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Alphaviruses cause severe arthritogenic or encephalitic disease. The E1 structural glycoprotein is highly conserved in these viruses and mediates viral fusion with host cells. However, the role of antibody responses to the E1 protein in immunity is poorly understood. We isolated E1-specific human monoclonal antibodies (mAbs) with diverse patterns of recognition for alphaviruses (ranging from Eastern equine encephalitis virus [EEEV]-specific to alphavirus cross-reactive) from survivors of natural EEEV infection. Antibody binding patterns and epitope mapping experiments identified differences in E1 reactivity based on exposure of epitopes on the glycoprotein through pH-dependent mechanisms or presentation on the cell surface prior to virus egress. Therapeutic efficacy in vivo of these mAbs corresponded with potency of virus egress inhibition in vitro and did not require Fc-mediated effector functions for treatment against subcutaneous EEEV challenge. These studies reveal the molecular basis for broad and protective antibody responses to alphavirus E1 proteins.
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Alphavirus/inmunología , Anticuerpos Antivirales/inmunología , Reacciones Cruzadas/inmunología , Proteínas Virales/inmunología , Liberación del Virus/fisiología , Animales , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/aislamiento & purificación , Anticuerpos Neutralizantes/inmunología , Antígenos Virales/inmunología , Línea Celular , Virus Chikungunya/inmunología , Virus de la Encefalitis Equina del Este/inmunología , Encefalomielitis Equina/inmunología , Encefalomielitis Equina/virología , Mapeo Epitopo , Femenino , Caballos , Humanos , Concentración de Iones de Hidrógeno , Articulaciones/patología , Masculino , Ratones Endogámicos C57BL , Modelos Biológicos , Unión Proteica , ARN Viral/metabolismo , Receptores Fc/metabolismo , Temperatura , Virión/metabolismo , Internalización del VirusRESUMEN
BACKGROUND: A next-generation Vero cell rabies vaccine (PVRV-NG2) was developed using the same Pitman-Moore strain as in the licensed purified Vero cell vaccine (PVRV; Verorab) and the human diploid cell vaccine (HDCV; Imovax Rabies®). METHODS: This dual-center, modified, double-blind, phase 3 study evaluated the immunogenic non-inferiority and safety of PVRV-NG2 with and without concomitant intramuscular human rabies immunoglobulin (HRIG) versus PVRV + HRIG and HDCV + HRIG in a simulated post-exposure prophylaxis (PEP) regimen. Healthy adults ≥18 years old (N = 640) were randomized 3:1:1:1 to PVRV-NG2 + HRIG, PVRV + HRIG, HDCV + HRIG, or PVRV-NG2 alone (administered as single vaccine injections on days [D] 0, D3, D7, D14, and 28, with HRIG on D0 in applicable groups). Rabies virus neutralizing antibodies (RVNA) titers were assessed pre- (D0) and post-vaccination (D14, D28, and D42) using the rapid fluorescent focus inhibition test. Non-inferiority, based on the proportion of participants achieving RVNA titers ≥0.5â IU/mL (primary objective), was demonstrated if the lower limit of the 95% CI of the difference in proportions between PVRV-NG2 + HRIG and PVRV + HRIG/HDCV + HRIG was >-5% at D28. Safety was assessed up to 6 months after the last injection. RESULTS: Non-inferiority of PVRV-NG2 + HRIG compared with PVRV + HRIG and HDCV + HRIG was demonstrated. Nearly all participants (99.6%, PVRV-NG2 + HRIG; 100%, PVRV + HRIG; 98.7%, HDCV + HRIG; 100%, PVRV-NG2 alone) achieved RVNA titers ≥0.5â IU/mL at D28. Geometric mean titers were similar between groups with concomitant HRIG administration at all time points. Safety profiles were similar between PVRV-NG2 and comparator vaccines. CONCLUSIONS: In a simulated PEP setting, PVRV-NG2 + HRIG showed comparable immunogenicity and safety to current standard-of-care vaccines. CLINICAL TRIALS REGISTRATION: NCT03965962.
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Anticuerpos Neutralizantes , Anticuerpos Antivirales , Profilaxis Posexposición , Vacunas Antirrábicas , Virus de la Rabia , Rabia , Humanos , Vacunas Antirrábicas/inmunología , Vacunas Antirrábicas/administración & dosificación , Vacunas Antirrábicas/efectos adversos , Adulto , Masculino , Rabia/prevención & control , Profilaxis Posexposición/métodos , Femenino , Anticuerpos Antivirales/sangre , Método Doble Ciego , Persona de Mediana Edad , Adulto Joven , Células Vero , Anticuerpos Neutralizantes/sangre , Francia , Virus de la Rabia/inmunología , Animales , Chlorocebus aethiops , Adolescente , Inmunogenicidad Vacunal , Voluntarios SanosRESUMEN
OBJECTIVES: We aimed to assess the awareness, willingness to use and use of doxycycline post-exposure prophylaxis (doxyPEP) among men who have sex with men (MSM) and transgender women (TGW) in Belgium. Additionally, we aimed to identify factors associated with doxyPEP use and concerns regarding antimicrobial resistance (AMR). METHODS: Cross-sectional online survey among MSM and TGW in Belgium in April 2024. Participants were recruited through sexual networking applications and social media of community-based organisations. Numerical variables were compared with Wilcoxon rank-sum test and categorical variables with χ2 or Fisher's exact tests. Factors associated with doxyPEP use were assessed using logistic regression. Willingness to use doxyPEP and concerns about side effects/AMR were assessed before and after presenting a brief paragraph on the potential effects of doxyPEP on AMR. RESULTS: 875 individuals initiated the survey. Almost all identified as men (860/875, 98.3%) with a median age of 40 years (IQR 32-48), 40.4% (n=352/875) had heard of doxyPEP and 9.4% (n=82/875) had used it, among whom the majority used it within the previous 6 months (70/81, 86.4%). In multivariable logistic regression, doxyPEP use was associated with reporting ≥1 sexually transmitted infection (STI) in the previous 12 months, engagement in chemsex, HIV status and pre-exposure prophylaxis use, and education level.About 80% of the participants initially reported being willing to use doxyPEP, and about 50% reported being concerned about side effects. After reading about the potential effects of doxyPEP on AMR, willingness to use decreased to 60% and concerns of side effects/AMR increased to around 70%. CONCLUSIONS: Approximately 1 in 10 MSM in Belgium reported using doxyPEP. A recent history of STIs and STI risk factors were positively associated with doxyPEP use. Importantly, concerns about AMR and side effect influenced willingness to use doxyPEP. If doxyPEP is introduced, informing patients about doxyPEP benefits and risks is crucial to enable informed decision-making.
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INTRODUCTION/OBJECTIVES: The use of non-occupational post-exposure prophylaxis (nPEP) emerges as a strategic intervention to reduce HIV infection risk following sexual encounters in our setting. Notwithstanding, there is a scarcity of contemporary data regarding adherence to this treatment, its effectiveness and tolerance. Our study aims to delve into these factors among individuals who have resorted to nPEP after high-risk sexual encounters. METHODS: We conducted a retrospective observational study of cases administered nPEP for HIV from 1 January 2018 to 31 December 2021 at a tertiary hospital in Madrid. The study included all adults over 18 years who sought care at the emergency department of the Fundación Jiménez Díaz Hospital following a risky sexual encounter and were subsequently recommended HIV nPEP treatment. RESULTS: 878 individuals received nPEP for HIV and underwent initial serological tests. Of these, 621 had comprehensive follow-ups. The prescribed regimen for all was raltegravir (RAL) 1200 mg combined with tenofovir/emtricitabine (TDF/FTC) 245/200 mg daily for 28 days. The study revealed a 1.1% rate (n=10) of previously undetected infection and a 0.16% (n=1) failure rate of nPEP. Regarding regimen tolerability, 5.6% (n=35) experienced symptoms linked to the treatment, yet none necessitated discontinuation of the regimen. On the contrary, six per cent (n=53) reported symptoms consistent with an STI during one of the medical visits; specifically, 4.4% had urethritis, and 1.6% had proctitis. CONCLUSION: nPEP with RAL/TDF/FTC demonstrates high efficacy and safety, contingent on proper adherence. There is an observed increase in STI prevalence in this cohort, with nearly half of the participants not engaging in appropriate follow-up after initiating nPEP.
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Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Posexposición , Humanos , Infecciones por VIH/prevención & control , Infecciones por VIH/epidemiología , Masculino , Estudios Retrospectivos , Adulto , Femenino , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/administración & dosificación , Persona de Mediana Edad , España/epidemiología , Cumplimiento de la Medicación/estadística & datos numéricos , Adulto JovenRESUMEN
OBJECTIVES: This systematic review aimed to identify the efficacy, adherence, safety and impact on antimicrobial resistance of postexposure prophylaxis with doxycycline (Doxy-PEP) in different populations. METHODS: We searched MEDLINE (via PubMed), Embase and Cochrane CENTRAL databases from inception to 29 May 2024. Two reviewers independently screened the studies and extracted data. We included randomised clinical trials that evaluated the efficacy of Doxy-PEP within 72 hours after condomless sex. A random-effects meta-analysis was conducted to compare the risk of bacterial sexually transmitted infections (STIs) between Doxy-PEP and no prophylaxis. The risk of bias was assessed with the risk-of-bias tool for randomized trials (RoB 2) and the certainty of evidence (CoE) with Grading of Recommendations Assessment, Development and Evaluation (GRADE). RESULTS: Four studies were included in the systematic review, totalling 1727 participants. Studies were conducted between 2015 and 2022. Most participants (73%) were men who have sex with men, and the median age of participants varied from 24 to 43 years. Doxy-PEP reduced the risk of having any bacterial STI in different populations by 46% (hazard ratio (HR) 0.54; 95% CI 0.39 to 0.75; CoE moderate), the risk of chlamydia by 65% (relative risk (RR) 0.35; 95% CI 0.15 to 0.82; CoE low) and syphilis by 77% (RR 0.23; 95% CI 0.13 to 0.41; CoE high), without significant effect for risk of gonorrhoea infection (RR 0.90; 95% CI 0.64 to 1.26; CoE very low). The self-reported adherence rate of Doxy-PEP was approximately 80% and one drug-related serious adverse event was reported. CONCLUSION: Doxy-PEP reduced the incidence of chlamydia and syphilis infections. No significant reduction in gonorrhoea infection was observed. This strategy seems promising for some high-risk groups; however, there is still a lack of information on the induction of bacterial resistance and long-term adverse events. PROSPERO REGISTRATION NUMBER.
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BACKGROUND: People who report sexual assault express concerns regarding contracting sexually transmitted infection (STI); however, published literature regarding the risk of STI transmission in this context is sparse. METHOD: We audited STI and blood-borne virus (BBV) testing at a forensic and medical sexual assault care service in the Australian Capital Territory between 2004 and 2022. Eligibility for testing among 1928 presentations was defined based on risk (eg, reported penetration). Testing at presentation included chlamydia and gonorrhoea 1850, syphilis and BBV 1472, and after 2-6 weeks, 890 out of 1928 (46.2%) and after 3 months 881 out of 1928 (45.7%), respectively. RESULTS: At presentation, 100 out of 1928 (5.2%) individuals were diagnosed with chlamydia, of those, 95 out of 1799 (5.3%) were female, and 5 out of 121 (4.1%) were male. Gonorrhoea was diagnosed in 7 out of 1920 (0.4%), 5 out of 95 female and 2 out of 5 male. Hepatitis B, which was all pre-existing, was diagnosed in 5 out of 1799 (0.3%). Overall, chlamydia prophylaxis was given to 203 out of 1928 (10.5%) and HIV post-exposure prophylaxis to 141 out of 1928 (7.3%).At 2-6 weeks of follow-up, 10 out of 890 (1.1%) individuals were diagnosed with chlamydia, with no gonorrhoea diagnosed. There were no cases of syphilis, hepatitis B or HIV diagnosed at 3-month serology testing in 881 individuals. Chlamydia detection at follow-up was more common in the group aged 15-29 years. Of those provided with chlamydia prophylaxis, 203 out of 1928, only 16 out of 203 (7.9%) were diagnosed with chlamydia. CONCLUSIONS: The offer of STI testing is almost universally accepted by individuals presenting for post-sexual assault care. There were no identifiable factors to justify the routine use of chlamydia prophylaxis. STI testing provided an opportunity for screening and should remain part of the clinical care of people who report sexual assault.
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Infecciones por Chlamydia , Chlamydia , Gonorrea , Infecciones por VIH , Hepatitis B , Delitos Sexuales , Enfermedades de Transmisión Sexual , Sífilis , Masculino , Femenino , Humanos , Gonorrea/diagnóstico , Gonorrea/epidemiología , Sífilis/diagnóstico , Sífilis/epidemiología , Australia/epidemiología , Enfermedades de Transmisión Sexual/diagnóstico , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/prevención & control , Infecciones por VIH/prevención & control , Infecciones por Chlamydia/diagnóstico , Infecciones por Chlamydia/epidemiología , Homosexualidad MasculinaRESUMEN
BACKGROUND: Sexual assault (SA) is a prevalent issue with enduring consequences. Post-SA medical care mainly focuses on injuries, sexually transmitted infection (STI) prevention and detection, as well as preventing unwanted pregnancies. Swift access to post-SA medical care is vital with sexual assault treatment units (SATUs) streamlining this care. The primary aim of our study is to report on post-SA care provided at the national SATU network in Ireland with a secondary aim of analysing factors associated with follow-up attendance for STI testing. METHODS: This is a retrospective cohort study of all acute attendances (<7 days from incident) at the national SATU network between 1 January 2017 to 31 December 2022. RESULTS: A total of 4159 acute cases presented during the study period. Emergency contraception (EC) was administered to 53.8% (n=1899/3529) of cases, while postexposure prophylaxis (PEP) for chlamydia was given in 75.1% (n=3124/4159) and for HIV in 11.0% (n=304/3387). Hepatitis B vaccination was initiated in 53.7% (n=2233/4159) of cases. 1.4% (n=59/4159) of the attendees were referred to an emergency department for the treatment of injuries. Follow-up appointments were scheduled for 75.8% (3151/4159) of acute cases. 71.6% (n=2257/3151) attended follow-up.Certain factors were found to correlate with a higher likelihood of attending follow-up appointments: adolescents (p<0.0001), concern about drug-facilitated SA (DFSA) (p=0.01), no consumption of recreational drugs before the incident (p<0.0001), alcohol consumption prior to the incident (p=0.01), and not reporting the crime to the police (p<0.001). However, gender (p=0.06) and the presence of injury at time of primary attendance (p=0.97) were not predictive of likelihood of follow-up attendance. CONCLUSION: This study demonstrates that EC, chlamydia PEP, HIV PEP and hepatitis B vaccination were all administered at SATU. A small proportion of attenders required emergency injury care. Factors influencing attendance at follow-up include age, drug use, alcohol use and police involvement, highlighting the need for tailored patient-centred support.
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Infecciones por VIH , Hepatitis B , Delitos Sexuales , Enfermedades de Transmisión Sexual , Embarazo , Femenino , Adolescente , Humanos , Estudios Retrospectivos , Estudios de Seguimiento , Profilaxis Posexposición , Enfermedades de Transmisión Sexual/diagnóstico , Enfermedades de Transmisión Sexual/epidemiología , Enfermedades de Transmisión Sexual/prevención & control , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Hepatitis B/diagnóstico , Hepatitis B/epidemiología , Hepatitis B/prevención & controlRESUMEN
BACKGROUND: Antibiotic prophylaxis to prevent brucellosis after accidental exposure to Brucella is an important topic in public health. This study aimed to systematically review the efficacy of antibiotic prophylaxis following accidental exposure to Brucella in preventing human brucellosis disease. METHODS: The study protocol was registered in PROSPERO (CRD42023456812). The outcomes included the incidence of brucellosis disease, adverse events rate, and antibiotic prophylaxis adherence. A comprehensive literature search, conducted until 20 November, 2023, involved Medline, Embase, Cochrane Library, and LILACS databases. Descriptive analysis and meta-analysis using R software were performed, risk of bias was assessed using JBI Critical appraisal tools, and certainty of evidence was assessed using the GRADE tool. RESULTS: Among 3102 initially identified records, eight studies involving 97 individuals accidentally exposed, all focused on high-risk accidental exposure to Brucella in laboratory settings, were included in the review. All studies reported the prophylactic treatment comprising doxycycline at a dosage of 100 mg twice daily, combined with rifampicin at 600 mg, both administered over 21 days. Prophylaxis adherence was reported in 86% of cases, and incidence of brucellosis post-treatment was 0.01. Adverse events, mainly gastrointestinal, occurred in 26% of cases. Critical appraisal revealed limitations in reporting demographics and clinical information. The certainty of evidence was rated as 'very low,' emphasising the need for caution in interpreting the observed outcomes due to study design constraints and the absence of comparative groups. CONCLUSIONS: PEP is an alternative practice reported in the literature, used in accidents with high-risk exposure to Brucella. The currently available evidence of the efficacy of antibiotic prophylaxis is insufficient to support a recommendation for or against the widespread use of antibiotic prophylaxis, so caution is needed in interpreting results due to the very low certainty of evidence, primarily stemming from case series and lack of comparative groups.
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Antibacterianos , Profilaxis Antibiótica , Brucelosis , Brucelosis/prevención & control , Humanos , Antibacterianos/uso terapéutico , Doxiciclina/uso terapéutico , Rifampin/uso terapéutico , BrucellaRESUMEN
PURPOSE: Doxycycline post-exposure prophylaxis (Doxy-PEP) reduces the likelihood of Chlamydia and early syphilis by approximately two-thirds. Currently, data on the frequency of Doxy-PEP use in men who have sex with men (MSM) are limited. This study aimed to assess knowledge, attitude towards, and frequency of Doxy-PEP use among MSM in Germany. METHODS: We conducted a national online survey in Germany from summer to fall 2023, recruiting MSM and transgender women. Participants were invited to complete the online survey through social media, online dating platforms, and print media advertisements with active recruitment and poster advertising in private practices, tertiary outpatient clinics, and MSM community events in Germany. RESULTS: In total, 438 participants completed the survey and were included in the analysis, and 285 (65.1%) were living with the human immunodeficiency virus (HIV) or taking HIV-pre-exposure prophylaxis (PrEP). Overall, 170 participants (38.8%) had heard of Doxy-PEP, and 275 (62.8%) would consider taking it, but only 32 (7.3%) reported having ever taken Doxy-PEP. The most common reason for a negative attitude towards Doxy-PEP were apprehension about insufficient detailed information, and concerns about antibiotic resistance. Doxy-PEP users were more likely to be on HIV-PrEP, had a higher self-reported risk of bacterial sexually transmitted infections (STIs), and often had a history of bacterial STIs. CONCLUSION: The study demonstrated high awareness and strong interest in Doxy-PEP among MSM in Germany, most of whom were living with HIV or taking HIV-PrEP; however, the actual usage of Doxy-PEP remains low in the summer and fall of 2023.
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BACKGROUND: Rabies is an incessant public health threat in China. The Ministry of Health implemented the Central Payment for Rabies Prevention and Control Project to assist with rabies prevention and control in a few representative provinces in 2006. METHODS: Data on human rabies cases reported by the National Infectious Disease Reporting Information Management System and national surveillance sites from 2006 to 2022 were collected, and statistical and multivariate analyses were then used to assess the effectiveness of current prevention and control efforts. RESULTS: During 2006-2022, a total of 2025 human rabies cases were collected by the national surveillance sites, with incidence rates far above the national average, but the incidence rate was consistent with the national trend. Human rabies cases demonstrated a dual peak distribution in terms of exposure and onset dates, with the peak exposure dates falling mostly in the spring and summer and the peak onset dates occurring mostly in the summer and autumn. Three danger categories are shown by the geographical distribution: high, medium and low. Dogs had a high infection rate (86.93%), with own domesticated dogs accounting for the majority of infections. The rates of post-exposure prophylaxis are not constant. The median incubation period was 71 days. CONCLUSIONS: Various measures and policies implemented by the government have played a key role in reducing the incidence of rabies. To effectively prevent and control the resurgence of epidemics and halt the spread of the virus among host animals, it is imperative to prioritize and implement a robust dog management system, accelerate research and development of animal vaccines and improve the level of post-exposure prophylaxis.
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Rabia , Rabia/epidemiología , Rabia/prevención & control , Rabia/veterinaria , China/epidemiología , Humanos , Animales , Perros , Incidencia , Masculino , Femenino , Adolescente , Niño , Adulto , Persona de Mediana Edad , Estaciones del Año , Preescolar , Adulto Joven , Enfermedades de los Perros/epidemiología , Enfermedades de los Perros/virología , Enfermedades de los Perros/prevención & control , Lactante , Anciano , Profilaxis Posexposición , Vacunas Antirrábicas/administración & dosificaciónRESUMEN
BACKGROUND: Leprosy is an infectious disease with a slow decline in global annual caseload in the past two decades. Active case finding and post-exposure prophylaxis (PEP) with a single dose of rifampicin (SDR) are recommended by the World Health Organization as measures for leprosy elimination. However, more potent PEP regimens are needed to increase the effect in groups highest at risk (i.e., household members and blood relatives, especially of multibacillary patients). The PEP++ trial will assess the effectiveness of an enhanced preventive regimen against leprosy in high-endemic districts in India, Brazil, Bangladesh, and Nepal compared with SDR-PEP. METHODS: The PEP++ study is a cluster-randomised controlled trial in selected districts of India, Brazil, Bangladesh, and Nepal. Sub-districts will be allocated randomly to the intervention and control arms. Leprosy patients detected from 2015 - 22 living in the districts will be approached to list their close contacts for enrolment in the study. All consenting participants will be screened for signs and symptoms of leprosy and tuberculosis (TB). In the intervention arm, eligible contacts receive the enhanced PEP++ regimen with three doses of rifampicin (150 - 600 mg) and clarithromycin (150 - 500 mg) administered at four-weekly intervals, whereas those in the control arm receive SDR-PEP. Follow-up screening for leprosy will be done for each individual two years after the final dose is administered. Cox' proportion hazards analysis and Poisson regression will be used to compare the incidence rate ratios between the intervention and control areas as the primary study outcome. DISCUSSION: Past studies have shown that the level of SDR-PEP effectiveness is not uniform across contexts or in relation to leprosy patients. To address this, a number of recent trials are seeking to strengthen PEP regimens either through the use of new medications or by increasing the dosage of the existing ones. However, few studies focus on the impact of multiple doses of chemoprophylaxis using a combination of antibiotics. The PEP++ trial will investigate effectiveness of both an enhanced regimen and use geospatial analysis for PEP administration in the study communities. TRIAL REGISTRATION: NL7022 on the Dutch Trial Register on April 12, 2018. Protocol version 9.0 updated on 18 August 2022 https://www.onderzoekmetmensen.nl/en/trial/23060.
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Lepra , Rifampin , Humanos , Rifampin/uso terapéutico , Profilaxis Posexposición/métodos , Lepra/tratamiento farmacológico , Lepra/prevención & control , Lepra/diagnóstico , Antibacterianos/uso terapéutico , Claritromicina/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND: The effectiveness of post-exposure prophylaxis (PEP) depends on participants adherence, making it crucial to assess and compare regimen options to enhance human immunodeficiency virus (HIV) prophylaxis strategies. However, no prospective study in China has shown that the completion rate and adherence of single-tablet regimens in HIV PEP are higher than those of multi-tablet preparations. Therefore, this study aimed to assess the completion rate and adherence of two HIV PEP regimens. METHODS: In this single-center, prospective, open-label cohort study, we included 179 participants from May 2022 to March 2023 and analyzed the differences in the 28-day medication completion rate, adherence, safety, tolerance, and effectiveness of bictegravir/emtricitabine/tenofovir alafenamide (BIC/FTC/TAF) and tenofovir disoproxil fumarate, emtricitabine, and dolutegravir (TDF/FTC + DTG). RESULTS: The PEP completion rate and adherence were higher in the BIC/FTC/TAF group than in the TDF/FTC + DTG group (completion rate: 97.8% vs. 82.6%, P = 0.009; adherence: 99.6 ± 2.82% vs. 90.2 ± 25.29%, P = 0.003). The incidence of adverse reactions in the BIC/FTC/TAF and TDF/FTC + DTG groups was 15.2% and 10.3% (P = 0.33), respectively. In the TDF/FTC + DTG group, one participant stopped PEP owing to adverse reactions (1.1%). No other participants stopped PEP due to adverse events. CONCLUSIONS: BIC/FTC/TAF and TDF/FTC + DTG have good safety and tolerance as PEP regimens. BIC/FTC/TAF has a higher completion rate and increased adherence, thus, is recommended as a PEP regimen. These findings emphasize the importance of regimen choice in optimizing PEP outcomes. TRIAL REGISTRATION: The study was registered in the Chinese Clinical Trial Registry (registration number: ChiCTR2200059994(2022-05-14), https://www.chictr.org.cn/bin/project/edit?pid=167391 ).
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Amidas , Fármacos Anti-VIH , Combinación de Medicamentos , Emtricitabina , Infecciones por VIH , Compuestos Heterocíclicos con 3 Anillos , Profilaxis Posexposición , Piridonas , Tenofovir , Humanos , Infecciones por VIH/prevención & control , Estudios Prospectivos , Masculino , Emtricitabina/uso terapéutico , Emtricitabina/administración & dosificación , Tenofovir/uso terapéutico , Tenofovir/administración & dosificación , Tenofovir/análogos & derivados , China , Adulto , Femenino , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/administración & dosificación , Amidas/uso terapéutico , Amidas/administración & dosificación , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/administración & dosificación , Persona de Mediana Edad , Profilaxis Posexposición/métodos , Cumplimiento de la Medicación/estadística & datos numéricos , Compuestos Heterocíclicos de 4 o más Anillos/uso terapéutico , Compuestos Heterocíclicos de 4 o más Anillos/administración & dosificación , Alanina/uso terapéutico , Alanina/administración & dosificación , Adenina/análogos & derivados , Adenina/uso terapéutico , Adenina/administración & dosificación , Adulto Joven , PiperazinasRESUMEN
BACKGROUND: Rabies is a neglected tropical disease endemic in 150 countries, including India where it is present in all states and union territories except Andaman and Nicobar Islands Lakshadweep. Kerala reports high incidence of animal bites. This article discusses the preventable death of a 17-year-old tribal girl due to rabies in Kerala and the equity concerns it raises. METHODS: The case study was conducted using qualitative methods such as rapid key informant interviews, interactions in tribal assembly meetings, unstructured participant observations, and document verification. Thematic analysis was used, and the results are presented as an ethnographic summary with the use of quotes to substantiate the observations. RESULTS: The girl had gone to a town with her sister for a few days when she developed difficulty in eating, behavioral abnormalities, and injuries on her body. She subsequently died, and a post-mortem revealed Negri bodies in her brain, confirming rabies as the cause of death. The girl had been bitten by a puppy from the forest eight months prior, but she did not receive post-exposure prophylaxis. Multiple dogs are kept in each household in the settlement, and the community takes good care of them since they protect them from wild animals. However, awareness about the need for post-exposure prophylaxis is low, and access to it is difficult for this population. The social problems in the settlement affect their quality of life and their interactions with the outside world. CONCLUSIONS: To prevent such deaths, it is essential to increase awareness and ensure equitable access to life-saving vaccines and immunoglobulin in hard-to-reach tribal areas. The cost-effectiveness of pre-exposure prophylaxis for children in high-risk areas such as this tribal settlement should be evaluated and compared with the WHO-recommended strategies of mass canine vaccination and One Health.
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Mordeduras y Picaduras , Rabia , Adolescente , Animales , Perros , Femenino , Humanos , Mordeduras y Picaduras/complicaciones , India , Profilaxis Posexposición , Vacunas Antirrábicas/uso terapéuticoRESUMEN
BACKGROUND: Following the outbreak of the COVID-19 pandemic, several clinical trials have evaluated postexposure prophylaxis (PEP) among close contacts of an index individual with a confirmed SARS-CoV-2 infection. Because index individuals do not directly inform the efficacy of prevention interventions, they are seldom enrolled in COVID-19 PEP studies. However, adjusting for prognostic covariates such as an index individual's COVID-19 illness and risk behaviors can increase precision in PEP efficacy estimates, so approaches to accurately collecting this information about the index individual are needed. This analysis aimed to assess whether surveying household contacts captures the same information as surveying the index individual directly. METHODS: REGN 2069/CoVPN 3502, a randomized controlled trial of COVID-19 PEP, enrolled household contacts of SARS-CoV-2 index individuals. CoVPN 3502-01 retrospectively enrolled and surveyed the index individuals. We compared responses to seven similar questions about the index individuals' transmission cofactors that were asked in both studies. We estimated the percent concordance between index individuals and their household contacts on each question, with 50% concordance considered equivalent to random chance. RESULTS: Concordance between index individuals and contacts was high on the most objective questions, approximately 97% (95% CI: 90-99%) for index individual age group and 96% (88-98%) for hospitalization. Concordance was moderate for symptoms, approximately 85% (75-91%). Concordance on questions related to the index individual's behavior was only slightly better or no better than random: approximately 62% (51-72%) for whether they received COVID-19 treatment, 68% (57-77%) for sharing a bedroom, 70% (59-79%) for sharing a common room, and 49% (39-60%) for mask wearing at home. However, while contacts were surveyed within 96 h of the index individual testing positive for SARS-CoV-2, the median time to enrollment in CoVPN 3502-01 was 240 days, which may have caused recall bias in our results. CONCLUSIONS: Our results suggest a need to survey index individuals directly in order to accurately capture their transmission cofactors, rather than relying on their household contacts to report on their behavior. The lag in enrolling participants into CoVPN 3502-01 also highlights the importance of timely enrollment to minimize recall bias.
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COVID-19 , Humanos , COVID-19/epidemiología , Tratamiento Farmacológico de COVID-19 , Pandemias/prevención & control , Estudios Retrospectivos , SARS-CoV-2 , AutoinformeRESUMEN
BACKGROUND: Associations between perceived and actual risk of HIV infection and HIV prevention services uptake are inconclusive. This study aimed to evaluate the discrepancy between the perceived and actual HIV risk, and quantify the associations between perceived and actual risk of HIV infection and three HIV prevention services utilization among men who have sex with men (MSM) in Shandong province, China. METHODS: A cross-sectional study was conducted in Shandong province in June 2021. Participants were eligible if they were born biologically male, aged 18 years or older, had negative or unknown HIV status, and had sex with men in the past year. Participants were recruited online. The discrepancy between their perceived and actual risk of HIV infection was evaluated by calculating the Kappa value. Bayesian model averaging was used to assess the associations between perceived and actual risk of HIV infection and HIV prevention services uptake. RESULTS: A total of 1136 MSM were recruited, most of them were 30 years old or younger (59.9%), single (79.5%), with at least college education level (74.7%). Most participants (97.4%) perceived that they had low risk of HIV infection, and 14.1% were assessed with high actual risk. The discrepancy between their perceived and actual risk of HIV infection was evaluated with a Kappa value of 0.076 (P < 0.001). HIV testing uptake had a weak association with perceived high HIV prevalence among social networks (aOR = 1.156, post probability = 0.547). The perceived high HIV prevalence among national MSM was positive related to willingness to use PrEP (aOR = 1.903, post probability = 0.943) and PEP (aOR = 1.737, post probability = 0.829). Perceived personal risk (aOR = 4.486, post probability = 0.994) and perceived HIV prevalence among social networks (aOR = 1.280, post probability = 0.572) were related to history of using PrEP. Perceived personal risk (aOR = 3.144, post probability = 0.952), actual risk (aOR = 1.890, post probability = 0.950), and perceived risk among social networks (aOR = 1.502, post probability = 0.786) were related to history of using PEP. CONCLUSIONS: There is discordance between perceived and actual personal risk of HIV infection among MSM in China. HIV risk assessment and education on HIV prevalence among MSM should be strengthened to assist high-risk populations aware their risk accurately and hence access HIV prevention services proactively.
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Infecciones por VIH , Homosexualidad Masculina , Humanos , Masculino , Estudios Transversales , China/epidemiología , Infecciones por VIH/prevención & control , Infecciones por VIH/epidemiología , Adulto , Homosexualidad Masculina/estadística & datos numéricos , Homosexualidad Masculina/psicología , Adulto Joven , Conocimientos, Actitudes y Práctica en Salud , Adolescente , Persona de Mediana Edad , Medición de Riesgo , Aceptación de la Atención de Salud/estadística & datos numéricos , Aceptación de la Atención de Salud/psicología , Encuestas y CuestionariosRESUMEN
Biomedical tools for HIV prevention such as post-exposure prophylaxis (PEP) continue to be underutilized by subgroups experiencing significant HIV inequities. Specifically, factors associated with both PEP awareness and uptake both cross-sectionally and longitudinally are under-researched, despite PEP being a part of the United States' Plan for Ending the HIV Epidemic. The current study examined longitudinal predictors of PEP awareness among Latino sexual minority men (LSMM) living in South Florida. This current study (N = 290) employed hierarchal linear modeling across three timepoints (baseline, 4-months, 8-months) to assess within-person and between-person effects over time for several psychosocial and structural factors. Most participants (67.5%) reported little to no awareness of PEP at baseline with general PEP awareness growing slightly across the study (60.5% reporting little to no awareness of PEP at 8 months). Results of the final conditional model suggest significant within-person effects of PrEP knowledge (p = 0.02) and PrEP self-efficacy (p < 0.001), as well as a significant positive between-person effect of PrEP knowledge (p < 0.01) on PEP awareness. Between-person HIV knowledge was also a significant predictor in this model (p = 0.01). This longitudinal analysis of LSMM's PEP awareness indicates that more must be done to increase PEP awareness among this subgroup. Future studies should explore how to build on existing interventions focused on HIV and PrEP knowledge and PrEP self-efficacy to incorporate information about PEP to increase the reach of this effective biomedical HIV prevention tool.
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Infecciones por VIH , Minorías Sexuales y de Género , Masculino , Humanos , Homosexualidad Masculina , Infecciones por VIH/psicología , Profilaxis Posexposición , FloridaRESUMEN
BACKGROUND: Adolescents account for 15% of new HIV cases in Kenya. HIV pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) are highly effective prevention tools, but uptake is low among adolescents, particularly in resource-limited settings. We assessed awareness and acceptability of PrEP and PEP among Kenyan adolescents. METHOD: Focus group discussions were conducted with 120 adolescent boys and girls ages 15 to 19 in Kisumu. Data were analyzed using the Framework Approach. RESULTS: Adolescent participants often had not heard of or could not differentiate between PrEP and PEP. They also confused these HIV prevention tools with emergency contraceptives. Taking a daily pill to prevent HIV was perceived as analogous to taking a pill to treat HIV. Boys were aware of and willing to consider using PrEP and PEP due to their dislike for using condoms. Adolescents identified insufficient information, cost, and uncomfortableness speaking with healthcare workers about their HIV prevention needs due to sexuality stigma as barriers to using PrEP and PEP. CONCLUSION: Low awareness and poor understanding of PrEP and PEP among adolescents reveal the need for increased education and sensitization about these HIV prevention options. Expanding access to sexual and reproductive health services that are tailored to the needs of adolescents and staffed with non-judgmental providers could help reduce sexuality stigma as a barrier to accessing care. New HIV prevention approaches such as long-acting injectables or implants, on-demand regimens, and multipurpose prevention technologies may encourage increased uptake of PrEP and PEP by adolescents.
RESUMEN
HIV affects an estimated 1.2 million individuals in the United States and is disproportionately concentrated among African Americans, Latinos, and people of multiple races. Post-exposure prophylaxis (PEP) substantially decreases HIV transmission when started within 72 h after exposure, but problems of accessibility have hindered its widespread usage in communities at risk for HIV infection. Pharmacy-initiated PEP access was first permitted in New York City in 2017, allowing pharmacists to provide a 7-day supply of PEP without a prescription for consumers at high risk for HIV infection. It was expected that the broad reach and accessibility of community pharmacies would increase timely access to PEP for all individuals, especially those who already face significant barriers to accessing the healthcare system. Since then, eleven other states have followed suit and expanded the scope of outpatient pharmacy practice in order to increase the availability of HIV PEP but prescribing laws in over 75% of the US have not been changed. Much of the existing literature on HIV prevention focuses on PrEP access barriers with limited information on PEP access in the US. In this paper, we review the current status of pharmacist-initiated PEP in the US as part of the End the HIV Epidemic (EHE) initiative.
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Síndrome de Inmunodeficiencia Adquirida , Fármacos Anti-VIH , Infecciones por VIH , Farmacias , Humanos , Estados Unidos , Infecciones por VIH/epidemiología , Profilaxis Posexposición , Fármacos Anti-VIH/uso terapéuticoRESUMEN
We report a case of exposure to Coxiella burnetii in a surgical nurse who underwent an injury of her finger with a scalpel blade during a native aortic valve replacement with a bio-prosthetic cardiac valve conducted on a patient suffering from C. burnetii aortic endocarditis. Given the positivity of C. burnetii culture and PCR from the patient's aortic valve, she was prescribed prophylactic doxycycline 100 mg twice a day for 10 days. Q fever is an occupational zoonosis resulting usually of exposure to infected animals by inhalation of infected aerosols or consumption of contaminated raw milk. Apart from materno-foetal transmission, about 180 cases of human-to-human C. burnetii transmission have been published from 1949 to today, including transmission by blood transfusion, sexual relations, transmission in the healthcare setting to staff, patient attendants and other patients that were likely infected from inhalation of aerosol from respiratory or placental products, transmission to staff during autopsies of patients with Q fever and transmission in familial settings. As C. burnetii is a highly infectious bacterium, that may cause infection with a low inoculum, it should be added to the list of organisms which may be of concern following blood exposure among healthcare professionals.
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Procedimientos Quirúrgicos Cardíacos , Coxiella burnetii , Exposición Profesional , Fiebre Q , Humanos , Animales , Femenino , Embarazo , Coxiella burnetii/genética , Fiebre Q/microbiología , PlacentaRESUMEN
Since January 2024, Italy experiences a pertussis outbreak, primarily affecting neonates and unvaccinated infants at high risk of severe complications and mortality; 11 major paediatric centres noted 108 hospitalisations and three deaths by 10 May. The outbreak reflects increased circulation of Bordetella pertussis and non-adherence to immunisation recommendations during pregnancy. Public health interventions, including maternal immunisation, vaccination of infants as early as possible and post-exposure prophylaxis, are critical for reducing the burden of pertussis and preventing further mortality.