Primary resistance against integrase strand transfer inhibitors in integrase strand transfer inhibitor-naive patients failing first- and second-line ART in Tanzania.

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.

Altered Cervical Mucosal Gene Expression and Lower Interleukin 15 Levels in Women With Schistosoma haematobium Infection but Not in Women With Schistosoma mansoni Infection.

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.

Gene Expression Differences in Host Response to Schistosoma haematobium Infection.

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.

How gender and religion impact uptake of family planning: results from a qualitative study in Northwestern Tanzania.

BACKGROUND: Women in Tanzania report a high unmet need for both information about and access to family planning. Prior studies have demonstrated the complex and variable relationship between religious faith and beliefs about family planning in sub-Saharan Africa. We hypothesized that a major reason for the poor uptake of family planning in Tanzania is that women and their partners are uncertain about whether pregnancy prevention is compatible with their religious beliefs. METHODS: Twenty-four focus group discussions with 206 participants were conducted in Mwanza, Tanzania between 2016 and 2017: six groups were conducted among Christian men, six among Christian women, six among Muslim men, and six among Muslim women. Among Christians, 98% were Protestants. Focus groups were also divided by gender and religion to facilitate discussion about gender-specific and religion-specific factors influencing family planning utilization. Qualitative data were analyzed using a thematic, phenomenological approach. RESULTS: We identify two important themes regarding the intersections of religion and family planning practices. First, we report that dynamics of family planning are experienced differently based on gender, and that male authority conflicts with female embodied knowledge, leading to negotiation or covert contraceptive use. Second, religious acceptability of family planning methods is of central importance, though participants differed in their interpretations of their religion's stance on this question. Most who found family planning incompatible with their faith affirmed their responsibility to give birth to as many children as God would give them. Others found family planning to be acceptable given their moral responsibility to care for and protect their children by limiting the family size. CONCLUSIONS: Both religious tradition and gender dynamics strongly influence the uptake of family planning, with a wide range of interpretations of religious traditions affecting the perceived acceptability of family planning. Regardless of gender or religious affiliation, participants were unified by a desire to live according to religious tradition. Future efforts to improve uptake of family planning are likely to have maximal impact if they are tailored to inform, involve, and empower male heads of households, and to address questions of religious acceptability.

Educating religious leaders to promote uptake of male circumcision in Tanzania: a cluster randomised trial.

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 (<60 km) and the time that a free male circumcision outreach campaign from the Tanzanian Ministry of Health became available in their village. All villages received the standard male circumcision outreach activities provided by the Ministry of Health. Within the village pairs, villages were randomly assigned by coin toss to receive either additional education for Christian church leaders on scientific, religious, and cultural aspects of male circumcision (intervention group), or standard outreach only (control group). Church leaders or their congregations were not masked to random assignment. The educational intervention consisted of a 1-day seminar co-taught by a Tanzanian pastor and a Tanzanian clinician who worked with the Ministry of Health, and meetings with the study team every 2 weeks thereafter, for the duration of the circumcision campaign. The primary outcome was the proportion of male individuals in a village who were circumcised during the campaign, using an intention-to-treat analysis that included all men in the village. This trial is registered with ClinicalTrials.gov, number NCT 02167776. FINDINGS: Between June 15, 2014, and Dec 10, 2015, we provided education for church leaders in eight intervention villages and compared the outcomes with those in eight control villages. In the intervention villages, 52·8% (30 889 of 58 536) of men were circumcised compared with 29·5% (25 484 of 86 492) of men in the eight control villages (odds ratio 3·2 [95% CI, 1·4-7·3]; p=0·006). INTERPRETATION: Education of religious leaders had a substantial effect on uptake of male circumcision, and should be considered as part of male circumcision programmes in other sub-Saharan African countries. This study was conducted in one region in Tanzania; however, we believe that our intervention is generalisable. We equipped church leaders with knowledge and tools, and ultimately each leader established the most culturally-appropriate way to promote male circumcision. Therefore, we think that the process of working through religious leaders can serve as an innovative model to promote healthy behaviour, leading to HIV prevention and other clinically relevant outcomes, in a variety of settings. FUNDING: Bill & Melinda Gates Foundation, National Institutes of Health, and the Mulago Foundation.

Prevalence of pretreatment HIV drug resistance in Mwanza, Tanzania.

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.

High prevalence of sexually transmitted infections in pregnant adolescent girls in Tanzania: a multi-community cross-sectional study.

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 world's 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.

Hepatocellular carcinoma: clinicopathological profile and challenges of management in a resource-limited setting.

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 <200 cells/µl, high histological grade, advanced stage of the tumor, presence of distant metastases at the time of diagnosis, and associated complications (P < 0.001). The overall median duration of hospital stay was 14 days. The majority of patients (71.1%) were lost to follow-up at the end of the follow-up period. 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.

"If I chose to listen to people, I possibly wouldn't be using family planning": Impact of external influences on women's contraceptive autonomy in rural Northwest Tanzania.

BACKGROUND: There is an increasing emphasis on promoting women's autonomy in reproductive decision-making, particularly given global efforts to increase contraceptive access and uptake. Scales to quantify autonomy have inconsistently included the effect of external influences and focused primarily on influences of partners. OBJECTIVES: This study aimed to gain greater depth in understanding how influences including and beyond a woman's partner affect her contraceptive decision-making, as well as how external influences can overlap and further complicate contraceptive decision-making. DESIGN: A phenomenological, qualitative study in which in-depth interviews were conducted in three phases from May 2021 to February 2022 with women living in northwest Tanzania who had varying histories of contraceptive use or non-use. METHODS: One-on-one, in-depth interviews were conducted in Swahili, the national language of Tanzania, by trained female interviewers. Interviews were digitally recorded, transcribed, translated into English, and independently coded by three investigators. Analysis was conducted using NVivo. The codes developed from the transcripts were grouped into overarching themes with supporting illustrative quotes. RESULTS: A total of 72 women were interviewed. Partners were the most influential in women's family planning decision-making, followed by friends, relatives, community religious leaders, and healthcare providers. Out of the 52 women with a partner who had ever used family planning, 76.9% had discussed their desire to use family planning with their partner and nearly all reported strong pressures to use or not to use family planning from partners, family, and friends. Rarely, participants stated that they were devoid of any influence. CONCLUSION: In rural Tanzania, women's decision-making about family planning was highly impacted by external influences, including not only partners but also family, friends, and community. Indicators of women's reproductive autonomy and measurements of interventions to promote contraceptive use should incorporate measures of these external influences.

Clinical and Demographic Factors Associated With Kaposi Sarcoma-Associated Herpesvirus Shedding in Saliva or Cervical Secretions in a Cohort of Tanzanian Women.

Background: Reasons for the high prevalence of Kaposi sarcoma-associated herpesvirus (KSHV) in sub-Saharan Africa, and risk factors leading to viral reactivation and shedding, remain largely undefined. Preliminary studies have suggested that schistosome infection, which has been associated with impaired viral control, is associated with KSHV. In this study we sought to determine the relationship between active Schistosoma mansoni or Schistosoma haematobium infection and KSHV shedding. Methods: We quantified KSHV DNA in saliva and cervical swabs from 2 cohorts of women living in northwestern Tanzanian communities endemic for S mansoni or S haematobium by real-time polymerase chain reaction. χ2 and Fisher exact tests were used to determine differences in clinical and demographic factors between those who were and were not shedding KSHV. Results: Among 139 total women, 44.6% were KSHV seropositive. Six percent of those with S mansoni and 17.1% of those with S haematobium were actively shedding KSHV in saliva and none in cervical samples. Women from the S mansoni cohort who were shedding virus reported infertility more frequently (80% vs 19.5%, P = .009). There was no difference in frequency of KSHV salivary shedding between schistosome-infected and -uninfected women. Conclusions: In an area with high KSHV seroprevalence and endemic schistosome infections, we provide the first report with data demonstrating no association between schistosome infection and salivary or cervical herpesvirus shedding. KSHV salivary shedding was associated with infertility, a known effect of another herpesvirus, human herpesvirus 6.

Detectable urogenital schistosome DNA and cervical abnormalities 6 months after single-dose praziquantel in women with Schistosoma haematobium infection.

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.

Prevalence of chronic kidney disease in diabetic adult out-patients in Tanzania.

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 < 60 ml/min. None of these patients were aware of their renal disease, and only 5 (1.3%) had a diagnosis of diabetic nephropathy recorded in their file. Older age was significantly associated with CKD in this population [OR 1.03, p = 0.03, 95%CI (1.00-1.05)]. CONCLUSIONS: Chronic kidney disease is highly prevalent among adult diabetic outpatients attending our clinic in Tanzania, but is usually undiagnosed. Nearly » of patients had an eGFR low enough to require dose adjustment of diabetic medications. More diagnostic resources are needed for CKD screening among adults in Tanzania in order to slow progression and prevent complications.

Perspectives of Muslim Religious Leaders to Shape an Educational Intervention About Family Planning in Rural Tanzania: A Qualitative Study.

INTRODUCTION: Uptake of effective contraceptive methods can be hindered by poor understanding and uncertainty about its compatibility with religious beliefs. We sought to understand the perspectives of Muslim religious leaders in rural Tanzania on family planning (FP) and acceptable strategies for providing FP education to leaders and their communities. METHODS: We conducted in-depth interviews with Muslim leaders from 4 communities in northwest Tanzania. Open-ended questions explored leaders' views on FP in relation to their communities, Muslim texts and teaching, and their experience as leaders. We also investigated how FP education could be provided in their communities and asked practical questions regarding seminar implementation. Interviews were conducted in Kiswahili and transcribed and translated into English. Data were coded independently by 2 investigators using NVivo 1.5.1 and analyzed thematically. RESULTS: We interviewed 17 male and 15 female Muslim leaders. All leaders supported FP as a concept in which births are spaced, interpreting this as espoused by the Qur'an and a basic right of children raised in Islam. Leaders uniformly endorsed the use of breastfeeding and the calendar method to space births but had divergent and sometimes opposing views on other methods, including condom use, oral contraceptives, and intrauterine devices. All leaders acknowledged the need for FP education among their congregants and were in favor of helping to teach an FP seminar in their communities. CONCLUSION: Our data reveal insights into how education for Muslim leaders may equip them to promote birth spacing and enhance understanding of FP in their communities in ways that are concordant with Islamic teaching. Our findings will guide the design and pilot-testing of an educational intervention for Muslim religious leaders to promote knowledge and uptake of FP in rural Tanzania.

Partnerships with religious leaders to promote family planning in rural Tanzania: an open-label, cluster randomised trial.

BACKGROUND: Family planning benefits maternal-child health, education, and economic wellbeing. Despite global efforts, an unsatisfied demand for family planning persists in sub-Saharan Africa. Based on previous successful partnerships, the aim of this study was to determine whether an educational intervention for religious leaders would increase community knowledge, demand for, and ultimately uptake of family planning. METHODS: In this open-label, cluster randomised trial in Tanzania, 24 communities were randomised (1:1) to intervention or control arm. Communities, defined as the catchment area of a single public health facility, were eligible if they were at least 15 km from Mwanza City and had not previously participated in a health intervention for religious leaders. Random allocations were determined by coin toss and were not revealed to clinicians at health facilities in intervention and control communities, nor to the data entry team; however, due to the nature of the intervention, masking of religious leaders in the intervention communities was not possible. All Christian religious institutions were invited to send four leaders to an educational intervention that incorporated cultural, theological, and medical teaching about family planning. The primary outcome was contraceptive uptake at the community health facility during the year post intervention versus the year before the intervention. This trial was registered at clinicaltrials.gov, NCT03594305. FINDINGS: 75 communities in three districts were assessed for eligibility. 19 communities were excluded and 56 were eligible for study inclusion and were placed in random order to be invited to participate. The first 24 communities that were invited agreed to participate and were randomly assigned to receive the educational intervention either during the trial or after trial completion. Between July 10, 2018 and Dec 11, 2021, we provided the intervention in 12 communities and compared contraceptive uptake with 12 control communities. All were followed up for 12 months. In intervention communities, contraceptive uptake increased by a factor of 1·47 (95% CI 1·41-1·53) in the post-intervention (prospective) versus pre-intervention (historical) year (geometric mean of contraceptive uptake, 466 in the prospective year vs 312 in the historical year), versus 1·24 (95% CI 1·20-1·29) in control communities (geometric mean, 521 in the prospective year vs 429 in the historical year). The rate of change in contraceptive uptake was greater in intervention communities (between-group ratio of geometric mean ratios over time, 1·19 [95% CI 1·12-1·25]; p<0·0001). The COVID-19 pandemic was associated with decreased contraceptive uptake (geometric mean, 365 during the pandemic in communities that had the majority of their prospective 12-month data collection periods occur after March 16, 2020, vs 494 before the pandemic; geometric mean ratio, 0·72 [95% CI 0·57-0·90]; p=0·0040). INTERPRETATION: This intervention offers a scalable model, leveraging influence of trusted religious leaders to increase knowledge and uptake of family planning. New strategies such as this could help to overcome setbacks that occurred during the COVID-19 pandemic. FUNDING: John Templeton Foundation and Weill Cornell Medicine Dean's Diversity and Healthcare Disparity Award. TRANSLATION: For the Kiswahili translation of the abstract see Supplementary Materials section.

Stroke characteristics and outcomes in urban Tanzania: Data from the Prospective Lake Zone Stroke Registry.

BACKGROUND: Stroke is a second leading cause of death globally, with an estimated one in four adults suffering a stroke in their lifetime. We aimed to describe the clinical characteristics, quality of care, and outcomes in adults with stroke in urban Northwestern Tanzania. METHODS: We analyzed de-identified data from a prospective stroke registry from Bugando Medical Centre in Mwanza, the second largest city in Tanzania, between March 2020 and October 2022. This registry included all adults ⩾18 years admitted to our hospital who met the World Health Organization clinical definition of stroke. Information collected included demographics, risk factors, stroke severity using the National Institutes of Health Stroke Scale, brain imaging, indicators for quality of care, discharge modified Rankin Scale, and in-hospital mortality. We examined independent factors associated with mortality using logistic regression. RESULTS: The cohort included 566 adults, of which 52% (294) were female with a mean age of 65 ± 15 years. The majority had a first-ever stroke 88% (498). Premorbid hypertension was present in 86% (488) but only 41% (200) were taking antihypertensive medications before hospital admission; 6% (32) had HIV infection. Ischemic strokes accounted for 66% (371) but only 6% (22) arriving within 4.5 h of symptom onset. In-hospital mortality was 29% (127). Independent factors associated with mortality were severe stroke (adjusted odds ratio (aOR) = 1.81, 95% confidence interval (CI) = 1.47-2.24, p < 0.001), moderate to severe stroke (aOR = 1.49, 95% CI = 1.22-1.84, p < 0.001), moderate stroke (aOR = 1.80, 95% CI = 1.52-2.14, p < 0.001), leukocytosis (aOR = 1.19, 95% CI = 1.03-1.38, p = 0.022), lack of health insurance coverage (aOR = 1.15, 95% CI = 1.02-1.29, p = 0.025), and not receiving any form of venous thromboembolism prophylaxis (aOR = 1.18, 95% CI = 1.02-1.37, p = 0.027). CONCLUSION: We report a stroke cohort with poor in-hospital outcomes in urban Northwestern Tanzania. Early diagnosis and treatment of hypertension could prevent stroke in this region. More work is needed to raise awareness about stroke symptoms and to ensure that people with stroke receive guidelines-directed therapy.

Schistosoma mansoni Infection Is Associated With Increased Monocytes and Fewer Natural Killer T Cells in the Female Genital Tract.

Schistosoma mansoni infection may impair genital mucosal antiviral immunity, but immune cell populations have not been well characterized. We characterized mononuclear cells from cervical brushings of women with and without S mansoni infection. We observed lower frequencies of natural killer T cells and higher frequencies of CD14+ monocytes in infected women.

Cervicovaginal bacterial communities in reproductive-aged Tanzanian women with Schistosoma mansoni, Schistosoma haematobium, or without schistosome infection.

Schistosome infection is recognized as a potentially modifiable risk factor for HIV in women by the World Health Organization. Alterations in cervicovaginal bacteria have been associated with HIV acquisition and have not been studied in schistosome infection. We collected cervical swabs from Tanzanian women with and without S. mansoni and S. haematobium to determine effects on cervicovaginal microbiota. Infected women were treated, and follow-up swabs were collected after 3 months. 16S rRNA sequencing was performed on DNA extracted from swabs. We compared 39 women with S. mansoni with 52 uninfected controls, and 16 with S. haematobium with 27 controls. S. mansoni-infected women had increased abundance of Peptostreptococcus (p = 0.026) and presence of Prevotella timonesis (p = 0.048) compared to controls. High-intensity S. haematobium infection was associated with more diverse cervicovaginal bacterial communities than uninfected controls (p = 0.0159). High-intensity S. mansoni infection showed a similar trend (p = 0.154). At follow-up, we observed increased alpha diversity in S. mansoni (2.53 vs. 1.72, p = 0.022) and S. haematobium (2.05 vs. 1.12, p = 0.066) infection groups compared to controls. Modifications in cervicovaginal microbiota, particularly increased diversity and abundance of taxa associated with bacterial vaginosis and HIV (Peptostreptococcus, Prevotella), were associated with schistosome infection.

Insufficiency of annual praziquantel treatment to control Schistosoma mansoni infections in adult women: A longitudinal cohort study in rural 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.

Refining Diagnosis of Schistosoma haematobium Infections: Antigen and Antibody Detection in Urine.

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 <2%), clinical samples from 44 women aged 18 to 35 years were analyzed for Schistosoma infection. Urine and stool samples were examined microscopically for eggs, and serum samples were analyzed for the presence of the anodic antigen. Urines were further subjected to a set of LF assays detecting (circulating) anodic (CAA) and cathodic antigen (CCA) as well as antibodies against soluble egg antigens (SEA) and crude cercarial antigen preparation (SCAP). Results: The urine LF anodic antigen assay utilizing luminescent upconverting reporter particles (UCP) confirmed its increased sensitivity when performed with larger sample volume. Qualitatively, the anodic antigen assay performed on 250 µL urine matched the performance of the standard anodic antigen assay performed on 20 µL serum. However, the ratio of anodic antigen levels in urine vs. serum of individual patients varied with absolute levels always higher in serum. The 10 µL urine UCP-LF cathodic antigen assay correlated with the commercially available urine POC-CCA (40 µL) test, while conferring better sensitivity with a quantitative result. Urinary antibodies against SEA and SCAP overlap and correlate with the presence of urinary egg and serum anodic antigen levels. Conclusions: The UCP-LF anodic antigen assay using 250 µL of urine is an expedient user-friendly assay and a suitable non-invasive alternative to serum-based antigen testing and urinary egg detection. Individual biological differences in the clearance process of the circulating antigens are thought to explain the observed high variation in the type and level of antigen (anodic or cathodic) measured in urine or serum. Simultaneous detection of anodic and cathodic antigen may be considered to further increase accuracy.

HIV-1 Viral Loads Are Not Elevated in Individuals Co-infected With Schistosoma spp. After Adjustment for Duration of HIV-1 Infection.

Studies of the role of Schistosoma co-infections on plasma HIV-1 RNA (HIV-1 viral load) have yielded incongruent results. The role of duration of HIV-1 infection on the link between Schistosoma and HIV-1 viral load has not been previously investigated. We aimed to assess the impact of HIV-1/Schistosoma co-infections on viral load in Antiretroviral Treatment (ART)-naïve HIV-1 infected people taking into account the duration of HIV-1 infection. We describe 79 HIV-infected outpatients greater than 18 years of age who had never used ART in Mwanza, Tanzania. Schistosomiasis testing was done by urine and stool microscopy and by serum Schistosoma circulating anodic antigen (CAA) testing. Schistosoma positivity was defined as having either test positive. We conducted univariable and multivariable linear regressions to assess the relationship between Schistosoma infection and the log10 of viral load. Duration of HIV infection was calculated using the first measured CD4+ T-cell (CD4) count as a function of normal CD4 count decay per calendar year in drug naïve individuals. An active Schistosoma infection was demonstrated in 46.8% of the patients. The median log10 viral load was 4.5[3.4-4.9] log10 copies/mL in Schistosoma uninfected patients and 4.3[3.7-4.6] log10 copies/mL in Schistosoma infected patients. Schistosoma co-infection was negatively associated with the log10 of viral load after adjustment for Schistosoma intensity as measured by CAA, CD4 counts at time of testing, and duration of HIV-1 infection (ß = -0.7[-1.3;-0.1], p = 0.022). Schistosoma co-infection was not associated with viral load in univariable analysis. There was also no interaction between Schistosoma positivity and duration of HIV-1 infection. Our study is the first, to our knowledge, to report adjustment for duration of HIV-1 infection when analyzing the relationship between HIV-1 viral load and Schistosoma spp. We found that time infected with HIV-1 has a major effect on the relationship between HIV-1 viral load and Schistosoma infection and may be a critical explanatory factor in the disparate findings of studies on HIV-1 viral load and schistosomiasis. The log10 viral load difference found indicates that Schistosoma co-infection does not make HIV progression worse, and could possibly lead to slower HIV disease progression.