International Image Concordance Study to Compare a Point-of-Care Tampon Colposcope With a Standard-of-Care Colposcope.

OBJECTIVE: Barriers to cervical cancer screening in low-resource settings include lack of accessible, high-quality services, high cost, and the need for multiple visits. To address these challenges, we developed a low-cost, intravaginal, optical cervical imaging device, the point-of-care tampon (POCkeT) colposcope and evaluated whether its performance is comparable with a standard-of-care colposcope. MATERIALS AND METHODS: There were 2 protocols, which included 44 and 18 patients. For the first protocol, white-light cervical images were collected in vivo, blinded by device, and sent electronically to 8 physicians from high-, middle-, and low-income countries. For the second protocol, green-light images were also collected and sent electronically to the highest performing physician from the first protocol who has experience in both a high- and low-income country. For each image, physicians completed a survey assessing cervix characteristics and severity of precancerous lesions. Corresponding pathology was obtained for all image pairs. RESULTS: For the first protocol, average percent agreement between devices was 70% across all physicians. The POCkeT and standard-of-care colposcope images had 37% and 51% agreement with pathology for high-grade squamous intraepithelial lesions (HSILs), respectively. Investigation of HSIL POCkeT images revealed decreased visibility of vascularization and lack of contrast in lesion margins. After changes were made for the second protocol, the 2 devices achieved similar agreement to pathology for HSIL lesions (55%). CONCLUSIONS: Based on the exploratory study, physician interpretation of cervix images acquired using a portable, low-cost POCkeT colposcope was comparable to a standard-of-care colposcope.

Frequency, risk factors and feto-maternal outcomes of abruptio placentae in Northern Tanzania: a registry-based retrospective cohort study.

BACKGROUND: Abruptio placentae remains a major cause of maternal and perinatal morbidity and mortality in developing countries. Little is known about the burden of abruptio placentae in Tanzania. This study aimed to determine frequency, risk factors for abruptio placentae and subsequent feto-maternal outcomes in women with abruptio placentae. METHODS: We designed a retrospective cohort study using maternally-linked data from Kilimanjaro Christian Medical Centre (KCMC) medical birth registry. Data on all women who delivered live infants and stillbirths at 28 or more weeks of gestation at KCMC hospital from July 2000 to December 2010 (n = 39,993) were analysed. Multivariate logistic models were used to calculate odds ratios (OR) and 95% confidence intervals (CIs) for risk factors, and feto-maternal outcomes associated with abruptio placentae. RESULTS: The frequency of abruptio placentae was 0.3% (112/39,993). Risk factors for abruptio placentae were chronic hypertension (OR 4.1; 95% CI 1.3-12.8), preeclampsia/eclampsia (OR 2.1; 95% CI 1.1-4.1), previous caesarean delivery (OR 1.3; 95% CI 1.2-4.2), previous abruptio placentae (OR 2.3; 95% CI 1.8-3.4), fewer antenatal care visits (OR 1.3; 95% 1.1-2.4) and high parity (OR 1.4; 95% CI 1.2-8.6). Maternal complications associated with abruptio placentae were antepartum haemorrhage (OR 11.5; 95% CI 6.3-21.2), postpartum haemorrhage (OR 17.9; 95% 8.8-36.4),), caesarean delivery (OR 5.6; 95% CI 3.6-8.8), need for blood transfusions (OR 9.6; 95% CI 6.5-14.1), altered liver function (OR 5.3; 95% CI 1.3-21.6) and maternal death (OR 1.6; 95% CI 1.5-1.8). In addition, women with abruptio placentae had prolonged duration of hospital stay (more than 4 days) and were more likely to have been referred during labour. Adverse fetal outcomes associated with abruptio placentae include low birth weight (OR 5.9; 95% CI 3.9-8.7), perinatal death (OR 17.6; 95% CI 11.3-27.3) and low Apgar score (below 7) at 1 and 5 min. CONCLUSIONS: Frequency of abruptio placentae is comparable with local and international studies. Chronic hypertension, preeclampsia, prior caesarean section delivery, prior abruptio placentae, poor attendance to antenatal care and high parity were independently associated with abruptio placentae. Abruptio placentae was associated with adverse maternal and foetal outcomes. Clinicians should identify risk factors for abruptio placentae during prenatal care when managing pregnant women to prevent adverse maternal and foetal outcomes.

Clinical and genetic determinants of plasma nevirapine exposure following an intrapartum dose to prevent mother-to-child HIV transmission.

OBJECTIVE: Nevirapine is metabolized by cytochrome P450 (CYP) 2B6 and CYP3A4. We characterized relationships between clinical parameters, human genetics, pharmacokinetics, and human immunodeficiency virus type 1 (HIV-1) drug resistance mutations in pregnant women following single-dose intrapartum nevirapine. METHODS: In AIDS Clinical Trials Group study A5207, women received nevirapine at onset of labor and were randomly assigned to receive lamivudine/zidovudine, emtricitabine/tenofovir, or lopinavir/ritonavir for 7 or 21 days. Plasma nevirapine level was quantified on postpartum day 1 and on weeks 1, 3, and 5. We assayed 214 polymorphisms in CYP2B6 and other genes and evaluated associations with pharmacokinetic parameters, including elimination constant, time to protein-adjusted 50% inhibitory concentration (IC50), and week 5 nevirapine level below the quantification limit. RESULTS: Among 301 women with evaluable pharmacokinetic and genotype data, lower body mass index and random assignment to receive lopinavir/ritonavir were associated with more rapid nevirapine elimination. Among those of African ancestry, longer time to IC50 was associated with CYP2B6 983T → C (P = .004) but not with CYP2B6 516G → T (P = .8). Among Indians, slower nevirapine elimination was associated with CYP2B6 516G → T (P = .04). Emergent resistance was infrequent and not associated with pharmacokinetics or CYP2B6 genotype. CONCLUSIONS: The effects on plasma drug exposure following single-dose nevirapine may be greater for CYP2B6 983T → C than for 516G → T and are less pronounced than at steady state.

An Implementation Evaluation of the Smartphone-Enhanced Visual Inspection with Acetic Acid (SEVIA) Program for Cervical Cancer Prevention in Urban and Rural Tanzania.

INTRODUCTION: The World Health Organization (WHO) recommends visual inspection with acetic acid (VIA) for cervical cancer screening (CCS) in lower-resource settings; however, quality varies widely, and it is difficult to maintain a well-trained cadre of providers. The Smartphone-Enhanced Visual Inspection with Acetic acid (SEVIA) program was designed to offer secure sharing of cervical images and real-time supportive supervision to health care workers, in order to improve the quality and accuracy of visual assessment of the cervix for treatment. The purpose of this evaluation was to document early learnings from patients, providers, and higher-level program stakeholders, on barriers and enablers to program implementation. METHODS: From 9 September to 8 December 2016, observational activities and open-ended interviews were conducted with image reviewers (n = 5), providers (n = 17), community mobilizers (n = 14), patients (n = 21), supervisors (n = 4) and implementation partners (n = 5) involved with SEVIA. Sixty-six interviews were conducted at 14 facilities, in all five of the program regions Results SEVIA was found to be a highly regarded tool for the enhancement of CCS services in Northern Tanzania. Acceptability, adoption, appropriateness, feasibility, and coverage of the intervention were highly recognized. It appeared to be an effective means of improving good clinical practice among providers and fit seamlessly into existing roles and processes. Barriers to implementation included network connectivity issues, and community misconceptions and the adoption of CCS more generally. CONCLUSIONS: SEVIA is a practical and feasible mobile health intervention and tool that is easily integrated into the National CCS program to enhance the quality of care.

Factors associated with prenatal folic acid and iron supplementation among 21,889 pregnant women in Northern Tanzania: a cross-sectional hospital-based study.

BACKGROUND: Folate and iron deficiency during pregnancy are risk factors for anaemia, preterm delivery, and low birth weight, and may contribute to poor neonatal health and increased maternal mortality. The World Health Organization recommends supplementation of folic acid (FA) and iron for all pregnant women at risk of malnutrition to prevent anaemia. We assessed the use of prenatal folic acid and iron supplementation among women in a geographical area with a high prevalence of anaemia, in relation to socio-demographic, morbidity and health services utilization factors. METHODS: We analysed a cohort of 21,889 women who delivered at Kilimanjaro Christian Medical Centre (KCMC), Moshi, Tanzania, between 1999 and 2008. Logistic regression models were used to describe patterns of reported intake of prenatal FA and iron supplements. RESULTS: Prenatal intake of FA and iron supplements was reported by 17.2% and 22.3% of pregnant women, respectively. Sixteen percent of women reported intake of both FA and iron. Factors positively associated with FA supplementation were advanced maternal age (OR = 1.17, 1.02-1.34), unknown HIV status (OR = 1.54, 1.42-1.67), a diagnosis of anaemia during pregnancy (OR = 12.03, 9.66-14.98) and indicators of lower socioeconomic status. Women were less likely to take these supplements if they reported having had a malaria episode before (OR = 0.57, 0.53-0.62) or during pregnancy (OR = 0.45, 0.41-0.51), reported having contracted other infectious diseases (OR = 0.45, 0.42-0.49), were multiparous (OR = 0.73, 0.66-0.80), had preeclampsia/eclampsia (OR = 0.48, 0.38-0.61), or other diseases (OR = 0.55, 0.44-0.69) during pregnancy. Similar patterns of association emerged when iron supplementation alone and supplementation with both iron and FA were evaluated. CONCLUSIONS: FA and iron supplementation are low among pregnant women in Northern Tanzania, in particular among women with co-morbidities before or during pregnancy. Attempts should be made to increase supplementation both in general and among women with pregnancy complications.

Willingness to HPV self-sampling for cervical cancer screening and its predictors among women attending outpatient clinics in Meru District, Arusha Region, Northern Tanzania.

Background: The ability for women to self-collect human papillomavirus (HPV) samples can potentially reduce the risk of cervical cancer and increase screening coverage. Objectives: To assess the willingness to HPV self-sampling for cervical cancer screening and its predictors among women attending outpatient clinics in Arusha region, northern Tanzania. Methods: A hospital-based cross-sectional study was conducted among 706 women aged 18-55 years in Meru District Hospital and Usa River Health Centre from March to April 2019. Face-to-face intervies were conducted using a questionnaire. Data analysis was performed using Stata version 14.0. The log-binomial regression was used to determine factors associated with willingness to self-collection of HPV samples. Results: Majority (70%) of the women were willing to self-collection of HPV samples for cervical cancer screening and was associated with attending Meru District hospital (PR=2.02, 95%CI 1.77-2.31); good knowledge about cervical cancer warning signs (PR=1.11, 95%CI 1.01-1.22), prevention (PR=1.13, 95%CI 1.04-1.20), and symptoms (PR=1.61, 95%CI 1.33-1.93); and having formal employment (PR=1.22, 95%CI 1.07-1.37). Conclusion: The majority of women were willing to self-collect HPV samples for cervical cancer screening. Self-collection is, therefore, an acceptable and viable means of screening for cervical cancer, which has great implications for Tanzania from a health policy perspective.

Caesarean section among referred and self-referred birthing women: a cohort study from a tertiary hospital, northeastern Tanzania.

BACKGROUND: The inequity in emergency obstetric care access in Tanzania is unsatisfactory. Despite an existing national obstetric referral system, many birthing women bypass referring facilities and go directly to higher-level care centres. We wanted to compare Caesarean section (CS) rates among women formally referred to a tertiary care centre versus self-referred women, and to assess the effect of referral status on adverse outcomes after CS. METHODS: We used data from 21,011 deliveries, drawn from the birth registry of a tertiary hospital in northeastern Tanzania, during 2000-07. Referral status was categorized as self-referred if the woman had bypassed or not accessed referral, or formally-referred if referred by a health worker. Because CS indications were insufficiently registered, we applied the Ten-Group Classification System to determine the CS rate by obstetric group and referral status. Associations between referral status and adverse outcomes after CS delivery were analysed using multiple regression models. Outcome measures were CS, maternal death, obstetric haemorrhage ≥ 750 mL, postpartum stay > 9 days, neonatal death, Apgar score < 7 at 5 min and neonatal ward transfer. RESULTS: Referral status contributed substantially to the CS rate, which was 55.0% in formally-referred and 26.9% in self-referred birthing women. In both groups, term nulliparous singleton cephalic pregnancies and women with previous scar(s) constituted two thirds of CS deliveries. Low Apgar score (adjusted OR 1.42, 95% CI 1.09-1.86) and neonatal ward transfer (adjusted OR 1.18, 95% CI 1.04-1.35) were significantly associated with formal referral. Early neonatal death rates after CS were 1.6% in babies of formally-referred versus 1.2% in babies of self-referred birthing women, a non-significant difference after adjusting for confounding factors (adjusted OR 1.37, 95% CI 0.87-2.16). Absolute neonatal death rates were > 2% after CS in breech, multiple gestation and preterm deliveries in both referral groups. CONCLUSIONS: Women referred for delivery had higher CS rates and poorer neonatal outcomes, suggesting that the formal referral system successfully identifies high-risk birth, although low volume suggests underutilization. High absolute rates of post-CS adverse outcomes among breech, multiple gestation and preterm deliveries suggest the need to target self-referred birthing women for earlier professional intrapartum care.

Birthweight, preterm birth and perinatal mortality: a comparison of black babies in Tanzania and the USA.

OBJECTIVES: Adverse conditions in Africa produce some of the highest rates of infant mortality in the world. Fetal growth restriction and preterm delivery are commonly regarded as major pathways through which conditions in the developing world affect infant survival. The aim of this article was to compare patterns of birthweight, preterm delivery, and perinatal mortality between black people in Tanzania and the USA. DESIGN: Registry-based study. SETTINGS: Referral hospital data from North Eastern Tanzania and US Vital Statistics. SAMPLE: 14 444 singleton babies from a hospital-based registry (1999-2006) and 3 530 335 black singletons from US vital statistics (1995-2000). MAIN OUTCOME MEASURES: Birthweight, gestational age and perinatal mortality. METHODS: Restricting our study to babies born at least 500g, we compared birthweight, gestational age, and perinatal mortality (stillbirths and deaths in the first week) in the two study populations. RESULTS: Perinatal mortality in the Tanzanian sample was 41/1 000, compared with 10/1 000 among USA blacks. Tanzanian babies were slightly smaller on average (43g), but fewer were preterm (<37 weeks) (10.0 vs. 16.2%). Applying the USA weight-specific mortality rates to Tanzanian babies born at term suggested that birthweight does not play a role in their increased mortality relative to USA blacks. CONCLUSIONS: Higher mortality independent of birthweight and preterm delivery for Tanzanian babies suggests the need to address the contribution of other pathways to further reduce the excess perinatal mortality.

Feasibility and acceptability of human papillomavirus self-sampling in a semi-urban area in northern Tanzania.

OBJECTIVE: To assess the feasibility and acceptability of HPV self-sampling in Arusha region, northern Tanzania, because the ability for women to self-collect HPV samples can help reduce the number of health facility visits and improve cervical cancer screening coverage rates. METHODS: We conducted a facility- and community-based cross-sectional study among 350 women aged 25-55 years in Arumeru district, Arusha region, northern Tanzania. Women were trained to self-collect an HPV sample, and follow-up visits were used to provide results after laboratory testing. Data were analyzed using Stata version 15.1 and summarized using mean and standard deviation for numeric variables and frequencies and percentages for categorical variables. RESULTS: Among 350 women, 65 (18.6%) ever screened for cervical cancer, all provided self-collected samples, and 349 (99.4%) would advise their female friends to undergo the same procedure. The prevalence of positive HPV results was 31 (8.9%), of which 26 (83.9%) were further examined. Two women found with lesions were treated following the national guidelines. CONCLUSION: This study has demonstrated that the HPV self-sampling intervention for cervical cancer screening is a feasible and acceptable intervention, especially in resource-limited countries like Tanzania. Scaling-up policies should consider addressing the potential barriers to the uptake of this intervention.

Recording of maternal deaths in an East African university hospital.

OBJECTIVE: To trace all maternal deaths at a tertiary East African university hospital with a systematic registration of all births. DESIGN: Descriptive study. SAMPLE: One hundred and nineteen cases of maternal death which occurred in the period from 2000 to 2007 (including). METHODS: Identification through the birth registry and separate manual tracing of all case records. Account of practical problems concerning identification of cases and analysis of time trends, mothers' domicile, occurrence by phase of pregnancy, birth and puerperium, and diagnoses. RESULTS: There was considerable under-reporting of deaths in the medical birth registry. Twenty of 119 mothers died before 23 weeks' gestational age, most of them of unsafe abortion. Other prevalent direct causes of death were hemorrhage, eclampsia and other hypertensive complications. HIV/AIDS was primary cause in 20 cases. CONCLUSION: Even with relatively complete ascertainment of births, single hospital-based medical birth registries have limitations in studies of maternal deaths. They may identify risks among women who arrive for delivery at the hospital, but are not well suited for estimation of total maternal mortality within the hospital walls. This would require additional data. Extending the birth registry monitoring system to all health institutions with obstetrical services in a region will give more reliable estimates to be followed over time and serve as a basis for regular auditing, to the benefit of mothers and their children.

Smartphone-Enhanced Training, QA, Monitoring, and Evaluation of a Platform for Secondary Prevention of Cervical Cancer: Opportunities and Challenges to Implementation in Tanzania.

PURPOSE: Until human papillomavirus (HPV)-based cervical screening is more affordable and widely available, visual inspection with acetic acid (VIA) is recommended by the WHO for screening in lower-resource settings. Visual inspection will still be required to assess the cervix for women whose screening is positive for high-risk HPV. However, the quality of VIA can vary widely, and it is difficult to maintain a well-trained cadre of providers. We developed a smartphone-enhanced VIA platform (SEVIA) for real-time secure sharing of cervical images for remote supportive supervision, data monitoring, and evaluation. METHODS: We assessed programmatic outcomes so that findings could be translated into routine care in the Tanzania National Cervical Cancer Prevention Program. We compared VIA positivity rates (for HIV-positive and HIV-negative women) before and after implementation. We collected demographic, diagnostic, treatment, and loss-to-follow-up data. RESULTS: From July 2016 to June 2017, 10,545 women were screened using SEVIA at 24 health facilities across 5 regions of Tanzania. In the first 6 months of implementation, screening quality increased significantly from the baseline rate in the prior year, with a well-trained cadre of more than 50 health providers who "graduated" from the supportive-supervision training model. However, losses to follow-up for women referred for further evaluation or to a higher level of care were considerable. CONCLUSION: The SEVIA platform is a feasible, quality improvement, mobile health intervention that can be integrated into a national cervical screening program. Our model demonstrates potential for scalability. As HPV screening becomes more affordable, the platform can be used for visual assessment of the cervix to determine amenability for same-day ablative therapy and/or as a secondary triage step, if needed.

SMS behaviour change communication and eVoucher interventions to increase uptake of cervical cancer screening in the Kilimanjaro and Arusha regions of Tanzania: a randomised, double-blind, controlled trial of effectiveness.

BACKGROUND: Cervical cancer, although almost entirely preventable through cervical cancer screening (CCS) and human papillomavirus vaccination, is the leading cause of cancer deaths among women in Tanzania. Barriers to attending CCS include lack of awareness of CCS, affordability concerns regarding screening and travel cost. We aimed to compare the effectiveness of SMS (short message service) behaviour change communication (BCC) messages and of SMS BCC messages delivered with a transportation electronic voucher (eVoucher) on increasing uptake of CCS versus the control group. METHODS: Door-to-door recruitment was conducted between 1 February and 13 March 2016 in randomly selected enumeration areas in the catchment areas of two hospitals, one urban and one rural, in Northern Tanzania. Women aged 25-49 able to access a mobile phone were randomised using a computer-generated 1:1:1 sequence stratified by urban/rural to receive either (1) 15 SMS, (2) an eVoucher for return transportation to CCS plus the same SMS, or (3) one SMS informing about the nearest CCS clinic. Fieldworkers and participants were masked to allocation. All areas received standard sensitisation including posters, community announcements and sensitisation similar to community health worker (CHW) sensitisation. The primary outcome was attendance at CCS within 60 days of randomisation. FINDINGS: Participants (n=866) were randomly allocated to the BCC SMS group (n=272), SMS + eVoucher group (n=313), or control group (n=281), with 851 included in the analysis (BCC SMS n=272, SMS + eVoucher n=298, control group n=281). By day 60 of follow-up, 101 women (11.9%) attended CCS. Intervention group participants were more likely to attend than control group participants (SMS + eVoucher OR: 4.7, 95% CI 2.9 to 7.4; SMS OR: 3.0, 95% CI 1.5 to 6.2). TRIAL REGISTRATION NUMBER: NCT02680613.

Willingness to HPV self-sampling for cervical cancer screening and its predictors among women attending outpatient clinics in Meru District, Arusha Region, Northern Tanzania

Background: The ability for women to self-collect human papillomavirus (HPV) samples can potentially reduce the risk of cervical cancer and increase screening coverage. Objectives: To assess the willingness to HPV self-sampling for cervical cancer screening and its predictors among women attending outpatient clinics in Arusha region, northern Tanzania. Methods: A hospital-based cross-sectional study was conducted among 706 women aged 18-55 years in Meru District Hospital and Usa River Health Centre from March to April 2019. Face-to-face intervies were conducted using a questionnaire. Data analysis was performed using Stata version 14.0. The log-binomial regression was used to determine factors associated with willingness to self-collection of HPV samples. Results: Majority (70%) of the women were willing to self-collection of HPV samples for cervical cancer screening and was associated with attending Meru District hospital (PR=2.02, 95%CI 1.77-2.31); good knowledge about cervical cancer warning signs (PR=1.11, 95%CI 1.01-1.22), prevention (PR=1.13, 95%CI 1.04-1.20), and symptoms (PR=1.61, 95%CI 1.33-1.93); and having formal employment (PR=1.22, 95%CI 1.07-1.37). Conclusion: The majority of women were willing to self-collect HPV samples for cervical cancer screening. Self-collection is, therefore, an acceptable and viable means of screening for cervical cancer, which has great implications for Tanzania from a health policy perspective.

Evaluation of a Smartphone-Based Training Strategy Among Health Care Workers Screening for Cervical Cancer in Northern Tanzania: The Kilimanjaro Method.

PURPOSE: Almost nine of 10 deaths resulting from cervical cancer occur in low-income countries. Visual inspection under acetic acid (VIA) is an evidence-based, cost-effective approach to cervical cancer screening (CCS), but challenges to effective implementation include health provider training costs, provider turnover, and skills retention. We hypothesized that a smartphone camera and use of cervical image transfer for real-time mentorship by experts located distantly across a closed user group through a commercially available smartphone application would be both feasible and effective in enhancing VIA skills among CCS providers in Tanzania. METHODS: We trained five nonphysician providers in semirural Tanzania to perform VIA enhanced by smartphone cervicography with real-time trainee support from regional experts. Deidentified images were sent through a free smartphone application on the available mobile telephone networks. Our primary outcomes were feasibility of using a smartphone camera to perform smartphone-enhanced VIA and level of agreement in diagnosis between the trainee and expert reviewer over time. RESULTS: Trainees screened 1,072 eligible women using our methodology. Within 1 month of training, the agreement rate between trainees and expert reviewers was 96.8%. Providers received a response from expert reviewers within 1 to 5 minutes 48.4% of the time, and more than 60% of the time, feedback was provided by regional expert reviewers in less than 10 minutes. CONCLUSION: Our method was found to be feasible and effective in increasing health care workers' skills and accuracy. This method holds promise for improved quality of VIA-based CCS programs among health care providers in low-income countries.

IL-10, IL-15, IL-17, and GMCSF levels in cervical cancer tissue of Tanzanian women infected with HPV16/18 vs. non-HPV16/18 genotypes.

BACKGROUND: Despite comparable screening rates for precancerous lesions, higher incidence and mortality related to cervical cancer in minority women persists. Recent evidence suggests that minority women with precancerous cervical lesions harbor a wider range of human papillomavirus (HPV) genotypes, many of these distinct from HPV16/18, those most commonly found in Caucasian women. The goal of the analysis was to determine if inflammatory cytokines and chemokines varied by HPV 16/18 versus other genotypes in cervical cancer tissues from Tanzanian women. METHODS: HPV genotypes and concentrations of chemokines and cytokines were measured from homogenized fresh tumor tissue of thirty-one women with invasive cervical cancer (ICC). Risk factors for cervical cancer including age, parity, hormonal contraceptive use and cigarette smoking were obtained by questionnaire. Generalized linear models were used to evaluate differences between chemokines/cytokine levels in women infected with HPV16/18 and those infected with other HPV genotypes. RESULTS: After adjusting for age, parity and hormonal contraceptives, IL-17 was found significantly more frequently in invasive cervical cancer samples of women infected with HPV16/18 compared to women infected with other HPV genotypes (p = 0.033). In contrast, higher levels for granular macrophage colony-stimulating factor (p = 0.004), IL-10 (p = 0.037), and IL-15 (p = 0.041) were found in ICC tissues of women infected with genotypes other than HPV16/18 when compared to those of women infected with HPV16/18. CONCLUSIONS: While the small sample size limits inference, our data suggest that infection with different HPV genotypes is associated with distinct pro-inflammatory cytokine expression profiles; whether this explains some of the racial differences observed in cervical cancer is still unclear. Future studies are needed to confirm these findings.

Cervical cancer screening and HPV vaccine acceptability among rural and urban women in Kilimanjaro Region, Tanzania.

OBJECTIVE: To determine cervical cancer screening coverage and the knowledge, attitudes and barriers toward screening tests among women in rural and urban areas of Tanzania, as well as explore how they view the acceptability of the HPV vaccine and potential barriers to vaccination. SETTING: A cross-sectional study using interview-administered questionnaires was conducted using multistage random sampling within urban and rural areas in Kilimanjaro Region, Tanzania. PARTICIPANTS: Women aged 18-55 were asked to participate in the survey. The overall response rate was 97.5%, with a final sample of 303 rural and 272 urban dwelling women. PRIMARY AND SECONDARY OUTCOME MEASURES: Descriptive and simple test statistics were used to compare across rural and urban strata. Multivariate logistic regression models were used to estimate ORs and 95% CIs. RESULTS: Most women (82%) reported they had heard of cervical cancer, while self-reported cervical cancer screening among women was very low (6%). In urban areas, factors associated with screening were: older age (OR=4.14, 95% CI 1.86 to 9.24 for ages 40-49, and OR=8.38, 95% CI 2.10 to 33.4 for >50 years), having health insurance (OR=4.15, 95% CI 1.52 to 11.4), and having knowledge about cervical cancer (OR=5.81, 95% CI 1.58 to 21.4). In contrast, among women residing in rural areas, only condom use (OR=6.44, 95% CI 1.12 to 37.1) was associated with screening. Women from both rural and urban areas had low vaccine-related knowledge; however, most indicated they would be highly accepting if it were readily available (93%). CONCLUSIONS: The current proportion of women screened for cervical cancer is very low in Kilimanjaro Region, and our study has identified several modifiable factors that could be addressed to increase screening rates. Although best implemented concurrently, the availability of prophylactic vaccination for girls may provide an effective means of prevention if they are unable to access screening in the future.

Religious coping among women with obstetric fistula in Tanzania.

Religion is an important aspect of Tanzanian culture, and is often used to cope with adversity and distress. This study aimed to examine religious coping among women with obstetric fistulae. Fifty-four women receiving fistula repair at a Tanzanian hospital completed a structured survey. The Brief RCOPE assessed positive and negative religious coping strategies. Analyses included associations between negative religious coping and key variables (demographics, religiosity, depression, social support and stigma). Forty-five women also completed individual in-depth interviews where religion was discussed. Although participants utilised positive religious coping strategies more frequently than negative strategies (p < .001), 76% reported at least one form of negative religious coping. In univariate analysis, negative religious coping was associated with stigma, depression and low social support. In multivariate analysis, only depression remained significant, explaining 42% of the variance in coping. Qualitative data confirmed reliance upon religion to deal with fistula-related distress, and suggested that negative forms of religious coping may be an expression of depressive symptoms. Results suggest that negative religious coping could reflect cognitive distortions and negative emotionality, characteristic of depression. Religious leaders should be engaged to recognise signs of depression and provide appropriate pastoral/spiritual counselling and general psychosocial support for this population.

Cancer registration needs assessment at a tertiary medical centre in Kilimanjaro, Tanzania.

Cancer burden is increasing in Africa more than in any other continent, but population-based tracking of cancer incidence is incomplete. Cancer registries can improve understanding of cancer incidence. To assess organizational readiness to sustain registry development, we conducted a survey assessing change efficacy, resource availability and change commitment at the Kilimanjaro Christian Medical Centre (KCMC), an academic hospital in Moshi, Tanzania. Fifty-two surveys were returned (80% response rate). There was strong reliability among change efficacy and commitment survey items, with Cronbach's alphas of 0.93 and 0.77, respectively. Clinicians, nurses and administrators conveyed similar responses regarding change efficacy. Clinicians had similar responses for change commitment. Echoing opinion in many low- and middle-income countries, approximately one-third of respondents indicated there were no funds to maintain the registry, and funds were not obtainable. For most resources, respondents felt that resources were sufficient or attainable. Respondents were generally confident and committed to registry implementation. Lessons learned at KCMC may be more broadly relevant.

Associations between methylation of paternally expressed gene 3 (PEG3), cervical intraepithelial neoplasia and invasive cervical cancer.

Cytology-based screening for invasive cervical cancer (ICC) lacks sensitivity and specificity to discriminate between cervical intraepithelial neoplasia (CIN) likely to persist or progress from cases likely to resolve. Genome-wide approaches have been used to identify DNA methylation marks associated with CIN persistence or progression. However, associations between DNA methylation marks and CIN or ICC remain weak and inconsistent. Between 2008-2009, we conducted a hospital-based, case-control study among 213 Tanzania women with CIN 1/2/3 or ICC. We collected questionnaire data, biopsies, peripheral blood, cervical scrapes, Human papillomavirus (HPV) and HIV-1 infection status. We assessed PEG3 methylation status by bisulfite pyrosequencing. Multinomial logistic regression was used to estimate odds ratios (OR) and confidence intervals (CI 95%) for associations between PEG3 methylation status and CIN or ICC. After adjusting for age, gravidity, hormonal contraceptive use and HPV infection, a 5% increase in PEG3 DNA methylation was associated with increased risk for ICC (OR = 1.6; 95% CI 1.2-2.1). HPV infection was associated with a higher risk of CIN1-3 (OR = 15.7; 95% CI 5.7-48.6) and ICC (OR = 29.5, 95% CI 6.3-38.4). Infection with high risk HPV was correlated with mean PEG3 differentially methylated regions (DMRs) methylation (r = 0.34 p<0.0001), while the correlation with low risk HPV infection was weaker (r = 0.16 p = 0.047). Although small sample size limits inference, these data support that PEG3 methylation status has potential as a molecular target for inclusion in CIN screening to improve prediction of progression. Impact statement: We present the first evidence that aberrant methylation of the PEG3 DMR is an important co-factor in the development of Invasive cervical carcinoma (ICC), especially among women infected with high risk HPV. Our results show that a five percent increase in DNA methylation of PEG3 is associated with a 1.6-fold increase ICC risk. Suggesting PEG3 methylation status may be useful as a molecular marker for CIN screening to improve prediction of cases likely to progress.

Distribution of HPV genotypes in cervical intraepithelial lesions and cervical cancer in Tanzanian women.

BACKGROUND: Infection with human papillomavirus (HPV) is associated with uterine cervical intraepithelial neoplasia (CIN) and invasive cancers (ICC). Approximately 80% of ICC cases are diagnosed in under-developed countries. Vaccine development relies on knowledge of HPV genotypes characteristic of LSIL, HSIL and cancer; however, these genotypes remain poorly characterized in many African countries. To contribute to the characterization of HPV genotypes in Northeastern Tanzania, we recruited 215 women from the Reproductive Health Clinic at Kilimanjaro Christian Medical Centre. Cervical scrapes and biopsies were obtained for cytology and HPV DNA detection. RESULTS: 79 out of 215 (36.7%) enrolled participants tested positive for HPV DNA, with a large proportion being multiple infections (74%). The prevalence of HPV infection increased with lesion grade (14% in controls, 67% in CIN1 cases and 88% in CIN2-3). Among ICC cases, 89% had detectable HPV. Overall, 31 HPV genotypes were detected; the three most common HPV genotypes among ICC were HPV16, 35 and 45. In addition to these genotypes, co-infection with HPV18, 31, 33, 52, 58, 68 and 82 was found in 91% of ICC. Among women with CIN2-3, HPV53, 58 and 84/83 were the most common. HPV35, 45, 53/58/59 were the most common among CIN1 cases. CONCLUSIONS: In women with no evidence of cytological abnormalities, the most prevalent genotypes were HPV58 with HPV16, 35, 52, 66 and 73 occurring equally. Although numerical constraints limit inference, findings that 91% of ICC harbor only a small number of HPV genotypes suggests that prevention efforts including vaccine development or adjuvant screening should focus on these genotypes.