Sexually transmitted infections (STIs) are among the most common communicable diseases globally and are associated with significant morbidity and mortality worldwide. Point-of-care tests have the potential to revolutionize the prevention and control of STIs by enabling rapid diagnosis and early treatment of infections, thus interrupting transmission and preventing the sequelae of untreated infections. Currently, there are several point-of-care (POC) tests available for the diagnosis of Treponema pallidum, Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis infections, although these tests differ with regard to their performance, turnaround time, and cost. To provide an updated review of the POC tests available and under development for the diagnosis of T pallidum, C trachomatis, N gonorrhoeae, and T vaginalis infections, to discuss the context for which these tests might be used, and to highlight future directions for test development. We reviewed the literature pertaining to the recent development and performance evaluations of POC tests for the diagnosis of syphilis, chlamydia, gonorrhea, and trichomonas. Recently, there has been rapid development of new POC tests for STIs. Although there are inexpensive, rapid, and accurate POC tests available for syphilis, there are few such tests available for the diagnosis of chlamydia, gonorrhea, or trichomonas, and currently none with the ability to detect antimicrobial resistance in N gonorrhoeae. Research evaluating implementation strategies for the currently available tests and the development of additional POC tests that are rapid, accurate, and affordable are urgently needed to address the rising number of STIs worldwide.

Listeria monocytogenesis a Gram-positive intracellular pathogen that is naturally resistant to lysozyme. Recently, it was shown that peptidoglycan modification by N-deacetylation or O-acetylation confers resistance to lysozyme in various Gram-positive bacteria, includingL. monocytogenes.L. monocytogenespeptidoglycan is deacetylated by the action ofN-acetylglucosamine deacetylase (Pgd) and acetylated byO-acetylmuramic acid transferase (Oat). We characterized Pgd⁻, Oat⁻, and double mutants to determine the specific role ofL. monocytogenespeptidoglycan acetylation in conferring lysozyme sensitivity during infection of macrophages and mice. Pgd⁻and Pgd⁻Oat⁻double mutants were attenuated approximately 2 and 3.5 logs, respectively,in vivo. In bone-marrow derived macrophages, the mutants demonstrated intracellular growth defects and increased induction of cytokine transcriptional responses that emanated from a phagosome and the cytosol. Lysozyme-sensitive mutants underwent bacteriolysis in the macrophage cytosol, resulting in AIM2-dependent pyroptosis. Each of thein vitrophenotypes was rescued upon infection of LysM⁻macrophages. The addition of extracellular lysozyme to LysM⁻macrophages restored cytokine induction, host cell death, andL. monocytogenesgrowth inhibition. This surprising observation suggests that extracellular lysozyme can access the macrophage cytosol and act on intracellular lysozyme-sensitive bacteria.

Neisseria gonorrhoeae is the second most common bacterial sexually transmitted infection in the world after Chlamydia trachomatis. The pathogen has developed resistance to every antibiotic currently approved for treatment, and multidrug-resistant strains have been identified globally. The current treatment recommended by the World Health Organization is ceftriaxone and azithromycin dual therapy. However, resistance to azithromycin and ceftriaxone are increasing and treatment failures have been reported. As a result, there is a critical need to develop novel strategies for mitigating the spread of antimicrobial-resistant N. gonorrhoeae through improved diagnosis and treatment of resistant infections. Strategies that are currently being pursued include developing molecular assays to predict resistance, utilizing higher doses of ceftriaxone, repurposing older antibiotics, and developing newer agents. In addition, efforts to discover a vaccine for N. gonorrhoeae have been reignited in recent years with the cross-protectivity provided by the N. meningitidis vaccine, with several new strategies and targets. Despite the significant progress that has been made, there is still much work ahead to combat antimicrobial-resistant N. gonorrhoeae globally.

HIV increases women’s risk for high-risk human papillomavirus (hrHPV) infection and invasive cervical cancer. South Africa has a high HIV prevalence but low cervical cancer screening coverage. Self-collection of cervical specimens and hrHPV testing, including hrHPV messenger-RNA (mRNA) testing, are methods aimed at increasing screening rates. However, data are limited on the acceptability and accuracy of tampon-based self-collection for hrHPV mRNA testing in HIV-infected women. We recruited 325 HIV-infected women seeking care at a government HIV clinic in Pretoria, South Africa. A clinician performed a pelvic examination and obtained an endocervical specimen. Study participants performed self-collection using a tampon. Both clinician- and self-collected specimens were tested for hrHPV mRNA. Acceptability of both collection methods was assessed, the prevalence of hrHPV mRNA in our study population was estimated, test positivity of the two collection methods were compared, and test agreement was assessed by calculating the κ-statistic, sensitivity, and specificity. Over 90% of women reported no difficulties self-collecting specimens and 82% were willing to perform the tampon-collection at home. Based on clinician-collection specimens, the prevalence of hrHPV mRNA in our study population was 36.7% (95% CI: 31.4%– 42.0%). There was no difference in test positivity between clinician-collection, 36.7%, and tampon-collection, 43.5% (p-value = 0.08). Using clinician-collection as the reference test, the sensitivity and specificity for hrHPV mRNA of tampon-collection were 77.4% (95% CI: 69.8–85.0%) and 77.8% (95% CI: 71.9–83.6%), respectively. Tampon-based self-collection is acceptable to women and has similar hrHPV mRNA positivity rates as clinician-collection, but has reduced sensitivity and specificity compared to clinician-collection. The hrHPV mRNA prevalence in our study population is high, but similar to other high-risk populations, and highlights the need for improved cervical cancer screening. Further research into the optimal use of tampon-based collection as a cervical cancer screening tool is warranted.

Worldwide, testing capacity for SARS-CoV-2 is limited and bottlenecks in the scale up of polymerase chain reaction (PCR-based testing exist. Our aim was to develop and evaluate a machine learning algorithm to diagnose COVID-19 in the inpatient setting. The algorithm was based on basic demographic and laboratory features to serve as a screening tool at hospitals where testing is scarce or unavailable. We used retrospectively collected data from the UCLA Health System in Los Angeles, California. We included all emergency room or inpatient cases receiving SARS-CoV-2 PCR testing who also had a set of ancillary laboratory features (n = 1,455) between 1 March 2020 and 24 May 2020. We tested seven machine learning models and used a combination of those models for the final diagnostic classification. In the test set (n = 392), our combined model had an area under the receiver operator curve of 0.91 (95% confidence interval 0.87–0.96). The model achieved a sensitivity of 0.93 (95% CI 0.85–0.98), specificity of 0.64 (95% CI 0.58–0.69). We found that our machine learning algorithm had excellent diagnostic metrics compared to SARS-CoV-2 PCR. This ensemble machine learning algorithm to diagnose COVID-19 has the potential to be used as a screening tool in hospital settings where PCR testing is scarce or unavailable.

Background: While India has made significant progress in reducing maternal mortality, attaining further declines will require increased skilled birth attendance and institutional delivery among marginalized and difficult to reach populations. Methods: A population-based survey was carried out among 16 randomly selected rural villages in rural Mysore District in Karnataka, India between August and September 2008. All households in selected villages were enumerated and women with children 6 years of age or younger underwent an interviewer-administered questionnaire on antenatal care and institutional delivery. Results: Institutional deliveries in rural areas of Mysore District increased from 51% to 70% between 2002 and 2008. While increasing numbers of women were accessing antenatal care and delivering in hospitals, large disparities were found in uptake of these services among different castes. Mothers belonging to general castes were almost twice as likely to have an institutional birth as compared to scheduled castes and tribes. Mothers belonging to other backward caste or general castes had 1.8 times higher odds (95% CI: 1.21, 2.89) of having an institutional delivery as compared to scheduled castes and tribes. In multivariable analysis, which adjusted for inter- and intra-village variance, Below Poverty Line status, caste, and receiving antenatal care were all associated with institutional delivery. Conclusion: The results of the study suggest that while the Indian Government has made significant progress in increasing antenatal care and institutional deliveries among rural populations, further success in lowering maternal mortality will likely hinge on the success of NRHM programs focused on serving marginalized groups. Health interventions which target SC/ST may also have to address both perceived and actual stigma and discrimination, in addition to providing needed services. Strategies for overcoming these barriers may include sensitization of healthcare workers, targeted health education and outreach, and culturally appropriate community-level interventions. Addressing the needs of these communities will be critical to achieving Millennium Development Goal Five by 2015.