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.

Prevalence of Schistosomes and Soil-Transmitted Helminths among Schoolchildren in Lake Victoria Basin, Tanzania.

The objectives of this study was to conduct a survey on schistosomiasis and soil-transmitted helminth (STH) infections in order to come up with feasible control strategies in Lake Victoria basin, Tanzania. Depending on the size of the school, 150-200 schoolchildren were recruited for the study. Duplicate Kato-Katz stool smears were prepared from each child and microscopically examined for Schistosoma mansoni and STHs. Urine specimens were examined for Schistosoma haematobium eggs using the filtration technique. After the survey, mass drug administration was done using praziquantel and albendazole for schistosomiasis and STHs infections, respectively. A total of 5,952 schoolchildren from 36 schools were recruited for the study and had their stool and urine specimens examined. Out of 5,952 schoolchildren, 898 (15.1%) were positive for S. mansoni, 754 (12.6%) for hookworms, 188 (3.2%) for Ascaris lumblicoides, and 5 (0.008%) for Trichuris trichiura. Out of 5,826 schoolchildren who provided urine samples, 519 (8.9%) were positive for S. haematobium eggs. The results revealed that intestinal schistosomiasis, urogenital schistosomiasis, and STH infections are highly prevalent throughought the lake basin. The high prevalence of intestinal and urogenital schistosomisiasis in the study area was a function of the distance from Lake Victoria, the former being more prevalent at localities close to the lake, whilst the latter is more so away from it. Control of schistosomiasis and STHs in the study area requires an integrated strategy that involves provision of health education to communities, regular treatments, and provision of adequate safe water supply and sanitation facilities.

Prevalence of Schistosomes and Soil-Transmitted Helminths and Morbidity Associated with Schistosomiasis among Adult Population in Lake Victoria Basin, Tanzania.

The objective of this study was to carry out a community survey on schistosomiais and soil-transmitted helminth (STH) infections in order to suggest feasible and effective intervention strategies in Lake Victoria basin, Tanzania. A total of 37 communities selected from 23 districts of the 4 regions in the Lake Victoria basin of Tanzania were involved in the study. From each of the selected locality, 50 adult community members, 25 males and 25 females, were recruited for the study. Each study participant was requested to submit stool and urine specimens. From each stool specimen, duplicate Kato-Katz thick smears were prepared and microscopically examined for Schistosoma mansoni and STH eggs. Urine specimens were processed by the filtration technique and microscopically examined for Schistosoma haematobium eggs. Ultrasound examination for morbidity due to schistosomiasis was performed. Mass treatment was done using praziquantel and albendazole for schistosome and STHs infections, respectively. Out of 1,606 adults who provided stool specimens, 199 (12.4%) were positive for S. mansoni, 349 (21.7%) for hookworms, 133 (8.3%) for Ascaris lumbricoides, and 33 (2.0%) for Trichuris trichiura. Out of 1,400 participants who provided urine specimens, 25 (1.8%) were positive for S. haematobium eggs. Because of the co-endemicity of these afflictions and their impact on vulnerable population groups, the helminthiasis could be simultaneously treated with 2 drugs, praziquantel for schistosomiasis and albendazole for STHs.

Integrated Schistosomiasis and Soil-Transmitted Helminthiasis Control over Five Years on Kome Island, Tanzania.

Integrated control strategies are important for sustainable control of schistosomiasis and soil-transmitted helminthiasis, despite their challenges for their effective implementation. With the support of Good Neighbors International in collaboration with National Institute of Medical Research, Mwanza, Tanzania, integrated control applying mass drug administration (MDA), health education using PHAST, and improved safe water supply has been implemented on Kome Island over 5 years for controlling schistosomiasis and soil-transmitted helminths (STHs). Baseline surveys for schistosomiasis and STHs was conducted before implementation of any integrated control strategies, followed by 4 cross-sectional follow-up surveys on randomly selected samples of schoolchildren and adults in 10 primary schools and 8 villages, respectively, on Kome islands. Those follow-up surveys were conducted for impact evaluation after introduction of control strategies interventions in the study area. Five rounds of MDA have been implemented from 2009 along with PHAST and improved water supply with pumped wells as other control strategies for complementing MDA. A remarkable steady decline of schistosomiasis and STHs was observed from 2009 to 2012 with significant trends in their prevalence decline, and thereafter infection rate has remained at a low sustainable control. By the third follow-up survey in 2012, Schistosoma mansoni infection prevalence was reduced by 90.5% and hookworm by 93.3% among schoolchildren while in adults the corresponding reduction was 83.2% and 56.9%, respectively. Integrated control strategies have successfully reduced S. mansoni and STH infection status to a lower level. This study further suggests that monitoring and evaluation is a crucial component of any large-scale STH and schistosomiasis intervention.

Schistosoma mansoni-Related Hepatosplenic Morbidity in Adult Population on Kome Island, Sengerema District, Tanzania.

Schistosomiasis is one of the important neglected tropical diseases (NTDs) in Tanzania, particularly in Lake Victoria zone. This baseline survey was a part of the main study of integrated control of schistosomiasis and soil-transmitted helminths (STHs) aimed at describing morbidity patterns due to intestinal schistosomiasis among adults living on Kome Island, Sengerema District, Tanzania. Total 388 adults from Kome Islands (about 50 people from each village) aged between 12 and 85 years, were examined by abdominal ultrasound according to the Niamey protocol. Liver image patterns (LIPs) A and B were considered normal, and C-F as distinct periportal fibrosis (PPF). The overall prevalence of PPF was 42.2%; much higher in males than in females (47.0% in male vs 34.4% in females, P=0.007). Abnormal increase of segmental branch wall thickness (SBWT) and dilated portal vein diameter (PVD) were also more common in males than in females. Hepatosplenomegaly was frequently encountered; 68.1% had left liver lobe hepatomegaly and 55.2% had splenomegaly. Schistosoma mansoni-related morbidity is quite high among adults in this community justifying the implementation of integrated control strategies through mass drug administration, improved water supply (pumped wells), and health education that had already started in the study area.

Improved Socio-Economic Status of a Community Population Following Schistosomiasis and Intestinal Worm Control Interventions on Kome Island, North-Western Tanzania.

Research on micro-level assessment of the changes of socio-economic status following health interventions is very scarce. The use of household asset data to determine wealth indices is a common procedure for estimating socio-economic position in resource poor settings. In such settings information about income is usually lacking, and the collection of individual consumption or expenditure data would require in-depth interviews, posing a considerable risk of bias. In this study, we determined the socio-economic status of 213 households in a community population in an island in the north-western Tanzania before and 3 year after implementation of a participatory hygiene and sanitation transformation (PHAST) intervention to control schistosomiasis and intestinal worm infections. We constructed a household 'wealth index' based housing construction features (e.g., type of roof, walls, and floor) and durable assets ownership (e.g., bicycle, radio, etc.). We employed principal components analysis and classified households into wealth quintiles. The study revealed that asset variables with positive factor scores were associated with higher socio-economic status, whereas asset variables with negative factor scores were associated with lower socio-economic status. Overall, households which were rated as the poorest and very poor were on the decrease, whereas those rated as poor, less poor, and the least poor were on the increase after PHAST intervention. This decrease/increase was significant. The median shifted from -0.4376677 to 0.5001073, and the mean from -0.2605787 (SD; 2.005688) to 0.2605787 (SD; 1.831199). The difference in socio-economic status of the people between the 2 phases was highly statistically significant (P<0.001). We argue that finding of this study should be treated with caution as there were other interventions to control schistosomiasis and intestinal worm infections which were running concurrently on Kome Island apart from PHAST intervention.

Improved Perceptions and Practices Related to Schistosomiasis and Intestinal Worm Infections Following PHAST Intervention on Kome Island, North-Western Tanzania.

Schistosomiasis and intestinal worm infections are widespread diseases of public health importance in Tanzania. A study on perceptions and practices related to schistosomiasis and intestinal worm infections was undertaken among a community population of Kome Island in Sengerema District, north-western Tanzania, where intestinal schistosomiasis and intestinal worm infections are endemic. Schistosomiasis and intestinal worm-related perceptions and practices were assessed before and 3 years after implementation of a participatory hygiene and sanitation transformation (PHAST) intervention as a control measure. Data were obtained from baseline and post-intervention knowledge, attitudes, and practices (KAP) questionnaire surveys conducted twice in 2009 and 2012 among 82 individuals aged ≥15 years. We found significant increases in respondents' knowledge of the cause, transmission, symptoms, health consequences, and prevention of schistosomiasis and intestinal worm infections after PHAST intervention. The increase in respondents' knowledge on almost all aspects of the said infections was translated into actions to control schistosomiasis and intestinal worm infections. This has not been achieved by chance, but due to well-designed and locally-adapted PHAST intervention. We conclude that despite criticisms, PHAST approach is still useful in empowering communities to control water, sanitation, and hygiene related infectious diseases such as schistosomiasis and intestinal worm infections.

High Malaria Prevalence among Schoolchildren on Kome Island, Tanzania.

In order to determine the status of malaria among schoolchildren on Kome Island (Lake Victoria), near Mwanza, Tanzania, a total of 244 schoolchildren in 10 primary schools were subjected to a blood survey using the fingerprick method. The subjected schoolchildren were 123 boys and 121 girls who were 6-8 years of age. Only 1 blood smear was prepared for each child. The overall prevalence of malaria was 38.1% (93 positives), and sex difference was not remarkable. However, the positive rate was the highest in Izindabo Primary School (51.4%) followed by Isenyi Primary School (48.3%) and Bugoro Primary School (46.7%). The lowest prevalence was found in Muungano Primary School (16.7%) and Nyamiswi Primary School (16.7%). These differences were highly correlated with the location of the school on the Island; those located in the peripheral area revealed higher prevalences while those located in the central area showed lower prevalences. Plasmodium falciparum was the predominant species (38.1%; 93/244), with a small proportion of them mixed-infected with Plasmodium vivax (1.6%; 4/244). The results revealed that malaria is highly prevalent among primary schoolchildren on Kome Island, Tanzania, and there is an urgent need to control malaria in this area.

Effects of Schistosoma haematobium infection and treatment on the systemic and mucosal immune phenotype, gene expression and microbiome: A systematic review.

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.

Flow-S: A Field-Deployable Device with Minimal Hands-On Effort to Concentrate and Quantify Schistosoma Circulating Anodic Antigen (CAA) from Large Urine Volumes.

A laboratory-based lateral flow (LF) test that utilizes up-converting reporter particles (UCP) for ultrasensitive quantification of Schistosoma circulating anodic antigen (CAA) in urine is a well-accepted test to identify active infection. However, this UCP-LF CAA test requires sample pre-treatment steps not compatible with field applications. Flow, a new low-cost disposable, allows integration of large-volume pre-concentration of urine analytes and LF detection into a single field-deployable device. We assessed a prototype Flow-Schistosoma (Flow-S) device with an integrated UCP-LF CAA test strip, omitting all laboratory-based steps, to enable diagnosis of active Schistosoma infection in the field using urine. Flow-S is designed for large-volume (5-20 mL) urine, applying passive paper-based filtration and antibody-based CAA concentration. Samples tested for schistosome infection were collected from women of reproductive age living in a Tanzania region where S. haematobium infection is endemic. Fifteen negative and fifteen positive urine samples, selected based on CAA levels quantified in paired serum, were analyzed with the prototype Flow-S. The current Flow-S prototype, with an analytical lower detection limit of 1 pg CAA/mL, produced results correlated with the laboratory-based UCP-LF CAA test. Urine precipitates occurred in frozen banked samples and affected accurate quantification; however, this should not occur in fresh urine. Based on the findings of this study, Flow-S appears suitable to replace the urine pre-treatment required for the laboratory-based UCP-LF CAA test, thus allowing true field-based applications with fresh urine samples. The urine precipitates observed with frozen samples, though less important given the goal of testing fresh urines, warrant additional investigation to evaluate methods for mitigation. Flow-S devices permit testing of pooled urine samples with applications for population stratified testing. A field test with fresh urine samples, a further optimized Flow-S device, and larger statistical power has been scheduled.

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.

Effects of helminths and anthelmintic treatment on cardiometabolic diseases and risk factors: A systematic review.

BACKGROUND: Globally, helminth infections and cardiometabolic diseases often overlap in populations and individuals. Neither the causal relationship between helminth infections and cardiometabolic diseases nor the effect of helminth eradication on cardiometabolic risk have been reviewed systematically in a large number of human and animal studies. METHODS: We conducted a systematic review assessing the reported effects of helminth infections and anthelmintic treatment on the development and/or severity of cardiometabolic diseases and risk factors. The search was limited to the most prevalent human helminths worldwide. This study followed PRISMA guidelines and was registered prospectively in PROSPERO (CRD42021228610). Searches were performed on December 10, 2020 and rerun on March 2, 2022 using Ovid MEDLINE ALL (1946 to March 2, 2022), Web of Science, Cochrane Library, Global Index Medicus, and Ovid Embase (1974 to March 2, 2022). Randomized clinical trials, cohort, cross-sectional, case-control, and animal studies were included. Two reviewers performed screening independently. RESULTS: Eighty-four animal and human studies were included in the final analysis. Most studies reported on lipids (45), metabolic syndrome (38), and diabetes (30), with fewer on blood pressure (18), atherosclerotic cardiovascular disease (11), high-sensitivity C-reactive protein (hsCRP, 5), and non-atherosclerotic cardiovascular disease (4). Fifteen different helminth infections were represented. On average, helminth-infected participants had less dyslipidemia, metabolic syndrome, diabetes, and atherosclerotic cardiovascular disease. Eleven studies examined anthelmintic treatment, of which 9 (82%) reported post-treatment increases in dyslipidemia, metabolic syndrome, and diabetes or glucose levels. Results from animal and human studies were generally consistent. No consistent effects of helminth infections on blood pressure, hsCRP, or cardiac function were reported except some trends towards association of schistosome infection with lower blood pressure. The vast majority of evidence linking helminth infections to lower cardiometabolic diseases was reported in those with schistosome infections. CONCLUSIONS: Helminth infections may offer protection against dyslipidemia, metabolic syndrome, diabetes, and atherosclerotic cardiovascular disease. This protection may lessen after anthelmintic treatment. Our findings highlight the need for mechanistic trials to determine the pathways linking helminth infections with cardiometabolic diseases. Such studies could have implications for helminth eradication campaigns and could generate new strategies to address the global challenge of cardiometabolic diseases.

High Prevalence of Sexually Transmitted and Reproductive Tract Infections (STI/RTIs) among Patients Attending STI/Outpatient Department Clinics in Tanzania.

We determined the prevalence and reported risk factors associated with sexually transmitted and reproductive tract infections (STI/RTIs) among patients who presented with genital symptoms in STI/outpatient department (OPD) clinics in two regional referral hospitals and six health centres in six regions in Tanzania. Methods: The patients were consecutively recruited, and the data collection was conducted in eight health care facilities from 2014 to 2016. Genital swabs were collected for the detection of the aetiological pathogens of STI/RTIs. Results: A total of 1243 participants were recruited in the study; the majority (1073, 86%) were women. The overall median age was 27.8. The prevalence of Neisseria gonorrhoeae was 25.7% (319/1243), with proportions of 50.9 and 21.5% for men and women, respectively, of Chlamydia trachomatis 12.9% (160/1241) and Mycoplasma genitalium 4.7% (53/1134). Unmarried men were more often likely to be infected with gonococcal infections as compared to their women counterparts (57.9 vs. 24.1%) p < 0.001. The majority presented with genital discharge syndrome (GDS) 93.6% (1163/1243), genital ulcer disease (GUD) 13.0% (162/1243) and GDS + GUD 9.6% (119/1243). GDS was more common in the health centres, 96.1% (1195/1243), vs. the regional referral hospitals, 92.2% (1146/1243) (p = 0.01), but those reported to the regional referral hospitals were more likely to be infected with N. gonorrhoeae (OR = 2.5) and C. trachomatis (OR = 2.1) than those from the health centres (p < 0.001). The prevalence of bacterial vaginosis (BV) and vaginal candidiasis (VC) was 24.1 and 10.4%, respectively. Interestingly, unmarried and BV-positive women were less likely to be infected with VC (p = 0.03), though VC was strongly inversely associated with an N. gonorrhoeae infection (p < 0.001). High proportions of N. gonorrhoeae (51.1%) and C. trachomatis (23.3%) were found in the Dodoma and Dar es Salaam regions, respectively. M. genitalium (7.6%) was found to be the highest in Mwanza. Conclusion: We reported a high prevalence of STI/RTIs. The findings suggest that these infections are common and prevalent in STI/OPD clinics in six regions of Tanzania. We recommend surveillance to be conducted regularly to elucidate the true burden of emerging and classical STI/RTIs by employing modern and advanced laboratory techniques for the detection and monitoring of STI/RTIs in low- and high-risk populations, including the community settings.

Effects of Schistosoma mansoni and praziquantel treatment on the lower gastrointestinal mucosa: A cohort study in Tanzania.

Schistosomes infect over 200 million people worldwide, but few studies have characterized the effects of Schistosoma mansoni infection and effective treatment on the lower gastrointestinal mucosa. In this prospective cohort study, we compared the clinical findings on sigmoidoscopy and laboratory measures in Tanzanian adults with and without S. mansoni infection at baseline and 6 months after praziquantel treatment. Grading of the endoscopic findings was done using the Mayo Scoring System for Assessment of Ulcerative Colitis Activity. Schistosome infection was confirmed by stool microscopy and serum circulating anodic antigen (CAA). Baseline comparisons were performed in Stata using Fisher's exact and Wilcoxon rank-sum tests, and pre- and post-treatment comparisons using Wilcoxon matched-pairs signed-rank and McNemar's tests. We investigated the clinical characteristics of 48 individuals: 32 with and 16 without S. mansoni infection. Infected individuals had greater severity of sigmoid and rectal mucosal abnormalities and higher Mayo scores and serum eosinophils (all p < 0.05) than uninfected individuals at initial evaluation. At 6 months, 28 individuals completed repeat blood tests and sigmoidoscopy. Of these, 14 cleared their baseline infection (n = 7) or experienced a greater than 7-fold decrease in serum CAA (n = 7). Follow-up sigmoidoscopies revealed some improvements in sigmoid and rectal mucosal findings, although Mayo scores were not significantly lower. Both the median erythrocyte sedimentation rates (32.5→12.5 mm/hr) and percent of eosinophils (7.1→3.1%) decreased in this group from baseline to follow-up. S. mansoni infection was associated with mild-to-moderate lower gastrointestinal mucosal abnormalities that were grossly visible during sigmoidoscopy, and these improved partially 6 months after effective treatment with praziquantel. Additional studies, of longer duration and focused on both clinical and mucosal immunologic effects of S. mansoni, could provide additional insight.

Antimicrobial Susceptibility Testing Patterns of Neisseria gonorrhoeae from Patients Attending Sexually Transmitted Infections Clinics in Six Regions in Tanzania.

Antimicrobial resistance (AMR) is global health threat that is on the increase, and it has been adversely affecting the proper management of sexually transmitted infections (STI). Data on antimicrobial susceptibility testing patterns of N. gonorrhoeae are limited in local settings. We determined in vitro antimicrobial susceptibility and phenotypic profiles of N. gonorrhoeae isolated from STI/Outpatient Department (OPD) clinics. Minimum Inhibitory Concentrations (MIC) (µg/mL) were determined using E-Test and agar dilution methods for previously and currently recommended antimicrobial agents. A total of 164 N. gonorrhoeae isolates from urethral discharge and endocervical swabs were tested. The prevalence of resistant N. gonorrhoeae to tetracycline, norfloxacin, penicillin and ciprofloxacin were 98.6%, 82.2%, 84.3% and 75.6%, respectively. None of the isolates was resistant to kanamycin. Penicillinase producing N. gonorrhoeae (PPNG) was found to be 73.7%, with 56.7% and 43.3% observed among isolates from women and men, respectively. Tetracycline resistant-N. gonorrhoeae (TRNG) was found to be 34.0%, and QRNG with HLR to ciprofloxacin was 79.9%. The overall MDR-NG was 79.9%, and XDR-NG was 3.6%. MIC50 and MIC90 were 4.0 and 8.0 and 2.0 and 4.0 µg/mL for ciprofloxacin and norfloxacin, respectively. Dendrograms showed that 44 phenotypic groups are associated with a high rate of AMR among high MDR-NG and moderate XDR-NG isolates. The predominant groups of quinolone-resistant N. gonorrhoeae (QRNG)+PPNG (34.7%) and QRNG+PPNG+TRNG (32.9%) were observed among the isolates having HLR to ciprofloxacin. We reported a high prevalence of AMR (>90%) to previously recommended antimicrobials used for the treatment of gonorrhoea. Multidrug resistant N. gonorrhoeae (MDR-NG) was highly reported, and extensively drug resistant (XDR-NG) has gradually increased to the currently recommended cephalosporins including ceftriaxone and cefixime. Heterogeneous groups of QRNG+PPNG+ and QRNG+PPNG+TRNG were highly resistant to penicillin, tetracycline, ciprofloxacin and norfloxacin. A surveillance program is imperative in the country to curb the spread of AMR.

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.

Impact of schistosome infection on long-term HIV/AIDS outcomes.

BACKGROUND: Africa bears the burden of approximately 70% of global HIV infections and 90% of global schistosome infections. We sought to investigate the impact of schistosome infection at the time of HIV-1 seroconversion on the speed of HIV-1 disease progression, as measured by the outcome CD4+ T-cell (CD4) counts <350 cells/µL and/or death. We hypothesized that people who had been infected with Schistosoma spp. at the time they acquired HIV-1 infection would have impaired antiviral immune response, thus leading them to progress twice as fast to a CD4 count less than 350 cells/µL or death than would people who had been free of schistosomes at time of HIV-1 seroconversion. METHODS AND PRINCIPAL FINDINGS: We conducted a longitudinal study in Tanzania from 2006 to 2017 using stored blood spot samples, demographic surveillance and sero-survey data from the community, and a review of clinical charts. A competing risk analysis was performed to look at the difference in time to reaching CD4 counts < 350 cells/µL and/or death in HIV-1-infected people who were infected versus not infected with Schistosoma spp. at time of HIV-1 seroconversion. We found an 82% reduction in risk of reaching the outcome in seroconverters who had been infected with Schistosoma (subHazard Ratio = 0.18[0.068,0.50], p = 0.001) after adjusting for age, occupation, clinic attendance and time-dependent covariates. CONCLUSIONS: Our study demonstrates that people with schistosome infection at the time of HIV-seroconversion develop adverse HIV outcomes more slowly than those without. The findings are contrary to our original hypothesis. Our current longitudinal findings suggest complex interactions between HIV-1 and schistosome co-infections that may be modulated over time. We urge new immunological studies to investigate the long-term impact of schistosome infection on HIV-1 viral load and CD4 counts as well as related immunologic pathways.

Effects of schistosomiasis on susceptibility to HIV-1 infection and HIV-1 viral load at HIV-1 seroconversion: A nested case-control study.

BACKGROUND: Schistosomiasis affects 218 million people worldwide, with most infections in Africa. Prevalence studies suggest that people with chronic schistosomiasis may have higher risk of HIV-1 acquisition and impaired ability to control HIV-1 replication once infected. We hypothesized that: (1) pre-existing schistosome infection may increase the odds of HIV-1 acquisition and that the effects may differ between men and women, and (2) individuals with active schistosome infection at the time of HIV-1 acquisition may have impaired immune control of HIV-1, resulting in higher HIV-1 viral loads at HIV-1 seroconversion. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a nested case-control study within a large population-based survey of HIV-1 transmission in Tanzania. A population of adults from seven villages was tested for HIV in 2007, 2010, and 2013 and dried blood spots were archived for future studies with participants' consent. Approximately 40% of this population has Schistosoma mansoni infection, and 2% has S. haematobium. We tested for schistosome antigens in the pre- and post-HIV-1-seroconversion blood spots of people who acquired HIV-1. We also tested blood spots of matched controls who did not acquire HIV-1 and calculated the odds that a person with schistosomiasis would become HIV-1-infected compared to these matched controls. Analysis was stratified by gender. We compared 73 HIV-1 seroconverters with 265 controls. Women with schistosome infections had a higher odds of HIV-1 acquisition than those without (adjusted OR = 2.8 [1.2-6.6], p = 0.019). Schistosome-infected men did not have an increased odds of HIV-1 acquisition (adjusted OR = 0.7 [0.3-1.8], p = 0.42). We additionally compared HIV-1 RNA levels in the post-seroconversion blood spots in HIV-1 seroconverters with schistosomiasis versus those without who became HIV-infected in 2010, before antiretroviral therapy was widely available in the region. The median whole blood HIV-1 RNA level in the 15 HIV-1 seroconverters with schistosome infection was significantly higher than in the 22 without schistosomiasis: 4.4 [3.9-4.6] log10 copies/mL versus 3.7 [3.2-4.3], p = 0.017. CONCLUSIONS/SIGNIFICANCE: We confirm, in an area with endemic S. mansoni, that pre-existing schistosome infection increases odds of HIV-1 acquisition in women and raises HIV-1 viral load at the time of HIV-1 seroconversion. This is the first study to demonstrate the effect of schistosome infection on HIV-1 susceptibility and viral control, and to differentiate effects by gender. Validation studies will be needed at additional sites.

AMBITION-cm: intermittent high dose AmBisome on a high dose fluconazole backbone for cryptococcal meningitis induction therapy in sub-Saharan Africa: study protocol for a randomized controlled trial.

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