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Abstract Background Antiretroviral therapy (ART) has been proven to be highly effective in reducing the impact of human immunodeficiency virus (HIV) infection. However, as more people receive initial ART treatment, the risk of developing resistance and eventual treatment failure increases, leading to the need for second-line treatment regimens. Understanding the factors that contribute to virologic failure to second-line ART is crucial in preventing switching to the more expensive and toxic third-line regimens. This study provides information on the prevalence, rate, and predictors of virologic failure (VF) among clients on second-line ART in Tanzania. Results We followed 4718 clients for 15100 person-years (PY) of observations. Of them, 1402 (29.72%) experienced virologic failure at a rate of 92.85 per 1000 PY of observations (95% CI 88.11, 97.84). Factors that were associated with VF included: having a viral load count of ≥ 1000 copies/mL during first-line ART, with a hazard ratio (HR) 4.65 (95% CI 3.57, 6.07), using lopinavir (LPV/r) as a protease inhibitor during second-line ART (HR 4.20 (95% CI 3.12, 7.10), having a CD4 count

Abstract Background Antimicrobial resistance affects the treatment of several bacterial infections, including pneumonia. This subsequently increased the morbidity and mortality rates of patients with bacterial pneumonia, especially in resource-limited settings. In this study, we aimed to determine the patterns of multidrug-resistant (MDR) bacteria isolated from the sputum samples of patients with bacterial pneumonia attending a tertiary hospital in Tanzania. Methodology A retrospective cross-sectional study was conducted. It involved reviewing the laboratory sputum data in the laboratory information system at Muhimbili National Hospital in Tanzania. The sputum samples were previously processed using standard methods (culture, Gram staining, and biochemical tests) to isolate and identify the bacteria. At the same time, antibiogram profiles were determined using antimicrobial susceptibility tests. Bacterial isolates that expressed MDR patterns were identified. Demographic information was collected from patients' medical records. We used the chi-square test to determine factors associated with MDR. A p-value

Abstract Background Pantoea agglomerans (P. agglomerans) is an environmental gram-negative bacterium that rarely infects humans. P. agglomerans infections have never been reported in Tanzania. We investigated the occurrence of P. agglomerans bloodstream infections among neonates in the Intensive Care Unit (NICU) and their subsequent clinical outcome that occurred in 2019. Methodology Blood samples were collected from neonates with sepsis. A total of 19 P. agglomerans were isolated from 17 infected neonates; two of the neonates had P. agglomerans isolated twice. A total of 14 patient files were retrieved from medical records. Results The mean age of the infected neonates were 3.75 ± 7.95 days. Isolated P. agglomerans showed high sensitivity to the antibiotics particularly chloramphenicol (94.7%), piperacillin-tazobactam (94.7%) and meropenem (94.7%). The mortality rate was 71.4% with 35.7% of infected neonates dying before Antibiotic Susceptibility Test results for appropriate management. The Infection Prevention and Control (IPC) team shut the NICU for thorough decontamination which helped to stop the P. agglomerans occurrence. Conclusions P. agglomerans occurrence at the NICU was an uncommon aetiology pathogen for neonatal sepsis associated with high rates of mortality despite high sensitivity to multiple antibiotics. This calls for the strengthening of infection control measures and introduction of surveillance for environmental pathogens capable of causing human infections.

Abstract The ongoing vaccination efforts and exposure to endemic and emerging coronaviruses can shape the population's immunity against this group of viruses. In this study, we investigated neutralizing immunity against endemic and emerging coronaviruses in 200 Tanzanian frontline healthcare workers (HCWs). Despite low vaccination rates (19.5%), we found a high SARS-CoV-2 seroprevalence (94.0%), indicating high exposure in these HCWs. Next, we determined the neutralization capacity of antisera against human coronavirus NL63, and 229E, SARS-CoV-1, MERS-CoV and SARS-CoV-2 (including Omicron subvariants: BA.1, BQ.1.1 and XBB.1.5) using pseudovirus neutralization assay. We observed a broad range of neutralizing activity in HCWs, but no neutralization activity detected against MERS-CoV. We also observed a strong correlation between neutralizing antibody titers for SARS-CoV-2 and SARS-CoV-1, but not between other coronaviruses. Cross-neutralization titers against the newer Omicron subvariants, BQ.1.1 and XBB.1.5, was significantly reduced compared to BA.1 and BA.2 subvariants. On the other hand, the exposed vaccinated HCWs showed relatively higher median cross-neutralization titers against both the newer Omicron subvariants and SARS-CoV-1, but did not reach statistical significance. In summary, our findings suggest a broad range of neutralizing potency against coronaviruses in Tanzanian HCWs with detectable neutralizing immunity against SARS-CoV-1 resulting from SARS-CoV-2 exposure.

Background Resistance to antiretrovirals against human immunodeficiency virus (HIV) poses a threat to zero transmission of HIV by 2030. Few studies have been conducted on HIV drug resistance (HIVDR) mutations targeting adolescents. We determined the prevalence, pattern of HIVDR mutations, and factors associated with unsuppressed HIV viral load among adolescents on antiretroviral therapy (ART). Methods From March to June 2020, we conducted a cross-sectional study at the Infectious Disease Clinic in Dar es Salaam, Tanzania. HIV‐1 viral load was tested using m2000rt Real-Time HIV‐1 assay. A sample with a viral load equal or more than 1,000 copies/ml was tested for HIVDR mutations. We determined the factors associated with unsuppressed viral load using logistic regression. A p-value less than 0.05 was considered significant. Results We enrolled 131 participants with a median age (interquartile range) of 15 (13–18) years. Of all, 24(18.3%) had a viral load above 1000 copies/ml. HIVDR mutations were found in 19/24(68.4%). Mutation to protease inhibitors, nucleotide reverse transcriptase inhibitors, and non-nucleoside reverse transcriptase inhibitors were 1(5.2%), 9(47.4%), and 11(57.9%), respectively. Non-antiretroviral therapy and orphanages were independently associated with unsuppressed viral load. Conclusion The prevalence of HIVDR and unsuppressed HIV viral load among adolescents are relatively high. The use of non-antiretroviral therapy and orphanage influenced the persistence of high viral load. Strategies for surveillance of HIVDR early warning signs should be devised among adolescents.

Abstract Background HIV and malaria are serious public health concerns, particularly in Tanzania. HIV-infected individuals are more likely to get malaria and its complications. However, data on the interaction of the two diseases in Tanzania are limited. This cross-sectional study aimed to determine the prevalence of malaria infection and associated factors among HIV-infected adults attending HIV care and treatment clinic at Kitete regional referral hospital in Tabora region, Tanzania. Methodology The cross-sectional study was carried out between March and May 2022 at Kitete regional referral hospital in Tanzania. A total of 246 HIV-infected adults were selected by systematic random sampling. Malaria was diagnosed using both malaria rapid diagnostic test (mRDT) and malaria microscopy. Social demographic data were collected using a structured questionnaire, while clinical history and laboratory parameters were extracted from patients’ files. Data were analyzed using STATA version 15.1, and a p value

BackgroundTanzania has made significant progress in improving access to HIV care and treatment. However, virologic suppression among people living with HIV (PLHIV) has not been fully realized. In March 2019, Tanzania introduced a World Health Organization (WHO)-recommended dolutegravir-based regimen as the default first-line regimen. Eighteen months later we investigated the HIV viral suppression rates and the factors associated with lack of viral suppression among PLHIV (children and adults) in Tanzania.MethodologyA cross-sectional survey was conducted from September to December 2020 among PLHIV on antiretroviral therapy (ART) in Tanzania. Whole blood samples, demographic data and clinical information were obtained from eligible adults (≥15 years) and children (< 15 years) attending thirty-six HIV care and treatment centres located in 22 regions of Tanzania mainland. A whole blood sample from each participant was processed into plasma and HIV viral load was estimated using real-time PCR. HIV viral suppression was defined at a cut-off of < 50 copies/mL as recommended by WHO. Analyses were conducted using descriptive statistics to establish the national representative prevalence of viral suppression, and logistic regression analyses to determine independent factors associated with non-suppression.ResultsA total of 2,039 PLHIV on ART were recruited; of these, adults and children were 57.5% (n = 1173) and 42.5% (n = 866), respectively. Among the adult population, the mean age and standard deviation (SD) was 42.1 ± 12.4 years, with 64.7% being female. Among children, the mean age and SD were 9.6 ± 3 years, and 53.2% were female. Overall viral suppression at < 50 copies/mL (undetectable) was achieved in 87.8% of adults and 74.4% of children. Adults and children on dolutegravir-based regimen recorded viral suppression rates of 89.7% and 85.1% respectively. Factors independently associated with lack of viral suppression status in the adult population were age and ART adherence while in the children population, the factors were sex, ART adherence, and current ART regimen (pConclusionDolutegravir-based regimens are promising to help attain epidemic control in Tanzania. More efforts especially on ART adherence are needed to attain optimal treatment outcomes for children and adults PLHIV in Tanzania.

Abstract Background Hepatitis B virus (HBV) infection continues to be a global public health problem. As of 2019, there were 296 million people chronically infected with HBV, resulting in nearly 1 million deaths from decompensated cirrhosis or hepatocellular carcinoma. The seroprevalence of HBV infection among pregnant women in Tanzania was reported to range between 3.8 and 8.03%. However, data on HBV infection in HIV-infected pregnant women is limited. We aimed to determine the seroprevalence and associated risk factors for HBV infection among HIV-infected pregnant women in selected health facilities in the Mtwara region. This was a health facility-based quantitative cross-sectional study conducted for three months (from February to April 2022). A structured questionnaire was used to collect information from the study participants. A total of 4 ml of blood was collected for HBV screening and confirmatory tests using rapid diagnostic tests and automated Enzyme-Linked Immunosorbent Assay (ELISA) tests, respectively. The logistic regression model was used to identify significant variables for HBV infection. Results Two hundred and twenty (n = 220) pregnant women living with HIV were enrolled in this study, with a median age of 32.7 years (Interquartile range (IQR) 27.6–37.6). The seroprevalence of HBV, chronic, and acute HBV infections were 10.5%, 10.0%, and 0.5%, respectively. We found that the multiparous women [aOR 11.99: 95% CI 1.11–129.01, p = 0.040], being infected with syphilis [aOR 27.65: 95% CI 9.07–84.30, p

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.

Objectives This study aimed to determine the oral carriage prevalence of Candida species and identify factors associated with the carriage of Candida species among patients with cancer on treatment.Design A hospital-based cross-sectional study.Setting The study was conducted at a tertiary-level cancer hospital Ocean Road Cancer Institute (ORCI), Dar es Salaam, Tanzania.Participants We enrolled 196 participants who consented to join the study. Oral swabs were collected from all participants and inoculated onto Sabouraud dextrose agar supplemented with 50 mg/mL gentamicin and 50 mg/mL chloramphenicol, and chromogenic agar for phenotypic identification of Candida species.Primary outcome The study reported the high prevalence of oral carriage of Candida species among patients with cancer on treatment at the tertiary-level cancer hospital in Dar es Salaam, Tanzania.Results A total of 196 participants were enrolled in the study. The overall oral carriage of Candida species was 37.8% (74/196). The prevalence was higher among patients undergoing chemotherapy and radiotherapy (44.4%) than those in monotherapy (13.3% chemotherapy, 20% radiotherapy). Candida krusei was the most common isolated species, 48.6% (36/74). Head and neck (adjusted OR (aOR) 15.09, 95% CI 3.05 to 74.59, p=0.00), gastrointestinal (aOR 14.14, 95% CI 2.25 to 88.63, p=0.00) malignancies and diabetes (aOR 3.18, 95% CI 1.03 to 9.77, p=0.04) were factors independently associated with oral carriage of Candida species.Conclusion The oral carriage of Candida species among patients with cancer receiving treatment at ORCI is high, mainly due to C. krusei species. This is alarming since C. krusei has intrinsic resistance to fluconazole, a common antifungal agent used to manage adult fungal infections. Therefore, efforts should be put into conducting regular check-ups for such opportunistic pathogens as they can lead to subsequent infections. Furthermore, studies conducted to determine the antifungal profile of the causative agents are warranted since different causative agents might have different profiles.

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.

BackgroundFor successful HIV response, updated information on the burden and progress toward HIV elimination targets are required to guide programmatic interventions. We used data from the 2020 HIV sentinel surveillance to update on the burden and factors associated with HIV infection, HIV status awareness, and ART coverage among pregnant women in Tanzania mainland.MethodologyWe conducted the surveillance in 159 antenatal clinics (ANC) from all 26 regions of Tanzania's mainland from September to December 2020. This cross-sectional study included all pregnant women (≥15 years) on their first ANC visit in the current pregnancy during the survey period. Routine HIV counselling and testing were done at the facility. A multivariable logistic regression model accounting for the survey design was used to examine factors associated with HIV infections.Results38,783 pregnant women were enrolled (median age (IQR) = 25 (21-30) years). HIV prevalence was 5.9% (95%CI: 5.3% - 6.6%), ranging from 1.9% in the Manyara region to 16.4% in the Njombe region. Older age, lower and no education, not being in a marital union, and living in urban or semi-urban areas were associated with higher odds of HIV infection. HIV status awareness among women who tested positive was 70.9% (95% CI: 67.5%- 74.0%). ART coverage among those aware of their status was 91.6% (86.5%- 94.9%). Overall, 66.6% (95% CI: 62.4%- 70.6%) of all pregnant women who tested positive for HIV knew their HIV status and were on ART.ConclusionHIV is increasingly prevalent among pregnant women in Tanzania mainland especially among older, those with lower or no formal education, those outside marital union, and pregnant women living in urban and semi-urban areas. Behind the global fast-target to end HIV/ AIDS, about a third of pregnant women living with HIV initiating ANC were not on ART. Interventions to increase HIV testing and linkage to care among women of reproductive age should be intensified.

Background Syphilis has detrimental effects on the health of the mother and that of both fetuses and newborns exposed in utero or at delivery. Understanding its local epidemiology is essential for policies, planning, and implementation of targeted preventive interventions. Using data from the 2020 National Sentinel Surveillance of pregnant women attending antenatal clinics (ANCs) in Tanzania we determined the prevalence and determinants of syphilis among pregnant women in Tanzania mainland. Methodology The ANC surveillance was conducted in 159 ANC sites from all 26 regions of Tanzania’s mainland from September to December 2020. It included all pregnant women 15 years and above on their first ANC visit in the current pregnancy during the survey period. Counseling for syphilis was done using standard guidelines at the ANC and testing was done using rapid SD Bioline HIV/Syphilis Duo test kits. Analysis was done using both descriptive statistics to determine the prevalence and characteristics of syphilis, whereas, logistic regressions were used to examine the independent association between syphilis and dependent variables. Results A total of 38,783 women [median age (Interquartile range (IQR)) = 25 (21–30) years] participated in the surveillance. Of them, 582 (1.4%) tested positive for syphilis. A wide regional variation was observed with the highest burden in Kagera (4.5%) to the lowest burden in Kigoma (0.3%). The odds of syphilis infections were higher among older women and those with no formal education. Compared with primigravids, women with 1–2, those with 3–4 and those with more than four previous pregnancies had 1.8 (aOR = 1.8, 95% CI: 1.2–2.5), 2.1 (aOR = 2.1, 95% CI: 1.4–3.1) and 2.6 (aOR = 2.6, 95% CI: 1.7–3.9) higher odds of syphilis infection respectively. Conclusion Syphilis is still prevalent among pregnant women in Tanzania with a wide regional disparity. Efforts to prevent new infections, screen pregnant women, and treat those infected should be strategized to include all regions and renewed emphasis on regions with high burden, and importantly among women who are multipara, with a low level of education, and advanced age.

BackgroundThe World Health Organization (WHO) recommends periodic evaluations of influenza surveillance systems to identify areas for improvement and provide evidence of data reliability for policymaking. However, data on the performance of established influenza surveillance systems are limited in Africa, including Tanzania. We aimed to assess the usefulness of the Influenza surveillance system in Tanzania and to ascertain if the system meets its objectives, including; estimating the burden of disease caused by the Influenza virus in Tanzania and identifying any circulating viral strains with pandemic potential.MethodologyFrom March to April 2021, we collected retrospective data through a review of the Tanzania National Influenza Surveillance System electronic forms for 2019. Furthermore, we interviewed the surveillance personnel about the system's description and operating procedures. Case definition (ILI-Influenza Like Illness and SARI-Severe Acute Respiratory Illness), results, and demographic characteristics of each patient were obtained from the Laboratory Information System (Disa*Lab) at Tanzania National Influenza Center. The United States Centers for disease control and prevention updated guidelines for evaluating public health surveillance systems were used to evaluate the system's attributes. Additionally, the system's performance indicators (including turnaround time) were obtained by evaluating Surveillance system attributes, each being scored on a scale of 1 to 5 (very poor to excellent performance).ResultsA total of 1731 nasopharyngeal and oropharyngeal samples were collected from each suspected influenza case in 2019 from fourteen (14/14) sentinel sites of the influenza surveillance system in Tanzania. Laboratory-confirmed cases were 21.5% (373/1731) with a predictive value positive of 21.7%. The majority of patients (76.1%) tested positive for Influenza A. Thirty-seven percent of patients' results met the required turnaround time, and 40% of case-based forms were incompletely filled. Although the accuracy of the data was good (100%), the consistency of the data was below (77%) the established target of ≥ 95%.ConclusionThe overall system performance was satisfactory in conforming with its objectives and generating accurate data, with an average performance of 100%. The system's complexity contributed to the reduced consistency of data from sentinel sites to the National Public Health Laboratory of Tanzania. Improvement in the use of the available data could be made to inform and promote preventive measures, especially among the most vulnerable population. Increasing sentinel sites would increase population coverage and the level of system representativeness.

BackgroundThe emergence of HIV drug resistance mutations (DRMs) is of significant threat to achieving viral suppression (VS) in the quest to achieve global elimination targets. We hereby report virologic outcomes and patterns of acquired DRMs and its associated factors among adolescents and young adults (AYA) from a broader HIV drug resistance surveillance conducted in Tanzania.MethodsData of AYA was extracted from a cross-sectional study conducted in 36 selected facilities using a two-stage cluster sampling design. Dried blood spot (DBS) samples were collected and samples with a viral load (VL) ≥1000 copies/mL underwent genotyping for the HIV-1 pol gene. Stanford HIV database algorithm predicted acquired DRMs, Fisher's exact test and multivariable logistic regression assessed factors associated with DRMs and VS, respectively.FindingsWe analyzed data of 578 AYA on antiretroviral therapy (ART) for 9-15 and ≥ 36 months; among them, 91.5% and 88.2% had VS (VLConclusionsVS amongst AYA is lower than the third UNAIDs target. Additionally, a high prevalence of ADR and high levels of circulating clinically relevant DRMs may compromise the long-term VS in AYA. Furthermore, the first VL result of ≥1000copies/ml after ART initiation is a significant risk factor for developing DRMs. Thus, strict VL monitoring for early identification of treatment failure and genotypic testing during any ART switch is recommended to improve treatment outcomes for AYA.

Abstract 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

Summary: Background: Multi-drug resistant (MDR) bacteria pose a major global threat to public-health and are of particular concern to hospitalized intensive care unit (ICU) patients. This study aimed at addressing the burden of MDR and the associated factors at admission to ICU. Methods: This was a cross-sectional study conducted at the ICU of a tertiary hospital in Tanzania. Rectal and anterior nares swabs were collected within 48 hours of ICU admission to screen for extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-PE) and meticillin-resistant Staphylococcus aureus (MRSA), respectively. Results: The proportion of fecal carriage for ESBL-PE at admission to ICU was 54.54% (95% CI, 47.52–61.39), and nasal carriage for MRSA was 9.32% (95%CI, 5.67–14.93). The nasal MRSA colonization (OR = 1.52) and fecal carriage for ESBL-PE (OR=1.38) were more likely in participants who had received antibiotics before ICU admission than not, but association was not statistically significant. Hospitalization for ≥2 days (OR=1.18) was associated with fecal carriage of ESBL-PE, though not statistically significant. Overall, 66% and 73.5% of patients received antibiotics before and upon admission to ICU, respectively. Ceftriaxone, metronidazole and meropenem were commonly prescribed antibiotics. More than 84% of Enterobacterales were resistant to ciprofloxacin and trimethoprim-sulfamethoxazole, and 2.90% were resistant to meropenem. MRSA isolates showed a high rate of resistance to gentamicin and erythromycin. Conclusion: MDR bacteria are common in patients admitted to ICU. To reduce the risk associated with MDR, we recommend use of simple screening methods to screen for MDR at ICU admission as part of infection control and prevention.

Abstract 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.

Abstract 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. Stillbirth adversely affects pregnancy outcomes in low- and middle-income countries (LMICs). Viral infections have been implicated as one of the causes of stillbirths. Despite high rates of stillbirths and high viral prevalence in LMICs, there is limited information regarding their association. This study investigated the magnitude of herpes simplex 2 virus (HSV-2) and human cytomegalovirus (HCMV) among women with macerated stillbirth. Methods. A cross-sectional hospital-based study was conducted involving 279 women with macerated stillbirth between July and August 2018 at different health facilities in Mwanza, Tanzania. Detection of HSV-2 was done by immunochromatographic test while that of HCMV was done using enzyme-linked immunosorbent assay (ELISA). Descriptive data analysis was done using STATA version 13. Results. A total of 28 (10.04%, 95% CI: 6.8-13.9) tested positive for HSV-2 IgG antibodies with only 4 (1.43%, 95% CL: 0.3-2.8) testing positive for HSV-2 IgM antibodies. HCMV IgG antibodies were detected in 131 (77.98%, 95% CI: 71-84) of 168 women tested. By multivariate logistic regulation analysis, advanced age (OR: 0.93, 95% CI: 0.87-0.99, p=0.025) was significantly associated with negative HSV-2 IgG antibodies. By log multinomial regression analysis, only urban residence (RRR.4.43: 95% CI 1.53-12.80, p=0.006) independently predicted HCMV IgG seropositivity among women with stillbirth. Twenty-one (30.9%) of women with positive HCMV IgG antibodies had low avidity index (

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. 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.

A host cellular transmembrane protein, SERINC5, inhibits HIV-1 infectivity when incorporated into progeny virions. Recent studies suggest that certain Envelope glycoproteins can resist SERINC5-mediated restriction. However, the underlying mechanism of Envelope glycoprotein-mediated resistance to SERINC5 restriction remains unclear. Here, we investigated the extent of sensitivity of patient-derived HIV-1 Envelope sequences to SERINC5-mediated restriction and examined Envelopes’ characteristics in relation to SERINC5. A nef-deficient HIV-1 reporter was pseudotyped with Envelope sequences isolated from a total of 50 Tanzanians infected with non-B HIV-1 subtypes in the presence and absence of SERINC5 expression. The infectivity of resultant pseudoviruses was differentially reduced by SERINC5 by a median of 5.1-fold (IQR: 3.2–8.6) including five outliers showing ≥20-fold reduction, whereas the pseudovirus with the control NL4-3 envelope was reduced by 64-fold. The pseudovirus sensitivity to SERINC5-mediated restriction differed significantly among the subtypes of the envelope sequences but was not associated with any other Envelope characteristics or clinical parameters tested. Within some hosts, the pseudovirus sensitivity to SERINC5 varied substantially among Envelope sequences, with sensitive ones (as defined by ≥20-fold reduction) being underrepresented. Analysis of chimeric constructs between intra-host clones revealed that both N- and C-terminus of the Envelope sequences were responsible for SERINC5-mediated restriction. Taken together, these results demonstrate that the majority of naturally occurring Envelope sequences across multiple subtypes are relatively less sensitive to SERINC5-mediated restriction of infectivity and that naturally occurring polymorphisms at N- and C-terminal parts are important for this sensitivity. IMPORTANCE Pathogenesis of HIV-1 is enhanced through several viral-encoded proteins that counteract a range of host restriction molecules. HIV-1 Nef counteracts the cell membrane protein SERINC5 by downregulating it from the cell surface, thereby enhancing virion infectivity. Some subtype B reference Envelope sequences have shown the ability to bypass SERINC5 infectivity restriction independent of Nef. However, it is not clear if and to what extent circulating HIV-1 strains can exhibit resistance to SERINC5 restriction. Using a panel of Envelope sequences isolated from 50 Tanzanians infected with non-B HIV-1 subtypes, we show that the lentiviral reporters pseudotyped with patient-derived Envelopes have reduced sensitivity to SERINC5 and that this sensitivity differed among viral subtypes. Moreover, we found that SERINC5 sensitivity within patient-derived Envelopes can be modulated by separate regions, highlighting the complexity of viral/host interactions. [ABSTRACT FROM AUTHOR]