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Background: Urogenital schistosomiasis caused by Schistosoma haematobium affects approximately 110 million people globally, with the majority of cases in low- and middle-income countries. Schistosome infections have been shown to impact the host immune system, gene expression, and microbiome composition. Studies have demonstrated variations in pathology between schistosome subspecies. In the case of S. haematobium, infection has been associated with HIV acquisition and bladder cancer. However, the underlying pathophysiology has been understudied compared to other schistosome species. This systematic review comprehensively investigates and assimilates the effects of S. haematobium infection on systemic and local host mucosal immunity, cellular gene expression and microbiome. Methods: We conducted a systematic review assessing the reported effects of S. haematobium infections and anthelmintic treatment on the immune system, gene expression and microbiome in humans and animal models. This review followed PRISMA guidelines and was registered prospectively in PROSPERO (CRD42022372607). Randomized clinical trials, cohort, cross-sectional, case-control, experimental ex vivo, and animal studies were included. Two reviewers performed screening independently. Results: We screened 3,177 studies and included 94. S. haematobium was reported to lead to: (i) a mixed immune response with a predominant type 2 immune phenotype, increased T and B regulatory cells, and select pro-inflammatory cytokines; (ii) distinct molecular alterations that would compromise epithelial integrity, such as increased metalloproteinase expression, and promote immunological changes and cellular transformation, specifically upregulation of genes p53 and Bcl-2; and (iii) microbiome dysbiosis in the urinary, intestinal, and genital tracts. Conclusion: S. haematobium induces distinct alterations in the host's immune system, molecular profile, and microbiome. This leads to a diverse range of inflammatory and anti-inflammatory responses and impaired integrity of the local mucosal epithelial barrier, elevating the risks of secondary infections. Further, S. haematobium promotes cellular transformation with oncogenic potential and disrupts the microbiome, further influencing the immune system and genetic makeup. Understanding the pathophysiology of these interactions can improve outcomes for the sequelae of this devastating parasitic infection. Author summary: The parasitic trematode S. haematobium affects 110 million people worldwide. Many studies have described the effects of schistosome infections on humans and animals, but data focusing solely on S. haematobium infections, which cause urogenital schistosomiasis are scarce. Our goal was to evaluate, in a systematic manner, how S. haematobium infection affects the immune system, gene expression and microbiome of the host. These effects are important because they could lead to increased risk of infections, such as HIV, and bladder cancer. We screened 3,179 studies for potential relevance and included 94 of them in this review. Our analysis showed that S. haematobium infection profoundly alters the immune system with a mixed pro-inflammatory and anti-inflammatory response, though with a predominant type 2 immune phenotype and increased regulatory cells. We further found consistent evidence that it impairs local mucosal epithelial barrier integrity, promotes cellular transformation with pro-oncogenic changes in the host, and is associated with microbial alterations in urine, stool, and genital tracts. We discuss how these findings might be interpreted, and the additional research needed, to improve our understanding of S. haematobium pathophysiology and ameliorate the potential sequelae of S. haematobium infection, such as increased viral infections and cancer. [ABSTRACT FROM AUTHOR]

IntroductionLittle is known about outcomes after hospitalization for HIV-infected adults in sub-Saharan Africa. We determined 12-month, posthospital mortality rates in HIV-infected vs. uninfected adults and predictors of mortality.MethodsIn this prospective cohort study, we enrolled adults admitted to the medical wards of a public hospital in northwestern Tanzania. We conducted standardized questionnaires, physical examinations, and basic laboratory analyses including HIV testing. Participants or proxies were called at 1, 3, 6, and 12 months to determine outcomes. Predictors of in-hospital and posthospital mortality were determined using logistic regression. Cox regression models were used to analyze mortality incidence and associated factors. To confirm our findings, we studied adults admitted to another government hospital.ResultsWe enrolled 637 consecutive adult medical inpatients: 38/143 (26.6%) of the HIV-infected adults died in hospital vs. 104/494 (21.1%) of the HIV-uninfected adults. Twelve-month outcomes were determined for 98/105 (93.3%) vs. 352/390 (90.3%) discharged adults, respectively. Posthospital mortality was 53/105 (50.5%) for HIV-infected adults vs. 126/390 (32.3%) for HIV-uninfected adults (adjusted P = 0.006). The 66/105 (62.9%) HIV-infected adults who attended clinic within 1 month after discharge had significantly lower mortality than the other HIV-infected adults [adjusted hazards ratio = 0.17 (0.07-0.39), P < 0.001]. Adults admitted to a nearby government hospital had similar high rates of posthospital mortality.ConclusionsPosthospital mortality is disturbingly high among HIV-infected adult inpatients in Tanzania. The posthospital period may offer a window of opportunity to improve survival in this population. Interventions are urgently needed and should focus on increasing posthospital linkage to primary HIV care.

Schistosoma haematobium, the parasite that causes urogenital schistosomiasis, is widely prevalent in Tanzania. In addition to well-known effects on the urinary tract, S. haematobium also causes clinically- evident damage to the reproductive tract in approximately half of infected women, which is known as female genital schistosomiasis (FGS). FGS has major gynecologic and social consequences on women's reproductive health, yet little information is available regarding FGS in Tanzania. To cover that gap, we conducted the present scoping review to examine the epidemiology of FGS in Tanzania (both in the mainland and Zanzibar island) and to make recommendations for future work in this area. The available evidence from community-based and hospital-based retrospective studies indicates that FGS is a significant health problem in the country. Very few community-based studies have been reported from mainland Tanzania, and Zanzibar. Our review highlights the scarcity of efforts to address FGS in Tanzania and the need for additional community-based studies. The studies will help us understand the true burden of the disease nationwide, to assess the impact of praziquantel on FGS lesions, and to address social and mental health in relation to FGS. This review emphasizes integration of delivery of FGS related services in primary health care systems through the reproductive health clinics which covers sexually transmitted infections, HIV and cervical cancer screening. These actions are essential if this neglected gynecological disease is to be addressed in Tanzania. Author summary: Female genital schistosomiasis (FGS) caused by Schistosoma haematobium affects mostly the reproductive tract of girls and women in rural and marginalized communities. This disease has been largely neglected by the schistosomiasis endemic communities and public health professionals. The present review aimed at assessing the evidence/epidemiology of FGS among women/girls in Tanzania. Furthermore, the review assessed the availability of information, published literature on FGS including comorbidities that address FGS in Tanzania mainland and Zanzibar islands. The evidence generated was important to inform the need to address FGS key gaps among researchers, healthcare workers and communities. Overall, the findings indicated that the knowledge of FGS was lacking among the endemic communities and healthcare workers. Findings from this review have shown the available gaps in literature on FGS in Tanzania, from very few community-and-hospitals based studies reported from mainland Tanzania, and Zanzibar. To address this gap, further research is essential to understanding the true burden of disease-associated morbidity, to assessing the impact of single dose praziquantel in FGS lesions, to understanding mental health in relation to FGS, and to integrating delivery of FGS related services in primary health care systems. [ABSTRACT FROM AUTHOR]

Problem In the United Republic of Tanzania, the incidence of non-neonatal circumcision-related tetanus is probably underreported. Approach 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. Local setting 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. Relevant changes 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. Lessons learnt 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. Probleme En Republique-Unie deTanzanie, l'incidence du tetanos non neonatal lie a la circoncision est probablement sous-estimee. Approche Nous avons analyse des tableaux et extrait des informations concernant les suites et l'emplacement de la plaie des cas de tetanos non neonatal admis dans le service de soins intensifs du centre medical Bugando entre 2001 et 2016. Environnement local Le centre medical Bugando, l'un des quatre hopitaux centraux d'enseignement de la Republique-Unie de Tanzanie, dispose d'un service de soins intensifs dote de 13 lits qui prend en charge tous les patients admis avec le tetanos. Dans la Republique-Unie de Tanzanie, les programmes formels de vaccination contre le tetanos ciblent les nourrissons ou les femmes. Changements significatifs Nous avons releve, dans nos registres d'hospitalisation, six patients atteints de tetanos non neonatal parmi les patients masculins ayant recemment subi une circoncision. Seul un de ces patients avait ete circoncis dans le cadre d'un programme infranational de circoncision masculine medicale volontaire. Les cinq autres avaient ete circoncis en-dehors de ce programme, par exemple dans de petits dispensaires ruraux ou par un praticien traditionnel sans formation medicale formelle. Ces six patients etaient ages de 11 a 55 ans et cinq (83%) d'entre eux sont decedes a l'hopital, tous de septicemie. Lecons tirees Dans le cadre du programme tanzanien de circoncision masculine medicale volontaire, l'education a l'hygiene de la plaie contribue probablement a reduire l'incidence du tetanos non neonatal lie a la circoncision. L'incidence correspondante chez les garcons et les hommes qui sont circoncis en-dehors de ce programme infranational est probablement plus importante. La formation en matiere 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 beneficier de vaccins contre le tetanos apres la petite enfance sont recommandees. Problema En la Republica Unida de Tanzania, es posible que no se comunique la incidencia del tetanos relacionado con la circuncision no neonatal. Enfoque Hemos analizado graficos y extraido informacion sobre las consecuencias y la localizacion de la herida para los casos no neonatales de tetanos ingresados en la unidad de cuidados intensivos del Bugando Medical Centre entre 2001 y 2016. Marco regional El Bugando Medical Centre, uno de los cuatro hospitales de referencia en la Republica Unida de Tanzania, cuenta con una unidad de cuidados intensivos de 13 camas que se ocupa de todos los pacientes ingresados con tetanos. En la Republica Unida de Tanzania, los programas oficiales de vacunacion contra el tetanos estan orientados a infantes o mujeres. Cambios relevantes A partir de los registros de pacientes hospitalizados, se identificaron a seis pacientes con tetanos no neonatal entre los pacientes varones con un historial reciente de circuncision. Solo uno de estos pacientes habia sido circuncidado dentro de un programa subnacional para la circuncision masculina voluntarla medica. Los otros cinco habian sido circuncidados fuera del programa, por ejemplo, en pequenos dispensarlos rurales o atendidos por un proveedor tradicional sin formacion medica oficial. Los seis pacientes tenian entre 11 y 55 anos de edad y cinco (83%) de ellos murieron en el hospital, todos a causa de una sepsis Incontenible. Lecciones aprendidas Dentro del programa de Tanzania para la circuncision masculina voluntaria medica, probablemente la educacion sobre la higiene de las heridas ayude a reducir la Incidencia del tetanos relacionado con la circuncision no neonatal. Es probable que la Incidencia correspondiente entre los ninos y hombres circuncidados fuera de este programa subnacional sea mayor. Se recomienda la formacion de todos los proveedores de circuncision en el cuidado de heridas y un programa de vacunacion para asegurar que los varones de Tanzania sean vacunados contra el tetanos despues de la Infancia., Introduction By 2012, 14 countries in eastern and southern Africa--including the United Republic of Tanzania--had been prioritized for the scale-up of voluntary medical male circumcision. (1) The goal of the [...]

Background: Cryptococcal meningitis is a leading cause of death among HIV‐infected individuals in sub‐Saharan Africa. Recent developments include the availability of intravenous fluconazole, cryptococcal antigen assays and new data to support fluconazole pre‐emptive treatment. In this study, we describe the impact of screening HIV‐positive adult inpatients with serum cryptococcal antigen (CRAG) at a Tanzanian referral hospital. Methods: All adults admitted to the medical ward of Bugando Medical Centre are counseled and tested for HIV. In this prospective cohort study, we consecutively enrolled HIV‐positive patients admitted between September 2009 and January 2010. All patients were interviewed, examined and screened with serum CRAG. Patients with positive serum CRAG or signs of meningitis underwent lumbar puncture. Patients were managed according to standard World Health Organization treatment guidelines. Discharge diagnoses and in‐hospital mortality were recorded. Results: Of 333 HIV‐infected adults enrolled in our study, 15 (4.4%) had confirmed cryptococcal meningitis and 10 of these 15 (66%) died. All patients with cryptococcal meningitis had at least two of four classic symptoms and signs of meningitis: fever, headache, neck stiffness and altered mental status. Cryptococcal meningitis accounted for a quarter of all in‐hospital deaths. Conclusions: Despite screening of all HIV‐positive adult inpatients with the serum CRAG at the time of admission and prompt treatment with high‐dose intravenous fluconazole in those with confirmed cryptococcal meningitis, the in‐hospital mortality rate remained unacceptably high. Improved strategies for earlier diagnosis and treatment of HIV, implementation of fluconazole pre‐emptive treatment for high‐risk patients and acquisition of better resources for treatment of cryptococcal meningitis are needed., Background Cryptococcal meningitis is one of the most common and severe opportunistic infections among people infected with HIV: there are an estimated 720, 000 cases and 500, 000 deaths per [...]

The photolysis of CpW(CO)(sub 3)Me is demonstrated to produce methyl radicals and to cleave DNA in a single-stranded manner, and preliminary evidence implicated a carbon-centered radical in this process. The mechanism of strand scission in this reaction was determined to occur by hydrogen atom abstraction from the 4'- and 5'-positions of the deoxyribose moiety of the backbone of DNA.

Acetoacetanilide and 4'-chloroacetoacetanilide were trilithiated with excess lithium diisopropylamide and condensed with several aromatic esters, followed by neutralization, separate acid cyclization, and rearrangements. After C-acylation of trilithiated acetoacetanilides and cyclization to 4H-pyran-4-ones, these compounds underwent multistep rearrangements to 4-anilino-6-aryl-2H-pyran-2-ones. Key words: pyranones, trianions, Claisen-type condensations, rearrangements.

* Early diagnosis of infants infected perinatally with HIV in sub-Saharan Africa depends on completion of multiple steps for results to reach an infant's caregivers in a timely manner. * This project, designed by a pediatric HIV nurse in Tanzania, applied sequential quality improvement interventions to reduce the lengthy turnaround time between dried blood collection from exposed infants and return of test results. * Low-cost interventions successfully reduced the turnaround time from 55 to 38 days, and increased the number of results given to caregivers to >90%. * This work can serve as a model for implementation to improve identification of HIV-infected infants in other resource-poor settings., Introduction Newborns infected with HIV before, during, or shortly after delivery have high mortality, with 50% dying before one year of age, and 20% of these early deaths occurring between [...]

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Background: Detection of subclinical cryptococcal disease using cryptococcal antigen screening among HIV‐positive individuals presents a potential opportunity for prevention of both clinical disease and death if patients with detectable cryptococcal antigen are identified and treated pre‐emptively. Recently developed point‐of‐care cryptococcal antigen tests may be useful for screening, particularly in resource‐limiting settings, but few studies have assessed their utility. Methodology: The objectives of this study were to determine the prevalence and factors associated with cryptococcal antigenemia in HIV‐positive patients with CD4[sup.+] T‐cell counts ≤200 cells/µL who were initiating ART, and also to evaluate the utility of the point‐of‐care urine lateral flow assay (LFA) cryptococcal antigen test using two different diluents, compared to gold standard serum antigen testing, as a screening tool. Urine and serum of outpatients initiating antiretroviral therapy at two hospitals in Mwanza were tested for cryptococcal antigen, and demographic and clinical characteristics were obtained using structured questionnaires and patients’ files. Patients with asymptomatic cryptococcal antigenemia received oral fluconazole in accordance with World Health Organization recommendations. Results: Among 140 patients screened, 10 (7.1%) had asymptomatic cryptococcal antigenemia with a positive serum cryptococcal antigen. Four of these ten patients had CD4 counts between 100 and 200 cells/µL. The prevalence of cryptococcal antigen detected in urine using a standard (older) and a test (newer) diluent were 44 (31.4%) and 19 (13.6%), with Kappa coefficients compared to serum of 0.28 and 0.51 (p Conclusions: Our findings suggest that HIV‐positive outpatients with CD4 counts, Introduction Cryptococcus neoformans is one of the leading opportunistic infections in people living with HIV/AIDS in sub‐Saharan Africa [1–4]. It is estimated that 3% of HIV‐positive individuals in sub‐Saharan Africa [...]