The impact of DNA tumor viruses in low-to-middle income countries (LMICS): A literature review.

DNA viruses are common in the human population and act as aetiological agents of cancer on a large scale globally. They include the human papillomaviruses (HPV), Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), hepatitis viruses, and human polyomaviruses. Oncogenic viruses employ different mechanisms to induce cancer. Notably, cancer only develops in a minority of individuals who are infected, usually following protracted years of chronic infection. The human papillomaviruses (HPVs) are associated with the highest number of cancer cases, including cervical cancer and other epithelial malignancies. Hepatitis B virus (HBV) and the RNA virus hepatitis C (HCV) are significant contributors to hepatocellular cancer (HCC). Other oncoviruses include Epstein-Barr virus (EBV), Kaposi sarcoma-associated herpes virus (KSHV), human T-cell leukemia virus (HTLV-I), and Merkel cell polyomavirus (MCPyV). The identification of these infectious agents as aetiological agents for cancer has led to reductions in cancer incidence through preventive interventions such as HBV and HPV vaccination, HPV-DNA based cervical cancer screening, antiviral treatments for chronic HBV and HCV infections, and screening of blood for transfusion for HBV and HCV. Successful efforts to identify additional oncogenic viruses in human cancer may provide further understanding of the aetiology and development of cancer, and novel approaches for prevention and treatment. Cervical cancer, caused by HPV, is the leading gynaecological malignancy in LMICs, with high age-standardised incidence and mortality rates, HCC due to HBV is an important cause of cancer deaths, and the burden of other cancer attributable to infections continues to rise globally. Hence, cancers attributable to DNA viruses have become a significant global health challenge. These viruses hence warrant continued attention and interrogation as efforts to understand them further and device further preventive interventions are critical.

Protein dose-sparing effect of AS01B adjuvant in a randomized preventive HIV vaccine trial of ALVAC-HIV (vCP2438) and adjuvanted bivalent subtype C gp120.

BACKGROUND: HVTN 120 is a phase 1/2a randomized double-blind placebo-controlled HIV vaccine trial that evaluated the safety and immunogenicity of ALVAC-HIV (vCP2438) and MF59- or AS01B-adjuvanted bivalent subtype C gp120 Env protein at two dose levels in healthy HIV-uninfected adults. Trial registration URL https://clinicaltrials.gov/ct2/show/NCT03122223 and registration number NCT03122223. METHODS: Participants received ALVAC-HIV (vCP2438) alone or placebo at months 0 and 1. At months 3 and 6, participants received either placebo, ALVAC-HIV (vCP2438) with 200µg of bivalent subtype C gp120 adjuvanted with MF59 or AS01B, or ALVAC-HIV (vCP2438) with 40µg of bivalent subtype C gp120 adjuvanted with AS01B. Primary outcomes were safety and immune responses. RESULTS: We enrolled 160 participants, 55% females, 18-40 years old (median age 24 years) of whom 150 received vaccine and 10 placebo. Vaccines were generally safe and well tolerated. At months 6.5 and 12, CD4+ T-cell response rates and magnitudes were higher in the AS01B-adjuvanted groups than in the MF59-adjuvanted group. At month 12, HIV-specific Env-gp120 binding antibody response magnitudes in the 40µg gp120/AS01B group were higher than in either of the 200µg gp120 groups. CONCLUSIONS: The 40µg dose gp120/AS01B regimen elicited the highest CD4+ T-cell and binding antibody responses.

Correction: Self-collected and clinician-collected anal swabs show modest agreement for HPV genotyping.

[This corrects the article DOI: 10.1371/journal.pone.0250426.].

Impact of catch-up human papillomavirus vaccination on cervical cancer incidence in Kenya: A mathematical modeling evaluation of HPV vaccination strategies in the context of moderate HIV prevalence.

BACKGROUND: Cervical cancer incidence is high in Kenya due to HIV and limited access to cancer prevention services. Human papillomavirus (HPV) has been shown to increase HIV acquisition; however, the potential impact of HPV vaccination on HIV is unknown. We modeled the health impact of HPV vaccination in the context of the HIV epidemiology in Kenya. METHODS: Using a validated compartmental transmission model of HIV and HPV set in Kenya, we evaluated five scenarios of nonavalent HPV vaccination: single-age-vaccination of 10-year-old girls at 90% coverage; multi-age-cohort (MAC) vaccination of 10-14-year-old girls at 90% coverage; MAC plus moderate-coverage (50%) catch-up vaccination of 15-24-year-old women; MAC plus high-coverage (80%) catch-up of 15-24-year-old women; and MAC plus catch-up of 15-44-year-old women at 80% coverage (HPV-FASTER). We compared cervical cancer incidence, HIV prevalence, and cumulative cervical cancer and HIV cases averted after 50 years to a baseline scenario without vaccination. In all scenarios, we assumed the UNAIDS 90-90-90 goal for HIV treatment is attained by 2030. FINDINGS: In 2021, model-estimated cervical cancer incidence is 44/100,000 and HIV prevalence among women is 6·5%. In 2070, projected cancer incidence declines to 27/100,000 and HIV prevalence reaches 0·3% without vaccination. With single-age-vaccination, cancer incidence in 2070 is reduced by 68%, averting 64,529 cumulative cancer cases. MAC vaccination reduces cancer incidence by 75%, averting 206,115 cancer cases. Moderate and high-coverage catch-up and HPV-FASTER reduce cancer incidence by 80%, 82%, and 84%, averting 254,930, 278,690, and 326,968 cancer cases, respectively. In all scenarios, HIV prevalence in 2070 is reduced by a relative 8-11%, with 15,609-34,981 HIV cases averted after 50 years. INTERPRETATION: HPV vaccination can substantially reduce cervical cancer incidence in Kenya in the next 50 years, particularly if women up to age 24 are vaccinated. HIV treatment scale-up can also alleviate cervical cancer burden. However, HPV vaccination has modest additional impact on HIV when antiretroviral therapy coverage is high. FUNDING: National Institutes of Health, Bill and Melinda Gates Foundation.

Prevalent human papillomavirus infection increases the risk of HIV acquisition in African women: advancing the argument for human papillomavirus immunization.

OBJECTIVE: Vaccine-preventable human papillomavirus (HPV) infection is common, especially in sub-Saharan Africa where HIV risk is also high. However, unlike other sexually transmitted infections (STIs), HPV's role in HIV acquisition is unclear. We evaluated this relationship using data from MTN-003, a clinical trial of HIV chemoprophylaxis among cisgender women in sub-Saharan Africa. DESIGN: A case-control study. METHODS: We matched 138 women who acquired HIV (cases) to 412 HIV-negative controls. Cervicovaginal swabs collected within 6 months before HIV seroconversion were tested for HPV DNA. We estimated the associations between carcinogenic (high-risk) and low-risk HPV types and types targeted by HPV vaccines and HIV acquisition, using conditional logistic regression models adjusted for time-varying sexual behaviors and other STIs. RESULTS: Mean age was 23 (±4) years. Any, high-risk and low-risk HPV was detected in 84, 74 and 66% of cases, and 65, 55 and 48% of controls. Infection with at least two HPV types was common in cases (67%) and controls (49%), as was infection with nonavalent vaccine-targeted types (60 and 42%). HIV acquisition increased with any [adjusted odds ratio (aOR) 2.5, 95% confidence interval (95% CI) 1.3-4.7], high-risk (aOR 2.6, 95% CI 1.5-4.6) and low-risk (aOR 1.8, 95% CI 1.1-2.9) HPV. Each additional type detected increased HIV risk by 20% (aOR 1.2, 95% CI 1.1-1.4). HIV acquisition was associated with HPV types targeted by the nonavalent (aOR 2.1, 95% CI 1.3-3.6) and quadrivalent vaccines (aOR 1.9, 95% CI 1.1-3.2). CONCLUSION: HPV infection is associated with HIV acquisition in sub-Saharan African women. In addition to preventing HPV-associated cancers, increasing HPV vaccination coverage could potentially reduce HIV incidence.

Self-collected and clinician-collected anal swabs show modest agreement for HPV genotyping.

BACKGROUND & AIM: Women with HIV/HPV coinfection and cervical lesions are at increased risk of developing HPV related anal cancer. Self-collection of anal swabs may facilitate HPV molecular testing in anal cancer screening, especially in high-risk groups, and yet it is not adequately studied. We evaluated level of agreement between self-collected anal swabs (SCAS) and clinician-collected anal swabs (CCAS) when used for HPV genotyping. We also described the anal HPV genotype distribution and HIV/HPV coinfection. METHODS: We performed a cross sectional study with participants from a visual-inspection-with-acetic-acid and cervicography (VIAC) clinic, in Harare, Zimbabwe. In a clinic setting, the women aged ≥18 years provided anal swabs in duplicate; first CCAS and then SCAS immediately after. HPV detection and genotyping were performed using next generation amplicon sequencing of a 450bp region of the HPV L1 gene. Level of agreement of HPV genotypes between CCAS and SCAS was calculated using the kappa statistic. McNemar tests were used to evaluate agreement in the proportion of genotypes detected by either method. RESULTS: Three-hundred women provided 600 samples for HPV genotyping. HPV genotypes were detected in 25% of SCAS and in 22% of CCAS. The most common genotypes with CCAS were HPV52, HPV62 and HPV70 and with SCAS were HPV62, HPV44, HPV52, HPV53 and HPV68. Total HPV genotypes detected in CCAS were more than those detected in SCAS, 32 versus 27. The agreement of HPV genotypes between the two methods was 0.55 in kappa value (k). The test of proportions using McNemar gave a Chi-square value of 0.75 (p = 0.39). Multiple HPV infections were detected in 28/75 and 29/67 women for CCAS and SCAS respectively. CONCLUSIONS: SCAS and CCAS anal swabs showed moderate agreement, with no statistically significant difference in the proportion of genotypes detected by either methods. Although the differences between the two methods were not statistically significant, CCAS detected more HPV genotypes than SCAS and more HPV infections were detected in SCAS than in CCAS. Our data suggest that self-collected anal swabs can be used as an alternative to clinician-collected anal swabs for HPV genotyping.

Safety, uptake, and use of a dapivirine vaginal ring for HIV-1 prevention in African women (HOPE): an open-label, extension study.

BACKGROUND: Two phase 3 clinical trials showed that use of a monthly vaginal ring containing 25 mg dapivirine was well tolerated and reduced HIV-1 incidence in women by approximately 30% compared with placebo. We aimed to evaluate use and safety of the dapivirine vaginal ring (DVR) in open-label settings with high background rates of HIV-1 infection, an important step for future implementation. METHODS: We did a phase 3B open-label extension trial of the DVR (MTN-025/HIV Open-label Prevention Extension [HOPE]). Women who were HIV-1-negative and had participated in the MTN-020/ASPIRE phase 3 trial were offered 12 months of access to the DVR at 14 clinical research centres in Malawi, South Africa, Uganda, and Zimbabwe. At each visit (monthly for 3 months, then once every 3 months), women chose whether or not to accept the offer of the ring. Used, returned rings were tested for residual amounts of dapivirine as a surrogate marker for adherence. HIV-1 serological testing was done at each visit. Dapivirine amounts in returned rings and HIV-1 incidence were compared with data from the ASPIRE trial, and safety was assessed. This study is registered with ClinicalTrials.gov, NCT02858037. FINDINGS: Between July 16, 2016, and Oct 10, 2018, of 1756 women assessed for eligibility, 1456 were enrolled and participated in the study. Median age was 31 years (IQR 27-37). At baseline, 1342 (92·2%) women chose to take the DVR; ring acceptance was more than 79% at each visit up until 12 months and 936 (73·2%) of 1279 chose to take the ring at all visits. 12 530 (89·3%) of 14 034 returned rings had residual dapivirine amounts consistent with some use during the previous month (>0·9 mg released) and the mean dapivirine amount released was greater than in the ASPIRE trial (by 0·21 mg; p<0·0001). HIV-1 incidence was 2·7 per 100 person-years (95% CI 1·9-3·8, 35 infections), compared with an expected incidence of 4·4 per 100 person-years (3·2-5·8) among a population matched on age, site, and presence of a sexually transmitted infection from the placebo group of ASPIRE. No serious adverse events or grade 3 or higher adverse events observed were assessed as related to the DVR. INTERPRETATION: High uptake and persistent use in this open-label extension study support the DVR as an HIV-1 prevention option for women. With an increasing number of HIV-1 prophylaxis choices on the horizon, these results suggest that the DVR will be an acceptable and practical option for women in Africa. FUNDING: The Microbicide Trials Network and the National Institute of Allergy and Infectious Diseases, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, and the National Institute of Mental Health, all components of the US National Institutes of Health.

Effect of injectable progestin-only contraceptives, depot medroxyprogesterone acetate and norethisterone enanthate, on cytokine production during T-cell activation.

PROBLEM: There is paucity of human data about the effects of depot medroxyprogesterone (DMPA) and norethisterone enanthate (Net-En) use on systemic immune function, which may have implications for reproductive tract infection susceptibility and transmissibility. We sought to evaluate the impact of injectable contraceptive use on T-cell responsiveness using T cells exposed in vivo and tested ex vivo. METHODS: Peripheral blood mononuclear cells were obtained from healthy, HIV-negative women after 30, 90 and 180 days of DMPA, norethisterone enanthate (Net-En) or copper intrauterine device (Cu-IUD) contraceptive use. Cells were stimulated ex vivo with phorbol myristate acetate and ionomycin, stained and analysed using flow cytometry. Mixed-effects linear models were used to evaluate change in proportions of T cells producing IFN-γ, TNF-α, IL-4 and IL-13. RESULTS: Compared with baseline, decreased proportions of IFN-γ-producing CD4+ and CD8+ T cells (p = .003, p = .006, respectively) and TNF-α-producing CD4+ and CD8+ T cells (p = .039, p = .034, respectively) were observed after 180 days of DMPA use. Decreased IL-4-producing CD4+ and CD8+ T cells (p = .045 and p = .024, respectively) were noted after 180 days of Net-En use. Decreased IL-4-producing CD4+ T cells were observed after 30 days (p = .035) and not after 180 days of DMPA use (p = .49). There were no changes in proportion of T cells producing IL-13 in DMPA users, nor any changes in IFN-γ, TNF-α and IL-13 in Net-En and Cu-IUD users. CONCLUSION: In vivo exposure of CD4+ and CD8+ T cells to typical pharmacologic concentrations of DMPA does not cause broad suppression to stimuli; however, depletion of specific cytokine-producing T cells may occur after prolonged DMPA use.

Preferences and Acceptability of Vaginal Delivery Forms for HIV Prevention Among Women, Male Partners and Key Informants in South Africa and Zimbabwe: Qualitative Findings.

The attributes of an HIV microbicide may affect its acceptability, uptake and use. Quatro, a clinical study with a qualitative component, was conducted to elicit input from end-users and key informants (KIs) on four different placebo vaginal microbicide delivery forms; fast dissolving insert, ring, film and gel. In-depth interviews and focus group discussions were conducted with young women, their male partners and KIs, to explore acceptability and preferences of the four placebo products, with the intention of improving product attributes, adherence, and consequently, long term effectiveness. None of the four microbicide delivery forms stood well above others as the most preferred. Product attributes; long-action, ease of use, invisibility, female initiated and non-interference during sex were favourable in both countries. Despite preference for the long-action, on-demand products were the most liked by women. Qualitative data from the Quatro study provided rich feedback on specific attributes important to the acceptability of four HIV prevention product platforms currently in development, enabling more informed and guided product development efforts moving forward.

Estimated costs for the delivery of safer conception strategies for HIV-discordant couples in Zimbabwe: a cost analysis.

BACKGROUND: In recent years, safer conception strategies have been developed to help HIV-serodiscordant couples conceive a child without transmitting HIV to the seronegative partner. The SAFER clinical trial assessed implementation of these strategies in Zimbabwe. METHODS: As a part of the SAFER study, we estimated the costs (in 2017 $US) associated with individual and combination strategies, in the trial setting and real-world practice, from a healthcare system perspective. Safer conception strategies included: 1) ART with frequent viral load testing until achieving undetectable viral load (ART-VL); 2) daily oral pre-exposure prophylaxis (PrEP); 3) semen-washing with intrauterine insemination; and 4) manual self-insemination at home. For costs in the trial, we used a micro-costing approach, including a time and motion study to quantify personnel effort, and estimated the cost per couple for individual and combination strategies for a mean of 6 months of safer services. For real-world practice, we modeled costs for three implementation scenarios, representing differences from the trial in input prices (paid by the Ministry of Health and Child Care [MOHCC]), intervention intensity, and increments to current HIV prevention and treatment practices and guidelines. We used one-way sensitivity analyses to assess the impact of uncertainty in input variables. RESULTS: Individual strategy costs were $769-$1615 per couple in the trial; $185-$563 if using MOHCC prices. Under the target intervention intensity and using MOHCC prices, individual strategy costs were $73-$360 per couple over and above the cost of current HIV clinical practices. The cost of delivering the most commonly selected combination, ART-VL plus PrEP, ranged from $166-$517 per couple under the three real-world scenarios. Highest costs were for personnel, lab tests, and strategy-specific consumables, in variable proportions by clinical strategy and analysis scenario. Total costs were most affected by uncertainty in the price of PrEP, number of semen-washing attempts, and scale-up of semen-washing capacity. CONCLUSIONS: Safer conception methods have costs that may be affordable in many low-resource settings. These cost data will help implementers and policymakers add safer conception services. Cost-effectiveness analysis is needed to assess value for money for safer conception services overall and for safer strategy combinations. TRIAL REGISTRATION: Registry Name: Clinicaltrials.gov. TRIAL REGISTRATION NUMBER: NCT03049176 . Registration date: February 9, 2017.

Zim CHIC: A cohort study of immune changes in the female genital tract associated with initiation and use of contraceptives.

PROBLEM: Contraceptive hormones are systemically active, potent, and likely to invoke biological responses other than known fertility regulation impacts. We hypothesized that initiation of depot medroxyprogesterone acetate (DMPA) would increase genital HIV-target-cells and soluble immune mediators compared with baseline and initiation of other contraceptive methods. METHOD OF STUDY: We collected cervical cytobrushes and cervicovaginal fluid from healthy Zimbabwean women aged 18-34 to assess immune cell populations, cytokines, and innate anti-HIV activity at baseline and after 30, 90, and 180 days use of DMPA (n = 38), norethisterone enanthate (n = 41), medroxyprogesterone acetate/estradiol cypionate (n = 36), levonorgestrel implant (n = 43), etonogestrel implant (n = 47), or copper intrauterine device (Cu-IUD) (n = 45). Cells were quantified by flow cytometry, cytokines were detected by multiplex assays, and innate anti-HIV activity was assessed by in vitro HIV challenge. RESULTS: Compared to baseline, the number of cervical HIV target cells (#CD4 cells P < .04 and #CD11c cells P < .04), the concentration of the inflammatory cytokine IL-1ß (P < .01), and the innate in vitro anti-HIV activity (P < .001) significantly decreased following DMPA initiation. In Cu-IUD users, genital HIV target cells increased (#CD4 cells P < .001, #CD4CCR5 cells P = .02, #CD4CD69 cells P < .001, #CD8CD69 P = .01, and #CD11c cells P = .003) at day 30 and resolved by day 180. IFN-γ (P < .001), IL-1ß (P < .001), IL-6 (P < .001), IL-8 (P < .001), IL-10 (P < .01), and RANTES (P < .001) were also significantly increased at day 30. Minimal alterations were observed following initiation of subdermal implantable contraceptives. CONCLUSIONS: This head-to-head study compared six contraceptives and found increased HIV target cells and cervical inflammation temporally associated with Cu-IUD initiation. Use of hormonal contraception, including DMPA, did not increase cervical HIV target cells or inflammation. Clinical Trial Number: NCT02038335.

Use of the dapivirine vaginal ring and effect on cervical cytology abnormalities.

OBJECTIVE: We aimed to determine if the dapivirine vaginal ring and the ring device alone (flexible silicone matrix polymer) was associated with the development of cervical cytology abnormalities. DESIGN: Secondary analysis comparing cervical cytology results between two randomized controlled microbicide trials (MTN-020/ASPIRE and MTN-003/VOICE). METHODS: Data from ASPIRE, a phase III, placebo-controlled trial of the dapivirine vaginal ring, were used in this analysis. Cervical cytology smears were evaluated at baseline and at the final visit with product use. We compared cytology results between women randomized to dapivirine versus placebo vaginal ring. We further assessed for the effect of the vaginal ring device on cervical cytology by comparing results with data from the oral placebo arm of VOICE, a prior HIV-1 prevention trial conducted in a similar population. RESULTS: Cervical cytology results for 2394 women from ASPIRE (1197 per study arm) were used in this analysis; median time between baseline and final visit with product use was 22.1 months. Cytology smear findings were comparable between dapivirine and placebo vaginal ring arms: at final visit, normal: 90.6 versus 91.5%, ASC-US//LSIL: 7.8 versus 7.4%, ASC-H/HSIL/AGC/AGC-favor neoplastic: 1.7 versus 1.1%, P = 0.44. Cytology data from VOICE had findings (normal: 87.8%, ASC-US/LSIL: 9.8%, ASC-H/HSIL/AGC/AGC-favor neoplastic: 2.4%) comparable with that of both dapivirine (P = 0.93) and placebo vaginal ring arms (P = 0.24). CONCLUSION: These findings indicate that neither use of the dapivirine vaginal ring nor the vaginal ring device alone, over a period of 2 years, is associated with development of cervical cytology abnormalities that could lead to precancerous or cancerous lesions.

Depot medroxyprogesterone acetate and norethisterone enanthate differentially impact T-cell responses and expression of immunosuppressive markers.

PROBLEM: Injectable contraceptive use may impact immune cell responsiveness and susceptibility to infection. We measured responsiveness of T-cells from women before and after initiating depot medroxyprogesterone acetate (DMPA) or norethisterone enanthate (Net-En). METHOD OF STUDY: Peripheral blood mononuclear cells collected from women aged 18-34 years prior to, at steady state, and nadir concentrations after initiating DMPA (n = 30) or Net-En (n = 36) and from women initiating copper intrauterine device (CU-IUD; n = 32) were stimulated with phorbol myristate acetate and analyzed using flow cytometry. We evaluated percentage change in T-cells expressing programmed cell death-1 (PD-1) and cytotoxic T-lymphocyte associated protein-4 (CTLA-4). RESULTS: Compared to baseline, there were decreased numbers of CD4+CTLA4+ (P < .001) and CD8+CTLA4+ (P < .01) T-cells following ex vivo stimulation challenge at steady state DMPA concentrations and no differences at nadir concentrations (P = .781 and P = .463, respectively). In Net-En users, no differences in CD4+CTLA4+ T-cells at steady state (P = .087) and nadir concentrations (P = .217) were observed. DMPA users had fewer CD4+PD-1+ (P < .001) and CD8+PD-1+ (P < .001) T-cells at nadir concentrations. Number of CD4+PD-1+ and CD8+PD-1+ T-cells decreased at steady state concentration (P = .002 and P = .001, respectively) and at nadir concentrations after Net-En initiation (P < .001 and P < .001). In CU-IUD users, there were no changes in number of CD4+CTLA4+ (P = .426) and CD8+CTLA4+ (P = .169) and no changes in CD4+PD-1+ (P = .083) and CD8+PD-1+ (P = .936) compared to baseline. CONCLUSION: Activation of T-cells in response to ex vivo stimulation is suppressed at steady state DMPA concentration and resolves at nadir concentration, suggesting DMPA immunosuppressive effects may be transient.

Efficacy is Not Everything: Eliciting Women's Preferences for a Vaginal HIV Prevention Product Using a Discrete-Choice Experiment.

As new female-initiated HIV prevention products enter development, it is crucial to incorporate women's preferences to ensure products will be desired, accepted, and used. A discrete-choice experiment was designed to assess the relative importance of six attributes to stated choice of a vaginally delivered HIV prevention product. Sexually active women in South Africa and Zimbabwe aged 18-30 were recruited from two samples: product-experienced women from a randomized trial of four vaginal placebo forms and product-naïve community members. In a tablet-administered survey, 395 women chose between two hypothetical products over eight choice sets. Efficacy was the most important, but there were identifiable preferences among other attributes. Women preferred a product that also prevented pregnancy and caused some wetness (p < 0.001). They disliked a daily-use product (p = 0.002) and insertion by finger (p = 0.002). Although efficacy drove preference, wetness, pregnancy prevention, and dosing regimen were influential to stated choice of a product, and women were willing to trade some level of efficacy to have other more desired attributes.

Giant mucinous cystadenoma: a case report.

INTRODUCTION: Giant ovarian cysts are rarely described in the literature, owing to the availability of advanced imaging technologies in developed countries leading to early treatment. In resource-limited settings, various factors lead to late presentation. CASE PRESENTATION: We present a case of a 48-year-old black African woman with a giant mucinous cystadenoma who presented to a tertiary hospital with massive abdominal distention 5 years after being referred from a district hospital for the same problem. Surgical management resulted in fatal complications. CONCLUSIONS: The surgical management of these huge tumors is associated with many life-threatening complications. Transvaginal ultrasound should be used in resource-limited settings to delineate ovarian masses. Community health workers must be involved in scouting and follow up of community members with unusual abdominal swellings in developing countries to avoid delays in care.

Community-based self-collected human papillomavirus screening in rural Zimbabwe.

BACKGROUND: In low- and middle-income countries (LMIC), women have limited access to and uptake of cervical cancer screening. Delayed diagnosis leads to poorer outcomes and early mortality, and continues to impede cancer control disproportionately in LMIC. Integrating self-collected, community-based screening for High Risk-Human Papilloma Virus (HR-HPV) into existent HIV programs is a potential screening method to identify women at high risk for developing high-risk cervical lesions. METHODS: We implemented community-based cross-sectional study on self-collection HR-HPV screening in conjunction with existing community outreach models for the distribution of antiretroviral therapy (ART) and the World Health Organization Expanded Program on Immunization (EPI) outreach in villages in rural Zimbabwe from January 2017 through May 2017. RESULTS: Overall, there was an 82% response rate: 70% of respondents participated in self-collection and 12% were ineligible for the study (inclusion criteria: age 30-65, not pregnant, with an intact uterus). Women recruited in the first 2-3 months of the study had more opportunities to participate and therefore significantly higher participation: 81% participation (additional 11% ineligible), while those with fewer opportunities also had lower participation: 63% (additional 13% ineligible) (p < 0.001). Some village outreach centers (N = 5/12) had greater than 89% participation. CONCLUSIONS: Integration of HR-HPV screening into existing community outreach models for HIV and immunizations could facilitate population-based screening to scale cancer control and prevention programs in sub-Saharan Africa. Community/village health workers (CHW/VHW) and village outreach programs offer a potential option for cervical cancer screening programs to move towards improving access of sexual and reproductive health resources for women at highest risk.

A case of twin reversed arterial perfusion (TRAP) sequence managed conservatively.

The TRAP sequence, also known as acardiac twinning is a rare complication that is unique to monochorioinic multiple pregnancies affecting 1% of monochorioinic pregnancies and about 1 in 35000 of all pregnancies. In TRAP, blood flows from the umbilical artery of the pump twin to the umbilical artery of the perfused twin through artery to artery (AA) anastomosis. The perfused twin has poor development of the upper extremities and the normal or pump twin is at risk of a poor perinatal outcome. This is a report of a patient with TRAP sequence diagnosed in the second trimester who was managed conservatively and had a good outcome for the normal twin.

Validation of the GenoType® MTBDRplus Ver 2.0 assay for detection of rifampicin and isoniazid resistance in Mycobacterium tuberculosis complex isolates at UZCHS-CTRC TB research laboratory.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a public health concern globally. MDR-TB is defined as resistance to rifampicin (RIF) and isoniazid (INH), the two-major anti-TB first-line TB treatment drugs. Rapid identification of MDR-TB can contribute significantly to the control of TB. The GenoType® MTBDRplus Ver 2.0 assay is a molecular assay used to detect genetic mutations that result in RIF and INH resistance. The aim of this study was to validate the performance of the GenoType® MTBDRplus Ver 2.0 assay for the detection of INH and RIF resistance. METHODS: Fifty-five stored Mycobacterium tuberculosis isolates were tested using both the mycobacterial growth indicator tube (MGIT), antimicrobial susceptibility testing (AST), and the GenoType® MTBDRplus Ver 2.0 assay. The MGIT AST was done according to the BBL MGIT AST SIRE system with RIF and INH final critical concentrations of 1.0 µg/ml and 0.1 µg/ml, respectively. The GenoType® MTBDRplus assay (Hain Lifescience, Germany) was performed following the manufacturer's instructions. RESULTS: The GenoType® MTBDRplus Ver 2.0 assay had a sensitivity, specificity, positive predictive value, and negative predictive value of 100% for INH and RIF resistance. The intra-assay precision for the assay was 100%. CONCLUSION: The GenoType® MTBDRplus Ver 2.0 assay's sensitivity and specificity show that the assay is highly accurate for the detection of RIF and INH resistance and thus can be used as an alternate platform due to its shorter results turnaround time.

hrHPV prevalence and type distribution in rural Zimbabwe: A community-based self-collection study using near-point-of-care GeneXpert HPV testing.

OBJECTIVES: High-risk human papilloma viruses (hrHPV) are the causative agents of cervical cancer, the leading cause of cancer deaths among Zimbabwean women. The objective of this study was to describe the hrHPV types found in Zimbabwe for consideration in cervical cancer screening and vaccination efforts. DESIGN AND METHODS: To determine hrHPV prevalence and type distribution in Zimbabwe we implemented a community-based cross-sectional study of self-collected cervicovaginal samples with hrHPV screening using near-point-of-care Cepheid GeneXpert HPV. RESULTS: The hrHPV prevalence was 17% (112/643); 33% (41/123) vs. 14% (71/520) among HIV-1-positive and -negative participants, respectively (p=2.3E-07). Typing via Xpert HPV showed very good overall agreement (77.2%, kappa=0.698) with the Seegene Anyplex II HPV HR Detection kit. The most common types were HPV16, HPV18, HPV35, HPV52, HPV58, HPV68, HPV18, and HPV51, each of which appeared in 14-20% of infections. 37% (28/76) of women with positive cytology results (ASCUS+) had a type not included in the basic vaccine and 25% (19/76) had a type not currently in the nine-valent vaccine. CONCLUSIONS: hrHPV type distribution includes less common high-risk types in rural Zimbabwe. The distribution and carcinogenicity of hrHPV type distribution should be considered during screening assay design, program development, as well as vaccine distribution and design.

The association of puerperal sepsis with HIV infection at two tertiary hospitals in Zimbabwe.

OBJECTIVE: To evaluate the association between HIV infection and puerperal sepsis among women in Zimbabwe. METHODS: A subanalysis was performed using data from a prospective cohort study conducted between September 2, 2014, and July 1, 2015, at two tertiary hospitals in Zimbabwe. Eligible participants were consecutive women who met the WHO criteria for puerperal sepsis. Variables assessed included HIV-infection status and the use of antiretroviral therapy. Severity of immunosuppression was defined by the number of T cells that expressed cluster of differentiation 4 (CD4). Endocervical swabs and blood samples were collected for microbial culture and susceptibility testing. RESULTS: In all, 33 (21.9%) of the 151 women included in the present analysis had HIV. Among women with HIV, severe immunosuppression (CD4-positive T cell count <200/mm3 ) was associated with a mean hospital stay of 19.0 days versus 10.2 days for mild-advanced immunosuppression (CD4-positive T cell count 200-500/mm3 ) and insignificant immunosuppression (CD4-positive T cell count >500/mm3 ; P=0.030). Use of antiretroviral therapy did not independently influence clinical outcomes. Furthermore, infection with HIV did not influence the microorganisms isolated from blood or endocervical samples. CONCLUSION: Severe immunosuppression was associated with increased length of hospitalization among women with HIV who had puerperal sepsis.