Knee-to-chest flexion manoeuvre to reduce respiratory distress after planned caesarean birth: a feasibility study.

BACKGROUND: Planned caesarean section (CS) is a risk factor for neonatal respiratory distress caused by a greater volume of airway liquid in the absence of uterine contractions.Performing a newly conceptualised knee-to-chest flexion (KCF) manoeuvre at birth, mimicking uterine contraction-induced flexion may aid in expelling excess lung liquid. OBJECTIVES: To test whether performing a KCF manoeuvre at birth is feasible in infants born after planned CS and to test whether KCF leads to visible expulsion of lung liquid. METHODS: Single-centre prospective interventional study in term infants born by planned CS at Leiden University Medical Centre, Netherlands. KCF was performed for a maximum of 45 s. Baseline characteristics were collected, primary outcome was ability to perform KCF and secondary outcome was any visible expulsion of fluid. RESULTS: In 39 infants (mean (SD) gestational age 38.0 (0.7) weeks, birth weight 3537 (440) g), KCF could be performed in 21/39 (54%), whereas 18/39 (46.2%) starting vigorous breathing before KCF could be performed. Notably, visible lung liquid expulsion occurred in 9/21 (43%) infants. KCF duration averaged 29 (18) s. In 13/21 (62 %), KCF was not performed as per standard operating procedure. No adverse events were reported. CONCLUSION: It is feasible to perform KCF at birth in a large proportion of term infants born by planned CS, with visible expulsion of liquid in a significant proportion of these infants. Training healthcare providers to perform a standardised KCF could increase feasibility and success. Further studies are needed to assess feasibility and effectiveness of KCF. TRIAL REGISTRATION NUMBER: NL74285.058.20.

Bedaquiline-pretomanid-moxifloxacin-pyrazinamide for drug-sensitive and drug-resistant pulmonary tuberculosis treatment: a phase 2c, open-label, multicentre, partially randomised controlled trial.

BACKGROUND: The current tuberculosis (TB) drug development pipeline is being re-populated with candidates, including nitroimidazoles such as pretomanid, that exhibit a potential to shorten TB therapy by exerting a bactericidal effect on non-replicating bacilli. Based on results from preclinical and early clinical studies, a four-drug combination of bedaquiline, pretomanid, moxifloxacin, and pyrazinamide (BPaMZ) regimen was identified with treatment-shortening potential for both drug-susceptible (DS) and drug-resistant (DR) TB. This trial aimed to determine the safety and efficacy of BPaMZ. We compared 4 months of BPaMZ to the standard 6 months of isoniazid, rifampicin, pyrazinamide, and ethambutol (HRZE) in DS-TB. 6 months of BPaMZ was assessed in DR-TB. METHODS: SimpliciTB was a partially randomised, phase 2c, open-label, clinical trial, recruiting participants at 26 sites in eight countries. Participants aged 18 years or older with pulmonary TB who were sputum smear positive for acid-fast bacilli were eligible for enrolment. Participants with DS-TB had Mycobacterium tuberculosis with sensitivity to rifampicin and isoniazid. Participants with DR-TB had M tuberculosis with resistance to rifampicin, isoniazid, or both. Participants with DS-TB were randomly allocated in a 1:1 ratio, stratified by HIV status and cavitation on chest radiograph, using balanced block randomisation with a fixed block size of four. The primary efficacy endpoint was time to sputum culture-negative status by 8 weeks; the key secondary endpoint was unfavourable outcome at week 52. A non-inferiority margin of 12% was chosen for the key secondary outcome. Safety and tolerability outcomes are presented as descriptive analyses. The efficacy analysis population contained patients who received at least one dose of medication and who had efficacy data available and had no major protocol violations. The safety population contained patients who received at least one dose of medication. This study is registered with ClinicalTrials.gov (NCT03338621) and is completed. FINDINGS: Between July 30, 2018, and March 2, 2020, 455 participants were enrolled and received at least one dose of study treatment. 324 (71%) participants were male and 131 (29%) participants were female. 303 participants with DS-TB were randomly assigned to 4 months of BPaMZ (n=150) or HRZE (n=153). In a modified intention-to-treat (mITT) analysis, by week 8, 122 (84%) of 145 and 70 (47%) of 148 participants were culture-negative on 4 months of BPaMZ and HRZE, respectively, with a hazard ratio for earlier negative status of 2·93 (95% CI 2·17-3·96; p<0·0001). Median time to negative culture (TTN) was 6 weeks (IQR 4-8) on 4 months of BPaMZ and 11 weeks (6-12) on HRZE. 86% of participants with DR-TB receiving 6 months of BPaMZ (n=152) reached culture-negative status by week 8, with a median TTN of 5 weeks (IQR 3-7). At week 52, 120 (83%) of 144, 134 (93%) of 144, and 111 (83%) of 133 on 4 months of BPaMZ, HRZE, and 6 months of BPaMZ had favourable outcomes, respectively. Despite bacteriological efficacy, 4 months of BPaMZ did not meet the non-inferiority margin for the key secondary endpoint in the pre-defined mITT population due to higher withdrawal rates for adverse hepatic events. Non-inferiority was demonstrated in the per-protocol population confirming the effect of withdrawals with 4 months of BPaMZ. At least one liver-related treatment-emergent adverse effect (TEAE) occurred among 45 (30%) participants on 4 months of BPaMZ, 38 (25%) on HRZE, and 33 (22%) on 6 months of BPaMZ. Serious liver-related TEAEs were reported by 20 participants overall; 11 (7%) among those on 4 months of BPaMZ, one (1%) on HRZE, and eight (5%) on 6 months of BPaMZ. The most common reasons for discontinuation of trial treatment were hepatotoxicity (ten participants [2%]), increased hepatic enzymes (nine participants [2%]), QTcF prolongation (three participants [1%]), and hypersensitivity (two participants [<1%]). INTERPRETATION: For DS-TB, BPaMZ successfully met the primary efficacy endpoint of sputum culture conversion. The regimen did not meet the key secondary efficacy endpoint due to adverse events resulting in treatment withdrawal. Our study demonstrated the potential for treatment-shortening efficacy of the BPaMZ regimen for DS-TB and DR-TB, providing clinical validation of a murine model widely used to identify such regimens. It also highlights that novel, treatment-shortening TB treatment regimens require an acceptable toxicity and tolerability profile with minimal monitoring in low-resource and high-burden settings. The increased risk of unpredictable severe hepatic adverse events with 4 months of BPaMZ would be a considerable obstacle to implementation of this regimen in settings with high burdens of TB with limited infrastructure for close surveillance of liver biochemistry. Future research should focus on improving the preclinical and early clinical detection and mitigation of safety issues together and further efforts to optimise shorter treatments. FUNDING: TB Alliance.

Perinatal loss in Tanzania: Perspectives of maternal-child healthcare providers.

Over 98% of stillbirths and neonatal deaths occur in Low- and Middle-Income Countries, such as Tanzania. Despite the profound burden of perinatal loss in these regions, access to facility or community-based palliative and psychosocial care is poor and understudied. In this study we explore perinatal loss through the lens of front-line healthcare providers, to better understand the knowledge and beliefs that guide their engagement with bereaved families. A Knowledge Attitudes and Practices survey addressing perinatal loss in Tanzania was developed, translated into Swahili, and administered over a 4-month period to healthcare professionals working at the Kilimanjaro Christian Medical Center (KCMC). Results were entered into REDCap and analyzed in R Studio. 74 providers completed the survey. Pediatric providers saw a yearly average of 5 stillbirths and 32.7 neonatal deaths. Obstetric providers saw an average of 11.5 stillbirths and 13.12 neonatal deaths. Most providers would provide resuscitation beginning at 28 weeks gestational age. Respondents estimated that a 50% chance of survival for a newborn occurred at 28 weeks both nationally and at KCMC. Most providers felt that stillbirth and neonatal mortality were not the mother's fault (78.4% and 81.1%). However, nearly half (44.6%) felt that stillbirth reflects negatively on the woman and 62.2% agreed that women are at higher risk of abuse or abandonment after stillbirth. A majority perceived that women wanted hold their child after stillbirth (63.0%) or neonatal death (70.3%). Overall, this study found that providers at KCMC perceived that women are at greater risk of psychosocial or physical harm following perinatal loss. How women can best be supported by both the health system and their community remains unclear. More research on perinatal loss and bereavement in LMICs is needed to inform patient-level and health-systems interventions addressing care gaps unique to resource-limited or non-western settings.

The role of clinical breast examination and fine needle aspiration cytology in early detection of breast cancer: A cross-sectional study nested in a cohort in a low-resource setting.

BACKGROUND: Breast cancer is prevalent worldwide, with disparities in screening, diagnosis, treatment outcomes, and survival. In Africa, the majority of women are diagnosed at advanced stages, affecting treatment outcomes. Screening is one of the best strategies to reduce mortality rates caused by this cancer. Yet in a resource-constrained setting, there is limited access to screening and early detection services, which are available only at a few referral hospitals. OBJECTIVES: We aimed to evaluate the prevalence and screening results of breast cancer using clinical breast examination coupled with fine needle aspiration cytology in a resource-constraint setting. DESIGN: A combined cross-sectional and cohort study. METHODS: Women at risk of developing breast cancer in the Kilimanjaro region of Tanzania were invited, through public announcements, to their primary healthcare facilities. A questionnaire was used to assess the participants' characteristics. The women received a clinical breast examination, and detectable lesions were subjected to a confirmatory fine needle aspiration cytology or an excisional biopsy. Preliminary data from this ongoing breast cancer control program were extracted and analyzed for this study. RESULTS: A total of 3577 women were screened for breast cancer; their mean age was 47 ± 7.53 years. About a third of them (1145, 32%) were practicing self-breast examination at least once a month. Of 200 (5.6%) with abnormal clinical breast examination, 18 (9%) were confirmed to be breast cancer, making the prevalence to be 0.5%. The vast majority of participants with breast cancer (13, 72.2%) had early disease stages, and infiltrating ductal carcinoma, no special type, was the most common (15, 83.3%) histopathology subtype. Hormonal receptor status determination results indicated that 11 (61.1%), 7 (38.9%), and 5 (27.8%) of the tumors overexpressed estrogen receptor, progesterone receptor, and human epidermal receptor-2, respectively. CONCLUSION: Our study demonstrates 5.6% of Tanzanian women have abnormal clinical breast examination findings, with 9% having breast cancer. Nearly three-quarters (72.2%) of breast cancer screened for early disease were detected in the early disease stages. This finding suggests that organized screening with clinical breast examination coupled with fine needle aspiration cytology, which is a simple and cost-effective screening method, has the potential to improve early detection and outcomes for breast cancer patients in a resource-constraint setting.

Estimating the prevalence and predictors of musculoskeletal disorders in Tanzania: a cross-sectional pilot study.

Introduction: musculoskeletal (MSK) disorders account for approximately 20% of all years lived with disability worldwide however studies of MSK disorders in Africa are scarce. This pilot study aimed to estimate the community-based prevalence of MSK disorders, identify predictors, and assess the associated disability in a Tanzanian population. Methods: a cross-sectional study was conducted in one village in the Kilimanjaro region from March to June 2019. The Gait, Arms, Legs, Spine (GALS) or paediatric GALS (pGALS) examinations were used during household and school visits. Individuals positive in GALS/pGALS screening were assessed by the regional examination of the musculoskeletal system (REMS) and Modified Health Assessment Questionnaire (MHAQ). Results: among the 1,172 individuals enrolled in households, 95 (8.1%, 95% CI: 6.6 - 9.8) showed signs of MSK disorders using the GALS/pGALS examination and 37 (3.2%, 95% CI: 2.2 - 4.3) using the REMS. Among 682 schools enrolled children, seven showed signs of MSK disorders using the GALS/pGALS examination (1.0%, 95% CI: 0.4 - 2.1) and three using the REMS (0.4%, 95% CI: 0.0 - 1.3). In the household-enrolled adult population, female gender and increasing age were associated with GALS and REMS-positive findings. Among GALS-positive adults, increasing age was associated with REMS-positive status and increasing MHAQ score. Conclusion: this Tanzanian study demonstrates a prevalence of MSK disorders and identifies predictors of MSK disorders comparable to those seen globally. These findings can inform the development of rheumatology services and interventions in Tanzania and the design of future investigations of the determinants of MSK disorders, and their impacts on health, livelihoods, and well-being.

Efficacy of mobile phone intervention to increase male partner antenatal care attendance for HIV testing in Moshi municipal, Tanzania: a randomized controlled trial.

BACKGROUND: HIV partner counselling and testing in antenatal care (ANC) is a crucial strategy to raise the number of males who know their HIV status. However, in many settings like Tanzania, male involvement in antenatal care remains low, and there is a definite need for innovative strategies to increase male partner involvement. This study was designed to evaluate the efficacy of mobile phone intervention increase male partner ANC attendance for HIV testing in Moshi municipal, Tanzania. METHODS: Between April and July 2022, we enrolled pregnant women presenting to a first ANC visit at Majengo and St. Joseph reproductive health facilities without their male partners. Eligible pregnant women were randomly assigned to invitation of their male partners either via phone calls, text messages from clinic staff and verbal invites from pregnant partners (intervention arm) or verbal invites only from the pregnant partners (control arm). Neither healthcare provider nor participant were blinded. The primary outcome was the proportion of male partners who attended ANC with their pregnant partners during a follow-up period of two consecutive visits. The secondary outcome measure was HIV testing among male partners following the invitation. Participants were analyzed as originally assigned (intention to treat). RESULTS: A total of 350 pregnant women presenting to ANC for the first time were enrolled, with 175 women enrolled in each arm. The efficacy of male attendance with their pregnant women following the invitations was 83.4% (147/175) in the intervention arm and 46.3% (81/175) in the control arm. Overall, the results suggest a positive and statistically significant average treatment effect among men who received mobile phone intervention on ANC attendance. For the secondary outcome, the percent of male partners who accepted HIV counselling and testing was 99.3% (146/147) in the intervention arm and 93.8% (76/81) in the control arm. Married men were having higher odds of ANC attendance compared with single men (aOR:6.40(3.26-12.56), Males with multigravida women were having lower odds of ANC attendance compared with primigravida women (aOR:0.17(0.09-0.33). CONCLUSION: The study demonstrates that supplementing verbal invitations with mobile phone calls and text messages from clinic staff can significantly increase male partner ANC attendance and HIV testing. This combined approach is recommended in improving ANC attendance and HIV testing of male partners who do not accompany their pregnant partners to antenatal clinics in the first visits. TRIAL REGISTRATION: PACTR202209769991162.

Short reads-based characterization of pathotype diversity and drug resistance among Escherichia coli isolated from patients attending regional referral hospitals in Tanzania.

BACKGROUND: Escherichia coli is known to cause about 2 million deaths annually of which diarrhea infection is leading and typically occurs in children under 5 years old. Although Africa is the most affected region there is little information on their pathotypes diversity and their antimicrobial resistance. OBJECTIVE: To determine the pathotype diversity and antimicrobial resistance among E. coli from patients attending regional referral hospitals in Tanzania. MATERIALS AND METHODS: A retrospective cross-section laboratory-based study where a total of 138 archived E. coli isolates collected from 2020 to 2021 from selected regional referral hospitals in Tanzania were sequenced using the Illumina Nextseq550 sequencer platform. Analysis of the sequences was done in the CGE tool for the identification of resistance genes and virulence genes. SPSS version 20 was used to summarize data using frequency and proportion. RESULTS: Among all 138 sequenced E. coli isolates, the most prevalent observed pathotype virulence genes were of extraintestinal E. coli UPEC fyuA gene 82.6% (114/138) and NMEC irp gene 81.9% (113/138). Most of the E. coli pathotypes observed exist as a hybrid due to gene overlapping, the most prevalent pathotypes observed were NMEC/UPEC hybrid 29.7% (41/138), NMEC/UPEC/EAEC hybrid 26.1% (36/138), NMEC/UPEC/DAEC hybrid 18.1% (25/138) and EAEC 15.2% (21/138). Overall most E. coli carried resistance gene to ampicillin 90.6% (125/138), trimethoprim 85.5% (118/138), tetracycline 79.9% (110/138), ciprofloxacin 76.1% (105/138) and 72.5% (100/138) Nalidixic acid. Hybrid pathotypes were more resistant than non-hybrid pathotypes. CONCLUSION: Whole genome sequencing reveals the presence of hybrid pathotypes with increased drug resistance among E. coli isolated from regional referral hospitals in Tanzania.

Prostate cancer knowledge and barriers to screening among men at risk in northern Tanzania: A community-based study.

BACKGROUND: Although prostate cancer (Pca) screening plays important role in early diagnosis and reduction of mortality, Tanzanian men are relatively unscreened. We aimed to investigate Pca knowledge level and barriers to screening among at-risk men in northern Tanzania. METHODS: This community-based survey was conducted in northern Tanzania from May to September 2022, involving men age ≥40 years. Participants were invited by announcing in local churches, mosques, brochures, and social media groups. Participants attended a nearby health facility where survey questionnaires were administered. Knowledge level was measured on the Likert scale and scored as poor (<50 %) or good (≥50 %). RESULTS: A total of 6205 men with a mean age of 60.23 ± 10.98 years were enrolled in the study. Of these, 586 (9.5 %) had ever been screened for Pca. Overall, 1263 men (20.4 %) had good knowledge of Pca. Having health insurance, knowing at least 1 risk factor or symptoms of Pca, and hospital as the source of Pca information were significantly associated with ever being screened. The most common reasons for not being screened were a belief that they are healthy (n = 2983; 53.1 %), that Pca is not a serious disease (n = 3908; 69.6 %), and that digital rectal examination (DRE) as an embarrassing (n = 3634; 64.7 %) or harmful (n = 3047; 54.3 %) procedure. CONCLUSION: Having Pca knowledge, health insurance and hospital source of information were correlated with increased screening. False beliefs about DRE and the seriousness of Pca had negative effects on screening. Increasing community knowledge and universal health coverage would improve uptake of Pca screening.

Impact of the COVID-19 pandemic in childhood and adolescent cancer care in northern Tanzania: a cross-sectional study.

INTRODUCTION: The SARS-CoV-2 (COVID-19) pandemic has strained healthcare systems and presented unique challenges for children requiring cancer care, particularly in low- and middle-income countries. This study aimed to assess the impact of the COVID-19 pandemic on access to cancer care for children and adolescents in Northern Tanzania. METHODS: In this cross-sectional study, we assessed the demographic and clinical characteristics of 547 pediatric and adolescent cancer patients (ages 0-19 years old) between 2016 and 2022 using the population-based Kilimanjaro Cancer Registry (KCR). We categorized data into pre-COVID-19 (2016-2019) and COVID-19 (2020-2022) eras, and performed descriptive analyses of diagnostic, treatment, and demographic information. A secondary analysis was conducted on a subset of 167 patients with stage of diagnosis at presentation. RESULTS: Overall admissions nearly doubled during the pandemic (n = 190 versus 357). The variety of diagnoses attended at KCMC increased during the pandemic, with only five groups of diseases reported in 2016 to twelve groups of diseases in 2021. Most patients were diagnosed at a late stage (stage III or IV) across eras, with the proportion of under-five years old patients increasing late-diagnoses from 29.4% (before the pandemic), 52.8% (during the pandemic), when compared to the overall cohort. Around 95% of children in this age category reported late-stage diagnosis during the pandemic. Six out of the twelve cancer site groups also reported an increase in late-stage diagnosis. During the pandemic, the proportion of children receiving surgery increased from 15.8 to 30.8% (p < 0.001). CONCLUSION: Childhood and adolescent cancer care changed in Northern Tanzania during the COVID-19 pandemic, with increased late-stage diagnoses presentations among younger patients and the increased use of surgical therapies in the context of a growing practice. Understanding the impact of the COVID-19 pandemic on pediatric and adolescent cancer care can help us better adapt healthcare systems and interventions to the emerging needs of children and adolescents with cancer in the midst of a health crisis.

Who is most vulnerable? Factors associated with presenting to antenatal care without a male partner in Northern Tanzania.

OBJECTIVE: Male engagement in pregnancy care can be beneficial for maternal and child health outcomes. In Tanzania, pregnant women are strongly encouraged to present to their first antenatal care (ANC) appointment with a male partner, where they jointly test for HIV. For some, this presents a barrier to ANC attendance. The objectives of this study were to identify factors associated with presenting to ANC with a male partner using a cross-sectional design and to assess whether women presenting without partners had significantly delayed presentation. METHODS: Pregnant women (n = 1007) attending a first ANC appointment in Moshi, Tanzania were surveyed. Questions captured sociodemographic characteristics and measures of psychosocial constructs. RESULTS: Just over half (54%) of women presented to care with a male partner. Women were more likely to present with a male partner if they were younger than 25 years old, married, Muslim, attending ANC for their first pregnancy, and testing for HIV for the first time. Women presenting to ANC with a male partner were significantly more likely to attend ANC earlier in their pregnancy than those presenting without male partners. CONCLUSION: Policy change allowing women to present to care with other supportive family members could promote earlier presentation to first ANC. Unmarried women may be at a disadvantage in presenting to ANC when policies mandate attendance with a male partner. Male partners of multiparous women should be encouraged to provide pregnancy support even after first pregnancies, and a wholistic emphasis (beyond HIV testing) on first ANC could encourage male engagement beyond the initial appointment.

Outcomes of the MAMA Training: A Simulation and Experiential Learning Intervention for Labor and Delivery Providers to Improve Respectful Maternity Care for Women Living with HIV in Tanzania.

Respectful maternity care (RMC) for women living with HIV (WLHIV) improves birth outcomes and may influence women's long-term commitment to HIV care. In this study, we evaluated the MAMA training, a team-based simulation training for labor and delivery (L&D) providers to improve RMC and reduce stigma in caring for WLHIV. The study was conducted in six clinical sites in the Kilimanjaro Region of Tanzania. 60 L&D providers participated in the MAMA training, which included a two-and-a-half-day workshop followed by a half-day on-site refresher. We assessed the impact of the MAMA training using a pre-post quasi-experimental design. To assess provider impacts, participants completed assessments at baseline and post-intervention periods, measuring RMC practices, HIV stigma, and self-efficacy to provide care. To evaluate patient impacts, we enrolled birthing women at the study facilities in the pre- (n = 229) and post- (n = 214) intervention periods and assessed self-reported RMC and perceptions of provider HIV stigma. We also collected facility-level data on the proportion of patients who gave birth by cesarean section, disaggregated by HIV status. The intervention had a positive impact on all provider outcomes; providers reported using more RMC practices, lower levels of HIV stigma, and greater self-efficacy to provide care for WLHIV. We did not observe differences in self-reported patient outcomes. In facility-level data, we observed a trend in reduction in cesarean section rates for WLHIV (33.0% vs. 24.1%, p = 0.14). The findings suggest that the MAMA training may improve providers' attitudes and practices in caring for WLHIV giving birth and should be considered for scale-up.

Through the looking glass: empowering youth community advisory boards in Tanzania as a sustainable youth engagement model to inform policy and practice.

More young people are living in the world than ever before, 90% of whom reside in low and middle income countries (LMICs). To address their needs, it is critical to have sustainable youth engagement when determining policy and to advance effective implementation of youth-focused interventions. Youth Community Advisory Boards (CABs) are a sustainable mechanism to achieve this goal. This paper describes engagement with youth CAB members across four locations in Tanzania. To set youth CAB meeting agendas and priorities, we asked youth CAB members to write (using free text) the top five challenges faced by young people in their communities (highest to lower priority). The Google Forms survey link was presented at the May 2023 youth CAB meeting and disseminated through WhatsApp. The survey was completed by smartphone, tablet, or paper provided to the youth liaison for data entry. Results were translated from Swahili to English and coded using excel. Findings were then presented back to the youth CABs at the September 2023 meeting. At that meeting, youth CAB members were then asked to write (free text) potential solutions to the most commonly described challenges. The surveys had response rates of 90% (84/93) for challenges and 78% (71/93) for solutions. The number one reported challenge was unemployment and financial instability (45%). Gender based violence (13%), sexual reproductive health issues (8%), and alcohol and drug use (8%) were in the top four both by priority and frequency of report. Other important challenges included physical and mental health, malnutrition, relationships, education, and societal and environmental norms, among others. Solutions included job creation, improved education, expanded legal systems, youth-friendly health care services, and increased social support through peer networks and community support. The National Accelerated Action and Investment Agenda for Adolescent Health and Wellbeing (NAIA-AHW) 2021/22-2024/25 includes most, but not all, of these top challenges and solutions. Ensuring young people have a seat at the policy table is critical to effective youth-empowerment in health and other related programs. Including a youth CAB member to represent this collective in youth-related government activities is a sustainable model to achieve this goal.

Effects of preterm birth, maternal ART and breastfeeding on 24-month infant HIV-free survival in a randomized trial.

BACKGROUND: IMPAACT 1077BF/FF compared the safety/efficacy of two HIV antiretroviral therapy (ART) regimens to zidovudine (ZDV) alone during pregnancy for HIV prevention. PROMISE found an increased risk of preterm delivery (<37 weeks) with antepartum triple ART (TDF/FTC/LPV+r or ZDV/3TC/LPV+r) compared to ZDV alone. We assessed the impact of preterm birth, breastfeeding and antepartum ART regimen on 24-month infant survival. METHODS: We compared HIV-free and overall survival at 24-months for liveborn infants by gestational age, time-varying breastfeeding status, and antepartum ART arm at 14 sites in Africa and India. Kaplan-Meier survival probabilities and Cox proportional hazards ratios (HR) were estimated. RESULTS: 3,482 live-born infants (568 [16 3%] preterm and 2,914 [83 7%] term) were included. Preterm birth was significantly associated with lower HIV-free survival (0·85; 95% CI: 0·82-0·88) and lower overall survival (0·89; 95% CI: 0·86-0·91) versus term birth (0·96; 95% CI: 0·95-0·96). Very preterm birth (<34 weeks) was associated with low HIV-free survival (0·65; 95% CI: 0·54-0·73) and low overall survival (0·66; 95% CI: 0·56-0·74). Risk of HIV infection or death at 24-months was higher with TDF-ART than ZDV-ART (adjusted HR 2·37; 95% CI: 1·21-4·64). Breastfeeding initiated near birth decreased risk of infection or death at 24 months (adjusted HR 0·05; 95% CI: 0·03-0·08) compared to not breastfeeding. CONCLUSION: Preterm birth and antepartum TDF-ART were associated with lower 24-month HIV-free survival compared to term birth and ZDV-ART. Any breastfeeding strongly promoted HIV-free survival, especially if initiated close to birth. Reducing preterm birth and promoting infant feeding with breastmilk among HIV/ARV-exposed infants remain global health priorities.

Prevalence and risk factors for Q fever, spotted fever group rickettsioses, and typhus group rickettsioses in a pastoralist community of northern Tanzania, 2016-2017.

BACKGROUND: In northern Tanzania, Q fever, spotted fever group (SFG) rickettsioses, and typhus group (TG) rickettsioses are common causes of febrile illness. We sought to describe the prevalence and risk factors for these zoonoses in a pastoralist community. METHODS: Febrile patients ≥2 years old presenting to Endulen Hospital in the Ngorongoro Conservation Area were enrolled from August 2016 through October 2017. Acute and convalescent blood samples were collected, and a questionnaire was administered. Sera were tested by immunofluorescent antibody (IFA) IgG assays using Coxiella burnetii (Phase II), Rickettsia africae, and Rickettsia typhi antigens. Serologic evidence of exposure was defined by an IFA titre ≥1:64; probable cases by an acute IFA titre ≥1:128; and confirmed cases by a ≥4-fold rise in titre between samples. Risk factors for exposure and acute case status were evaluated. RESULTS: Of 228 participants, 99 (43.4%) were male and the median (interquartile range) age was 27 (16-41) years. Among these, 117 (51.3%) had C. burnetii exposure, 74 (32.5%) had probable Q fever, 176 (77.2%) had SFG Rickettsia exposure, 134 (58.8%) had probable SFG rickettsioses, 11 (4.8%) had TG Rickettsia exposure, and 4 (1.8%) had probable TG rickettsioses. Of 146 participants with paired sera, 1 (0.5%) had confirmed Q fever, 8 (5.5%) had confirmed SFG rickettsioses, and none had confirmed TG rickettsioses. Livestock slaughter was associated with acute Q fever (adjusted odds ratio [OR] 2.54, 95% confidence interval [CI] 1.38-4.76) and sheep slaughter with SFG rickettsioses case (OR 4.63, 95% CI 1.08-23.50). DISCUSSION: Acute Q fever and SFG rickettsioses were detected in participants with febrile illness. Exposures to C. burnetii and to SFG Rickettsia were highly prevalent, and interactions with livestock were associated with increased odds of illness with both pathogens. Further characterisation of the burden and risks for these diseases is warranted.

HIV-related Shame among Women Giving Birth in Tanzania: A Mixed Methods Study.

Women living with HIV (WLHIV) commonly experience HIV-related shame which can interfere with HIV care-seeking behavior and lead to poor clinical outcomes. HIV-related shame may be particularly heightened during the pregnancy and postpartum periods. This study aimed to describe HIV-related shame among WLHIV giving birth, identify associated factors, and qualitatively examine the impacts of HIV-related shame on the childbirth experience. Postpartum WLHIV (n = 103) were enrolled in the study between March and July 2022 at six clinics in the Kilimanjaro Region, Tanzania. Participants completed a survey within 48 h after birth, prior to being discharged. The survey included a 13-item measure of HIV-related shame, which assessed levels of HIV-related shame (Range: 0-52). Univariable and multivariable regression models examined factors associated with HIV-related shame. Qualitative in-depth interviews were conducted with pregnant WLHIV (n = 12) and postpartum WLHIV (n = 12). Thematic analysis, including memo writing, coding, and synthesis, was employed to analyze the qualitative data. The survey sample had a mean age of 29.1 (SD = 5.7), and 52% were diagnosed with HIV during the current pregnancy. Nearly all participants (98%) endorsed at least one item reflecting HIV-related shame, with an average endorsement of 9 items (IQR = 6). In the final multivariable model, HIV-related shame was significantly associated with being Muslim vs. Christian (ß = 6.80; 95%CI: 1.51, 12.09), attending less than four antenatal care appointments (ß = 5.30; 95%CI: 0.04, 10.55), and reporting experiences of HIV stigma in the health system (ß = 0.69; 95%CI: 0.27, 1.12). Qualitative discussions revealed three key themes regarding the impact of HIV-related shame on the childbirth experience: reluctance to disclose HIV status, suboptimal adherence to care, and the influence on social support networks. WLHIV giving birth experience high rates of HIV-related shame, and social determinants may contribute to feelings of shame. HIV-related shame impacts the childbirth experience for WLHIV, making the labor and delivery setting an important site for intervention and support.The study is funded by the National Institutes of Health (R21 TW012001) and is registered on clinicaltrials.gov (NCT05271903).

Antimicrobial resistance and heterogeneity of Neisseria gonorrhoeae isolated from patients attending sexually transmitted infection clinics in Lusaka, Zambia.

BACKGROUND: Antimicrobial resistance (AMR) of Neisseria gonorrhoeae is a threat to public health as strains have developed resistance to antimicrobials available for the treatment of gonorrhea. Whole genome sequencing (WGS) can detect and predict antimicrobial resistance to enhance the control and prevention of gonorrhea. Data on the molecular epidemiology of N. gonorrhoeae is sparse in Zambia. This study aimed to determine the genetic diversity of N. gonorrhoeae isolated from patients attending sexually transmitted infection (STI) clinics in Lusaka, Zambia. METHODS: A cross-sectional study that sequenced 38 N. gonorrhoeae isolated from 122 patients with gonorrhea from 2019 to 2020 was conducted. The AMR profiles were determined by the E-test, and the DNA was extracted using the NucliSens easyMaG magnetic device. Whole genome sequencing was performed on the Illumina NextSeq550 platform. The Bacterial analysis pipeline (BAP) that is readily available at: https://cge.cbs.dtu.dk/services/CGEpipeline-1.1 was used for the identification of the species, assembling the genome, multi-locus sequence typing (MLST), detection of plasmids and AMR genes. Phylogeny by single nucleotide polymorphisms (SNPs) was determined with the CCphylo dataset. RESULTS: The most frequent STs with 18.4% of isolates each were ST7363, ST1921 and ST1582, followed by ST1583 (13%), novel ST17026 (7.9%), ST1588 (7.9%), ST1596 (5.3%), ST11181 (5.3%), ST11750 (2.6/%) and ST11241 (2.6%) among the 38 genotyped isolates. The blaTeM-1B and tetM (55%) was the most prevalent combination of AMR genes, followed by blaTeM-1B (18.4%), tetM (15.8%), and the combination of blaTeM-1B, ermT, and tetL was 2.6% of the isolates. The AMR phenotypes were predicted in ciprofloxacin, penicillin, tetracycline, azithromycin, and cefixime. The combination of mutations 23.7% was gryA (S91F), parC (E91G), ponA (L421) and rpsJ (V57M), followed by 18.4% in gyrA (S91F), ponA (L421P), rpsJ (V57M), and 18.4% in gyrA (D95G, S91F), ponA (L421P), and rpsJ (V57M). The combinations in gyrA (D95G, S91F) and rpsJ (V57M), and gyrA (D95G, S91F), parC (E91F), ponA (L421P) and rpsJ (V57M) were 13.2% each of the isolates. Plasmid TEM-1 (84.2%), tetM (15.8%), and gonococcal genetic island (GGI) was detected in all isolates. CONCLUSION: This study revealed remarkable heterogeneity of N. gonorrhoeae with blaTEM-1, tetM, ponA, gyrA, and parC genes associated with high resistance to penicillin, tetracycline, and ciprofloxacin demanding revision of the standard treatment guidelines and improved antimicrobial stewardship in Zambia.

Crimean-Congo Hemorrhagic Fever Virus Seroprevalence in Human and Livestock Populations, Northern Tanzania.

We conducted a cross-sectional study of Crimean-Congo hemorrhagic fever virus (CCHFV) in northern Tanzania. CCHFV seroprevalence in humans and ruminant livestock was high, as were spatial heterogeneity levels. CCHFV could represent an unrecognized human health risk in this region and should be included as a differential diagnosis for febrile illness.

Maternal and infant predictors of proinflammatory milk immune activity in Kilimanjaro, Tanzania.

OBJECTIVES: The immune system of milk (ISOM) creates a mother-infant immune axis that plays an important role in protecting infants against infectious disease (ID). Tradeoffs in the immune system suggest the potential for both protection and harm, so we conceive of two dimensions via which the ISOM impacts infants: promotion of protective activity and control of activity directed at benign targets. High variability in ISOM activity across mother-infant dyads suggests investment the ISOM may have evolved to be sensitive to maternal and/or infant characteristics. We assessed predictors of appropriate and misdirected proinflammatory ISOM activity in an environment of high ID risk, testing predictions drawn from life history theory and other evolutionary perspectives. METHODS: We characterized milk in vitro interleukin-6 (IL-6) responses to Salmonella enterica (a target of protective immune activity; N = 96) and Escherichia coli (a benign target; N = 85) among mother-infant dyads in rural Kilimanjaro, Tanzania. We used ordered logistic regression and mixture models to evaluate maternal and infant characteristics as predictors of IL-6 responses. RESULTS: In all models, IL-6 responses to S. enterica increased with maternal age and decreased with gravidity. In mixture models, IL-6 responses to E. coli declined with maternal age and increased with gravidity. No other considered variables were consistently associated with IL-6 responses. CONCLUSIONS: The ISOM's capacities for appropriate proinflammatory activity and control of misdirected proinflammatory activity increases with maternal age and decreases with gravidity. These findings are consistent with the hypothesis that the mother-infant immune axis has evolved to respond to maternal life history characteristics.

"When a man drinks alcohol it's cool but when a woman drinks she is a hoe": A qualitative exploration of alcohol, gender, stigma, and sexual assault in Moshi, Tanzania.

Alcohol's ever-increasing global use poses a distinct threat to human well-being, with intake and associated burdens rising especially quickly in low- and middle-income countries like Tanzania. Prior research has shown alcohol use and related consequences differ by gender in Moshi, Tanzania, with important implications for both clinical care and future alcohol-reduction interventions. This study builds upon this knowledge by providing a deeper understanding of how gender differences affect alcohol-related stigma and sexual assault among Emergency Department (ED) and Reproductive Health Center (RHC) patients at Kilimanjaro Christian Medical Center (KCMC) in Moshi. In-depth interviews were conducted among ED and RHC KCMC patients (n = 19) selected for participation via purposive sampling. A mix of inductive and deductive coding schemes was used to identify themes and subthemes. All data were analyzed through a grounded theory approach. Gender roles that linked men with financial responsibilities and women with child caretaking led to different expectations on alcohol intake, with alcohol use encouraged for men but vilified for women. Women who drank, for example, were deemed poor mothers and undesirable spouses. Patients likewise emphasized that both alcohol-related stigma and sexual violence disproportionately impacted women, the latter fueled through alcohol use, with serious and lasting acts of discrimination and isolation from community members seen among women alcohol users but not for men. Women alcohol users in Moshi are subject to severe social consequences, facing disproportionate stigma and sexual violence as compared to men. Alcohol-related treatment for women should be mindful of the disproportionate burdens present in this context while treatment for men should be cognizant of the social pressures to drink. Strategies to address and/or mitigate these factors should be incorporated in subsequent care and interventions.

Treatment seeking behaviours, antibiotic use and relationships to multi-drug resistance: A study of urinary tract infection patients in Kenya, Tanzania and Uganda.

Antibacterial resistance (ABR) is a major public health threat. An important accelerating factor is treatment-seeking behaviour, including inappropriate antibiotic (AB) use. In many low- and middle-income countries (LMICs) this includes taking ABs with and without prescription sourced from various providers, including health facilities and community drug sellers. However, investigations of complex treatment-seeking, AB use and drug resistance in LMICs are scarce. The Holistic Approach to Unravel Antibacterial Resistance in East Africa (HATUA) Consortium collected questionnaire and microbiological data from adult outpatients with urinary tract infection (UTI)-like symptoms presenting at healthcare facilities in Kenya, Tanzania and Uganda. Using data from 6,388 patients, we analysed patterns of self-reported treatment seeking behaviours ('patient pathways') using process mining and single-channel sequence analysis. Among those with microbiologically confirmed UTI (n = 1,946), we used logistic regression to assess the relationship between treatment seeking behaviour, AB use, and the likelihood of having a multi-drug resistant (MDR) UTI. The most common treatment pathway for UTI-like symptoms in this sample involved attending health facilities, rather than other providers like drug sellers. Patients from sites in Tanzania and Uganda, where over 50% of patients had an MDR UTI, were more likely to report treatment failures, and have repeat visits to providers than those from Kenyan sites, where MDR UTI proportions were lower (33%). There was no strong or consistent relationship between individual AB use and likelihood of MDR UTI, after accounting for country context. The results highlight the hurdles East African patients face in accessing effective UTI care. These challenges are exacerbated by high rates of MDR UTI, suggesting a vicious cycle of failed treatment attempts and sustained selection for drug resistance. Whilst individual AB use may contribute to the risk of MDR UTI, our data show that factors related to context are stronger drivers of variations in ABR.