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Background: HIV-syphilis co-infection is a combination that enhances rapid progression of early syphilis or late latent syphilis to neurosyphilis and can cause catastrophic neurological complications. In studies in Mwanza, syphilis affects ~8% of healthy outpatients, and older studies have suggested that up to 23.5% of HIV-syphilis co-infected patients also have neurosyphilis. The study aimed at determining the prevalence of syphilis, neurosyphilis and associated factors among HIV infected patients attending Bugando Medical Center.Methods: This was a cross sectional study in which HIV infected patients who were hospitalized or attending the outpatient Care and Treatment Clinic (CTC) were interviewed using structured questionnaire and screened for syphilis using serum Treponema Pallidum hemagglutination assay (TPHA). We included all HIV-infected persons aged 18 years and above who consented. Blood was also taken for CD4+ T cells and viral load. Those who were found to have syphilis underwent neurological examination for any neurologic deficit and offered lumbar puncture.Results: The prevalence of syphilis in HIV infected patients was found to be 9.6%. The majority of these were female (72.5%) and median age was 42 years [interquartile range, 32-50]. Most patients were on ART (99.4%).The majority of participants with syphilis (89.2%) reported not knowing that they had syphilis, and had not previously been treated. One hundred forty one participants with syphilis had neurological examinations performed, 4 of whom had abnormal findings that necessitated that they undergo lumbar puncture. One of these had confirmed neurosyphilis.Conclusion: The high prevalence of syphilis in HIV infected patients indicates that there is a need to increase efforts in targeting this population to reduce sexually transmitted infections. Screening for syphilis should be done for all HIV patients given the high prevalence of the infection and the risk that aggressive forms of neurosyphilis can occur despite recovery of CD4+Tcell counts in untreated syphilis.

Background Tanzania has a high prevalence (7.17%) of chronic hepatitis B infection. Mother to Child transmission is very common, resulting in high rate of chronic infections. Currently, there is no screening program for HBV in pregnant women. This study investigated the prevalence and risk factors for chronic HBV infection in pregnant women in a tertiary hospital in Mwanza, Tanzania. Methods Seven hundred and forty-three women attending antenatal care and/or delivering at the Bugando Medical Centre were enrolled. All answered a questionnaire on sociodemographic and other risk factors and were tested for HBsAg using a rapid test. In HBsAg positive mothers, maternal blood and umbilical cord blood samples collected after delivery were analyzed for serological (HBsAg, HBeAg and anti-HBe) and virologic (HBV-DNA viral load and genotype) markers. All their babies were vaccinated within 24 h of delivery. The children were followed up at 3 years of age. Data was analyzed using the Mann-Whitney U-test, independent sample T-test and logistic regression. Results Of the 743 participants, 22 (3%) were positive for HBsAg, and 2 (9%) had detectable HBe-antigen. Low condom use was the only statistically significant risk factor for chronic HBV infection (OR = 3.514, 95%CI = 1.4–8.0). Of 14 maternal blood samples genotyped, 10 (71%) were genotype A and 4 (29%) were genotype D. HBV-DNA was detected in 21/22 samples, with a median of 241 IU/ml (range: 27.4–25.9 × 107 IU/ml). Five (33%) of 15 available cord blood samples were positive for HBsAg and 10 (67%) were negative. At follow-up, one child showed chronic HBV infection characteristics, one had anti-HBs level of 7 mIU/ml and 5/7(71%) had protective anti-HBs levels (> 10 mIU/ml). Conclusion This cohort of pregnant women showed a lower-intermediate prevalence of HBV of 3%. In the 3 years follow-up only 1 out of 7 children showed evidence of chronic HBV infection. The child’s mother with high viral load (25.9 × 107 IU/ml), was positive for HBeAg with a high degree of sequence similarity suggesting vertical transmission. These results highlight a need for improved diagnosis and treatment of HBV infection in pregnant women in Tanzania, in order to prevent vertical transmission.

Introduction Sub-Saharan African countries are introducing integrase strand transfer inhibitors (INSTIs) in their ART programmes as the preferred first-line regimen, and dolutegravir is the INSTI of choice due to its potency, tolerability and high genetic barrier to resistance. Dolutegravir was introduced into the first-line ART regimen in Tanzania in 2019. However, there is a paucity of data on the occurrence of mutations in HIV lineages circulating in Tanzania. This study aimed to determine the prevalence of INSTI primary resistance mutations in Tanzanian patients exposed to ART but not INSTIs. Methods Plasma samples from 50 INSTI-naive patients failing first- or second-line ART [median (IQR) age: 40 (21.93–46.41) years; 68% women] were subjected to Sanger sequencing of the HIV integrase gene. Participants had been on ART for a median (IQR) duration of 7.32 (4.73–9.29) years, with 80% and 20% failing first- and second-line ART, respectively. Results No major INSTI mutations were found, but 2 (4%) participants had the accessory mutation T97A. Using the REGA HIV-1 subtyping tool, HIV subtype A1 (53.1%) was found to be dominant, followed by subtypes C (30.6%) and D (16.3%). Conclusions This study found no current evidence for transmitted resistance against INSTIs among unexposed patients failing ART and supports the scale-up of INSTI-based regimens. However, the presence of accessory mutations calls for the surveillance of INSTI resistance mutations to ensure that the anticipated long-term desired outcomes are achieved.

Background Ebola vaccine development was accelerated in response to the 2014 Ebola virus infection outbreak. This phase 1 study (VAC52150EBL1004) assessed safety, tolerability, and immunogenicity of heterologous 2-dose Ad26.ZEBOV, MVA-BN-Filo vaccination regimens in the Lake Victoria Basin of Tanzania and Uganda in mid-level altitude, malaria-endemic settings. Methods Healthy volunteers aged 18–50 years from Tanzania (n = 25) and Uganda (n = 47) were randomized to receive placebo or active vaccination with Ad26.ZEBOV or MVA-BN-Filo (first vaccination), followed by MVA-BN-Filo or Ad26.ZEBOV (second vaccination) dose 2, respectively, with intervals of 28 or 56 days. Results Seventy-two adults were randomized to receive vaccine (n = 60) or placebo (n = 12). No vaccine-related serious adverse events were reported. The most frequent solicited local and systemic adverse events were injection site pain (frequency, 70%, 66%, and 42% per dose for MVA-BN-Filo, Ad26.ZEBOV, and placebo, respectively) and headache (57%, 56%, and 46%, respectively). Adverse event patterns were similar among regimens. Twenty-one days after dose 2, 100% of volunteers demonstrated binding antibody responses against Ebola virus glycoprotein, and 87%–100% demonstrated neutralizing antibody responses. Ad26.ZEBOV dose 1 vaccination induced more-robust initial binding antibody and cellular responses than MVA-BN-Filo dose 1 vaccination. Conclusions Heterologous 2-dose vaccination with Ad26.ZEBOV and MVA-BN-Filo against Ebola virus is well tolerated and immunogenic in healthy volunteers. Clinical trials registration NCT02376400., This phase 1 study demonstrated that heterologous prime-boost vaccination with Ad26.ZEBOV and MVA-BN-Filo Ebola vaccines at intervals of 28 or 56 days was well tolerated and immunogenic in healthy African adult volunteers.

Background Schistosomiasis increases the risk of human immunodeficiency virus (HIV) acquisition in women by mechanisms that are incompletely defined. Our objective was to determine how the cervical environment is impacted by Schistosoma haematobium or Schistosoma mansoni infection by quantifying gene expression in the cervical mucosa and cytokine levels in cervicovaginal lavage fluid. Methods We recruited women with and those without S. haematobium infection and women with and those without S. mansoni infection from separate villages in rural Tanzania with high prevalences of S. haematobium and S. mansoni, respectively. Infection status was determined by urine and stool microscopy and testing for serum circulating anodic antigen. RNA was extracted from cervical cytobrush samples for transcriptome analysis. Cytokine levels were measured by magnetic bead immunoassay. Results In the village where S. haematobium was prevalent, 110 genes were differentially expressed in the cervical mucosa of 18 women with versus 39 without S. haematobium infection. Among the 27 cytokines analyzed in cervicovaginal lavage fluid from women in this village, the level of interleukin 15 was lower in the S. haematobium-infected group (62.8 vs 102.9 pg/mL; adjusted P = .0013). Differences were not observed in the S. mansoni-prevalent villages between 11 women with and 29 without S. mansoni infection. Conclusions We demonstrate altered cervical mucosal gene expression and lower interleukin 15 levels in women with S. haematobium infection as compared to those with S. mansoni infection, which may influence HIV acquisition and cancer risks. Studies to determine the effects of antischistosome treatment on these mucosal alterations are needed.

In the United Republic of Tanzania, the incidence of non-neonatal circumcision-related tetanus is probably underreported.We analysed charts and extracted information on outcome and wound location for non-neonatal cases of tetanus admitted to the intensive care unit of Bugando Medical Centre between 2001 and 2016.Bugando Medical Centre, which is one of four teaching referral hospitals in the United Republic of Tanzania, has a 13-bed intensive care unit that manages all admitted patients with tetanus. Within the United Republic of Tanzania, formal programmes of tetanus immunization are targeted at infants or women.From our inpatient logs, we identified six patients with non-neonatal tetanus among male patients with a recent history of circumcision. Only one of these patients had been circumcised within a subnational programme of voluntary medical male circumcision. The other five had been circumcised outside of the programme - e.g. at small rural dispensaries or by a traditional provider with no formal medical training. The six patients were aged 11-55 years and five (83%) of them died in hospital - all of overwhelming sepsis.Within the Tanzanian programme of voluntary medical male circumcision, education on wound hygiene probably helps to reduce the incidence of non-neonatal circumcision-related tetanus. The corresponding incidence among the boys and men who are circumcised beyond this subnational programme is probably higher. The training of all circumcision providers in wound care and a vaccination programme to ensure that male Tanzanians receive tetanus immunization post-infancy are recommended.En République-Unie de Tanzanie, l'incidence du tétanos non néonatal lié à la circoncision est probablement sous-estimée.Nous avons analysé des tableaux et extrait des informations concernant les suites et l'emplacement de la plaie des cas de tétanos non néonatal admis dans le service de soins intensifs du centre médical Bugando entre 2001 et 2016.Le centre médical Bugando, l'un des quatre hôpitaux centraux d'enseignement de la République-Unie de Tanzanie, dispose d'un service de soins intensifs doté de 13 lits qui prend en charge tous les patients admis avec le tétanos. Dans la République-Unie de Tanzanie, les programmes formels de vaccination contre le tétanos ciblent les nourrissons ou les femmes.Nous avons relevé, dans nos registres d'hospitalisation, six patients atteints de tétanos non néonatal parmi les patients masculins ayant récemment subi une circoncision. Seul un de ces patients avait été circoncis dans le cadre d'un programme infranational de circoncision masculine médicale volontaire. Les cinq autres avaient été circoncis en-dehors de ce programme, par exemple dans de petits dispensaires ruraux ou par un praticien traditionnel sans formation médicale formelle. Ces six patients étaient âgés de 11 à 55 ans et cinq (83%) d'entre eux sont décédés à l'hôpital, tous de septicémie.Dans le cadre du programme tanzanien de circoncision masculine médicale volontaire, l'éducation à l'hygiène de la plaie contribue probablement à réduire l'incidence du tétanos non néonatal lié à la circoncision. L'incidence correspondante chez les garçons et les hommes qui sont circoncis en-dehors de ce programme infranational est probablement plus importante. La formation en matière de soin des plaies de toutes les personnes qui pratiquent des circoncisions et la mise en place d'un programme de vaccination permettant aux Tanzaniens de bénéficier de vaccins contre le tétanos après la petite enfance sont recommandées.En la República Unida de Tanzania, es posible que no se comunique la incidencia del tétanos relacionado con la circuncisión no neonatal.Hemos analizado gráficos y extraído información sobre las consecuencias y la localización de la herida para los casos no neonatales de tétanos ingresados en la unidad de cuidados intensivos del Bugando Medical Centre entre 2001 y 2016.El Bugando Medical Centre, uno de los cuatro hospitales de referencia en la República Unida de Tanzania, cuenta con una unidad de cuidados intensivos de 13 camas que se ocupa de todos los pacientes ingresados con tétanos. En la República Unida de Tanzania, los programas oficiales de vacunación contra el tétanos están orientados a infantes o mujeres.A partir de los registros de pacientes hospitalizados, se identificaron a seis pacientes con tétanos no neonatal entre los pacientes varones con un historial reciente de circuncisión. Solo uno de estos pacientes había sido circuncidado dentro de un programa subnacional para la circuncisión masculina voluntaria médica. Los otros cinco habían sido circuncidados fuera del programa, por ejemplo, en pequeños dispensarios rurales o atendidos por un proveedor tradicional sin formación médica oficial. Los seis pacientes tenían entre 11 y 55 años de edad y cinco (83%) de ellos murieron en el hospital, todos a causa de una sepsis incontenible.Dentro del programa de Tanzania para la circuncisión masculina voluntaria médica, probablemente la educación sobre la higiene de las heridas ayude a reducir la incidencia del tétanos relacionado con la circuncisión no neonatal. Es probable que la incidencia correspondiente entre los niños y hombres circuncidados fuera de este programa subnacional sea mayor. Se recomienda la formación de todos los proveedores de circuncisión en el cuidado de heridas y un programa de vacunación para asegurar que los varones de Tanzania sean vacunados contra el tétanos después de la infancia.من المرجح وجود قصور في الإبلاغ عن حدوث الإصابة بالكزاز (التيتانوس) غير المرتبط بالولادة في جمهورية تنزانيا المتحدة.قمنا بتحليل الرسوم البيانية واستخلاص المعلومات المتعلقة بنتائج ومواقع الجروح الخاصة بحالات الإصابة بالكزاز في غير حالات الأطفال حديثي الولادة الخاضعة للعناية المركزة في مركز بوغاندو الطبي بين عامي 2001 و2016.يُعد مركز بوغاندو الطبي واحدًا من أربع مستشفيات جامعية تستقبل التحويلات الطبية في جمهورية تنزانيا المتحدة، كما أنه مجهز بوحدة للعناية المركزة تشتمل على 13 سريرًا للتعامل مع جميع حالات الإصابة بالكزاز التي يتم قبولها. وفي جمهورية تنزانيا المتحدة، تستهدف البرامج الرسمية لتمنيع الكزاز الرضع أو النساء.حددنا من بين سجلات المرضى الداخليين لدينا ستة حالات إصابة بالكزاز من غير الحالات المرتبطة بالأطفال حديثي الولادة وذلك بين المرضى الذكور الذين خضعوا مؤخرًا للختان. ولم يخضع سوى مريض فقط من بين هؤلاء المرضى للختان في إطار برنامج دون وطني لختان الذكور التطوعي. وقد تم ختان الخمسة الآخرين خارج نطاق البرنامج – على سبيل المثال في المستوصفات الريفية الصغيرة أو من قبل مقدم تقليدي للخدمات الطبية دون تدريب طبي رسمي. وتتراوح أعمار المرضى الستة ما بين 11 إلى 55 عامًا، وتوفي خمسة منهم (‏83‏%) في المستشفى بسبب الإنتان الشديد.من المرجح أن تفيد التوعية بشأن نظافة الجروح في الحد من الإصابة بالكزاز الناتج عن الختان وغير المرتبط بحديثي الولادة، وذلك في إطار البرنامج التنزاني للختان الطبي التطوعي للذكور. ومن المرجح أن تكون النسبة المقابلة بين الأولاد والرجال الذين يتم ختانهم خارج هذا نطاق البرنامج دون الوطني أعلى. ويوصى بتدريب جميع القائمين على إجراء الختان على كيفية العناية بالجروح وبرنامج التطعيم لضمان حصول الذكور التنزانيين على التمنيع ضد الكزاز بعد مرحلة الطفولة.在坦桑尼亚联合共和国,与非新生儿割礼相关的破伤风发病率可能少报了。.我们分析了关于 2001 年至 2016 年间入住布坎多医疗中心 (Bugando Medical Centre) 重症监护病房的非新生儿破伤风病例的治疗效果和伤口位置的图表,并提取了信息。.作为坦桑尼亚联合共和国四家教学类转诊医院之一的布坎多医疗中心 (Bugando Medical Centre) 拥有 13 个床位的重症监护病房,管理所有入院的破伤风患者。坦桑尼亚联合共和国正式的破伤风免疫计划目标人群是婴儿或女性。.根据我们住院患者记录,我们在近期进行过割礼的男性患者中确定了六位非新生儿破伤风患者。其中只有一名患者是通过地方性自愿医疗男性割礼计划实施割礼的。其余五人均非通过该计划实施割礼 – 例如:通过小型的农村诊疗所,或通过没有经过正式医疗培训的传统提供者。这六位患者年龄在 11–55 岁之间,其中五人 (83%) 在医院死亡——全部为爆发性败血症。.坦桑尼亚联合共和国自愿医疗男性割礼计划以及伤口卫生教育可能有助于降低非新生儿与割礼相关的破伤风患病率。未通过这项地方性计划实施割礼的男孩和男性的相应患病率可能会增加。应面向所有割礼提供者进行关于伤口护理的培训,并推荐实施一项可确保坦桑尼亚男性居民在婴儿期之后的阶段接受破伤风免疫的免疫接种计划。.Показатели заболеваемости столбняком, связанным с обрезанием крайней плоти, проводимым не над младенцами, в Объединенной Республике Танзания, вероятно, являются заниженными.Мы проанализировали графики и получили данные об исходах и местоположении раны для случаев заболеваемости столбняком у пациентов старше младенческого возраста, поступивших в отделение интенсивной терапии Медицинского центра Бугандо в период с 2001 по 2016 год.Медицинский центр Бугандо, который является одной из четырех учебных многопрофильных больниц в Объединенной Республике Танзания, располагает отделением интенсивной терапии на 13 койко-мест, куда поступают все пациенты со столбняком. Официальные программы иммунизации против столбняка, действующие на территории Объединенной Республики Танзания, нацелены на детей или женщин.На основе информации, полученной из наших стационарных журналов, мы выявили шесть пациентов старше младенческого возраста со столбняком среди пациентов мужского пола с обрезанием в недавнем анамнезе. Только один из этих пациентов был обрезан в рамках субнациональной программы добровольного мужского медицинского обрезания. Остальные пять были обрезаны вне программы, например в небольших сельских диспансерах или традиционными специалистами по обрезанию крайней плоти без официального медицинского образования. Шесть пациентов были в возрасте 11–55 лет, из них пять (83%) умерли в больнице — все по причине развития генерализованного сепсиса.Проведение обучения по обработке и гигиене раны в рамках танзанийской программы добровольного медицинского обрезания крайней плоти у мужчин, вероятно, способствует снижению заболеваемости столбняком в возрасте старше младенческого, связанным с проведением обрезания. Соответствующая заболеваемость среди мальчиков и мужчин, прошедших обрезание вне этой субнациональной программы, вероятно, выше. Рекомендуется обучать всех специалистов по обрезанию крайней плоти у мужчин надлежащей обработке и лечению ран, а также соблюдать программы вакцинации для обеспечения того, чтобы мужчины Танзании в раннем детстве проходили иммунизацию от столбняка.

Background Heterosexual transmission is the main driver of the HIV epidemic in Tanzania. Only one estimate of the incidence rate of intra-marital HIV seroconversion in Tanzania has been reported and was derived from data collected between 1991 and 1995. Moreover, little is known about the specific risk factors for intra-marital seroconversion in Tanzania. Improved evidence around factors that increase the risk of HIV transmission to a serodiscordant spouse is needed to develop and improve evidence-based interventions. We sought to investigate the rate of intra-marital HIV seroconversion among HIV sero-discordant couples in Tanzania as well as its associated risk factors. Methods We identified all HIV positive individuals in the TAZAMA HIV-serosurvey cohort and followed up their serodiscordant spouse from 2006 to 2016. The rate of seroconversion was analyzed by survival analysis using non-parametric regressions with exponential distribution. Results We found 105 serodiscordant couples, 14 of which had a seroconverting spouse. The overall HIV-1 incidence rate among spouses of people with HIV-1 infection was 38.0 per 1000 person/years [22.5–64.1]. Notably, the HIV-1 incidence rate among HIV-1 seronegative male spouses was 6.7[0.9–47.5] per 1000 person/years, compared to 59.3 [34.4–102.1] per 1000 person/years among female spouses. Sex of the serodiscordant spouse was the only significant variable, even after adjusting for other variables (Hazard rate = 8.86[1.16–67.70], p = 0.036). Conclusions Our study suggests that rates of HIV-1 seroconversion of sero-discordant partners are much higher within marriage than in the general population in Tanzania. The major risk factor for HIV-1 seroconversion is sex of the serodiscordant spouse, with female spouses being at very high risk of acquiring HIV infection. This suggests that future programs that target serodiscordant couples could be a novel and effective means of preventing HIV-1 transmission in Tanzania.

Background Current World Health Organization (WHO) guidelines recommend annual mass drug administration using praziquantel in areas with high schistosome endemicity. Yet little is known about incidence and reinfection rates after treatment in women with frequent exposure to schistosomes. We sought to quantify response to anti-schistosome treatment and incident S. mansoni infections in a cohort of rural women living in a schistosome-endemic area of northwest Tanzania. Methods and principal findings We enrolled women with and without S. mansoni infection into a 12-month longitudinal cohort. Every 3 months, women were tested for schistosome infection using microscopic examinations for ova on filtered urine, Kato Katz slides, and serum Circulating Anodic Antigen (CAA). Those with schistosome infection received treatment with praziquantel 40 mg/kg according to the standard of care. We studied 35 women who were S. mansoni positive by stool microscopy and 46 women without schistosome infection who returned for at least one follow-up. Of the women who were initially infected, 14 (40%) were schistosome-positive at a follow-up visit. Four women developed incident infections, for a cumulative incidence of 8.7% and incidence rate of 0.99 per 100 person-months throughout the year among initially uninfected women. Only 3 women were egg-positive at any follow-up. Women with persistent, recurrent, or incident infection during the study period were significantly younger (p = 0.032) and had fewer children than women who remained uninfected or those who cleared the infection and did not experience recurrence (p = 0.003). Having fewer children remained significant after controlling for age (p = 0.023). There was no difference in initial intensity of infection by CAA or stool egg count, HIV status, or socioeconomic status. Although most water contact behaviors were comparable between the two groups, women with recurrent or incident schistosome infections were significantly more likely to have recently swum in the lake (p = 0.023). Conclusions Our data suggests that annual praziquantel treatment reduces intensity of schistosome infections but is insufficient in providing stable parasite eradication in over a third of women in endemic communities. Furthermore, microscopy lacks adequate sensitivity to evaluate efficacy of treatment in this population. Our work demonstrates that further investigation into treatment efficacy and reinfection rates is warranted and suggests that increased frequency of praziquantel treatment is needed to improve cure rates in high-risk populations., Author summary Schistosomiasis is a parasitic infection transmitted through contaminated water that primarily affects the gastrointestinal and urogenital tracts. Previous studies in Tanzania have shown that adult women infected with schistosomes also have a higher risk of contracting HIV. Although it is recommended that people living in areas where they are exposed to schistosomes be treated with praziquantel once a year, the rate of new infections or reinfection after treatment in adult women is not known. We followed a group of schistosome-infected women and an uninfected control group for 12 months. They were tested for schistosomes every 3 months, and treated with praziquantel if they were infected. Over 40% of the women tested positive for schistosome infection at some point during the follow-up period, and the majority of them were from the group that was infected at the beginning of the study. These women may not have fully cleared the infection after one treatment, or they may be more susceptible to reinfection due to variations in their immune systems. Further studies are recommended to investigate whether a higher frequency of treatment is needed to control schistosome infection in adult women, especially given that reducing schistosome infection may help to reduce HIV risk in populations similar to ours.

Background Schistosoma sp. infection has been shown to interact with HIV-1 by modifying susceptibility to the virus and impacting AIDS outcome, but very little is known about the potential impact of Schistosoma sp. infection on the efficiency of antiretroviral treatment (ART) in HIV-1 infected individuals. One study suggested increased immunological failure in patients infected with schistosomes compared to those uninfected. To our knowledge, no report exists on the virological response to ART in schistosome-infected individuals. In addition, viral load in HIV-1 infected individuals changes over the course of the HIV infection. This study assessed the impact of HIV-1/Schistosoma sp. co-infections on viral load in people with immunological failure on ART, taking into account the duration of HIV-1 infection. Methods We enrolled HIV-1 infected Tanzanian adults over 18 years of age who had used first line ART for more than 6 months and were identified to have immunological failure by the WHO criteria (50% drop from peak CD4 count, or CD4 count equal to or below baseline after 6 months of ART, or CD4 count below 100cells/mm3 after 1 year of ART). Patients were also tested for schistosome infection by microscopy for ova in urine and stool and by circulating anodic antigen (CAA) levels in serum. The duration of HIV-1 infection was calculated using baseline CD4+ T-cell (CD4) counts determined at enrollment. Univariable and multivariable analyses were conducted to compare viral loads in schistosome infected and uninfected patients. Results A total of 188 patients were enrolled. After univariable analysis, female sex, lower peak CD4 counts, lower current CD4 counts, anemia, and shorter time infected with HIV-1 were all significantly associated with higher viral load. Schistosome infection was not associated with viral load even after adjusting for sex, current CD4 counts and duration of HIV-1 infection. Conclusions The current study of HIV-infected patients with immunological failure on ART suggests that once ART is introduced, ART is the dominant driver of viral load and schistosome infection may no longer have an impact.

Summary Background Male circumcision is being widely deployed as an HIV prevention strategy in countries with high HIV incidence, but its uptake in sub-Saharan Africa has been below targets. We did a study to establish whether educating religious leaders about male circumcision would increase uptake in their village. Methods In this cluster randomised trial in northwest Tanzania, eligible villages were paired by proximity (

Schistosome worms infect over 200 million people worldwide. They live in the host’s bloodstream and alter host immunity. Epidemiological data suggest that males and females have different responses to schistosome infection, but the effect of sex on systemic response is undetermined. Our objective was to characterize differences in peripheral blood transcriptional profiles in people with or without active S. haematobium infection, and to determine whether this signature differs between males and females. Messenger RNA was isolated using poly(A) selection and sequenced on an Illumina Hi-Seq4000 platform. Transcripts were aligned to the human hg19 reference genome and counted with the HTSeq package. Genes were compared for differential expression using DESeq2. Ingenuity Pathway Analysis was used to identify gene networks altered in the presence of S. haematobium . We enrolled 33 participants from villages in rural Tanzania where S. haematobium is endemic. After correction for multiple comparisons, we observed 383 differentially-expressed genes between those with and without S. haematobium infection when sex was included as a covariate. Heat-mapping of the genes with greater than 1.5-fold differences in gene expression revealed clustering by S. haematobium infection status. Top networks included development, cell death and survival, cell signaling, and immunologic disease pathways. We observed a distinct whole blood transcriptional profile, as well as differences in men and women, with S. haematobium infection. Additional studies are needed to determine the clinical effects of these divergent responses. Attention to sex-based differences should be included in studies of human schistosome infection.

Background: Traditional microscopic examination of urine or stool for schistosome eggs lacks sensitivity compared to measurement of schistosome worm-derived circulating antigens in serum or urine. The ease and non-invasiveness of urine collection makes urine an ideal sample for schistosome antigen detection. In this study several user-friendly, lateral-flow (LF) based urine assays were evaluated against a composite reference that defined infection as detection of either eggs in urine or anodic antigen in serum. Method: In a Tanzanian population with a S. haematobium prevalence of 40–50% (S. mansoni prevalence

Background: In a 2008-10 study, we found a pretreatment HIV drug resistance (PDR) prevalence of 18.2% in patients at Bugando Medical Centre (BMC) in Mwanza, Tanzania. Objectives: To determine the prevalence of PDR and transmitted HIV drug resistance (TDR) in patients visiting the BMC from 2013 to 2015. Methods: Adult outpatients were sequentially enrolled into two groups, separated by whether they were initiating ART. Previous exposure to antiretroviral drugs, except for prevention of mother-to-child transmission, was an exclusion criterion. HIV pol sequences were analysed according to WHO guidelines for surveillance of PDR and TDR. Results: Two hundred and thirty-five sequences were analysed (138 ART initiators, 97 non-initiators). The prevalence of PDR was 4.7% (95% CI 2.6%-8.2%) overall, 3.1% (95% CI 1.1%-8.7%) for non-initiators and 5.8% (95% CI 3.0%-11.0%) for ART initiators. PDR to NNRTIs and nucleoside or nucelotide reverse transcriptase inhibitors was found in 3.0% (95% CI 1.5%-6.0%) and 1.7% (95% CI 0.7%-4.3%) of patients, respectively. Resistance to PIs was not observed. The prevalence of TDR was 6.0% (95% CI 3.6%-9.8%). Conclusions: Prevalence of PDR significantly decreased compared with 2008-10 and was below the WHO-defined threshold for triggering a public health response. National and systematic surveillance is needed to inform Tanzania's public health strategy.

Background Africa bears the burden of approximately 70% of global HIV infections and 90% of global schistosome infections. We sought to investigate the impact of schistosome infection at the time of HIV-1 seroconversion on the speed of HIV-1 disease progression, as measured by the outcome CD4+ T-cell (CD4) counts, Author summary Several studies had shown that people infected with schistosome parasites were at risk of getting HIV and that they may have higher HIV viral concentrations in their blood as well. The authors explored the impact of the parasite on HIV disease after infection, expecting that people co-infected with the parasite at time of HIV-infection would develop worse HIV outcomes than people who did not have the parasite. HIV seroconverters were identified among a large cohort tested regularly for HIV in northwest Tanzania and were followed-up in clinics to determine their CD4 + T-cells counts and mortality. The seroconverters’ stored blood samples were tested for infection with the parasite and outcomes were compared between seroconverters who were and were not infected with the parasites at the time that they became HIV-infected. The authors surprisingly found that people with the parasite experienced fewer negative outcomes of HIV than people who did not have the parasite. To the investigators’ knowledge, this is the first longitudinal study to find this result. Long-term immunological changes may explain this protective effect and more studies are recommended to explore this research question.

Schistosome worms infect over 200 million people worldwide. They live in the host’s bloodstream and alter host immunity. Epidemiological data suggest that males and females have different responses to schistosome infection, but the effect of sex on systemic response is undetermined. Our objective was to characterize differences in peripheral blood transcriptional profiles in people with or without active Schistosoma haematobium infection and to determine whether this signature differs between males and females. mRNA was isolated using poly(A) selection and sequenced on an Illumina Hi-Seq4000 platform. Transcripts were aligned to the human hg19 reference genome and counted with the HTSeq package. Genes were compared for differential expression using DESeq2. Ingenuity Pathway Analysis (IPA) was used to identify gene networks altered in the presence of S. haematobium. We enrolled 33 participants from villages in rural Tanzania where S. haematobium is endemic. After correction for multiple comparisons, we observed 383 differentially expressed genes between those with or without S. haematobium infection when sex was included as a covariate. Heat-mapping of the genes with >1.5-fold differences in gene expression revealed clustering by S. haematobium infection status. The top networks included development, cell death and survival, cell signaling, and immunologic disease pathways. We observed a distinct whole blood transcriptional profile, as well as differences in men and women, with S. haematobium infection. Additional studies are needed to determine the clinical effects of these divergent responses. Attention to sex-based differences should be included in studies of human schistosome infection.

Background Tetanus is a vaccine-preventable, neglected disease that is life threatening if acquired and occurs most frequently in regions where vaccination coverage is incomplete. Challenges in vaccination coverage contribute to the occurrence of non-neonatal tetanus in sub-Saharan countries, with high case fatality rates. The current WHO recommendations for the management of tetanus include close patient monitoring, administration of immune globulin, sedation, analgesia, wound hygiene and airway support [1]. In response to these recommendations, our tertiary referral hospital in Tanzania implemented a standardized clinical protocol for care of patients with tetanus in 2006 and a subsequent modification in 2012. In this study we aimed to assess the impact of the protocol on clinical care of tetanus patients and their outcomes. Methods and findings We examined provision of care and outcomes among all patients admitted with non-neonatal tetanus to the ICU at Bugando Medical Centre between 2001 and 2016 in this retrospective cohort study. We compared three groups: the pre-protocol group (2001–2005), the Early protocol group (2006–2011), and the Late protocol group (2012–2016) and determined associations with mortality by univariable logistic regression. We observed a significant increase in provision of care as per protocol between the Early and Late groups. Patients in the Late group had a significantly higher utilization of mechanical ventilation (69.9% vs 22.0%, p< 0.0001), provision of surgical wound care (39.8% vs 20.3%, p = 0.011), and performance of tracheostomies (36.8% vs 6.7%, 40%). Institution of a standardized tetanus management protocol, in accordance with WHO recommendations, decreased immediate mortality related to primary causes of death after tetanus. However, this was offset by an increase in death due to later ICU complications such as sepsis. Our results illustrate the complexity in achieving mortality reduction even in illnesses thought to require few critical care interventions. Improving basic ICU care and strengthening vaccination programs to prevent tetanus altogether are essential components of efforts to decrease the mortality caused by this lethal, neglected disease.

Introduction Little is known about hepatotoxicity in patients with schistosome and HIV co-infections. Several studies have reported increased liver enzymes and bilirubin levels associated with schistosome infection. We investigated whether HIV-infected adults on antiretroviral therapy who had S. mansoni co-infection had a higher prevalence of hepatotoxicity than those without. Methodology/Principal findings We determined the presence and grade of hepatotoxicity among 305 HIV-infected outpatients who had been on medium-term (3–6 months) and long-term (>36 months) antiretroviral therapy in a region of northwest Tanzania where S. mansoni is hyperendemic. We used the AIDS Clinical Trial Group definition to define mild to moderate hepatotoxicity as alanine aminotransferase, alanine aminotransferase, and/or bilirubin elevations of grade 1 or 2, and severe hepatotoxicity as any elevation of grade 3 or 4. We determined schistosome infection status using the serum circulating cathodic antigen rapid test and used logistic regression to determine factors associated with hepatotoxicity. The prevalence of mild-moderate and severe hepatotoxicity was 29.6% (45/152) and 2.0% (3/152) in patients on medium-term antiretroviral therapy and 19.6% (30/153) and 3.3% (5/153) in the patients on long-term antiretroviral therapy. S. mansoni infection was significantly associated with hepatotoxicity on univariable analysis and after controlling for other factors associated with hepatotoxicity including hepatitis B or C and anti-tuberculosis medication use (adjusted odds ratio = 3.0 [1.6–5.8], p = 0.001). Conclusions/Significance Our work demonstrates a strong association between S. mansoni infection and hepatotoxicity among HIV-infected patients on antiretroviral therapy. Our study highlights the importance of schistosome screening and treatment for patients starting antiretroviral therapy in schistosome-endemic settings. Additional studies to determine the effects of schistosome-HIV co-infections are warranted., Author summary Schistosoma sp. are parasitic worms that infect at least 218 million people worldwide. Over 90% of these individuals live in Africa, where HIV infection is also endemic. Schistosome worms lay eggs that damage the gastrointestinal and genitourinary tracts, causing extensive morbidity and mortality. Patients who have HIV and Schistosoma mansoni co-infections are at risk for damage to the liver due to both the effects of the schistosome parasite and the side-effects of antiretroviral therapy. However, little is known about the additional liver effects of schistosome infection in patients already taking antiretroviral therapy. Therefore, we conducted a study in northwest Tanzania, where our prior work has shown that approximately one-third of HIV-infected patients also have schistosome infections, to investigate the effect of co-infection with Schistosoma mansoni on liver damage in patients taking antiretroviral therapy. We studied 305 HIV-infected outpatients on medium and long-term antiretroviral therapy and determined both liver damage and S.mansoni infection in those patients. We found that among patients on antiretroviral therapy, those with HIV-schistosome co-infection were 3 times more likely to have liver damage than those with HIV infection alone. Our work shows the importance of screening and treating for Schistosoma mansoni to decrease the risk of liver damage in patients infected with HIV.

Aims Diabetes increases the risk of tuberculosis and the prevalence of diabetes is rising in tuberculosis-endemic regions such as sub-Saharan Africa. Resource-appropriate strategies for tuberculosis case finding among African adults with diabetes are needed. The aims of this study were to determine prevalence of tuberculosis and evaluate one screening strategy among adult Tanzanians with diabetes. Methods In this prospective cohort study, we evaluated a ‘cough-triggered’ strategy for tuberculosis case finding among adults with diabetes at our zonal hospital in Tanzania. All adults with diabetes and cough underwent further tuberculosis symptom assessment, and those with productive cough had sputum collected for microscopy and Mycobacterium tuberculosis culture. Results Between September 2011 and March 2012, 700 adults with diabetes attended our hospital. A total of 693 were enrolled, 121/693 (17.5%) had cough and 32/693 (4.6%) had at least two of the classic symptoms of tuberculosis. Of note, 87/121 (71.9%) of patients with cough could not produce sputum spontaneously. Nine patients were diagnosed with tuberculosis for a prevalence of 1299/100 000 (1.3%), sevenfold greater than the national average. Conclusions Tuberculosis is common among Tanzanian adults with diabetes, but tuberculosis case finding is challenging because of the high prevalence of non-productive cough. This low-cost, ‘cough-triggered’ tuberculosis case-finding strategy may serve as a reasonable first step for improving tuberculosis screening among adults with diabetes in sub-Saharan Africa.

Background The number of adults with diabetes mellitus is increasing worldwide, particularly in Asia and Africa. In sub-Saharan Africa, renal complications of diabetes may go unrecognized due to limited diagnostic resources. The prevalence of chronic kidney disease (CKD) among adult diabetics in sub-Saharan Africa has not been well described. Methods This study was conducted at the diabetes mellitus clinic of Bugando Medical Centre in Mwanza, Tanzania. A total 369 consecutive adult diabetic patients were enrolled and interviewed. Each patient provided a urine sample for microalbuminuria and proteinuria and a blood sample for serum creatinine level. Estimated glomerular filtration rate (eGFR) was calculated using the Cockroft-Gault equation. CKD was staged according to the Kidney Disease Improving Global Outcomes system. Results A total of 309 (83.7%) study participants had CKD; 295 (80.0%) had significant albuminuria and 91 (24.7%) had eGFR

Background.Limited information exists on the etiologies, clinical characteristics, and outcomes of meningitis among HIV-infected patients in Africa. We conducted a study to determine the etiology, clinical characteristics, and outcomes of meningitis among HIV-infected adults.Methods.A prospective cross-sectional hospital based study was conducted among HIV-infected patients aged ≥18 years admitted to the medical wards with symptoms and signs of meningitis. Sociodemographic and clinical information were collected using a standardized data collection tool. Lumbar puncture was performed to all patients; cerebrospinal fluid samples were sent for analysis.Results.Among 60 HIV-infected adults clinically diagnosed to have meningitis, 55 had CSF profiles consistent with meningitis. Of these, 14 (25.5%) had a laboratory-confirmed etiology while 41 (74.5%) had no isolate identified.Cryptococcus neoformanswas the commonest cause of meningitis occurring in 11 (18.3%) of patients followed byMycobacterium tuberculosis(6.7%). The in-hospital mortality was 20/55 (36.4%). Independent predictors of mortality were low baseline CD4 count and turbid CSF appearance.Conclusion.Cryptococcal meningitis is the most prevalent laboratory-confirmed etiological agent among adult HIV-infected patients with suspected meningitis admitted to medical wards in Western Tanzania. Mortality rate in this population remains unacceptably high. Improving diagnostic capacity and early treatment may help to decrease the mortality rate.

HIV-related renal dysfunction is associated with high mortality. Data on the prevalence of renal dysfunction among HIV-infected outpatients starting antiretroviral therapy (ART) in sub-Saharan Africa are limited. Recent recommendations to include the nephrotoxic drug tenofovir in first-line ART regimens make clarification of this issue urgent. We screened for renal dysfunction by measuring serum creatinine, proteinuria, and microalbuminuria in HIV-positive outpatients initiating ART in Mwanza, Tanzania. We excluded patients with pre-existing renal disease, hypertension, diabetes, or hepatitis C virus co-infection. Estimated glomerular filtration rates (eGFRs) were calculated by Cockroft-Gault and Modification of Diet in Renal Disease equations. Only 129 (36%) of 355 enrolled patients had normal eGFRs (grade 0 or 1) above 90 ml/min per 1.73 m. Grade 2 renal dysfunction (eGFR between 60 and 89 ml/min per 1.73 m) was present in 137 patients (38.6%), and 87 patients (25%) had grade 3 dysfunction (eGFR between 30 and 59 ml/min per 1.73 m). Microalbuminuria and proteinuria were detected in 72 and 36% of patients, respectively. Factors predictive of renal dysfunction in multivariate analysis included female sex [odds ratio (OR) 3.0, 95% confidence interval (1.8-5.1), P < 0.0001], BMI less than 18.5 [OR 2.3 (1.3-4.1), P = 0.004], CD4 T-cell count below 200 cells/μl [OR 2.3 (1.1-4.8), P = 0.04], and WHO clinical stage II or above [OR 1.6 (1.2-2.3), P = 0.001]. Renal dysfunction was highly prevalent in this population of HIV-positive outpatients initiating first ART in Tanzania. This highlights the critical and underappreciated need to monitor renal function in HIV-positive patients in sub-Saharan Africa, particularly given the increasing use of tenofovir in first-line ART.

Objectives? To describe the prevalence of distal sensory polyneuropathy (DSP), a complication of both advanced HIV disease and of antiretroviral therapy (ART), amongst Tanzanians with HIV, on and off ART (including stavudine) with CD4 counts above and below 200?cells/?l. Methods? We recruited participants attending ART clinic into four groups: >6?months ART exposure and (i) CD4? ?200?cells/?l (ART/CD4? ?200, respectively); ART-nai?½ve and (iii) CD4? ?200?cells/?l (noART/CD4? ?200, respectively). Primary outcome was DSP, as defined by presence of at least one symptom and one sign. Results? Of 326 evaluable participants, 81 (32 men, median age 38?years, median CD4 142?cells/?l) were enrolled in the ART/CD4? ?200, 81 (30 men, median age 37?years, median CD4 128?cells/?l) in noART/CD4? ?200. Numbness was the most commonly reported symptom. DSP prevalence ranged from 43.2% in ART/CD4? ?200. DSP was more common among men (adjusted odds ratio [aOR] 1.9, 95% confidence interval [CI] 1.2-3.3) and older participants (aOR 2.7, 95% CI 1.1-6.2 for age 40?+?vs.

OBJECTIVE: To describe the associations between socio-demographic, behavioural and clinical characteristics and the use of HIV voluntary counselling and testing (VCT) services among residents in a rural ward in Tanzania. METHODS: Eight thousand nine hundred and seventy participants from a community-based cohort were interviewed, provided blood for research HIV testing, and were offered VCT. Univariate and multivariate logistic regression was used to identify socio-demographic, clinical and behavioural factors associated with VCT use. RESULTS: Although 31% (1246/3980) of men and 24% (1195/4990) of women expressed an interest in the service, only 12% of men and 7% of women subsequently completed VCT. Socio-demographic factors, such as marital status, area of residence, religion and ethnicity influenced VCT completion among males and females in different ways, while self-perceived risk of HIV, prior knowledge of VCT, and sex with a high-risk partner emerged as important predictors of VCT completion among both sexes. Among males only, those infected with HIV for 5 years or less tended to self-select for VCT compared to HIV-negatives (adjusted odds ratio = 1.43; 95% CI: 0.99-2.14). This contributed to a higher proportion of HIV-positive males knowing their status compared to HIV-positive females. CONCLUSIONS: In this setting, a disproportionate number of HIV-positive women are failing to learn their status, which has implications for equitable access to onward referral for care and treatment services. Evidence that some high-risk behaviours may prompt VCT use is encouraging, although further interventions are required to improve knowledge about HIV risk and the benefits of VCT. Targeted interventions are also needed to promote VCT uptake among married women and rural residents.

OBJECTIVE: To compare short-term and long-term cardiovascular disease (CVD) risk scores and prevalence of metabolic syndrome in HIV-infected adults receiving and not receiving antiretroviral therapy (ART) to HIV-negative controls. METHODS: A cross-sectional study including 151 HIV-infected, ART-naive, 150 HIV-infected on ART and 153 HIV-negative adults. Traditional cardiovascular risk factors were determined by standard investigations. The primary outcome was American College of Cardiology/American Heart Association Atherosclerotic CVD (ASCVD) Risk Estimator lifetime CVD risk score. Secondary outcomes were ASCVD 10-year risk, Framingham risk scores, statin indication and metabolic syndrome. RESULTS: Compared with HIV-negative controls, more HIV-infected adults on ART were classified as high lifetime CVD risk (34.7% vs 17.0%, p CONCLUSIONS: HIV-infected ART-treated individuals have high lifetime cardiovascular risk, and this risk seems to develop rapidly in the first 3-4 years of ART as does the development of clusters of metabolic syndrome criteria. These data identify a new subgroup of low short-term/high-lifetime risk HIV-infected individuals on ART who do not currently meet criteria for CVD risk factor modification but require further study.

Objective In HIV-infected adults in sub-Saharan Africa, asymptomatic cryptococcal antigenemia at the time of antiretroviral therapy (ART) initiation is associated with more than 20% increased mortality. Provisional recommendations for treatment of asymptomatic cryptococcal antigenemia are neither well substantiated nor feasible in many resource-poor settings. After hospitals in Tanzania implemented a programme providing serum cryptococcal antigen (CrAg) screening with 4-week intensive fluconazole treatment for CrAg-positive patients, we were asked to assess the impact of this programme on mortality. Design In this retrospective operational research study, we documented 6-month outcomes of HIV-infected adults who had had CD4 cell counts less than 200 cells/μl at the time of starting ART and had been screened for cryptococcal antigenemia over a period of 15 months. Methods We randomly selected three CrAg-negative patients, matched for ART start date, for every CrAg-positive patient who had been identified and treated with the 4-week intensive fluconazole course. The primary outcome was 6-month mortality in CrAg-positive and CrAg-negative groups. Results Mortality of CrAg-positive HIV-infected adults who received short-course fluconazole was noninferior to CrAg-negative adults. At 6 months, 16 of 18 CrAg-positive and 46 of 54 CrAg-negative patients were alive [88.9% versus 85.1%, -3.9% absolute difference (one-sided 90% confidence interval +10.8%)]. No deaths in the CrAg-positive group seemed to be due to cryptococcal meningitis. Conclusion This study suggests that even short-course intensive fluconazole could reduce the mortality of patients with asymptomatic cryptococcal antigenemia. Further studies are needed to confirm if this dose is both optimal for patient survival and feasible for wide implementation in resource-poor settings where mortality of cryptococcal disease is highest.

Background Kaposi’s Sarcoma is the most common sarcoma and second most prevalent cancer seen in Tanzania. Little is known about Kaposi’s sarcoma in our setting as there is paucity of recent published data regarding this condition. This study describes the clinicopathological pattern and treatment outcome of Kaposi’s sarcoma at Bugando Medical Centre, a tertiary care hospital in northwestern Tanzania. Methods This was a prospective study of histologically confirmed Kaposi’s sarcoma that was conducted at Bugando Medical Center between July 2004 and June 2014. Results A total of 248 patients (M:F = 1.4:1) representing 2.4 % of all malignancies during the study period were enrolled into the study. The median age at presentation was 36 years. Females were younger than males (p = 0.04). Out of 248 patients, 122 (49.2 %) were HIV positive. Of these, 46 (37.7 %) were males and 76 (62.3 %) females. AIDS-related Kaposi’s sarcoma were younger than HIV negative Kaposi’s sarcoma patients (p = 0.011). Median duration of symptoms was 6 months. Kaposi’s sarcoma was the AIDS defining disease in 82 (67.2 %) patients while in the remaining 40 (32.8 %) it was diagnosed between 1 and 14 months after the initial diagnosis of AIDS. The lower limb was most frequently involved site in 28.9 % of patient. Females had more disseminated lesions compared with more localized lesions in the males (p = 0.001). The treatment modalities in this study included chemotherapy, radiotherapy, surgery and highly active antiretroviral therapy. Overall 126 (53.4 %) patients had significant improvement in quality of life at the end of 1 year follow up. Treatment related complication and mortality rates were 25.8 and 24.2 % respectively. Poor ACTG stage, CD4+ count

Background Limited data document sexually transmitted infections (STIs) among pregnant adolescents in sub-Saharan Africa, where prenatal screening typically includes only HIV and syphilis. Given that HIV incidence in this population is among the world9s highest, we sought to assess the prevalence and factors associated with STIs in a population of rural pregnant adolescents in Tanzania. Methods We enrolled 403 pregnant adolescent girls from 10 antenatal clinics near Mwanza, Tanzania. Girls answered structured interviews about sexual health and risk factors and were tested for six common STIs. Results 199 girls (49.4%) had at least one STI. Herpes Simplex Virus- Type 2 was most prevalent (139 girls, 34.5%), followed by trichomoniasis (54 girls, 13.4%), chlamydia (46 girls, 11.4%), gonorrhoea (27 girls, 6.7%), syphilis (21 girls, 5.2%) and HIV (30 girls, 4.7%). Of note, 53/199 (26.6%) of girls with laboratory-proven STIs were asymptomatic. On multivariable analysis, the presence of any STI was associated with being in a long-term (as opposed to short-term) relationship (OR=2.6 (1.4 to 4.9) p=0.004), younger age at first sexual debut (OR=0.9 per year (0.8 to 0.99), p=0.034), increasing age difference between the girl and her partner (OR=1.1 (1.0 to 1.1) per year, p=0.03) and history of prior pregnancy (OR=1.6 (1.0 to 2.6), p=0.04). Conclusions STIs affected half of rural pregnant adolescents in Tanzania. Our work demonstrates the urgent need to incorporate routine STI testing into antenatal care in Tanzania to prevent morbidity and mortality in young girls and their babies. We also identify behavioural and demographic risk factors that can be used to target interventions to those at highest risk.

Background: Sub-Saharan Africa has a high prevalence of hepatitis B virus (HBV) infections. Health care workers (HCWs) are at high risk of contracting HBV infection through their occupation. Vaccination of HCWs against HBV is standard practice in many countries, but is often not implemented in resource-poor settings. We aimed with this cross-sectional study to determine HBV prevalence, HCW vaccination status, and the risk factors for HCWs contracting HBV infection in Tanzania. Methods: We enrolled 600 HCWs from a tertiary Tanzanian hospital. Their demographics, medical histories, HBV vaccination details and risk factors for contracting blood-borne infections were collected using a standardized questionnaire. Serum samples were tested for HBV and hepatitis C virus (HCV) markers by ELISA techniques, PCR and an anti-HBs rapid test. HCWs were divided in two subgroups: those at risk of contracting HBV (rHCW 79.2 %) via exposure to potentially infectious materials, and those considered not at risk of contracting HBV (nrHCW, 20.8 %). Results: The overall prevalence of chronic HBV infection (HBsAg+, anti-HBc+, anti-HBs-) was 7.0 % (42/598). Chronic HBV infection was found in 7.4 % of rHCW versus 5.6 % of nrHCW(p-value = 0.484). HCWs susceptible to HBV (HBsAg-, anti-HBc-, anti-HBs-) comprised 31.3 %. HBV immunity achieved either by healed HBV infection (HBsAg-, anti-HBc+, anti-HBs+) or by vaccination (HBsAg-, anti-HBc-, anti-HBs+) comprised 36.5 % and 20.2 %, respectively. 4.8 % of participants had indeterminate results (HBsAg-, anti-HBc+, anti-HBc-IgM-, anti-HBs-). Only 77.1 % of HCWs who received a full vaccination course had an anti-HBs titer > 10 ml/U. An anti-HBs point-of-care test was 80.7 % sensitive and 96.9 % specific. There was a significantly higher risk for contracting HBV (anti-HBc+) among those HCW at occupational risk (rHCW) of older age (odds ratios (OR) in rHCW 3.297, p < 0.0001 vs. nrHCW 1.385, p = 0.606) and among those HCW being employed more than 11 years (OR 2.51, p < 0.0001***). HCV prevalence was low (HCV antibodies 1.2 % and HCV-RNA 0.3 %). Conclusions: Chronic HBV infection is common among Tanzanian HCWs. One third of HCWs were susceptible to HBV infection, highlighting the need for vaccination. Due to high prevalence of naturally acquired immunity against HBV pre-testing might be a useful tool to identify susceptible individuals.

IntroductionMillions of HIV-infected Africans are living longer due to long-term antiretroviral therapy (ART), yet little is known about glucose metabolism disorders in this group. We aimed to compare the prevalence of glucose metabolism disorders among HIV-infected adults on long-term ART to ART-naïve adults and HIV-negative controls, hypothesizing that the odds of glucose metabolism disorders would be 2-fold greater even after adjusting for possible confounders.MethodsIn this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years) attending an HIV clinic in Tanzania were enrolled in 3 groups: 153 HIV-negative controls, 151 HIV-infected, ART-naïve, and 150 HIV-infected on ART for ≥ 2 years. The primary outcome was the prevalence of glucose metabolism disorders as determined by oral glucose tolerance testing. We compared glucose metabolism disorder prevalence between each HIV group vs. the control group by Fisher's exact test and used multivariable logistic regression to determine factors associated with glucose metabolism disorders.ResultsHIV-infected adults on ART had a higher prevalence of glucose metabolism disorders (49/150 (32.7%) vs.11/153 (7.2%), pConclusionsHIV-infected adults on long-term ART had 5-fold greater odds of glucose metabolism disorders than HIV-negative controls but were rarely aware of their diagnosis. Intensive glucose metabolism disorder screening and education are needed in HIV clinics in sub-Saharan Africa. Further research should determine how glucose metabolism disorders might be related to immune reconstitution.

Cryptococcal meningitis (CM) is a leading cause of mortality among HIV-infected individuals in Africa. Poor outcomes from conventional antifungal therapies, unavailability of flucytosine, and difficulties administering 14 days of amphotericin B are key drivers of this mortality. Novel treatment regimes are needed. This study examines whether short-course high-dose liposomal amphotericin B (AmBisome), given with high dose fluconazole, is non-inferior (in terms of microbiological and clinical endpoints) to standard-dose 14-day courses of AmBisome plus high dose fluconazole for treatment of HIV-associated CM. This is an adaptive open-label phase II/III randomised non-inferiority trial comparing alternative short course AmBisome regimens. Step 1 (phase II) will compare four treatment arms in 160 adult patients (≥18 years old) with a first episode of HIV-associated CM, using early fungicidal activity (EFA) as the primary outcome: 1) AmBisome 10 mg/kg day one (single dose); 2) AmBisome 10 mg/kg day one and AmBisome 5 mg/kg day three (two doses); 3) AmBisome 10 mg/kg day one, and AmBisome 5 mg/kg days three and seven (three doses); and 4) AmBisome 3 mg/kg/d for 14 days (control); all given with fluconazole 1200 mg daily for 14 days. STEP 2 (phase III) will enrol 300 participants and compare two treatment arms using all-cause mortality within 70 days as the primary outcome: 1) the shortest course AmBisome regimen found to be non-inferior in terms of EFA to the 14-day control arm in STEP 1, and 2) AmBisome 3 mg/kg/d for 14 days (control), both given with fluconazole 1200 mg daily for 14 days. STEP 2 analysis will include all patients from STEP 1 and STEP 2 taking the STEP 2 regimens. All patients will be followed for ten weeks, and mortality and safety data recorded. All patients will receive consolidation therapy with fluconazole 400–800 mg daily and ART in accordance with local guidelines. The primary analysis (for both STEP 1 and STEP 2) will be intention-to-treat. ISRCTN10248064 . Date of Registration: 22 January 2014

Background Hepatocellular carcinoma is one of the most common cancers worldwide and its incidence is reported to be increasing in resource-limited countries. There is a paucity of published data regarding hepatocellular carcinoma in Tanzania, and the study area in particular. This study describes the clinicopathological profile of hepatocellular carcinoma in our local setting and highlights the challenging problems in the management of this disease. Methods This was a retrospective study of histopathologically confirmed cases of hepatocellular carcinoma seen at Bugando Medical Center between March 2009 and February 2013. Results A total of 142 patients (M: F = 2.2: 1) were studied representing 4.6% of all malignancies. The median age of patients was 45 years. Hepatitis B virus infection (66.2%) and heavy alcohol consumption (60.6%) were the most frequently identified risk factors for hepatocellular carcinoma. The majority of patients (88.0%) presented late with advanced stages. HBsAg was positive in 66.2% of the patients and Hepatitis C Virus antibody in 16.9%. Thirteen (9.2%) patients tested positive for HIV infection. Most patients (52.8%) had both right and left lobe involvement. The trabecular pattern (47.9%) was the most frequent histopathological type. None of patients had curative therapy because of the advanced nature of the disease. Coagulopathy (45.7%) was the most common complications. The overall mortality rate was 46.5% and it was significantly associated with comorbidity, HIV positivity, CD4+ count P Conclusions Hepatocellular carcinoma patients in this region are relatively young at diagnosis and the majority of them present late with an advanced stage and high rate of distant metastasis. Lack of awareness of the disease, poor accessibility to healthcare facilities, and lack of screening programs in this region may contribute to advanced disease at the time of diagnosis. There is a need for early detection, adequate treatment, and proper follow-up to improve treatment outcome.

BACKGROUND: The epidemics of HIV and hypertension are converging in sub-Saharan Africa. Due to antiretroviral therapy (ART), more HIV-infected adults are living longer and gaining weight, putting them at greater risk for hypertension and kidney disease. The relationship between hypertension, kidney disease and long-term ART among African adults, though, remains poorly defined. Therefore, we determined the prevalences of hypertension and kidney disease in HIV-infected adults (ART-naive and on ART >2 years) compared to HIV-negative adults. We hypothesized that there would be a higher hypertension prevalence among HIV-infected adults on ART, even after adjusting for age and adiposity. METHODS: In this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years old) attending an HIV clinic in Tanzania were enrolled in three groups: 1) HIV-negative controls, 2) HIV-infected, ART-naive, and 3) HIV-infected on ART for >2 years. The main study outcomes were hypertension and kidney disease (both defined by international guidelines). We compared hypertension prevalence between each HIV group versus the control group by Fisher's exact test. Logistic regression was used to determine if differences in hypertension prevalence were fully explained by confounding. RESULTS: Among HIV-negative adults, 25/153 (16.3%) had hypertension (similar to recent community survey data). HIV-infected adults on ART had a higher prevalence of hypertension (43/150 (28.7%), P = 0.01) and a higher odds of hypertension even after adjustment (odds ratio (OR) = 2.19 (1.18 to 4.05), P = 0.01 in the best model). HIV-infected, ART-naive adults had a lower prevalence of hypertension (8/151 (5.3%), P = 0.003) and a lower odds of hypertension after adjustment (OR= 0.35 (0.15 to 0.84), P = 0.02 in the best model). Awareness of hypertension was ≤ 25% among hypertensive adults in all three groups. Kidney disease was common in all three groups (25.6% to 41.3%) and strongly associated with hypertension (P 2 years had two-fold greater odds of hypertension than HIV-negative controls. HIV-infected adults with hypertension were rarely aware of their diagnosis but often have evidence of kidney disease. Intensive hypertension screening and education are needed in HIV-clinics in sub-Saharan Africa. Further studies should determine if chronic, dysregulated inflammation may accelerate hypertension in this population.

AIMS: In Tanzania approximately 25% of adolescents give birth and 50% more become sexually active during adolescence. We hypothesised that reproductive health education and services for adolescent girls are inaccessible and conducted this study to gain insights into their perceptions of sexually transmitted infections (STIs) and barriers to reproductive health service utilisation in rural Mwanza Tanzania. METHODS: We conducted nine focus groups among pregnant adolescents aged 15-20 years. Data were transcribed translated and coded for relevant themes using NVivo10 software for qualitative data analysis. RESULTS: Most participants were aware of the dangers of STIs to themselves and their unborn babies but did not perceive themselves as at risk of acquiring STIs. They viewed condoms as ineffective for preventing STIs and pregnancies and unnecessary for those in committed relationships. Stigma long waiting times and lack of privacy in the clinics discouraged adolescent girls from seeking reproductive health care. CONCLUSION: Reproductive health care for adolescent girls who are not pregnant is practically nonexistent in Tanzania. Healthcare access for pregnant young women is also limited. Targeted changes to increase clinic accessibility and to provide reproductive health education to all rather than only pregnant women have the potential to address these gaps.

Background Cryptococcal meningitis (CM) has a mortality rate of ∼70% among HIV-infected adults in low-income countries. Controlling intracranial pressure (ICP) is essential in CM, but it is difficult in low-income countries because manometers and practical ICP management protocols are lacking. Methods As part of a continuous quality improvement project, our Tanzanian hospital initiated a new protocol for ICP management for CM. All adult inpatients with CM are included in a prospective patient registry. At the time of analysis, this registry included data from 2 years before the initiation of this new ICP management protocol and for a 9-month period after. ICP was measured at baseline and at days 3, 7, and 14 by both manometer and intravenous (IV) tubing set. All patients were given IV fluconazole according to Tanzanian treatment guidelines and were followed until 30 days after admission. Results Among adult inpatients with CM, 32 of 35 patients (91%) had elevated ICP on admission. Cerebrospinal fluid pressure measurements using the improvised IV tubing set demonstrated excellent agreement (r = 0.96) with manometer measurements. Compared with historical controls, the new ICP management protocol was associated with a significant reduction in 30-day mortality (16/35 [46%] vs. 48/64 [75%] in historical controls; hazard ratio = 2.1 [95% CI: 1.1 to 3.8]; P = 0.018]. Conclusions Increased ICP is almost universal among HIV-infected adults admitted with CM in Tanzania. Intensive ICP management with a strict schedule of serial lumbar punctures reduced in-hospital mortality compared with historical controls. ICP measurement with IV tubing sets may be a good alternative in resource-limited health facilities where manometers are not available.

Background Data regarding the outcomes of HIV-infected adults with baseline renal dysfunction who start antiretroviral therapy are conflicting. Methods We followed up a previously-published cohort of HIV-infected adult outpatients in northwest Tanzania who had high prevalence of renal dysfunction at the time of starting antiretroviral therapy (between November 2009 and February 2010). Patients had serum creatinine, proteinuria, microalbuminuria, and CD4+ T-cell count measured at the time of antiretroviral therapy initiation and at follow-up. We used the adjusted Cockroft-Gault equation to calculate estimated glomerular filtration rates (eGFRs). Results In this cohort of 171 adults who had taken antiretroviral therapy for a median of two years, the prevalence of renal dysfunction (eGFR

Setting Clinical trials have shown that early initiation of antiretroviral therapy in HIV-infected patients with tuberculosis saves lives, but models for implementation of this new strategy have been under-studied in real-world settings. Objective To identify the barriers and possible solutions for implementing concurrent early treatment with antiretroviral and anti-tuberculosis therapy in a large East African referral hospital where the prevalence of both infections is high. Design In-depth interviews among hospital administrators, laboratory technicians, nurses, pharmacists, and physicians. Results Twenty-six hospital staff identified six key barriers and corresponding solutions to promote rapid initiation of antiretroviral therapy in HIV-infected inpatients with tuberculosis. These include revising systems of medication delivery, integrating care between inpatient and outpatient systems, training hospital nurses to counsel and initiate medications in inpatients, and cultivating a team approach to consistent guideline implementation. Conclusion Most barriers identified by hospital staff were easily surmountable with reorganization, training, and policy changes at minimal cost. Efforts to reduce mortality for HIV and tuberculosis co-infected patients in accordance with new World Health Organization guidelines are currently hampered by implementation barriers in real-world settings. Our findings suggest that these can be overcome with strategic enactment of simple, realistic interventions to promote early dual treatment for HIV/tuberculosis co-infected patients.

We explored response to single-dose praziquantel therapy in a cohort of 33 women with Schistosoma haematobium infection in rural Mwanza, Tanzania. Women with S. haematobium infection confirmed both by eggs in urine and by polymerase chain reaction (PCR) received single-dose praziquantel and treatment of concomitant sexually transmitted infections. Macroscopic cervical abnormalities were also quantified. After 6 months, microscopically detectable egg excretion was eliminated, but 8 of 33 women (24%) were persistently positive for S. haematobium by PCR, and 11 (33%) had cervical abnormalities potentially attributable to schistosomiasis. This suggests that praziquantel treatment more frequently than every 6 months may be necessary for complete elimination of the parasite and prevention of genital tissue pathology. This aggressive therapy may in turn play a key role decreasing HIV susceptibility in millions of people living in regions in which S. haematobium is endemic. Nous avons explore la reponse au traitement par une dose unique de praziquantel dans une cohorte de 33 femmes presentant une infection a S chistosoma haematobium dans les regions rurales de Mwanza, en Tanzanie. Les femmes avec une infection de S . haematobium confirmee a la fois par des œufs dans les urines et par la reaction en chaine de la polymerase (PCR) ont recu une dose unique praziquantel et un traitement pour les infections sexuellement transmissibles concomitantes. Les anomalies cervicales macroscopiques ont ete egalement quantifiees. Apres six mois, l'excretion d’œufs detectables par microscopie a ete eliminee, mais 8 des 33 femmes (24%) sont restees constamment positives pour S . haematobium par PCR et 11 (33%) presentaient des anomalies cervicales potentiellement attribuables a la schistosomiase. Ceci suggere qu'un traitement par le praziquantel plus frequemment que tous les six mois serait necessaire pour l’elimination complete du parasite et pour la prevention de la pathologie des tissus genitaux. Cette therapie agressive peut a son tour jouer un role cle dans la diminution de la sensibilite au VIH chez des millions de personnes vivant dans des regions ou S . haematobium est endemique. Hemos explorado la respuesta a una terapia con una dosis unica de praziquantel en un estudio de cohortes de 33 mujeres con infeccion por S chistosoma haematobium en zonas rurales de Mwanza, Tanzania. Las mujeres con infeccion por S . haematobium, confirmadas tanto por presencia de huevos en la orina como mediante PCR, recibieron una dosis unica de praziquantel y tratamiento para infecciones de transmision sexual concomitantes. Las anormalidad macroscopicas del cervix tambien se cuantificaron. Tras seis meses, se eliminaron las excreciones de huevos detectables mediante microscopia, pero 8 de 33 mujeres (24%) continuaban siendo positivas para S . haematobium mediante PCR y 11 (33%) tenian anormalidades en el cervix potencialmente atribuibles a la esquistosomiasis. Esto sugiere que podria ser necesario un tratamiento con praziquantel con una frecuencia mayor a cada seis meses para eliminar completamente el parasito y prevenir la patologia del tejido genital. Esta terapia agresiva podria a su vez jugar un papel clave en la disminucion de la susceptibilidad al VIH en millones de personas viviendo en regiones en las cuales S . haematobium es endemico.

Background: Sub-therapeutic and supra-therapeutic plasma concentrations of antriretrovirals are the significant causes of treatment failure and toxicity respectively among HIV-infected patients. We conducted this study to determine the pattern of efavirenz and nevirapine plasma drug concentrations among adult HIV-infected patients with immunological failure attending at a tertiary hospital in North-western Tanzania. Materials and Methods: A cross-sectional study was conducted among adult HIV-infected patients with immunological failure who have been on either efavirenz or nevirapine based antiretroviral regimen for more than 6 months. Patients were serially enrolled through routine Care and Treatment Clinic (CTC) activities. Plasma drug concentrations for efavirenz and nevirapine were determined by high performance liquid chromatography (HPLC) and Gas Chromatography (GC) respectively. Demographic, clinical and laboratory data such as viral load and CD4 counts were collected. Data analysis was done using STATA 12. Results: Of the 152 patients with immunological failure enrolled, the sub-therapeutic, therapeutic and supra-therapeutic plasma antiretroviral drug concentrations were found in 43/152 (28.3%), 76/152 (50.0%) and 33/152 (21.7%) respectively. Half of the patients were outside therapeutic window with either sub-therapeutic or supra-therapeutic plasma ARV drug concentrations. There was a significant difference in distribution of ARV adherence (p-value

Animal and human studies suggest that Schistosoma mansoni infection may increase risk of human immunodeficiency virus (HIV) acquisition. Therefore, we tested 345 reproductive age women in rural Tanzanian villages near Lake Victoria, where S. mansoni is hyperendemic, for sexually transmitted infections (STIs) and schistosomiasis by circulating anodic antigen (CAA) serum assay. Over one-half (54%) had an active schistosome infection; 6% were HIV-seropositive. By univariate analysis, only schistosome infection predicted HIV infection (odds ratio [OR] = 3.9, 95% confidence interval = [1.3-12.0], P = 0.015) and remained significant using multivariate analysis to control for age, STIs, and distance from the lake (OR = 6.2 [1.7-22.9], P = 0.006). HIV prevalence was higher among women with more intense schistosome infections (P = 0.005), and the median schistosome intensity was higher in HIV-infected than -uninfected women (400 versus 15 pg CAA/mL, P = 0.01). This finding suggests that S. mansoni infection may be a modifiable HIV risk factor that places millions of people worldwide at increased risk of HIV acquisition.

SETTING: In Africa 10% of human immunodeficiency virus (HIV) infected adults starting antiretroviral therapy (ART) die within the first year and tuberculosis (TB) is the leading cause of death. OBJECTIVE: To investigate the predictors of ART-associated TB at an adult HIV clinic in Tanzania. DESIGN: In this nested case-control study adults starting ART were screened for TB according to the World Health Organization protocol. Those not diagnosed with TB were observed for 6 months. Patients diagnosed with TB were defined as cases and controls were selected from among the patients who did not develop TB using incidence density matching. RESULTS: Among the 2514 HIV-positive adults in our cohort 72 (3%) were diagnosed with TB during the first 6 months of ART. By multivariate analysis baseline characteristics predictive of TB were cough fever and night sweats; 76% (55/72) of the cases had at least one of these symptoms at the time of starting ART. CONCLUSION: Overall 75% of the patients who developed TB during the first 6 months of ART had TB symptoms at the time of starting ART. Improved TB diagnostics and/or better strategies for empirical anti-tuberculosis treatment are needed for patients with symptoms of TB at ART initiation.

We conducted a community-based study of 457 women aged 18–50 years living in eight rural villages in northwest Tanzania. The prevalence of female urogenital schistosomiasis (FUS) was 5% overall but ranged from 0% to 11%. FUS was associated with human immunodeficiency virus (HIV) infection (odds ratio [OR] = 4.0, 95% confidence interval [CI] = 1.2–13.5) and younger age (OR = 5.5 and 95% CI = 1.2–26.3 for ages < 25 years and OR = 8.2 and 95% CI = 1.7–38.4 for ages 25–29 years compared with age > 35 years). Overall HIV prevalence was 5.9% but was 17% among women with FUS. We observed significant geographical clustering of schistosomiasis: northern villages near Lake Victoria had more Schistosoma mansoni infections (P < 0.0001), and southern villages farther from the lake had more S. haematobium (P = 0.002). Our data support the postulate that FUS may be a risk factor for HIV infection and may contribute to the extremely high rates of HIV among young women in sub-Saharan Africa.

HIV infection, a major health problem worldwide, has been reported to be prevalent in trauma patients, thus presents an occupational hazard to health care workers who care for these patients. The purpose of this study was to establish the prevalence of HIV among trauma patients in our setting and to compare the outcome of these patients who are HIV positive with those who are HIV negative. This was a descriptive cross sectional study involving trauma patients aged 11 years and above, admitted to the surgical wards of Bugando Medical Centre in Mwanza, Tanzania over a six-month period from October 2008 to March 2009. All eligible patients were consecutively enrolled in the study. Data were collected using a pre-tested, coded questionnaire and analyzed using SPSS computer software. A total of 250 trauma patients were recruited and studied. The mean age of the study population was 36.37+/- 15.35. Males accounted for the majority (N=202; 80.8%) of the study population. The prevalence of HIV among trauma patients was 11.6%. Among the HIV positive patients, 26 (89.7%) were males and majority aged 31-40 years. Seventy two percent of HIV positive patients had CD4+ count ofor =200 cells/microl. Overall length of hospital stays (LOS) ranged from 1 - 90 days with mean of 19.11 +/- 15.84 days. Using multivariate logistic regression, injury severity score (ISS) (P=0.0026), revised trauma scores (RTS) (P= 0.002,), HIV seropositivity (P= 0.0012) and CD4+ count (P= 0.001) were significantly found to be associated with increased LOS. Mortality rate was 10.8% and was significantly associated with; the body region injured (P0.05), ISS (P = 0.026), RTS (P = 0.001), PTS (P= 0.01), HIV positivity (P= 0.0001) and CD4+ count (P= 0.035). HIV is prevalent among trauma patients in our setting. A substantial risk of exposure to HIV exists in health workers who care for these patients. Thus, all trauma health care workers in this region need to practice universal barrier precautions in order to reduce the risk of exposure to HIV infection. HIV positive patients with CD4+ countor =200cells/microl have similar prognosis as HIV negative patients and therefore should be treated the same way.