Development of a questionnaire to determine the case detection delay of leprosy: A mixed-methods cultural validation study

Background Delay in case detection is a risk factor for developing leprosy-related impairments, leading to disability and stigma. The objective of this study was to develop a questionnaire to determine the leprosy case detection delay, defined as the period between the first signs of the disease and the moment of diagnosis, calculated in total number of months. The instrument was developed as part of the PEP4LEP project, a large-scale intervention study which determines the most effective way to implement integrated skin screening and leprosy post-exposure prophylaxis with a single-dose of rifampicin (SDR-PEP) administration in Ethiopia, Mozambique and Tanzania. Methodology/Principal findings A literature review was conducted and leprosy experts were consulted. The first draft of the questionnaire was developed in Ethiopia by exploring conceptual understanding, item relevance and operational suitability. Then, the first draft of the tool was piloted in Ethiopia, Mozambique and Tanzania. The outcome is a questionnaire comprising nine questions to determine the case detection delay and two annexes for ease of administration: a local calendar to translate the patient’s indication of time to number of months and a set of pictures of the signs of leprosy. In addition, a body map was included to locate the signs. A ‘Question-by-Question Guide’ was added to the package, to provide support in the administration of the questionnaire. The materials will be made available in English, Oromiffa (Afaan Oromo), Portuguese and Swahili via https://www.infolep.org. Conclusions/Significance It was concluded that the developed case detection delay questionnaire can be administered quickly and easily by health workers, while not inconveniencing the patient. The instrument has promising potential for use in future leprosy research. It is recommended that the tool is further validated, also in other regions or countries, to ensure cultural validity and to examine psychometric properties like test-retest reliability and interrater reliability.

Awareness and Use of Post-exposure Prophylaxis for HIV Prevention Among Men Who Have Sex With Men: A Systematic Review and Meta-Analysis

Background: The use of post-exposure prophylaxis (PEP) is effective in reducing HIV risk, but it is underused by men who have sex with men (MSM) due to certain psychological and sociostructural factors. This article assessed the awareness and use of PEP among MSM in an effort to increase the visibility and uptake of PEP among at-risk populations.Methods: We conducted a systematic literature search of the PubMed, Web of Science, PsycINFO, and Google Scholar electronic databases. Studies were screened for inclusion, and relevant data were abstracted, assessed for bias, and synthesized. Pooled effect estimates were calculated using random effects meta-analysis, meta-regression and subgroup analysis, and a qualitative review and risk of bias assessment were performed (PROSPERO, CRD42019123815).Results: Twenty eligible studies involving 12,579 MSM were included in the meta-analysis. The pooled estimate of the proportions of MSM who were aware of PEP was modest at 59.9% (95% CI: 50.5~68.7) and that of MSM who previously used PEP was very low at 4.9% (95% CI: 2.4~9.8). PEP awareness showed no clear change over time, while PEP use significantly changed over time. Multiple factors affected awareness, including educational attainment, race/ethnicity, levels of HIV stigma, access to condoms, and so on. Many factors could potentially impede or facilitate the use of PEP, such as income, lack of PEP information, and partnership.Conclusion: We observed that PEP is an underused HIV prevention strategy among MSM and that once MSM become aware of PEP, the majority are willing to use it if they are supported appropriately in terms of a range of individual, social, and structural barriers.Systematic Review Registration: http://www.cdr.york.ac.uk/prospero, PROSPERO [CRD42019123815].

Post-Exposure Prophylaxis and Methamphetamine Use among Young Sexual Minority Men: The P18 Cohort Study

Methamphetamine use is associated with increased risk of HIV infection among young sexual minority men (SMM). Post-exposure prophylaxis (PEP) is an effective strategy for individuals who are exposed to HIV, but there is limited research about PEP use among young SMM and its relationship with methamphetamine use. This study analyzes the association between ever PEP use and recent methamphetamine use among young SMM in New York City, using cross-sectional data from the P18 Cohort Study (n = 429). Multivariable logistic regression models were used to assess the association between methamphetamine use and ever PEP use. Compared with those who had not used methamphetamine in the last 6 months, young SMM who did use methamphetamine were significantly more likely to have ever used PEP (AOR = 6.07, 95% CI: 2.10–16.86). Young SMM who had ever used PrEP had 16 times higher odds of ever using PEP (AOR = 16, 95% CI: 7.41–35.95). Those who completed bachelor’s degrees were 61% less likely to have ever used PEP (AOR = 0.39, 95% CI: 0.17–0.88). These data suggest that methamphetamine use could increase the risk of HIV infection, highlighting the critical need to target interventions for young SMM who use methamphetamine and are more likely to engage in unprotected intercourse.

BNT162b2 post-exposure-prophylaxis against COVID-19

Background: During the COVID-19 pandemic, post-exposure-prophylaxis is not a practice. Following exposure, only patient isolation is imposed. Moreover, no therapeutic prevention approach is applied. We asked whether evidence exists for reduced mortality rate following post-exposure-prophylaxis. Methods: To estimate the effectiveness of post-exposure-prophylaxis, we obtained data from the Israeli Ministry of Health (MoH) registry. The study population consisted of Israeli residents aged 12 years and older, identified for the first time as PCR-positive for SARS-CoV-2, between December 20th, 2020 (the beginning of the vaccination campaign) and October 7th, 2021. We compared 'recently injected' patients - that proved PCR-positive on the same day or on one of the five consecutive days after first vaccination (representing an unintended post-exposure-prophylaxis), to unvaccinated control group. Results: Among Israeli residents identified PCR-positive for SARS-CoV-2, 11,690 were found positive on the day they received their first vaccine injection (BNT162b2) or on one of the 5 days thereafter. In patients over 65 years, 143 deaths occurred among 1413 recently injected (10.12%) compared to 280 deaths among the 1413 unvaccinated (19.82%), odd ratio (OR) 0.46 (95% confidence interval (CI), 0.36 to 0.57; P<0.001). The most significant reduction in the death toll was observed among the 55 to 64 age group, with 8 deaths occurring among the 1322 recently injected (0.61%) compared to 43 deaths among the 1322 unvaccinated control (3.25%), OR 0.18 (95% CI, 0.07 to 0.39; P<0.001). Conclusion: Post-exposure-prophylaxis is effective against death in COVID-19 infection. Israeli MoH Registry Number: HMO-0372-20

Biodefense and Emergency Use Authorization: Different Originations, Purposes, and Evolutionary Paths of Institutions in the United States and South Korea

Background: Historical institutionalism (HI) determines that institutions have been transformed by a pattern of punctuated evolution due to exogenous shocks. Although scholars frequently emphasize the role of agency - endogenous factors – when it comes to institutional changes, but the HI analytic narratives still remain in the meso-level analysis in the context of structure and agency. This article provides domestic and policy-level accounts of where biodefense institutions of the United States and South Korea come from, seeing through emergency-use-authorization (EUA) policy, and how the EUA policies have evolved by employing the policy-learning concepts through the Event-related Policy Change Model. Results: By employing the Birkland’s model, this article complements the limitation of the meso-level analysis in addressing that the 2001 Amerithrax and the 2015 Middle East Respiratory Syndrome (MERS) outbreak rooted originations and purposes of the biodefense respectively. Since the crisis, a new post-crisis agenda in society contributed to establishing new domestic coalition, which begin to act as endogenous driving forces that institutionalize new biodefense institutions and even reinforce them through path dependent way when the institutions evolved. Therefore, EUA policy cores (Post-Exposure Prophylaxis (PEP) in the United States and Non-Pharmaceutical Intervention (NPI) in South Korea keep strengthened during the policy revisions. Conclusions: The United States and South Korea have different originations and purposes of biodefense, which are institutions evolving through self-reinforce dependent way based on the lessons learned from past crises. In sum, under the homeland security biodefense institution, the US EUA focuses on the development of specialized, unlicensed PEP in response to public health emergencies; on the other hand, under the disease containment-centric biodefense institution, the Korean EUA is specialized to conduct NPI missions in response to public health emergencies.

Daily Lactobacillus Probiotic versus Placebo in COVID-19-Exposed Household Contacts (PROTECT-EHC): A Randomized Clinical Trial

Background: The COVID-19 pandemic continues to pose unprecedented challenges to worldwide health. While vaccines are effective, supplemental strategies to mitigate the spread and severity of COVID-19 are urgently needed. Emerging evidence suggests susceptibility to infections, including respiratory tract infections, may be reduced by probiotic interventions. Therefore, probiotics may be a low-risk, widely implementable modality to mitigate risk of COVID-19 disease, particularly in areas with low vaccine availability and/or uptake. Methods: We conducted a randomized, double-blind, placebo-controlled trial across the United States testing the probiotic Lactobacillus rhamnosus GG (LGG) as post-COVID-19-exposure prophylaxis. We enrolled individuals > 1 year of age with a household contact with a recent (≤ 7 days) diagnosis of COVID-19. Participants were randomized to receive daily LGG or placebo for 28 days. Stool was collected to evaluate the microbiome. The primary outcome was development of symptoms of illness compatible with COVID-19 within 28 days. Findings: We enrolled 182 COVID-19-exposed participants. Intention-to-treat analysis showed that participants randomized to LGG were less likely to develop symptoms versus those randomized to placebo (26.4% vs. 42.9%, p=0.02). Further, LGG was associated with a statistically significant reduction in COVID-19 diagnosis (log rank p=0.049) via time-to-event analysis. Overall incidence of COVID-19 diagnosis was not significantly different between LGG (8.8%) and placebo (15.4%) (p=0.17). LGG was well-tolerated with no increased side effects versus placebo. Interpretation: These findings suggest that LGG probiotic may protect against the development of COVID-19 infection and symptoms when used as post-exposure prophylaxis within 7 days after exposure. Funding: This work was supported by a grant from the Duke Microbiome Center to A.D.S. and P.E.W. and private philanthropic donations to A.D.S. DSM/iHealth donated the LGG and placebo for the trial but had no role in its design, conduct, analysis, or writing. Trial registration: NCT04399252

Sedation-Paralysis as Cornerstone on Rabies Management (Milwaukee Protocol)

Rabies is a viral infection involving the central nervous system that is almost always fatal without proper post exposure prophylaxis. Here, we present a 38 years-old male with dog-bite and late attention whom, managed in intensive care unit. After 21 days, the disease progressed to serious neurologic and hemodynamic damage including motor disorders and imbalance in blood pressure and cardiac rhythm. Clinical management of the patient consisted of antiviral agents (Amantadine and Ribavirin), neuroprotection, sedation-paralysis and supportive care. Patient was survived 43 days from the clinical disease onset. Although our patient died in spite of intensive care, advances in the use of sedation-paralysis and early prescription of antiviral agents raised hopes that it may eventually be possible to save rabies patients.

History of Rabies Incidence and Rabies Control in Serbia in Support of the Zero by 2030 Campaign to Eliminate Dog-Mediated Human Rabies

Urban (principally canine-mediated) rabies has been a public health risk for people living in Serbia for centuries. The first legal act in urban rabies prevention in Serbia was established in 1834 by introducing high taxes for pet dog owners. Five years later in 1839, the first set of literature describing rabies prevention was issued by the health department from The Serbian Ministry of Interior. An overview of cauterization of rabies wounds was presented as the principal method of rabies post exposure prophylaxis. In 1890, a human rabies vaccination was introduced in Serbia with the royal government directive which ordered patients to be treated at the Pasteur Institute in Budapest in receipt of rabies vaccination. Urban (canine) rabies was eliminated during the 1980s, but sylvatic (principally fox-mediated) rabies still prevailed. The last human rabies case was recorded in the Province of Kosovo and Metohija in 1980. Sylvatic rabies in Serbia is in the final stages of elimination by orally vaccinating foxes (Vulpes vulpes). The only published finding of a lyssavirus among Serbian bats was made in 1954 by Dr Milan Nikolić in the vicinity of Novi Sad. In 2006, a comprehensive two-year active surveillance program of lyssaviruses in bats in Serbia was undertaken. In this single study, all of the bats from Serbia tested negative for a lyssavirus.

Tilorone-Dihydrochloride Protects against Rift Valley Fever Virus Infection and Disease in the Mouse Model

Rift Valley fever (RVF) is a mosquito-borne zoonotic disease endemic to Africa and the Middle East that can affect humans and ruminant livestock. Currently, there are no approved vaccines or therapeutics for the treatment of severe RVF disease in humans. Tilorone-dihydrochloride (Tilorone) is a broad-spectrum antiviral candidate that has previously shown efficacy against a wide range of DNA and RNA viruses, and which is clinically utilized for the treatment of respiratory infections in Russia and other Eastern European countries. Here, we evaluated the antiviral activity of Tilorone against Rift Valley fever virus (RVFV). In vitro, Tilorone inhibited both vaccine (MP-12) and virulent (ZH501) strains of RVFV at low micromolar concentrations. In the mouse model, treatment with Tilorone significantly improved survival outcomes in BALB/c mice challenged with a lethal dose of RVFV ZH501. Treatment with 30 mg/kg/day resulted in 80% survival when administered immediately after infection. In post-exposure prophylaxis, Tilorone resulted in 30% survival at one day after infection when administered at 45 mg/kg/day. These findings demonstrate that Tilorone has potent antiviral efficacy against RVFV infection in vitro and in vivo and supports further development of Tilorone as a potential antiviral therapeutic for treatment of RVFV infection.