The dawn of a cure for sickle cell disease through CRISPR-based treatment: A critical test of equity in public health genomics.

Equity in access to genomic technologies, resources, and products remains a great challenge. This was evident especially during the coronavirus disease 2019 (COVID-19) pandemic when the majority of lower middle-income countries were unable to achieve at least 10% population vaccination coverage during initial COVID-19 vaccine rollouts, despite the rapid development of those vaccines. Sickle cell disease (SCD) is an inherited monogenic red blood cell disorder that affects hemoglobin, the protein that carries oxygen through the body. Globally, the African continent carries the highest burden of SCD with at least 240,000 children born each year with the disease. SCD has evolved from a treatable to a curable disease. Recently, the UK medical regulator approved its cure through clustered regularly interspaced short palindromic repeat (CRISPR)-based treatment, whereas the US Food and Drug Administration has equally approved two SCD gene therapies. This presents a remarkable opportunity to demonstrate equity in public health genomics. This CRISPR-based treatment is expensive and therefore, a need for an ambitious action to ensure that they are affordable and accessible where they are needed most and stand to save millions of lives.

Unraveling cervical cancer screening dilemmas: histopathological insights from VIA and LEEP at bugando medical centre, Mwanza.

BACKGROUND: The single-visit strategy, also known as the "screen-and-treat" approach, is widely used to screen for cervical cancer in low- and middle-income countries. The screen-and-treat approach leads to unnecessary or inadequate treatment. Thus, a study was conducted to determine the histopathological patterns of aceto-white lesions on visual inspection with acetic acid (VIA) in patients who underwent a Loop Electrosurgical Excision Procedure (LEEP) at Bugando Medical Centre between January 2016 and December 2020. METHOD: A 5-year retrospective cross-sectional case record review was conducted on 329 women who had LEEP at Bugando Medical Centre following a positive VIA cervical screening test. A standard data abstraction form was used to collect patient information. Missing client information records and LEEP without histopathological results were exclusion criteria. For statistical analysis, STATA version 15 was used; in descriptive statistics, frequency, mean, and standard deviation were used. The Chi2 and Fisher's exact tests were used to investigate the relationship between patient characteristics and histopathological patterns, and a P-value of 0.05 was considered statistically significant in multinomial models. RESULTS: This study looked at 329 patients who had LEEP following a VIA positive but were not eligible for cryotherapy. Our study participants had a mean age of 40 ± 8.2 SD. There were 203 (61.7%) patients with benign lesions, including 4 with schistosomiasis and 2 with cervical tuberculosis. The precancerous lesions were discovered in 100 cases (30.4%), and 26 (7.9%) already had invasive cervical cancer. Out of 100 patients with precancerous lesions, 58 (17.6%) and 42 (12.8%) have high- and low-grade squamous intraepithelial (HSIL and LSIL) lesions, respectively. The presence of a precancerous lesion was found to be associated with age 31-40 years (P-value 0.042) and HIV positivity (P-value 0.004). CONCLUSION: Most patients in this study had benign cervical lesions, which do not require LEEP treatment. Nonetheless, a considerable percentage of invasive cervical malignancies and rare benign diseases such as schistosomiasis and cervical tuberculosis were identified. A screen-and-treat approach within well-equipped tertiary hospitals like Bugando Medical Centre should explore alternative options instead of relying solely on straight LEEP.

Serum gonadal hormones levels and hypogonadism in ART naïve newly diagnosed HIV infected adult males in Mwanza, Tanzania.

BACKGROUND: Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is an endemic chronic disease which is characterized with progressive depletion of CD4 T cells and increased susceptibility to opportunistic infections. Previous studies have associated HIV infection with increased hypogonadism. However, the prevalence of hypogonadism remained poorly defined and widely ranging in various studies. This study aims to evaluate the serum gonadal hormonal levels and hypogonadism in antiretroviral therapy (ART) naïve newly diagnosed HIV infected-males in Mwanza, Tanzania. METHODS: This was a comparison study involving 81 ART naïve newly diagnosed HIV-infected adult males as study group and 81 apparently healthy HIV-negative males as comparison group. The participants in the study group and comparison group were matched by body mass index and age. Serum hormones [Total testosterone (TT), follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E) were estimated. Serum testosterone < 300 ng/dl, or testosterone > 300 ng/dl with high LH and FSH (compensatory hypogonadism) were taken as markers of hypogonadism. Data were analyzed using STATA version 15. RESULTS: The median serum testosterone level among ART naïve newly diagnosed HIV-infected adult males was significantly lower as compared to their comparison group (447 [259-534] versus 517 [396-605]; p = 0.0074) and shown to decrease with decreasing CD4 level. The median [IQR] serum FSH level among ART naïve newly diagnosed HIV-infected adult males was significantly higher than among their comparison group (3.8 [2.1-6.5] versus 2.6 [1.8-4.2]; p = 0.0086). The differences in serum LH and Estradiol were not statistically significant. Furthermore, the proportion of hypogonadism was significantly higher among ART naïve newly diagnosed HIV-infected adult males than in their comparison group (37.0% [30/81] versus 14.8% [12/81]; p = 0.0006). Out of these 30, 24 HIV-infected males had secondary hypogonadism, one had primary, and the remaining five had compensatory hypogonadism. CONCLUSION: Serum testosterone was lower and follicle stimulating hormone was higher among ART naïve HIV-infected males as compared to the HIV negative controls. Hypogonadism, mainly secondary, is common endocrine abnormality among ART naïve HIV-infected male patients in this study. HIV is associated with variations in gonadal hormones which may lead to sexual dysfunction in infected individuals.

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.

Unraveling virulence determinants in extended-spectrum beta-lactamase-producing Escherichia coli from East Africa using whole-genome sequencing.

Escherichia coli significantly causes nosocomial infections and rampant spread of antimicrobial resistance (AMR). There is limited data on genomic characterization of extended-spectrum ß-lactamase (ESBL)-producing E. coli from African clinical settings. This hospital-based longitudinal study unraveled the genetic resistance elements in ESBL E. coli isolates from Uganda and Tanzania using whole-genome sequencing (WGS). A total of 142 ESBL multi-drug resistant E. coli bacterial isolates from both Tanzania and Uganda were sequenced and out of these, 36/57 (63.1%) and 67/85 (78.8%) originated from Uganda and Tanzania respectively. Mutations in RarD, yaaA and ybgl conferring resistances to chloramphenicol, peroxidase and quinolones were observed from Ugandan and Tanzanian isolates. We reported very high frequencies for blaCTX-M-15 with 11/18(61.1%), and blaCTX-M-27 with 12/23 (52.1%), blaTEM-1B with 13/23 (56.5%) of isolates originating from Uganda and Tanzania respectively all conferring resistance to Beta-lactam-penicillin inhibitors. We observed chloramphenicol resistance-conferring gene mdfA in 21/23 (91.3%) of Tanzanian isolates. Extraintestinal E. coli sequence type (ST) 131 accounted for 5/59 (8.4%) of Tanzanian isolates while enterotoxigenic E. coli ST656 was reported in 9/34 (26.4%) of Ugandan isolates. Virulence factors originating from Shigella dysenteriae Sd197 (gspC, gspD, gspE, gspF, gspG, gspF, gspH, gspI), Yersinia pestis CO92 (irp1, ybtU, ybtX, iucA), Salmonella enterica subsp. enterica serovar Typhimurium str. LT2 (csgF and csgG), and Pseudomonas aeruginosa PAO1 (flhA, fliG, fliM) were identified in these isolates. Overall, this study highlights a concerning prevalence and diversity of AMR-conferring elements shaping the genomic structure of multi-drug resistant E. coli in clinical settings in East Africa. It underscores the urgent need to strengthen infection-prevention controls and advocate for the routine use of WGS in national AMR surveillance and monitoring programs.Availability of WGS analysis pipeline: the rMAP source codes, installation, and implementation manual can free be accessed via https://github.com/GunzIvan28/rMAP .

Metabolic syndrome among people living with HIV on antiretroviral therapy in Mwanza, Tanzania.

BACKGROUND: HIV and antiretroviral drugs, particularly protease inhibitors and nucleoside reverse transcriptase inhibitors, may increase the risk of Metabolic Syndrome (MetS) among people living with HIV (PLHIV). However, following the introduction of better drugs like dolutegravir, data on the burden of MetS are limited. This study aimed to assess the prevalence of MetS and associated factors among PLHIV on antiretroviral therapy (ART) in Tanzania. METHODS: This was a cross-sectional study among PLHIV aged ≥ 18 years on antiretroviral therapy for ≥ 1 year at Bugando Medical Centre in Mwanza conducted in 2020. Demographic and healthy-lifestyle-related non-communicable disease risk factors data were collected. Additionally, data on lipid profile, blood glucose, blood pressure, and waist circumference were collected for analysis of MetS according to the International Diabetes Federation criteria. Factors associated with MetS were assessed using logistic regression. A P ≤ 0.05 was considered statistically significant. RESULTS: Data for 223 participants were analyzed. The mean (SD) age was 44 (± 12) years and 79.8% (178) were females. A majority 78% (174) were on a tenofovir, lamivudine,and dolutegravir regimen. About 12.1% (27) were either current or past smokers, 45.3% (101) were past alcohol drinkers, 22.9% (51) were current drinkers, 12.1% (27) reported taking ≥ 5 servings of vegetables and fruits per day and 5.8% (13) were physically inactive. The prevalence of MetS was 22.9%. The only factors that were associated with Mets were fat mass index and adequate intake of vegetables and fruits, (adjusted odds ratio (aOR) 2.9, 95% CI 1.0, 7.9, P = 0.04) and (aOR1.2, 95% CI 1.0, 1.3, P = 0.02), respectively). CONCLUSION: The prevalence of MetS remains high among PLHIV. Adiposity and adequate fruit and vegetable intake increased the risk. The introduction of new ART regimens shows no effect on MetS prevalence. Research is needed to understand how lifestyle changes could reduce MetS in PLHIV.

The efficacy of maternal health education and maternal screening on knowledge and the uptake of infant screening for sickle cell disease in Dar-Es-Salaam, Tanzania; a quasi experimental study.

BACKGROUND: Globally, Sickle cell disease (SCD) is one of the most common genetic disease with high childhood mortality. Early identification of babies with SCD through newborn screening (NBS) and linking them to care are among the recommended interventions. The purpose of this study was to assess the efficacy of maternal health education and maternal screening for SCD on knowledge and the uptake of infant screening for SCD among mother-infant pairs attending antenatal clinics at Government health facilities in Dar-es-salaam, Tanzania.  METHODS: This study was a pre-test post-test, quasi-experimental which involved pregnant women attending antenatal clinics at three hospitals; Mbagala hospital, Sinza hospital and Buguruni health center in Dar Es Salaam. A structured questionnaire was used in data collection. Knowledge on SCD was assessed for all participants before and after two sessions of health education. Participants in Mbagala and Buguruni were also screened for SCD using Sickle SCAN point-of-care test (BioMedomics Inc, USA). The efficacy for health education intervention was computed as the post-intervention minus baseline knowledge score. For proportions, a two-sample z-test was used. Univariate and multivariate logistic regression were used to analyze the efficacy of health education intervention and also predictors of infant diagnosis.  RESULTS: For two sessions of health education intervention, a total of 467 pregnant women completed the sessions. During antenatal visits, a total of 218 were screened for SCD. The proportion of participants with good knowledge of SCD had significantly increased to 85.9% from 12.4% at baseline following the education intervention. In multivariate analysis, sharing the received education on SCD was an independent predictor of the efficacy of health education intervention. Maternal occupation, maternal SCD status as well as sharing the received education on SCD were independent predictors of the uptake of SCD infant diagnosis. CONCLUSION: This study has demonstrated that maternal health education and maternal screening for SCD are feasible and efficacious interventions in raising knowledge and improving the uptake of infant diagnosis for SCD. These interventions are strongly recommended to be included in the comprehensive care package for pregnant women attending antenatal clinics, particularly in areas with a high burden of SCD.

Schistosoma mansoni-related periportal fibrosis; can we use APRI and PSDR levels in the real-time selection of patients for targeted endoscopy in a resource-limited setting? A case-control study.

BACKGROUND: Schistosoma mansoni related hepatic fibrosis is usually associated with hemodynamic alteration with increased mortality due to bleeding varices. The diagnosis of varices before bleeding imposes a big challenge in resource-limited countries using endoscopy. Published evidence on the utility of non-invasive clinical tools in predicting the presence of varices among patients with S. mansoni related periportal fibrosis is still inadequate including Aspartate to platelet ratio index (APRI) and Platelet to splenic diameter ratio (PSDR) levels. This study describes the determinants of portal varices and assesses the potential utility of the APRI and PSDR level in the discrimination of portal varices among patients with S. mansoni related periportal fibrosis (PPF). METHODS: A case-control study using cross-sectional data was done among patients with Schistosoma mansoni related periportal fibrosis at Bugando Medical Centre, in Mwanza Tanzania. The derivation cohort included patients enrolled between 2015 and 2019 and the validation cohort included patients enrolled from 2019 till March 2021. Socio-demographic, laboratory, ultrasound, and upper digestive endoscopic information were analyzed using STATA 13. The prevalence and determinants of varices were determined by logistic regression. The sensitivity and specificity of independent factors were determined to assess their utility in discriminating the presence of portal varices in patients with PPF. RESULTS: In total, 250 patients were included in the derivation cohort, 109 (43.6%; 95% CI 37.3-49.9) of them had varices. The odds of having varices were independently increased among patients with higher APRI levels than 1.51, (AOR: 5.8; 95% CI 3.1-11.1; p < 0.001) and PSDR levels that were lower than 5700 (AOR: 5.9; 95% CI 3.2-11.2; p < 0.001). Both APRI and PSDR levels had significantly high sensitivity and specificity in predicting the presence of esophageal varices. However, the combined values of APRI and PSDR had higher specificity than any of the two markers. Of the 200 patients in the validation cohort 94 (47.0%; 95% CI 40.0-54.2) had varices, the discriminative power of the final model and the predictive ability of both APRI, PSDR, and APRI-PSDR combined levels were highly maintained. CONCLUSIONS: This study indicates that varices are a common encounter among patients with S. mansoni related periportal fibrosis and it is independently associated with higher APRI and lower PSDR levels suggesting that these tools are potential discriminators of varices in this subgroup of patients. The reproducibility of these results should further be assessed longitudinally as potential non-invasive tools in selecting patients at high risk of having esophageal varices who could benefit from the targeted endoscopic intervention in a resource-limited setting like ours.

Building sustainable research capacity at higher learning institutions in Tanzania through mentoring of the Young Research Peers.

BACKGROUND: Sustainability of research culture in Sub-Saharan Africa is threatened in part by the lack of a critical mass of young researchers with the requisite skills and interest to undertake research careers. This paper describes an intensive mentorship programme combining hierarchical (vertical) and peer-to-peer (horizontal) mentoring strategies among young researchers in a resource limited setting in Sub-Saharan Africa. METHODS: A consortium of three partnering large Tanzanian health training institutions (MUHAS, CUHAS and KCMUCo) and two collaborating US institutions (UCSF and Duke University) was formed as part of the five-year Transforming Health Professions Education in Tanzania (THET) project, funded by the NIH through Health Professional Education Partnership Initiative (HEPI). Within THET, the Community of Young Research Peers (CYRP) was formed, comprising of inter-professional and cross-institutional team of 12 Master-level Young Research Peers and 10 co-opted fellows from the former MEPI-Junior Faculty (MEPI-JF) project. The Young Peers received mentorship from senior researchers from the consortium through mentored research awards and research training, and in turn provided reciprocal peer-to-peer mentorship as well as mentorship to undergraduate students. RESULTS: At the end of the first 2 years of the project, all 12 Young Peers were proceeding well with mentored research awards, and some were at more advanced stages. For example, three articles were already published in peer reviewed journals and two other manuscripts were in final stages of preparation. All 12 Young Peers participated in CYRP-wide thematic training workshops on mentoring and secondary data analysis; 11 had undertaken at least three research training short courses in identified areas of need; 9 joined at least one other ongoing research project; 5 made at least one scientific presentation, and 5 participated in at least one submitted grant application. Half of the Young Peers have enrolled in PhD programmes. A collective total of 41 undergraduate students were actively mentored by the Young Peers in research. CONCLUSION: The CYRP has demonstrated to be an effective model for dual vertical and horizontal mentorship in research to young investigators in resource-limited settings. This model is recommended to educators working on developing research competence of early career researchers, particularly in Sub-Saharan Africa.

The magnitude and correlates of esophageal Varices among newly diagnosed cirrhotic patients undergoing screening fibre optic endoscope before incident bleeding in North-Western Tanzania; a cross-sectional study.

BACKGROUND: Bleeding esophageal varices is a deadly complication of liver cirrhosis. Guidelines recommend an early diagnosis of esophageal varices before incident bleeding by screening all patients diagnosed with liver cirrhosis. Though it has been reported elsewhere that the presence of esophageal varices varies widely among cirrhotic patients this has not been assessed in Tanzania since endoscopy is not readily available for routine use in our setting. This study was designed to determine the prevalence of esophageal varices and assess the utility of clinical parameters in predicting the presence of varices among cirrhotic patients in northwestern Tanzania. METHODS: A cross-sectional analysis of adult patients with liver cirrhosis was done at Bugando Medical Centre. Demographic, clinical, laboratory and endoscopic data were collected and analyzed using STATA 13. The presence of esophageal varices was detected using endoscopic examination and associated factors were assessed by logistic regression. The predictive value of clinical predictors was also assessed by calculating sensitivity and specificity. RESULTS: A total of 223 patients were enrolled, where 88 (39.5%; 95%CI: 33.0-45.9) had esophageal varices. The varices were independently associated with increased age (OR: 1.02; 95%CI: 1.0-1.04; p = 0.030); increased splenic diameter (OR:1.3; 95%CI:1.2-1.5; p <  0.001), increased portal vein diameter (OR:1.2; 95%CI: 1.07-1.4; p = 0.003), having ascites (OR: 3.0; 95%CI: 1.01-8.7; p = 0.046), and advanced liver disease (OR: 2.9; 95%CI: 1.3-6.7; p = 0.008). PSDR least performed in predicting varices, (AUC: 0.382; 95%CI: 0.304-0.459; cutoff: < 640; Sensitivity: 58.0%; 95%CI: 46.9-68.4; specificity: 57.0%; 95%CI: 48.2-65.5). SPD had better prediction; (AUC: 0.713; 95%CI: 0.646-0.781; cut off: > 15.2 cm; sensitivity: 65.9%; (95% CI: 55-75.7 and specificity:65.2%; 95%CI: 56.5-73.2), followed by PVD, (AUC: 0.6392; 95%CI: 0.566-0.712;cutoff: > 1.45 cm; sensitivity: 62.5%; 95CI: 51.5-72.6; specificity: 61.5%; 95%CI: 52.7-69.7). CONCLUSION: Esophageal varices were prevalent among cirrhotic patients, most of which were at risk of bleeding. The non-invasive prediction of varices was not strong enough to replace endoscopic diagnosis. However, the predictors in this study can potentially assist in the selection of patients at high risk of having varices and prioritize them for endoscopic screening and appropriate management.

Prevalence of pretreatment HIV drug resistance in Mwanza, Tanzania.

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

Investigation of household contacts of pulmonary tuberculosis patients increases case detection in Mwanza City, Tanzania.

BACKGROUND: Tuberculosis (TB) contact tracing is a key strategy for containing TB and provides addition to the passive case finding approach. However, this practice has not been implemented in Tanzania, where there is unacceptably high treatment gap of 62.1% between cases estimated and cases detected. Therefore calls for more aggressive case finding for TB to close this gap. We aimed to determine the magnitude and predictors of bacteriologically-confirmed pulmonary TB among household contacts of bacteriologically-confirmed pulmonary TB index cases in the city of Mwanza, Tanzania. METHODS: This study was carried out from August to December 2016 in Mwanza city at the TB outpatient clinics of Tertiary Hospital of the Bugando Medical Centre, Sekou-Toure Regional Hospital, and Nyamagana District Hospital. Bacteriologically-confirmed TB index cases diagnosed between May and July 2016 were identified from the laboratory registers book. Contacts were traced by home visits by study TB nurses, and data were collected using a standardized TB screening questionnaire. To detect the bacterioriologically-confirmed pulmonary TB, two sputum samples per household contact were collected under supervision for all household contacts following standard operating procedures. Samples were transported to the Bugando Medical Centre TB laboratory for investigation for TB using fluorescent smear microscopy, GeneXpert MTB/RIF and Löwenstein-Jensen (LJ) culture. Logistic regression was used to determine predictors of bacteriologically-confirmed pulmonary TB among household contacts. RESULTS: During the study period, 456 household contacts from 93 TB index cases were identified. Among these 456 household contacts, 13 (2.9%) were GeneXpert MTB/RIF positive, 18 (3.9%) were MTB-culture positive and four (0.9%) were AFB-smear positive. Overall, 29 (6.4%) of contacts had bacteriologically-confirmed pulmonary TB. Predictors of bacteriologically-confirmed pulmonary TB among household contacts were7being married (Odds ratio [OR], 3.3; 95% confidence interval [CI], 1.4-8.0; p = 0.012) and consuming less than three meals a day (OR, 3.7; 95% CI, 1.6-8.7; p = 0.009). CONCLUSIONS: Our data suggest that in Mwanza, Tanzania, seven in 100 contacts living in the same house with a TB patient develop bacteriologically-confirmed pulmonary TB. These results therefore underscore the need to implement routine TB contact tracing to control tuberculosis in high TB burden countries such as Tanzania.

Rubella natural immunity among adolescent girls in Tanzania: the need to vaccinate child bearing aged women.

BACKGROUND: Rubella primary infection during early stages of pregnancy is associated with high risk of congenital Rubella syndrome (CRS). Prevention of CRS in the resource-limited countries requires multiple strategies. Here, we document the data on the magnitude of Rubella natural immunity among adolescent girls which is a crucial group in devising effective control strategies to prevent CRS. METHODS: A cross sectional study involving 397 adolescent girls was conducted in the city of Mwanza involving five secondary schools. Socio-demographic and other relevant information were collected using pre-tested data collection tool. Rubella IgG antibodies were determined using enzyme immunoassay. The presence of Rubella IgG titers of >10 IU/ml indicated natural immunity. RESULTS: The mean age of the study participants was 15.18 ± 1.48 years. Of 397 girls, 340 (85.6%) and 57 (14.4%) were from secondary schools representing peri-urban and rural areas, respectively. Out of 397 girls, 90.4% (95% CI: 87-93) were found to be naturally immune with median Rubella IgG antibodies titers of 56.7 IU/ml interquartile range (IQR): 40.8-137. The median Rubella IgG antibodies titers were significantly high in adolescent girls from families with high socio-economic status (63.96 vs. 47.13 IU/ml, P < 0.001) and in adolescent girls from peri-urban areas of the city (63.33 vs. 39.9 IU/ml, P < 0.001). CONCLUSION: The majority of adolescent girls in the city of Mwanza are naturally immune to Rubella virus. There is a need to compare the effectiveness of screening and vaccinating susceptible adolescent girls with the effectiveness of vaccinating all women of childbearing in controlling CRS in low-income countries.

Patient and disease characteristics associated with late tumour stage at presentation of cervical cancer in northwestern Tanzania.

BACKGROUND: About two thirds of patients with cervical cancer in Tanzania present with advanced tumor stage, leading to significant morbidity and mortality. We designed a study to determine the factors associated with the late tumour stage at presentation among patients with cervical cancer in Mwanza. METHODS: This cross-sectional study recruited women at Bugando Medical Centre (BMC) with histologically confirmed cervical cancer from November 2013 to April 2014. Patients were recruited serially until the sample size was reached. RESULTS: A total of 202 women with histologically confirmed cervical cancer were recruited. The mean age of the patients was 50.5 ± 13.3 years. The majority of patients (n = 129, 63.9%) were diagnosed with late stage disease (IIB-IVB). Patients also presented with severe anemia (n = 78, 38.6%), urinary tract infections (n = 74, 36.6%), hydronephrosis (n = 43, 21.2%), elevated serum creatinine levels (n = 33, 16.3%), vesicovaginal fistula (VVF), (n = 13, 6.4%), lung metastasis (n = 5, 2.4%), metastasis to the urinary bladder (n = 4, 1.9%), rectovaginal fistula (RVF) (n = 3, 1.4%), liver metastasis (n = 2, 0.9%) and hydroureter (n = 2, 0.9%). In multivariate logistic regression, factors associated with late stage at presentation were attending to alternative health practitioners and lack of personal initiative to seek care to formal health facilities (OR 2.3; 95% CI 1.2-4.2, p = 0.011 and OR 2.0; 95 % CI 1.0-3.8, p = 0.028) respectively. CONCLUSION: Communities should be sensitized to women's empowerment, provide community education on early symptoms of cervical cancer, and the importance of early hospital attendance.

Improving gross anatomy learning using reciprocal peer teaching.

BACKGROUND: The use of cadavers in human anatomy teaching requires adequate number of anatomy instructors who can provide close supervision of the students. Most medical schools are facing challenges of lack of trained individuals to teach anatomy. Innovative techniques are therefore needed to impart adequate and relevant anatomical knowledge and skills. This study was conducted in order to evaluate the traditional teaching method and reciprocal peer teaching (RPT) method during anatomy dissection. METHODS: Debriefing surveys were administered to the 227 first year medical students regarding merits, demerits and impact of both RPT and Traditional teaching experiences on student's preparedness prior to dissection, professionalism and communication skills. Out of this, 159 (70 %) completed the survey on traditional method while 148 (65.2 %) completed survey on RPT method. An observation tool for anatomy faculty was used to assess collaboration, professionalism and teaching skills among students. Student's scores on examinations done before introduction of RPT were compared with examinations scores after introduction of RPT. RESULTS: Our results show that the mean performance of students on objective examinations was significantly higher after introduction of RPT compared to the performance before introduction of RPT [63.7 ± 11.4 versus 58.6 ± 10, mean difference 5.1; 95 % CI = 4.0-6.3; p-value < 0.0001]. Students with low performance prior to RPT benefited more in terms of examination performance compared to those who had higher performance [Mean difference 7.6; p-value < 0.0001]. Regarding student's opinions on traditional method versus RPT, 83 % of students either agreed or strongly agreed that they were more likely to read the dissection manual before the RPT dissection session compared to 35 % for the traditional method. Over 85 % of respondents reported that RPT improved their confidence and ability to present information to peers and faculty compared to 38 % for the tradition method. The majority of faculty reported that the learning environment of the dissection groups was very active learning during RPT sessions and that professionalism was observed by most students during discussions. CONCLUSIONS: Introduction of RPT in our anatomy dissection laboratory was generally beneficial to both students and faculty. Both objective (student performance) and subjective data indicate that RPT improved student's performance and had a positive learning experience impact. Our future plan is to continue RPT practice and continually evaluate the RPT protocol.

Sero-positivity rate of rubella and associated factors among pregnant women attending antenatal care in Mwanza, Tanzania.

BACKGROUND: Sero-positivity rates of the rubella virus among pregnant women vary widely throughout the world. In Tanzania, rubella vaccination is not included in the national immunization schedule and there is therefore no antenatal screening for this viral disease. So far, there are no reports on the sero-prevalence of rubella among pregnant women in Tanzania. As a result, this study was undertaken to establish the sero-positivity rate of rubella and rubella risk factors among pregnant women attending antenatal care clinics in Mwanza, Tanzania. METHODS: From November 2012 to May 2013 a total of 350 pregnant women were enrolled and their serum samples collected and analyzed using the AXSYM anti-rubella virus IgG/IgM-MEIA test. Demographic and clinical data were collected using a standardized data collection tool. Data analysis was done using STATA version 12. RESULTS: Of 342 pregnant women tested for rubella antibodies, 317 (92.6%) were positive for anti-rubella IgG while only 1 (0.3%) was positive for IgM. Higher sero-positivity rates were found in the age group of 25-44 years. Furthermore, it was observed that with each year increase in age, the risk of contracting rubella increases by 12% (OR = 1.12, 95% CI: 1.02-1.22, P = 0.019). Women involved in farming and business women were at a higher risk of contracting rubella infection compared to formally employed women (OR: 4.9, P = 0.011; OR 7.1, p = 0.003 respectively). In univariate analysis, the risk of contracting rubella virus infection was found to increase with gestational age with a statistical significance. CONCLUSIONS: Sero-positivity rates of rubella are high in Mwanza and are significantly associated with an increase in age and being a farmer or a business woman. Screening of rubella and immunization of women at risk are highly recommended in this area with a high non-immune rate against rubella virus.

Utility of qualitative C- reactive protein assay and white blood cells counts in the diagnosis of neonatal septicaemia at Bugando Medical Centre, Tanzania.

BACKGROUND: Neonatal septicaemia diagnosis based on clinical features alone is non-specific leading to the initiation of unnecessary antibiotic treatment posing a danger of increased antibiotic resistance. In the present study the utility of serial qualitative C-reactive protein (CRP) assay and white blood cells count (WBC) in the diagnosis of neonatal septicaemia was investigated using blood culture as gold standard. METHODS: A total of 305 neonates admitted at Bugando Medical Centre (BMC) neonatal units between September 2013 and April 2014 were enrolled. Demographic and clinical data were collected using standardized data collection tool. Blood specimens were collected for blood culture, WBC count and qualitative CRP assay. RESULTS: Of 305 neonates; 224 (73.4%) were ≤ 72 hrs of age and 91(29.8%) had low birth weight. The positive CRP assay was observed in 67 (22.0%), 80 (26.2%) and 88 (28.9%) of neonates on day 1, 2 and 3 respectively; with any CRP positive occurred in 104 (34.1%) of neonates. The sensitivities of CRP assay in the diagnosis of septicaemia using culture as gold standard on day 1, 2, 3 and any positive were 40.4%, 53.2%, 54.8% and 62.9% respectively. While specificities were 82.7%, 80.7%, 77.8% and 73.3% respectively. Higher sensitivity of 75% was observed when CRP was used to diagnose gram negative septicaemia compared to 50% that was observed in the diagnosis of gram positive septicaemia. WBC count of ≥13 × 109 /L had sensitivity and specificity of 64.5% and 66.7% respectively with area under the curve of 0.694. When the any positive CRP and WBC of ≥13 × 109 /L were used the sensitivity increased to 90.3% with specificity of 50%. Neonates with septicaemia due to gram negative bacteria were significantly found to have higher rates of positive CRP than neonates with gram positive septicaemia and with negative culture (p < 0.001, OR 8.2, 95 CI; 2.9-26). CONCLUSION: In place where blood culture is limited neonates having clinical features of neonatal sepsis with positive qualitative CRP assay and increased WBC should urgently be initiated on appropriate sepsis management in order to reduce morbidity and mortality associated with neonatal sepsis.

Predominance of rotavirus G1[P8] genotype among under-five children with gastroenteritis in Mwanza, Tanzania.

We analyzed stool samples from underfives with gastroenteritis for rotavirus infection between January 2010 and June 2011. A total of 393 stool specimens were examined for rotavirus infection using enzyme-linked immunosorbent assay (ELISA). Hundred selected positive specimens were genotyped using multiplex polymerase chain reaction. Out of 393 underfives, 194 (49.4%) had rotavirus infection, with 96.9% of infected underfives being <2 years. Underfives infected with rotavirus had prolonged hospital stay than those without rotavirus infection (P = 0.0001). G1 was the most predominant G type (59%) followed by G8 (13%) while P[8] was the most predominant P type (25%). In single-type infection, common G-P combinations were G1P[8] (24%) and G1P[6] (17%). Common mixed infections were G1/G8 (16%) and P4/P8 (13%). G1 genotype is common among underfives with gastroenteritis in Mwanza. Diversity of genotypes causing gastroenteritis in Mwanza necessitates a continuous surveillance after the introduction of RotaRix® vaccine.

Prevalence of Hypogonadism and Associated Risk Factors among Newly Diagnosed ART Naïve HIV-Infected Males in Mwanza, Tanzania.

Background: Hypogonadism is frequent among HIV-infected males and might have significant clinical impact leading to sexual impairment and metabolic derangement. There is limited information about the magnitude of hypogonadism and its associated factors among people living with HIV in Tanzania. We aimed to determine the prevalence of hypogonadism and associated risk factors among newly diagnosed ART naïve HIV-infected men in Mwanza, Tanzania. Methods: Newly diagnosed ART naïve HIV-infected men were enrolled at Voluntary Counseling and Testing Centres of four selected hospitals in the Mwanza region and subjected to thorough clinical and general physical examination including anthropometric measurements. A prestructured questionnaire was used to collect sociodemographic characteristics and clinical data. Serum total testosterone, follicle-stimulating hormone, luteinizing hormone, and estradiol were estimated. Serum total testosterone <300 ng/dl or testosterone >300 ng/dl with high LH and FSH (compensatory hypogonadism) was taken as markers of hypogonadism. Data were analyzed using STATA version 15. Results: Of the 388 enrolled participants, hypogonadism was found in 47.9%, with secondary hypogonadism (83.9%, 156/186) being the most frequent form. Logistic regression analysis showed a significant association between hypogonadism and CD4+ count (OR 2.0; 95% CI 1.1-3.6; p=0.022), decreased libido (OR 1.6; 95% CI 1.1-2.4; p=0.024), age of above 46 years (OR 2.3; 95% CI 1.1-4.6; p=0.023), herbal medicine use (OR 2.4; 95% CI 1.5-3.9; p < 0.001), WHO clinical stage 3 (OR 2.7; 95% CI 1.4-5.2; p=0.003), and weight loss (OR 1.8; 95% CI 1.1-3.0; p=0.016). Conclusion: Hypogonadism was found in nearly half (47.9%) of ART naïve HIV-infected men. The majority (83.9%) had secondary hypogonadism. There was a significant association of hypogonadism with older age, herbal medicine use, weight loss, advanced clinical stage, CD4+ count, and decreased libido.

Single dose of gentamicin in combination with metronidazole versus multiple doses for prevention of post-caesarean infection at Bugando Medical Centre in Mwanza, Tanzania: a randomized, equivalence, controlled trial.

BACKGROUND: Caesarean section(C/S) has been found to increase rates of maternal infectious morbidities five times more than vaginal delivery. The provision of intravenous prophylactic antibiotics 30 to 60 minutes prior to C/S has been found to substantially reduce post-caesarean infection. At Bugando Medical Centre, there is no consistent protocol for the administration of antibiotic prophylaxis to patients who are undergoing emergency C/S. Providing repeated dosages of antibiotic prophylaxis after C/S is the common practice. This study aimed to determine the comparative efficacy of a single dose of gentamicin in combination with metronidazole versus multiple doses for prevention of post-caesarean infection. METHODS: From October 2011 to May 2012, a randomized, equivalence, non-blinding clinical trial was conducted at Bugando Medical Centre in Mwanza, Tanzania. A total of 500 eligible participants were enrolled in the study and were randomly allocated into two study arms -- "A" and "B". Participants in "A" received a single dose of gentamicin in combination with metronidazole 30 to 60 minutes prior to the operation, and participants in "B" received the same drugs prior to the operation but continued with for 24 hours. Both groups had 30 days of follow-up and were assessed for signs and symptoms of surgical-site infection as the primary outcome. The equivalence margin was set at 5%. The two-tailed equivalence was analyzed based on intention- to-treat analysis. RESULTS: The randomization was proper, as the distribution of various demographic and other baseline characteristics had a p-value of > 0.05. All 500 participants were included in our analysis; of these, no participants were lost to follow-up. Surgical-site infection occurred in 12 out of the 250 (4.8%) receiving single dose compared to 16 out of the 250 (6.4%) receiving multiple doses. There is an absolute proportion difference of 1.6% (95% Confidence interval: -2.4 - 5.6%) which lies outside the pre-specified 5% equivalence margin. CONCLUSION: We recommend the administration of pre-operative single dose antibiotic prophylaxis for emergency caesarean as this intervention proved to be not equivalent to multiple doses antibiotic prophylaxis in reducing surgical site infection. Single dose therapy also reduces staff workload along with medication costs.