained the main predictors of virological failure after IAC intervention.Conclusion: Even though virological suppression is influenced by ART adherence, the findings in this study have shown co-existence of other factors to be addressed. Unstable during ART initiation is a new factor identified in this study.Keywords: people living with HIV, virological failure, intensified adherence counseling, factors, Tanzania

In many low- and middle-income countries, there seems to be a mismatch between graduate skills and healthcare industry requirements due to variability in curricula. With the current increased global demand for competent health profession graduates, harmonizing competency-based curricula (CBC) is necessary to address this mismatch. This paper describes how three health professions training universities in Tanzania and their two long-standing United States partners embarked on developing harmonized CBC for undergraduate medicine and nursing degrees. The main goal of the activity was to develop templates to harmonize curricula that would support graduates to acquire mandatory national Graduate Minimum Essential Competencies (GMEC) irrespective of the institution of their training. The paper describes the processes of engaging multiple institutions, the professions of medicine and nursing and various stakeholders to develop mandatory curricula generic competencies, creating milestones for assessing competencies, training faculty at each of the three partnering institutions in curriculum delivery and assessments, resulting in the adoption of the curricula by the University leadership at each institution. Ultimately the Tanzania Commission for Universities (TCU) a regulatory body required all schools of medicine and nursing in the country to adopt the curricula, thus creating a harmonized national standard for teaching medicine and nursing beginning October 2022.

Background For over a decade, antiretroviral therapy (ART) in resource-limited countries was only recommended for patients with advanced HIV disease. We investigated this group of patients in order to determine any relationship between degree of immunosuppression during treatment initiation and the subsequent levels of inflammatory biomarkers, reservoir size and plasma marker of fungal translocation after achieving long-term virological control. Methods We analyzed 115 virally suppressed (female 83.5%) and 40 untreated (female 70%) subjects from Dar es Salaam, Tanzania. The size of HIV latent reservoir (proviral DNA copy) was determined using quantitative PCR. Inflammatory biomarkers; IL-6, IL-10, and soluble CD14 (sCD14), were measured using multiplex cytometric beads array. Antibody titers for Cytomegalovirus (CMV) and Epstein Barr virus (EBV), plasma level of 1-3-beta-d-Glucan (BDG) was measured using ELISA. High-sensitivity C-reactive protein (hsCRP) was measured using nephelometric method. Results The median age was 36 (IQR 32-44) and 47 (IQR 43–54) years in untreated and virally suppressed patients respectively. Median duration of treatment for virally suppressed patients was 9 years (IQR 7–12) and median baseline CD4 count was 147 cells/mm3 (IQR 65–217). Virally suppressed patients were associated with significantly lower plasma levels of IL-10, sCD14 and BDG (P 3) was associated with significantly higher plasma level of IL-6 (P = 0.02), hsCRP (P = 0.036) and BDG (P = 0.0107). This relationship was not seen in plasma levels of other tested markers. Degree of baseline immunosuppression was not associated with the subsequent proviral DNA copy. In addition, plasma levels of inflammatory marker were not associated with sex, CMV or EBV antibody titers, treatment duration or regimen. Conclusions Our data suggest that advanced immunosuppression at ART initiation is associated with severity of inflammation and elevated fungal translocation marker despite long term virological control. Further studies are needed to evaluate the potential increased burden of non-AIDS comorbidities that are linked to elevated inflammatory and fungal translocation markers as a result of the policy of HIV treatment at CD4 count 3 implemented for over a decade in Tanzania.

Tanzania has recently adapted World Health Organization antiretroviral guidelines that include integrase strand transfer inhibitors (INSTIs) in the first-line regimen. However, there is lack of evidence on integrase (IN) gene polymorphisms in viral strains circulating in Tanzania. In this study, we characterize IN gene polymorphisms in viral strains circulating in Dar es Salaam, Tanzania, before introduction of INSTIs. Plasma viral RNAs were prepared from 158 HIV-1-infected subjects, including 111 treated, but viremic (INSTI-naive), subjects. A part of the pol gene encompassing the IN-coding region was amplified and directly sequenced by the Sanger sequencing method. Subtype analysis revealed that subtypes A1, C, and D and intersubtype recombinants were 42%, 38%, 11%, and 9%, respectively. Although multiple subtypes cocirculate, the IN gene exhibited a relatively conserved amino acid sequence pattern with an average Shannon entropy score of 0.16. No major INSTI resistance mutations were found; however, accessory resistance mutations at positions T97A, E157Q, G163E/K, and 128A/T were detected in 5% of subjects.

Emmanuel Balandya,1 Bruno Sunguya,2 Benson Kidenya,3 Tumaini Nyamhanga,4 Irene K Minja,5 Michael Mahande,6 Blandina T Mmbaga,7 Stephen E Mshana,8 Kien Mteta,9 John Bartlett,10 Eligius Lyamuya11 1Department of Physiology, Muhimbili University of Health and Allied Sciences, Dar-es-salaam, Tanzania; 2Department of Community Health, Muhimbili University of Health and Allied Sciences, Dar-es-salaam, Tanzania; 3Department of Biochemistry and Molecular Biology, Catholic University of Health and Allied Sciences, Mwanza, Tanzania; 4Department of Development Studies, Muhimbili University of Health and Allied Sciences, Dar-es-salaam, Tanzania; 5Department of Restorative Dentistry, Muhimbili University of Health and Allied Sciences, Dar-es-salaam, Tanzania; 6Department of Epidemiology and Biostatistics, Kilimanjaro Christian Medical University College, Moshi, Tanzania; 7Department of Pediatrics and Child Health, Kilimanjaro Christian Medical University College, Moshi, Tanzania; 8Department of Microbiology and Immunology, Catholic University of Health and Allied Sciences, Mwanza, Tanzania; 9Department of Urology, Kilimanjaro Christian Medical University College, Moshi, Tanzania; 10Duke Global Health Institute, Duke University, Durham, NC, USA; 11Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar-es-salaam, TanzaniaCorrespondence: Emmanuel Balandya, Department of Physiology, Muhimbili University of Health and Allied Sciences, P.O. Box. 65001, Dar-es-salaam, Tanzania, Tel +255-768-431600, Fax +255-22-2150465, Email ebalandya@muhas.ac.tzBackground: Mentorship is pivotal for sustainability of a successful research culture at higher learning institutions. Various models have been proposed for provision of research mentorship in health sciences but are challenged by utilizing predominantly hierarchical mentoring, as well as being centred on one discipline or one institution. This paper describes the approach and successes of an inclusive mentorship model employed in a resource-limited setting in sub-Saharan Africa.Methods: Through the NIH-funded Transforming Health Professions Education in Tanzania (THET) project, a consortium of three prominent health sciences higher learning institutions in Tanzania (MUHAS, CUHAS and KCMUCo) and two collaborating US institutions (UCSF and Duke University) was formed. Within THET, the Community of Young Research Peers (CYRP) was constituted, comprised two cohorts of undergraduate students and young faculty (fellows), and senior scientists. Besides mentorship and research training, fellows received funded research awards and in turn mentored undergraduate students.Results: By the first quarter of project year four, the number of fellows and mentored undergraduate students had increased from 12 to 24 and from 41 to 67, respectively. Fellows in the second cohort (junior fellows) included medical doctors, nurses, dentist, biomedical scientist, sociologist and education psychologist. In fostering peer-to-peer mentoring, the cross-institutional pairs of fellows from the first cohort (senior fellows) were assigned to reciprocal pairs of junior fellow mentees and took a leading role in research training. Furthermore, the senior fellows had made significant strides, including eight enrolled in PhD programmes, eight publications from mentored research projects, and six small to medium-size research grants won.Conclusion: The unifying model of research mentorship employed by the CYRP has been demonstrated as an effective model for joint research mentorship of the diverse group of young investigators from collaborating higher learning institutions in Tanzania. This model is recommended for scale-up, particularly in sub-Saharan Africa.Keywords: health research, cross-institutional, inter-disciplinary, young faculty, mentorship, undergraduate

As more HIV patients start combination antiretroviral therapy (cART), the emergence of HIV drug resistance (HIVDR) is inevitable. This will have consequences for the transmission of HIVDR, the success of ART, and the nature and trend of the epidemic. We recruited a cohort of 223 patients starting or continuing their first-line cART in Tanzania towards the end of the stavudine era in 2010. Patients were then followed for one year. Of those with a viral load test at baseline and follow-up time, 34% had a detectable viral load at the one-year endpoint. For 41 patients, protease and reverse transcriptase genotyping were successful. Eighteen samples were from cART-naïve patients, and 23 samples were taken under therapy either at baseline for cART-experienced patients or from follow-up samples for both cART–naïve and cART–experienced patients. The isolates were subtype A, followed by C and D in 41.5%, 22%, and 12.2% of the patients, respectively. No transmitted HIVDR was detected, as scored using the surveillance drug resistance mutations (DRMs) list. However, in 3 of the 18 samples from cART-naïve patients, the clinical Rega interpretation algorithm scored 44D or 138A as non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated polymorphisms. The most observed nucleoside reverse transcriptase inhibitor (NRTI) mutation was 184V. The mutation was found in 16 patients, causing resistance to lamivudine and emtricitabine. Nineteen patients had NNRTI resistance mutations, the most common of which was 103N, observed in eight patients. These high levels of resistance call for regular drug resistance surveillance in Tanzania to inform the control of the emergence and transmission of HIVDR.

IntroductionAn increase in cardiovascular disease (CVD) among people living with HIV infection is linked to platelet and immune activation, a phenomenon unabolished by antiretroviral (ARV) drugs alone. In small studies, aspirin (acetylsalicylic acid [ASA]) has been shown to control immune activation, increase CD4+ count, halt HIV disease progression and reduce HIV viral load (HVL). We present a protocol for a larger ongoing randomised placebo controlled trial on the effect of an addition of ASA to ARV drugs on HIV disease progression.Methods and analysisA single-centre phase IIA double-blind, parallel-group randomised controlled trial intends to recruit 454 consenting ARV drug-naïve, HIV-infected adults initiating ART. Participants are randomised in blocks of 10 in a 1:1 ratio to receive, in addition to ARV drugs, 75 mg ASA or placebo for 6 months. The primary outcome is the proportion of participants attaining HVL of 1000 copies/mL at week 24, attaining a >30% rise of CD4 count from baseline value at week 12, experiencing adverse events, with normal levels of biomarkers of platelet and immune activation at weeks 12 and 24 and rates of morbidity and all-cause mortality. Intention-to-treat analysis will be done for all study outcomes.Ethics and disseminationEthical approval has been obtained from institutional and national ethics review committees. Findings will be submitted to peer-reviewed journals and presented in scientific conferences.Trial registration numberPACTR202003522049711.

All too frequent, valuable research output and scholarly materials from expensively conducted research work in different parts of the world end up in research desks, academic libraries, and scientific journals. Muhimbili University of Health and Allied Science (MUHAS) through the Directorate of Research and Publications initiated a series of symposia that aim to disseminate the evidence generated by the researchers to the policy makers and the community. In two of the six conducted University-wide symposia in the last one year, MUHAS produced two important policy briefs summarizing the impact of MUHAS research in two important—though distinct areas of local and global health impact—Elimination of Mother to Child Transmission (EMTCT) of HIV, and Diarrhea diseases.

A cohort of female sex workers (FSWs) was established to determine HIV prevalence and incidence, and associated factors in preparation for a phase IIb HIV vaccine and pre-exposure prophylaxis trial (PrEPVacc).A cohort of FSWs in Dar es Salaam, Tanzania.FSWs aged 18-45 years were recruited using a respondent-driven sampling method. Social demographic data, HIV risk behavioral assessments, and blood samples for testing of HIV, syphilis, hepatitis B (HBV), and hepatitis C (HCV) infections were collected at baseline and then at 3, 6, 9, and 12 months. Poisson regressions were used to estimate the prevalence ratios for factors associated with HIV prevalence and to estimate the 12-month HIV incidence rate.Between October and December 2018, a total of 773 FSWs were screened for eligibility and 700 were enrolled. The baseline prevalence of HIV, syphilis, HBV, and HCV was 7.6%, 1.2%, 1.7%, and 1.0%, respectively. HIV prevalence was associated with older age, using illicit drugs, and being infected with syphilis, HBV, or HCV. Attendance at 12 months was 80% (562/700). Twenty-one FSWs seroconverted during follow-up, giving a 12-month HIV incidence rate of 3.45 per 100 person-years at risk (95% CI; 2.25-5.28/100 person-years at risk). The HIV incidence rate was higher among FSWs aged 18-24 years, FSWs who used drugs, and those diagnosed with syphilis, HBV, or HCV.The high HIV incidence rate and retention rate among FSWs enrolled into the cohort demonstrate that this population is suitable for participation in HIV prevention trials.

Background. Human herpesvirus (HHV) infections can significantly increase the risk of human immunodeficiency virus (HIV) transmission and accelerate disease progression. In the population at high risk of HIV infection, also termed as key populations (female sex workers (FSW), men who have sex with men (MSM), and people who inject drugs (PWID)), and their sexual partners, HHV infections can potentially compromise the efforts to prevent and control HIV infection. Here, we investigated the seroprevalence of HHV infections among HIV-infected key populations in Dar es Salaam, Tanzania. Methodology. We analyzed 262 archived serum samples of HIV-infected key populations from the integrated biobehavioral surveillance (IBBS) study conducted in Dar es Salaam, Tanzania. The enzyme-linked immunosorbent assay was used to determine IgG and IgM titers for cytomegalovirus (CMV) and herpes simplex virus (HSV) types 1 and 2. Results. The overall seropositivity of HHV IgG was 92% (95% CI: 87.7–95.3%). HHV IgM was not detected in any of the samples. The most seroprevalent coinfection was CMV at 69.1% (181/262), followed by HSV-2 33.2% (87/262) and HSV-1 32.1% (84/262). HSV-2 infection differed by key population groups; it accounted for FSW (46.3%) ( p = 0. 0001 ) compared to PWID (21.6%) and MSM (22.7%). In contrast, seroprevalence for CMV and HSV-1 was comparable across the key population groups; whereby, CMV was 62%, 75.3%, and 75% and HSV-1 was 26.4%, 39.2%, and 31.8% for FSW, MSM, and PWID, respectively. We also observed that multiple coinfections with CMV-HSV-2 ( p = 0. 042 ) and CMV-HSV-1-HSV-2 ( p = 0. 006 ) were significantly associated with key population aged above 40 years. Conclusion. The IgG seroprevalence of CMV, HSV-1, and HSV-2 was high among HIV-positive key populations. These findings indicate that these individuals are prone to recurrence of HHV infections and may harbor replicating viruses that subsequently may affect HIV disease progression. Therefore, this warrants concerted efforts for integrated HIV and sexually transmitted infection prevention programs targeting key populations.

HIV human immunodeficiency virus type I (HIV-1) entry inhibitor potency is dependent on viral co-receptor tropisms and thereby tropism determination is clinically important. However, phenotypic tropisms of HIV-1 non-B subtypes have been poorly investigated and the genotypic prediction algorithms remain insufficiently validated. To clarify this issue, we recruited 52 treatment-naïve, HIV-1-infected patients in Tanzania, where multiple HIV-1 non-B subtypes co-circulate. Sequence analysis of 93 infectious envelope clones isolated from their plasma viral RNA revealed the co-circulation of subtypes A1, C, D, and inter-subtype recombinant forms (isRFs). Phenotypic tropism assays revealed that lentivirus reporters pseudotyped with 75 (80.6%) and 5 (5.4%) envelope clones could establish infection toward U87.CD4 cells expressing CCR5 (R5) and CXCR4 (X4), respectively; whereas the remaining 13 (14%) clones could infect both cells. Genotypic analyses by widely used algorithms including V3 net charge, Geno2pheno, WebPSSM, and PhenoSeq showed that almost all phenotypic X4-tropic clones and only 15 of 75 phenotypic R5-tropic clones were concordantly predicted. However, the remaining 60 phenotypic R5-tropic clones were discordantly predicted by at least one algorithm. In particular, 2 phenotypic R5-tropic clones were discordantly predicted by all algorithms tested. Taken together, the results demonstrate the limitation of currently available genotypic algorithms for predicting co-receptor inference among co-circulating multiple non-B subtypes and emerging isRFs. Also, the phenotypic tropism dataset presented here could be valuable for retraining of the widely used genotypic prediction algorithms to enhance their performance.

Background: HIV infection is a common risk for developing cervical cancer (CC). Routine screening for CC among women living with Human Immune Deficiency Virus (WLHIV) is recommended for early detection and control of pre-malignancies. Evidence on CC uptake and its associated factors is scanty among WLHIV in Tanzania similar to other sub-Saharan Africa (SSA) countries. This study therefore aimed to assess the uptake of CC screening and its associated factors among WLHIV in Tanzania. Methods: This cross-sectional study was conducted between June and September 2020 among WLHIV attending Care and Treatment Center (CTC) at the Kilimanjaro Christian Medical Center (KCMC). Data was collected through face to face interview using a pre-tested standardized questionnaire interviewed in Swahili. Analyses were conducted using descriptive statistics to establish the CC uptake and using regression analyses to characterize the CC screening uptake and factors associated with the CC uptake through SPSS version 23 software. Associations with PResults: A total of 341 WLHIV with mean age 45.6 years (SD 10.8) were recruited for interview. Of them, 184 (54%) WLHIV reported ever being screened for cervical cancer. After adjusting for confounders, knowledge of the screening methods was one of the factors associated with uptake of CC screening [AOR=15.61, (95% CI: 7.93-30.72), pConclusion: More than four in ten WLHIV attending CTC at KCMC have never been screened for cervical cancer. Knowledge of the available screening methods, the disease condition, and duration since fist HIV diagnosis were associated with CC uptake of the screening. Addressing low CC screening uptake in Tanzania call strengthening WLHIV’s knowledge on cervical cancer screening methods, its signs, symptoms and their risk profiles. Moreover, strengthening CC screening capacity through integrated care and strengthening health providers’ capacity for counseling and screening will lead into a sustainable and effective care.

Methicillin-resistant Staphylococcus aureus (MRSA) among health care workers (HCWs) increases the risk of spreading the organism in hospital settings. A cross-sectional study was conducted between June and October 2016 among HCWs in tertiary and regional hospitals in Dar es Salaam, Tanzania, to determine the MRSA nasal carriage rate. Nasal swabs were collected from HCWs and cultured on mannitol salt agar. S. aureus was identified based on colonial morphology, Gram staining, catalase, coagulase, and DNase test results. MRSA was detected using the cefoxitin disk. Among 379 HCWs enrolled, 157/379 (41.4%) were colonized with S. aureus, of whom 59 (37.6%) were MRSA carriers giving an overall prevalence of 59/379 (15.6%). MRSA carriage was high among HCWs in Temeke (56.9%) and Amana (37.5%) regional hospitals. A high proportion of MRSA carriage was detected among nurses (35, 45.5%). MRSA isolates showed high resistance toward kanamycin (83.7%), gentamicin (83.1%), ciprofloxacin (71.2%), and trimethoprim-sulphamethoxazole (46.8%) compared to methicillin-sensitive S. aureus isolates (p≤0.001). In conclusion, we found a high nasal carriage of MRSA and resistance to commonly prescribed antimicrobial agents among HCWs. Implementation of infection control measures including contact precautions, urgent reporting of MRSA laboratory results, and routine MRSA screening of HCWs is highly needed to reduce MRSA spreading.

We explored the duration of immune responses and the effect of a late third HIV-modified vaccinia virus Ankara (MVA) boost in HIV-DNA primed and HIV-MVA boosted Tanzanian volunteers. Twenty volunteers who had previously received three HIV-DNA and two HIV-MVA immunizations were given a third HIV-MVA immunization 3 years after the second HIV-MVA boost. At the time of the third HIV-MVA, 90% of the vaccinees had antibodies to HIV-1 subtype C gp140 (median titer 200) and 85% to subtype B gp160 (median titer 100). The majority of vaccinees had detectable antibody-dependent cellular cytotoxicity (ADCC)–mediating antibodies, 70% against CRF01_AE virus–infected cells (median titer 239) and 84% against CRF01_AE gp120–coated cells (median titer 499). A high proportion (74%) of vaccinees had IFN-γ ELISpot responses, 63% to Gag and 42% to Env, 3 years after the second HIV-MVA boost. After the third HIV-MVA, there was an increase in Env-binding antibodies and ADCC-mediating antibodies relative to the response seen at the time of the third HIV-MVA vaccination, p

ObjectivesWe investigated the prevalence and patterns of pre-treatment and acquired HIV drug resistance mutations (DRMs) in Tanzania as a ‘treat all’ strategy, virological monitoring and the progressive increase in usage of tenofovir are being implemented in HIV treatment programmes.MethodsViral RNA was isolated from plasma of 60 ART-naive and 166 treated-but-viraemic (>400 copies/mL) HIV-1-infected adults attending a care and treatment clinic at Muhimbili National Hospital, Dar es Salaam, Tanzania, between June and October 2017. Viral genes encoding protease and reverse transcriptase were amplified by PCR and directly sequenced.ResultsViral genotyping of successfully amplified samples revealed pre-treatment DRMs in 14/47 (29.8%) ART-naive subjects. Of these, 7/47 (14.9%) harboured mutations that confer high-level resistance to at least one drug of the default first-line regimen. In treated-but-viraemic subjects, DRMs were found in 100/111 (90%), where DRMs against NNRTI, NRTI and PI were observed in 95/100 (95%), 92/100 (92%) and 13/100 (13%), respectively. Tenofovir-resistance mutations K65R and K70G/E or ≥3 thymidine analogue resistance mutations including M41L and L210W were found in 18/36 (50%) subjects on a tenofovir-containing regimen at failure. Four patients harboured multiple DRMs, which can confer resistance to all available ART regimens in Tanzania.ConclusionsTaken together, pre-treatment and acquired DRMs were highly prevalent, which represents a major risk for the efficacy of ART programmes in Tanzania. Availability of a newer generation of antiretroviral drugs with a higher genetic barrier to resistance and robust treatment monitoring is warranted for effective and sustainable HIV treatment.

BackgroundWe evaluated the safety and immunogenicity of (i) an intradermal HIV-DNA regimen given with/without intradermal electroporation (EP) as prime and (ii) the impact of boosting with modified vaccinia virus Ankara (HIV-MVA) administered with or without subtype C CN54rgp140 envelope protein adjuvanted with Glucopyranosyl Lipid A (GLA-AF) in volunteers from Tanzania and Mozambique.MethodsHealthy HIV-uninfected adults (N = 191) were randomized twice; first to one of three HIV-DNA intradermal priming regimens by needle-free ZetaJet device at weeks 0, 4 and 12 (Group I: 2x0.1mL [3mg/mL], Group II: 2x0.1mL [3mg/mL] plus EP, Group III: 1x0.1mL [6mg/mL] plus EP). Second the same volunteers received 108 pfu HIV-MVA twice, alone or combined with CN54rgp140/GLA-AF, intramuscularly by syringe, 16 weeks apart. Additionally, 20 volunteers received saline placebo.ResultsVaccinations and electroporation did not raise safety concerns. After the last vaccination, the overall IFN-γ ELISpot response rate to either Gag or Env was 97%. Intradermal electroporation significantly increased ELISpot response rates to HIV-DNA-specific Gag (66% group I vs. 86% group II, p = 0.026), but not to the HIV-MVA vaccine-specific Gag or Env peptide pools nor the magnitude of responses. Co-administration of rgp140/GLA-AF with HIV-MVA did not impact the frequency of binding antibody responses against subtype B gp160, C gp140 or E gp120 antigens (95%, 99%, 79%, respectively), but significantly enhanced the magnitude against subtype B gp160 (2700 versus 300, pConclusionIntradermal electroporation increased DNA-induced Gag response rates but did not show an impact on Env-specific responses nor on the magnitude of responses. Co-administration of HIV-MVA with rgp140/GLA-AF significantly enhanced antibody responses.

Raphael Z Sangeda,1,2 Fausta Mosha,3 Said Aboud,4 Appolinary Kamuhabwa,5 Guerino Chalamilla,6,† Jurgen Vercauteren,2 Eric Van Wijngaerden,7 Eligius F Lyamuya,4 Anne-Mieke Vandamme2,8 1Department of Pharmaceutical Microbiology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; 2Department of Microbiology and Immunology, Rega Institute for Medical Research, Clinical and Epidemiological Virology, KU Leuven – University of Leuven, Leuven, Belgium; 3Ministry of Health, Community Development, Gender, Elderly and Children, Dar es Salaam, Tanzania; 4Department of Microbiology and Immunology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; 5Department of Clinical Pharmacy and Pharmacology, Muhimbili University of Health and Allied Sciences, Dar es Salaam, Tanzania; 6Management and Development for Health (MDH), Dar es Salaam, Tanzania; 7Department of General Internal Medicine, University Hospitals, KU Leuven – University of Leuven, Belgium; 8Center for Global Health and Tropical Medicine, Unidade de Microbiologia, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal †Dr Guerino Chalamilla passed away in November 2015 Background: Measurement of adherence to antiretroviral therapy (ART) can serve as a proxy for virologic failure in resource-limited settings. The aim of this study was to determine the factors underlying nonadherence measured by three methods. Patients and methods: This is a prospective longitudinal cohort of 220 patients on ART at Amana Hospital in Dar es Salaam, Tanzania. We measured adherence using a structured questionnaire combining a visual analog scale (VAS) and Swiss HIV Cohort Study Adherence Questionnaire (SHCS-AQ), pharmacy refill, and appointment keeping during four periods over 1 year. Overall adherence was calculated as the mean adherence for all time points over the 1 year of follow-up. At each time point, adherence was defined as achieving a validated cutoff for adherence previously defined for each method. Results: The proportion of overall adherence was 86.4% by VAS, 69% by SHCS-AQ, 79.8% by appointment keeping, and 51.8% by pharmacy refill. Forgetfulness was the major reported reason for patients to skip their medications. In multivariate analysis, significant predictors to good adherence were older age, less alcohol consumption, more advanced World Health Organization clinical staging, and having a lower body mass index with odds ratio (CI): 3.11 (1.55–6.93), 0.24 (0.09–0.62), 1.78 (1.14–2.84), and 0.93 (0.88–0.98), respectively. Conclusion: We found relatively good adherence to ART in this setting. Barriers to adherence include young age and perception of well-being. Keywords: self-report, appointment keeping, pharmacy refill, adherence barriers, resource-limited settings, AIDS

Prime-boost vaccination strategies against HIV-1 often include multiple variants for a given immunogen for better coverage of the extensive viral diversity. To study the immunologic effects of this approach, we characterized breadth, phenotype, function, and specificity of Gag-specific T cells induced by a DNA-prime modified vaccinia virus Ankara (MVA)-boost vaccination strategy, which uses mismatched Gag immunogens in the TamoVac 01 phase IIa trial. Healthy Tanzanian volunteers received three injections of the DNA-SMI vaccine encoding a subtype B and AB-recombinant Gag p37 and two vaccinations with MVA-CMDR encoding subtype A Gag p55 . Gag-specific T-cell responses were studied in 42 vaccinees using fresh peripheral blood mononuclear cells. After the first MVA-CMDR boost, vaccine-induced gamma interferon-positive (IFN-γ + ) Gag-specific T-cell responses were dominated by CD4 + T cells ( P < 0.001 compared to CD8 + T cells) that coexpressed interleukin-2 (IL-2) (66.4%) and/or tumor necrosis factor alpha (TNF-α) (63.7%). A median of 3 antigenic regions were targeted with a higher-magnitude median response to Gag p24 regions, more conserved between prime and boost, compared to those of regions within Gag p15 (not primed) and Gag p17 (less conserved; P < 0.0001 for both). Four regions within Gag p24 each were targeted by 45% to 74% of vaccinees upon restimulation with DNA-SMI-Gag matched peptides. The response rate to individual antigenic regions correlated with the sequence homology between the MVA- and DNA Gag-encoded immunogens ( P = 0.04, r 2 = 0.47). In summary, after the first MVA-CMDR boost, the sequence-mismatched DNA-prime MVA-boost vaccine strategy induced a Gag-specific T-cell response that was dominated by polyfunctional CD4 + T cells and that targeted multiple antigenic regions within the conserved Gag p24 protein. IMPORTANCE Genetic diversity is a major challenge for the design of vaccines against variable viruses. While including multiple variants for a given immunogen in prime-boost vaccination strategies is one approach that aims to improve coverage for global virus variants, the immunologic consequences of this strategy have been poorly defined so far. It is unclear whether inclusion of multiple variants in prime-boost vaccination strategies improves recognition of variant viruses by T cells and by which mechanisms this would be achieved, either by improved cross-recognition of multiple variants for a given antigenic region or through preferential targeting of antigenic regions more conserved between prime and boost. Engineering vaccines to induce adaptive immune responses that preferentially target conserved antigenic regions of viral vulnerability might facilitate better immune control after preventive and therapeutic vaccination for HIV and for other variable viruses.

BackgroundThere remains an urgent need for a prophylactic HIV vaccine to control generalised epidemics. PrEP has demonstrated effectiveness of 86% and is recommended by WHO; uptake is generally high, but retention is disappointing in some settings. The EDCTP2 project PrEPVacc will assess the efficacy of two combination prophylactic vaccine regimens (DNA, MVA and Env protein/adjuvant) each compared to placebo and the proportion of infections averted by F/TAF in comparison to TDF/FTC. A Registration Cohort, recruiting HIV negative volunteers at risk of HIV will precede the trial.MethodsThe PrEPVacc partnership agreed that 70% vaccine efficacy had public health relevance. The trial uses nstage software for multi-arm, multi-stage designs (MAMS) and the averted infections ratio (AIR) methodology with participants randomised (i) 1:1:1 to active product or placebo (ii) 1:1 to TDF/FTC : F/TAF until week 26 (presumed peak immunogenicity). Access to PrEP in the Registration Cohort and after week 26 will be standard of care. HIV seroconversions occurring between weeks 0–26 will inform the PrEP analysis, incorporating HIV incidence amongst those who do not take up PrEP locally in the Registration Cohort. Seroconversions after week 26 will inform vaccine analyses.ResultsUp to 556 participants per group affords 92% power to detect vaccine efficacy of 70% at the final analysis, assuming incidence of 4/100-person years and 10% loss with 81% and 97% power to conclude that F/TAF can avert half or more of the infections prevented by TDF/FTC if effectiveness of TDF/FTC is 70% and 80%, respectively.ConclusionPrEPVacc adopts a pragmatic approach to uncertainties around HIV incidence in settings where PrEP is increasingly available. This innovative adaptive trial design uses validated software to determine vaccine efficacy and a novel methodology to evaluate a new PrEP agent, overcoming the challenge of demonstrating non-inferiority when adherence to TDF/FTC is high and the number of outcome events very low.

This study aimed to determine the prevalence of Staphylococcus aureus and methicillin-resistant S. aureus (MRSA) carriage, risk factors of colonization and antimicrobial susceptibility patterns of S. aureus strains. The study was conducted at the Muhimbili National Hospital in Dar es Salaam, Tanzania. Nasal swabs were obtained from children and S. aureus was isolated and identified using conventional culture methods. MRSA was screened and confirmed using the cefoxitin disk and multiplex real-time polymerase chain reaction, respectively. Antibiotic susceptibility was performed using the Kirby-Bauer disk diffusion method. MRSA isolates were further characterized by pulsed field gel electrophoresis (PFGE) profiling. Of 285 children included in the study, S. aureus was detected in 114 (40%). Of the 114 isolates, 12 (10.5%) were MRSA. PFGE results showed that these MRSA isolates are epidemiologically unrelated. Resistance of all S. aureus to trimethoprim-sulfamethoxazole, tetracycline, gentamicin, and ciprofloxacin was 65.8%, 23.7%, 27.2%, and 4.4%, respectively. No resistance to vancomycin was found. The prevalence of inducible clindamycin resistance, constitutive clindamycin resistance, MS phenotype (resistance to erythromycin alone), and multidrug resistance was 16.7%, 1.8%, 14.0%, and 16.8%, respectively. None of the risk factors examined was found to be significant. This is the first report of S. aureus and nasal carriage of MRSA and a high rate of S. aureus carriage was found in Tanzanian under-5 children. The study findings support the need for proper health education and effective infection control measures for healthcare workers.

Background Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen responsible for hospital and community acquired infection. Colonization with MRSA is associated with a high risk of developing infection. This study aimed to determine the rate of MRSA carriage on admission and the associated risk factors among patients attending regional hospitals, in Dar es Salaam, Tanzania. Results A total of 258 patients were included in this study. Nasal swabs were collected on admission to the hospital and after 48 h of hospital stay for detection of MRSA. Of 258 patients enrolled, 89 (34.5%) were colonized with S. aureus and out them 22 (24.7%) were carriers of MRSA, giving an overall MRSA nasal carriage rate of 8.5% (22/258). One patient acquired MRSA while admitted in the hospital. Most of the S. aureus isolates 85 (95.5%) were resistant to penicillin. Resistance to gentamycin, ciprofloxacin, kanamycin, linezolid and mupirocin were 14.6, 11.2, 11.2, 3.4 and 1.1%, respectively. The prevalence of inducible clindamycin resistance, constitutive clindamycin resistance, MS phenotype (resistance to erythromycin alone), and multidrug resistance was 21.3, 3.4, 12.4, and 16.9%, respectively. We observed a statistically significant association between MRSA and multiple drugs resistance among S. aureus isolates (p = 0.001). Of the risk factors investigated none were statistically significant associated with MRSA. Conclusion There is a high prevalence of MRSA among patients on admission at the two municipal hospitals in Dar es Salaam. The high prevalence of MRSA and the increased rates of resistance to commonly used antimicrobials among MRSA isolates call for attention to the importance of including the screening of MRSA in our hospitals setting in order to prevent further spread of MRSA strains to other patients and to the communities. Control and prevention strategies should be emphasized including decolonization.

Introduction: Although there has been a worldwide emergence and spread of methicillin-resistant Staphylococcus aureus (MRSA), little is known about the molecular epidemiology of MRSA in Tanzania. Methodology: In this study, we characterized MRSA strains isolated from clinical specimens at the Bugando Medical Centre, Tanzania, between January and December 2008. Of 160 S. aureus isolates from 600 clinical specimens, 24 (15%) were found to be MRSA. Besides molecular screening for the Panton Valentine leukocidin (PVL) genes by PCR, MRSA strains were further characterized by Multi-Locus Sequence Typing (MLST) and spa typing. Results: Despite considerable genetic diversity, the spa types t690 (29.1%) and t7231 (41.6%), as well as the sequence types (ST) 88 (54.2%) and 1797 (29.1%), were dominant among clinical isolates. The PVL genes were detected in 4 isolates; of these, 3 were found in ST 88 and one in ST1820. Resistance to erythromycin, clindamicin, gentamicin, tetracycline and co-trimoxazole was found in 45.8%, 62.5%, 41.6%, 45.8% and 50% of the strains, respectively. Conclusion: We present the first thorough typing of MRSA at a Tanzanian hospital. Despite considerable genetic diversity, ST88 was dominant among clinical isolates at the Bugando Medical Centre. Active and standardized surveillance of nosocomial MRSA infection should be conducted in the future to analyse the infection and transmission rates and implement effective control measures.