Background: Despite the scale-up of ART and the rollout in Tanzania of dolutegravir, an integrase strand transfer inhibitor (INSTI), treatment success has not been fully realized. HIV drug resistance (HIVDR), including dolutegravir resistance, could be implicated in the notable suboptimal viral load (VL) suppression among HIV patients.Objectives: To determine the prevalence and patterns of acquired drug resistance mutations (DRMs) among children and adults in Tanzania.Methods: A national cross-sectional HIVDR survey was conducted among 866 children and 1173 adults. Genotyping was done on dried blood spot and/or plasma of participants with high HIV VL (≥1000 copies/mL). HIV genes (reverse transcriptase, protease and integrase) were amplified by PCR and directly sequenced. The Stanford HIVDR Database was used for HIVDR interpretation.Results: HIVDR genotyping was performed on blood samples from 137 participants (92 children and 45 adults) with VL ≥ 1000 copies/mL. The overall prevalence of HIV DRMs was 71.5%, with DRMs present in 78.3% of children and 57.8% of adults. Importantly, 5.8% of participants had INSTI DRMs including major DRMs: Q148K, E138K, G118R, G140A, T66A and R263K. NNRTI, NRTI and PI DRMs were also detected in 62.8%, 44.5% and 8% of participants, respectively. All the participants with major INSTI DRMs harboured DRMs targeting NRTI backbone drugs.Conclusions: More than 7 in 10 patients with high HIV viraemia in Tanzania have DRMs. The early emergence of dolutegravir resistance is of concern for the efficacy of the Tanzanian ART programme.

Despite the effective use of antiretroviral therapy, the remainder of a latently HIV-1-infected reservoir mainly in the resting memory CD4+ T lymphocyte subset has provided a great setback towards viral eradication. While host transcriptional silencing machinery is thought to play a dominant role in HIV-1 latency, HIV-1 protein such as Tat, may affect both the establishment and the reversal of latency. Indeed, mutational studies have demonstrated that insufficient Tat transactivation activity can result in impaired transcription of viral genes and the establishment of latency in cell culture experiments. Because Tat protein is one of highly variable proteins within HIV-1 proteome, it is conceivable that naturally occurring Tat mutations may differentially modulate Tat functions, thereby influencing the establishment and/or the reversal of viral latency in vivo. In this mini review, we summarize the recent findings of Tat naturally occurring polymorphisms associating with host immune responses and we highlight the implication of Tat sequence variations in relation to HIV latency.

Background: Multi-drug resistance pathogens such as Extended-Spectrum Beta-Lactamase (ESBL) producing Enterobacteriaceae (ESBL-PE) are of great global health concern, since they are associated with increased morbidity and mortality. Even in the absence of infections caused by these pathogens, colonization is a great threat and can lead to cross transfer among hospitalized patients. To date data on carriage of these pathogens is still limited in Tanzania. Therefore, this study aimed to determine ESBL-PE fecal carriage rate and associated factors among hospitalized patients at Referral hospitals in Dar es Salaam. Methods: This was a cross sectional study conducted from May to July 2017 among patients admitted in three referral hospitals in Dar es Salaam, Tanzania. Rectal swabs were collected and screened for ESBL production using MacConkey agar supplemented with Ceftazidime 2 μg/ml. Phenotypic confirmation of ESBL-PE was done by double disk diffusion method. Statistical analysis was performed using Statistical Package for Social Sciences (SPPS) software version 20. Results: Of the 196 enrolled participants, 59.7% (117/196) were confirmed to carry ESBL-PE. Diarrheic patients (57/79) had statistically significant high prevalence of ESBL colonization compared to those without diarrhea (60/117) (p = 0.01). A total of 131 ESBL-PE were isolated from 117 patients, whereby, Escherichia coli accounted for 68.7%, Klebsiella pneumoniae 28.2% and Citrobacter species 0.8%. ESBL-PE carriage was significantly higher in patients with diarrhea compared to those without diarrhea (72% vs 53.1%, p = 0.01). Recent antibiotic use was independently associated with carriage of ESBL-PE (aOR 14.65, 95%CI 3.07–69.88, p = 0.01). Conclusions: High prevalence of fecal carriage of ESBL-PE was observed in patients admitted in tertiary hospitals in Dar es Salaam, Tanzania. The use of antibiotics was associated with carriage of ESBL producers among the study population.

Background: Infections due to extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) are increasing worldwide. Evidence indicates that fecal carriage of ESBL-E in pregnancy predisposes women to potential life-threatening urinary tract infections and subsequently increasing the risk of neonatal infections. There is limited data regarding fecal carriage of ESBL-E and associated factors among pregnant women in Tanzania. We aimed to address the gap by determining the proportion of pregnant women with ESBL-E fecal carriage and identify the related factors. Methodology: A hospital-based cross-sectional study was conducted at Muhimbili National Hospital in Dar es Salaam, Tanzania. A total of 182 pregnant women at the gestational age of 37 weeks and above were enrolled. Participants’ socio-demographic, clinical, and hygienic information were collected by using a well-structured questionnaire. Rectal swabs were collected and processed for isolation of ESBL-E. The extended-spectrum β-lactamase production and antibiotic susceptibility test (AST) were performed using a double-disc synergy test and Kirby-Bauer disc diffusion method, respectively. Results: A total of 117 (64.3%) pregnant women were found to carry ESBL-E. Factors such as self-prescription of antibiotic medication during pregnancy, low education level, and toilet sharing were independently associated with ESBL-E fecal carriage. Five ESBL-E species that were isolated include Escherichia coli (84.6%), Klebsiella pneumoniae (8.9%), Klebsiella oxytoca (3.3%), Citrobacter spp. (1.6%), and Enterobacter spp. (1.6%). ESBL-E isolates demonstrated high resistance to aztreonam and sulphamethoxazole-trimethoprim. Conclusion: This study has revealed a relatively high fecal carriage of ESBL-E among pregnant women, suggesting that there is a need for routine screening among that population. We recommend further studies to explore comprehensively the factors associated with high fecal carriage of ESBL-E in pregnancy and the potential transmission kinetics to their newborn babies.

Objectives: To determine the aetiological pathogens causing ear infections and their antimicrobial susceptibility patterns among patients with ear complaints at a tertiary hospital in Dar es Salaam. Design: Hospital-based cross-sectional study. Settings: Otorhinolaryngology clinic at Muhimbili National Hospital, Dar es Salaam, Tanzania. Participants: Patients presenting with signs and symptoms of ear infection. Main outcome measure: Bacteria and fungi isolated from ear swab specimens of patients presenting with signs and symptoms of ear infection; and antimicrobial susceptibility patterns of isolated bacteria. Results: Two hundred and fifty-five participants were enrolled, with a median age of 31 years and an IQR of 15–49. Otitis externa was the predominant type of ear infection, accounting for 45.1%. We observed positive bacteria culture in 53.3% of study participants, in which 41% of isolates were obtained from patients with chronic suppurative otitis media. Moreover, Staphylococcus aureus (27.3%) and Pseudomonas aeruginosa (24.2%) were the most frequently isolated bacteria, while Candida spp, 12 (63.8%) and Aspergillus spp, 9 (36.2%) were the only isolated fungi. Furthermore, we report that 93% of isolated Enterobacterales were resistant to amoxicillin/clavulanic acid, and 73% were resistant to ceftazidime. In addition, we detected 34.4% extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) and 44.4% methicillin-resistance S. aureus (MRSA). We also found that 22% of the bacteria isolates were resistant to ciprofloxacin, a primary topical antibiotic used in managing ear infections. Conclusions: The findings from this study reveal that the leading aetiological agent of ear infection is bacteria. Furthermore, our findings show a significant proportion of ESBL-PE and MRSA-causing ear infections. Hence, detecting multidrug-resistant bacteria is crucial to improving ear infection management.

In sub-Saharan Africa (SSA) the burden of non-nucleoside reverse transcriptase inhibitor (NNRTI) HIV drug resistance (HIVDR) has been high over the years. Therefore, in 2018 the World Health Organization (WHO) recommended a regimen based on a integrase strand transfer inhibitor (INSTI), dolutegravir, as the default first-line antiretroviral therapy (ART) in countries in SSA. The scale-up of DTG-based regimens in SSA has gained significant momentum since 2018 and has continued to expand across multiple countries in recent years. However, whether or not the DTG robustness experienced in the developed world will also be achieved in SSA settings is still an important question. Evidence generated from in vitro and in vivo studies suggests that the emergence of DTG HIVDR is HIV-1 subtype dependent. These findings demonstrate that the extensive HIV-1 diversity in SSA can influence DTG effectiveness and the emergence of drug resistance. In addition, the programmatic approach to the transition to DTG adopted by many countries in the SSA region potentially exposes individuals to DTG functional monotherapy, which is associated with the emergence of DTG resistance. In this mini review, we describe the current trends of the effectiveness of DTG as reflected by viral suppression and DTG resistance. Furthermore, we explore how HIV-1 diversity and the programmatic approach in SSA could shape DTG effectiveness and DTG HIVDR in the region.