YfbA, a Yersinia pestis regulator required for colonization and biofilm formation in the gut of cat fleas.

For transmission to new hosts, Yersinia pestis, the causative agent of plague, replicates as biofilm in the foregut of fleas that feed on plague-infected animals or humans. Y. pestis biofilm formation has been studied in the rat flea; however, little is known about the cat flea, a species that may bridge zoonotic and anthroponotic plague cycles. Here, we show that Y. pestis infects and replicates as a biofilm in the foregut of cat fleas in a manner requiring hmsFR, two determinants for extracellular biofilm matrix. Examining a library of transposon insertion mutants, we identified the LysR-type transcriptional regulator YfbA, which is essential for Y. pestis colonization and biofilm formation in cat fleas.

Implementing SARS-CoV-2 antigen testing scale-up in Rwanda: retrospective analysis of national programme data and qualitative findings.

OBJECTIVES: Reverse transcriptase PCR is the most sensitive test for SARS-CoV-2 diagnosis. However, the scale-up of these tests in low-income and middle-income countries (LMICs) has been limited due to infrastructure and cost. Antigen rapid diagnostic tests are an alternative option for diagnosing active infection that may allow for faster, easier, less expensive and more widespread testing. We compared the implementation of antigen and PCR testing programmes in Rwanda. DESIGN: We retrospectively reviewed routinely collected PCR and antigen testing data for all reported tests conducted nationally. We administered semiquantitative surveys to healthcare workers (HCWs) involved in COVID-19 testing and care and clients receiving antigen testing. SETTING: Rwanda, November 2020-July 2021. PARTICIPANTS: National SARS-CoV-2 testing data; 49 HCWs involved in COVID-19 testing and care; 145 clients receiving antigen testing. INTERVENTIONS: None (retrospective analysis of programme data). PRIMARY AND SECONDARY OUTCOME MEASURES: Test volumes, turnaround times, feasibility and acceptability of antigen testing. RESULTS: Data from 906 204 antigen tests and 445 235 PCR tests were included. Antigen testing increased test availability and case identification compared with PCR and had a median results return time of 0 days (IQR: 0-0). In contrast, PCR testing time ranged from 1 to 18 days depending on the sample collection site/district. Both HCWs and clients indicated that antigen testing was feasible and acceptable. Some HCWs identified stockouts and limited healthcare staff as challenges. CONCLUSIONS: Antigen testing facilitated rapid expansion and decentralisation of SARS-CoV-2 testing across lower tier facilities in Rwanda, contributed to increased case identification, reduced test processing times, and was determined to be feasible and acceptable to clients and providers. Antigen testing will be an essential component of SARS-CoV-2 test and treat programmes in LMICs.

Human papillomavirus testing using existing nucleic acid testing platforms to screen women for cervical cancer: implementation studies from five sub-Saharan African countries.

OBJECTIVES: To demonstrate acceptability and operational feasibility of introducing human papillomavirus (HPV) testing as a principal cervical cancer screening method in public health programmes in sub-Saharan Africa. SETTING: 45 primary and secondary health clinics in Malawi, Nigeria, Senegal, Uganda and Zimbabwe. PARTICIPANTS: 15 766 women aged 25-54 years presenting at outpatient departments (Senegal only, general population) or at antiretroviral therapy clinics (all other countries, HIV-positive women only). Eligibility criteria followed national guidelines for cervical cancer screening. INTERVENTIONS: HPV testing was offered to eligible women as a primary screening for cervical cancer, and HPV-positive women were referred for visual inspection with acetic acid (VIA), and if lesions identified, received treatment or referral. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcomes were the proportion of HPV-positive women who received results and linked to VIA and the proportion of HPV-positive and VIA-positive women who received treatment. RESULTS: A total of 15 766 women were screened and tested for HPV, among whom 14 564 (92%) had valid results and 4710/14 564 (32%) were HPV positive. 13 837 (95%) of valid results were returned to the clinic and 3376 (72%) of HPV-positive women received results. Of women receiving VIA (n=2735), 715 (26%) were VIA-positive and 622 (87%) received treatment, 75% on the same day as VIA. CONCLUSIONS: HPV testing was found to be feasible across the five study countries in a public health setting, although attrition was seen at several key points in the cascade of care, namely results return to women and linkage to VIA. Once women received VIA, if eligible, the availability of on-site cryotherapy and thermal ablation allowed for same-day treatment. With sufficient resources and supportive infrastructure to ensure linkage to treatment, use of HPV testing for cervical cancer screening as recommended by WHO is a promising model in low-income and middle-income countries.

Benefits and harms of cervical screening, triage and treatment strategies in women living with HIV.

To support a strategy to eliminate cervical cancer as a public health problem, the World Health Organisation (WHO) reviewed its guidelines for screening and treatment of cervical pre-cancerous lesions in 2021. Women living with HIV have 6-times the risk of cervical cancer compared to women in the general population, and we harnessed a model platform ('Policy1-Cervix-HIV') to evaluate the benefits and harms of a range of screening strategies for women living with HIV in Tanzania, a country with endemic HIV. Assuming 70% coverage, we found that 3-yearly primary HPV screening without triage would reduce age-standardised cervical cancer mortality rates by 72%, with a number needed to treat (NNT) of 38.7, to prevent a cervical cancer death. Triaging HPV positive women before treatment resulted in minimal loss of effectiveness and had more favorable NNTs (19.7-33.0). Screening using visual inspection with acetic acid (VIA) or cytology was less effective than primary HPV and, in the case of VIA, generated a far higher NNT of 107.5. These findings support the WHO 2021 recommendation that women living with HIV are screened with primary HPV testing in a screen-triage-and-treat approach starting at 25 years, with regular screening every 3-5 years.

Benefits, harms and cost-effectiveness of cervical screening, triage and treatment strategies for women in the general population.

In 2020, the World Health Organization (WHO) launched a strategy to eliminate cervical cancer as a public health problem. To support the strategy, the WHO published updated cervical screening guidelines in 2021. To inform this update, we used an established modeling platform, Policy1-Cervix, to evaluate the impact of seven primary screening scenarios across 78 low- and lower-middle-income countries (LMICs) for the general population of women. Assuming 70% coverage, we found that primary human papillomavirus (HPV) screening approaches were the most effective and cost-effective, reducing cervical cancer age-standardized mortality rates by 63-67% when offered every 5 years. Strategies involving triaging women before treatment (with 16/18 genotyping, cytology, visual inspection with acetic acid (VIA) or colposcopy) had close-to-similar effectiveness to HPV screening without triage and fewer pre-cancer treatments. Screening with VIA or cytology every 3 years was less effective and less cost-effective than HPV screening every 5 years. Furthermore, VIA generated more than double the number of pre-cancer treatments compared to HPV. In conclusion, primary HPV screening is the most effective, cost-effective and efficient cervical screening option in LMICs. These findings have directly informed WHO's updated cervical screening guidelines for the general population of women, which recommend primary HPV screening in a screen-and-treat or screen-triage-and-treat approach, starting from age 30 years with screening every 5 years or 10 years.

Comparative analysis between self-collected and clinician-collected samples for HPV testing in public health facilities in Zimbabwe.

BACKGROUND: Cervical cancer screening programs that use visual inspection with acetic acid to identify women with pre-cancerous lesions in Zimbabwe have had limited success due to challenges with human resource constraints and patient acceptability. Nucleic acid amplification tests for human papillomavirus (HPV) have been endorsed by the World Health Organization for cervical cancer screening, along with self-collection of samples. As evidence shows self-collected sampling to be acceptable and preferable, Zimbabwe's Ministry of Health and Child Care (MOHCC) required a comparative analysis on the agreement between self- and clinician-collected samples for testing with Hologic Aptima HPV mRNA assay, to determine if self-collected samples could be used as another method to increase coverage of cervical cancer screening programs. METHODS: In four public health facilities in Zimbabwe from July to August 2020, self- and clinician-collected HPV samples were obtained from HIV-positive women aged 30-49 years for HPV testing. RESULTS: A total of 280 self- and clinician-collected samples were tested and results were found to have good agreement (κ: 0.75, 95% CI: 0.66-0.82). HPV prevalence was 43.0% (95% CI: 37.0%-49.3%) for self-samples and 48.0% (95% CI: 41.0%-54.2%) for clinician-samples. CONCLUSIONS: Self-collected sampling had good agreement with clinician-collected and its inclusion in the national cervical cancer screening policy by Zimbabwe's MOHCC is expected to increase testing coverage, especially among underserved communities such as women living with HIV, as well as decentralize access to cervical cancer screening services for lower-level facilities and increase the geographical scope of where HPV testing can be offered through the country.