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.

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.

Microbiology and clinical outcomes of puerperal sepsis: a prospective cohort study.

The objectives of this study were to determine the identity and antibacterial susceptibility profiles of bacteria colonising the female genital tract and blood stream and their association with clinical outcomes in women with puerperal sepsis. A prospective descriptive cohort study was conducted at two tertiary hospitals in Zimbabwe. Endocervical swabs and blood were collected for culture and susceptibility testing from 151 consecutive women who met the World Health Organisation criteria for puerperal sepsis. Medical records were reviewed for assessment of clinical outcomes. The commonest bacterial isolates were Escherichia coli (30.6%) and Klebsiella pneumoniae (15.3%). Multidrug-resistant organisms (MDRO) accounted for 10.9% of all isolates. MDRO were associated with prolonged hospital stay, 23.0 days compared to 10.5 days in women without MDRO (p = .009). Puerperal sepsis case fatality rate was 7.3%. Clinical culture surveillance to monitor epidemiologic trends, identify MDRO, robust infection control strategies and emphasis on rational drug use are recommended. Impact statement What is already known? Puerperal sepsis is often a polymicrobial infection. Escherichia coli has been reported as a common cause of severe maternal sepsis originating from the genital tract. Other bacteria include Group A Streptococcus, S. aureus, Streptococcus spp. Klebsiellae spp, Pseudomonas spp. and anaerobes. What does this study add? This study confirms Escherichia coli as the commonest cause of sepsis in Harare. There is high level resistance to first-line antibiotic regimens on most Gram-negative isolates from the endocervix among women with puerperal sepsis. Emerging resistance to carbapenems is demonstrated. MDRO significantly increased length of hospital stay, and there was a clinically important trend towards higher rates of pelvic abscess, septic shock, death, need for laparotomy and ICU admission specific to puerperal sepsis. What are the implications for clinical practice and further research? Clinical culture surveillance to monitor epidemiologic trends in conjunction with robust infection control strategies and rational drug use may assist in prevention of community acquired and nosocomial multidrug-resistant infections.

Risk Factors for Incidence of Sexually Transmitted Infections Among Women in a Human Immunodeficiency Virus Chemoprevention Trial: VOICE (MTN-003).

BACKGROUND: In sub-Saharan Africa, there are limited data on the incidence of sexually transmitted infections (STIs) among women, largely because routine screening for asymptomatic infection is not performed. We conducted a secondary analysis to measure STI incidence rates and determine risk factors for new STI acquisition among women enrolled in the VOICE trial. METHODS: We analyzed data from 4843 women screened for chlamydia, gonorrhoea, syphilis, and trichomonas infection at baseline, annually, at interim visits when clinically indicated and at their study termination visit. Risk reduction counseling and condoms were provided throughout the trial. RESULTS: Twenty percent of evaluable participants had one or more curable STIs at baseline. Over 5660 person-years at risk (PYAR) of observation, incidence rates were 13.8% (95% confidence interval [CI], 12.7-14.8) PYAR for chlamydia, 3.5% (95% CI, 3.0-4.1) PYAR gonorrhea, 0.1% (95% CI, 0.6-1.1) PYAR syphilis, and 6.6% (95% CI, 5.8-7.2) PYAR trichomoniasis. South African sites had the highest incidence of chlamydia. The Uganda site had the highest incidence of gonorrhoea and syphilis, and Zimbabwe the lowest incidence overall. The majority of these cases were diagnosed at a routine scheduled testing visit. In multivariate analysis, positive baseline STI, younger than 25 years, being unmarried, and some alcohol consumption were associated with acquiring a new STI. CONCLUSIONS: We observed high rates of STIs during follow up among women in the VOICE study. Women living in human immunodeficiency virus endemic countries should be screened for common STIs.

Reporting of Adherence in the VOICE Trial: Did Disclosure of Product Nonuse Increase at the Termination Visit?

VOICE-a phase 2B, placebo-controlled, randomized trial testing daily use of an antiretroviral tablet (tenofovir or Truvada) or daily use of tenofovir gel in 5029 women from South Africa, Uganda, and Zimbabwe-found none of the drug regimens effective in reducing HIV-1 acquisition in the intent-to-treat analysis. More than half of women assigned to active products in a case cohort sample had no drug detected in any plasma specimens tested during the trial. Yet, in response to questions asked of participants during the trial, ≥90 % of doses were reportedly taken. To explore factors associated with low adherence, a behavioral termination visit questionnaire was developed after early closure of the oral tenofovir and vaginal gel arms. We hypothesized that participants would be more forthcoming about nonuse after they exited the trial than during monthly/quarterly follow-up visits. Comparison of adherence reporting at routine follow-up visits with reporting at trial termination, however, indicates that disclosure of product nonadherence did not increase at the termination visit as anticipated. In resource-limited settings where women value the ancillary benefits provided by trial participation and are concerned that disclosure of nonuse may jeopardize trial participation, objective measures of adherence may yield more meaningful data regarding the inability or reluctance to use than measures of product use derived from self-report.

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.

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.

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 fourth generation AlereTM HIV Combo rapid test improves detection of acute infection in MTN-003 (VOICE) samples.

BACKGROUND: Early and accurate detection of HIV is crucial when using pre-exposure prophylaxis (PrEP) for HIV prevention to avoid PrEP initiation in acutely infected individuals and to minimize the risk of drug resistance in individuals with breakthrough infection. OBJECTIVE: To determine if fourth-generation antigen/antibody (Ag/Ab) rapid diagnostic tests (RDT) would have detected HIV infection earlier than the third-generation RDT used in MTN-003 (VOICE). STUDY DESIGN: 5029 VOICE participants were evaluated with third-generation Alere Determine™ HIV-1/2, OraQuick ADVANCE® Rapid HIV-1/2, Uni-Gold™ Recombigen® HIV-1/2 and Bio-Rad GS HIV-1/2+O EIA; and fourth-generation Alere Determine™ HIV-1/2 Ag/Ab Combo, Conformité Européene (CE)-Marked Alere™ HIV Combo and Bio-Rad HIV Combo Ag/Ab EIA. Multispot®, GS HIV-1 Western Blot (WB) and Geenius™ (Bio-Rad) were also evaluated. RESULTS: Of 57 antibody-negative pre-seroconversion plasma samples with HIV RNA >20 copies/mL identified, 16 (28%) were reactive by CE-Marked Alere™ HIV Combo (1 Ab; 9 Ag; 6 Ag/Ab reactive) and 4 (7%) by Alere Determine™ HIV-1/2 Ag/Ab Combo (2 Ab; 2 Ag; 0 Ag/Ab reactive) (p=0.0005). Multispot® confirmed only 1 of 16 acute infections while WB and Geenius™ confirmed none. GS HIV Combo Ag/Ab EIA identified 27 of 57 (47%) pre-seroconversion RNA-positive samples. CONCLUSION: In VOICE, 28% of infections missed by current third-generation RDT would have been identified with the use of CE-Marked Alere™ HIV Combo. Geenius™, Multispot® and WB were all insensitive (<10%) in confirming infections detected by fourth-generation assays. An improved diagnostic algorithm that includes a fourth-generation RDT with HIV RNA testing will be essential for efficiently identifying seroconverters on PrEP.

Healthcare providers' perspectives on the acceptability and uptake of HPV vaccines in Zimbabwe.

BACKGROUND: Human papillomavirus (HPV) vaccines are a critical strategy in the prevention of cervical cancer, especially in countries like Zimbabwe where cervical cancer screening rates are low. In Zimbabwe, cervical cancer is the leading cause of cancer-related deaths in women but the HPV vaccine is not yet widely available. This study examined healthcare providers': (1) perceptions of current hospital practices and issues in cervical cancer prevention and treatment in Zimbabwe; (2) knowledge of HPV and HPV vaccines; and (3) perspectives on introducing HPV vaccination programs in Zimbabwe, including potential facilitators and barriers to successful implementation. METHOD: In-depth semi-structured interviews were conducted at a rural hospital with 15 healthcare providers in Zimbabwe. Interviews included eight main questions and a number of additional probes that reflected the study's purpose. Data were analyzed using thematic analysis. RESULTS: Participants reported that women are not consistently being screened for cervical cancer. There were generally low levels of knowledge about HPV and HPV vaccines, but participants asked many questions indicating a desire to learn more. Although they were highly supportive of implementing HPV vaccination programs in Zimbabwe, they also identified a number of likely psychosocial, cultural, and logistical barriers to successful implementation, including cost, vaccine schedule, and hospital infrastructure. However, participants also provided a number of culturally relevant solutions, including education and community engagement. CONCLUSION: This study provides insight from healthcare providers about barriers to implementation and possible solutions that can be used by policy makers, practitioners, and other stakeholders to facilitate the successful implementation of forthcoming HPV immunization programs in Zimbabwe.