One-dose intradermal rabies booster enhances rabies antibody production and avidity maturation.

The incidence of rabies in Thailand reached its peak in 2018 with 18 human deaths. Preexposure prophylaxis (PrEP) vaccination is thus recommended for high-risk populations. WHO has recently recommended that patients who are exposed to a suspected rabid animal and have already been immunized against rabies should receive a 1-site intradermal (ID) injection of 0.1 mL on days 0 and 3 as postexposure prophylaxis (PEP). In Thailand, village health and livestock volunteers tasked with annual dog vaccination typically receive only a single lifetime PrEP dose and subsequent boosters solely upon confirmed animal bites. However, the adequacy of a single PrEP dose for priming and maintaining immunity in this high-risk group has not been evaluated. Therefore, our study was designed to address two key questions: (1) sufficiency of single-dose PrEP-to determine whether a single ID PrEP dose provides adequate long-term immune protection for high-risk individuals exposed to numerous dogs during their vaccination duties. (2) Booster efficacy for immune maturation-to investigate whether one or two additional ID booster doses effectively stimulate a mature and sustained antibody response in this population. The level and persistence of the rabies antibody were determined by comparing the immunogenicity and booster efficacy among the vaccination groups. Our study demonstrated that rabies antibodies persisted for more than 180 days after cost-effective ID PrEP or the 1st or the 2nd single ID booster dose, and adequate antibody levels were detected in more than 95% of participants by CEE-cELISA and 100% by indirect ELISA. Moreover, the avidity maturation of rabies-specific antibodies occurred after the 1st single ID booster dose. This smaller ID booster regimen was sufficient for producing a sufficient immune response and enhancing the maturation of anti-rabies antibodies. This safe and effective PrEP regimen and a single visit involving a one-dose ID booster are recommended, and at least one one-dose ID booster regimen could be equitably implemented in at-risk people in Thailand and other developing countries. However, an adequate antibody level should be monitored before the booster is administered.

Post-exposure prophylaxis in leprosy (PEOPLE): a cluster randomised trial.

BACKGROUND: Post-exposure prophylaxis (PEP) using single-dose rifampicin reduces progression from infection with Mycobacterium leprae to leprosy disease. We compared effectiveness of different administration modalities, using a higher (20 mg/kg) dose of rifampicin-single double-dose rifampicin (SDDR)-PEP. METHODS: We did a cluster randomised study in 16 villages in Madagascar and 48 villages in Comoros. Villages were randomly assigned to four study arms and inhabitants were screened once a year for leprosy, for 4 consecutive years. All permanent residents (no age restriction) were eligible to participate and all identified patients with leprosy were treated with multidrug therapy (SDDR-PEP was provided to asymptomatic contacts aged ≥2 years). Arm 1 was the comparator arm, in which no PEP was provided. In arm 2, SDDR-PEP was provided to household contacts of patients with leprosy, whereas arm 3 extended SDDR-PEP to anyone living within 100 m. In arm 4, SDDR-PEP was offered to household contacts and to anyone living within 100 m and testing positive to anti-phenolic glycolipid-I. The main outcome was the incidence rate ratio (IRR) of leprosy between the comparator arm and each of the intervention arms. We also assessed the individual protective effect of SDDR-PEP and explored spatial associations. This trial is registered with ClinicalTrials.gov, NCT03662022, and is completed. FINDINGS: Between Jan 11, 2019, and Jan 16, 2023, we enrolled 109 436 individuals, of whom 95 762 had evaluable follow-up data. Our primary analysis showed a non-significant reduction in leprosy incidence in arm 2 (IRR 0·95), arm 3 (IRR 0·80), and arm 4 (IRR 0·58). After controlling for baseline prevalence, the reduction in arm 3 became stronger and significant (IRR 0·56, p=0·0030). At an individual level SDDR-PEP was also protective with an IRR of 0·55 (p=0·0050). Risk of leprosy was two to four times higher for those living within 75 m of an index patient at baseline. INTERPRETATION: SDDR-PEP appears to protect against leprosy but less than anticipated. Strong spatial associations were observed within 75 m of index patients. Targeted door-to-door screening around index patients complemented by a blanket SDDR-PEP approach will probably have a substantial effect on transmission. FUNDING: European and Developing Countries Clinical Trials Partnership. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Comparative Effectiveness of Baloxavir Marboxil and Oseltamivir Treatment in Reducing Household Transmission of Influenza: A Post Hoc Analysis of the BLOCKSTONE Trial.

BACKGROUND: The transmission of influenza virus in households, especially by children, is a major route of infection. Prior studies suggest that timely antiviral treatment of ill cases may reduce infection in household contacts. The aim of the study was to compare the effects of oseltamivir (OTV) and baloxavir marboxil (BXM) treatment of index cases on the secondary attack rate (SAR) of influenza within household. METHODS: A post hoc analysis was done in BLOCKSTONE trial-a placebo-controlled, double-blinded post-exposure prophylaxis of BXM. Data were derived from the laboratory-confirmed index cases' household contacts who received placebo in the trial and also from household members who did not participate in the trial but completed illness questionnaires. To assess the SAR of household members, multivariate analyses adjusted for factors including age, vaccination status, and household size were performed and compared between contacts of index cases treated with BXM or OTV. RESULTS: In total, 185 index cases (116 treated with BXM and 69 treated with OTV) and 410 household contacts (201 from trial, 209 by questionnaire) were included. The Poisson regression modeling showed that the SAR in household contacts of index cases treated with BXM and OTV was 10.8% and 18.5%, respectively; the adjusted relative reduction in SAR was 41.8% (95% confidence interval: 1.0%-65.7%, p = 0.0456) greater with BXM than OTV. Similar reductions were found in contacts from the trial and those included by questionnaire. CONCLUSION: BXM treatment of index cases appeared to result in a greater reduction in secondary household transmission than OTV treatment.

[Perception of risk of HIV infection and knowledge about the use of antiretrovirals in prevention]. / Percepción de riesgo de infección por HIV y conocimiento sobre uso de antirretrovirales en prevención.

INTRODUCTION: Combined prevention (CP) is considered the key strategy against the HIV epidemic. The objective of the study was to evaluate the perception of risk of HIV infection and the knowledge about the use of antiretrovirals (ARV) for prevention, among patients who attend a Sexually Transmitted Infections (STI) clinic. METHODS: A survey on personal data and perception of risk of HIV infection, knowledge about post-exposure prophylaxis (PEP) and pre-exposure prophylaxis (PrEP), was administered to patients at the time of applying doses of penicillin for the treatment of syphilis, or when taking a blood sample for STI diagnosis, between May and December, 2022. RESULTS: 100 persons were surveyed: 43 were under 25 years of age, 67 reported male sex-gender and 33 females. Thirty of 91 (33%) perceived they had had some risk of infection in their lives, 19 of them in the last year; 77/96 (80%) stated that they had no knowledge about PEP, and 82/100, about PrEP. Only 22 out of 100 responded that antiretrovirals could provide benefit in preventing HIV; 26 (60%) of the 43 patients <25 years of age, and 18 of the 57 ≥ 25 years (31.6%) responded they have had two or more sexual partners in the last year. No statistically significant differences were observed related to gender and age group. DISCUSSION: The low perception of infection risk and knowledge about the use of antiretrovirals in HIV prevention, show the existing difficulties for the implementation of combined prevention (PEP-PrEP) in this population.

Introducción: La prevención combinada (PC) se considera la estrategia clave frente a la epidemia de HIV. El objetivo del estudio fue evaluar la percepción de riesgo de infección por HIV y el conocimiento sobre uso de antirretrovirales (ARV) para prevención, entre pacientes que concurren a un consultorio de Infecciones de Transmisión Sexual (ITS). Métodos: Una encuesta sobre datos personales y percepción de riesgo de infección por HIV, conocimiento sobre profilaxis posterior a la exposición (PEP) y previa a la exposición (PrEP), fue administrada a pacientes al momento de aplicar dosis de penicilina para tratamiento de sífilis, o de extraer muestra de sangre para diagnóstico de ITS, entre mayo y diciembre, 2022. Resultados: De 100 personas encuestadas, 43 eran menores de 25 años, 67 reportaron sexo-género masculino y 33 femenino. Treinta de 91, (33%), percibían haber tenido en su vida algún riesgo de infección, 19 de ellas en el último año; 77/96 (80%) manifestaron no tener conocimiento sobre PEP, y 82/100, sobre PrEP. Solo 22% respondió que los antirretrovirales podrían brindar beneficio para prevenir el HIV; 26 (60%) de los 43 menores de 25 años, y 18 de los 57 ≥ 25 años (31.6%) respondieron haber tenido dos o más parejas sexuales el último año. No se observaron diferencias estadísticamente significativas, relacionadas con género y grupo etario. Discusión: La baja percepción de riesgo de infección y del conocimiento sobre uso de antirretrovirales para prevención de HIV, evidencian las dificultades existentes en la implementación de prevención combinada (PEPPrEP) en esta población.

A behavioral economics approach to enhancing HIV preexposure and postexposure prophylaxis implementation.

PURPOSE OF REVIEW: The 'PrEP cliff' phenomenon poses a critical challenge in global HIV PrEP implementation, marked by significant dropouts across the entire PrEP care continuum. This article reviews new strategies to address 'PrEP cliff'. RECENT FINDINGS: Canadian clinicians have developed a service delivery model that offers presumptive PEP to patients in need and transits eligible PEP users to PrEP. Early findings are promising. This service model not only establishes a safety net for those who were not protected by PrEP, but it also leverages the immediate salience and perceived benefits of PEP as a natural nudge towards PrEP use. Aligning with Behavioral Economics, specifically the Salience Theory, this strategy holds potential in tackling PrEP implementation challenges. SUMMARY: A natural pathway between PEP and PrEP has been widely observed. The Canadian service model exemplifies an innovative strategy that leverages this organic pathway and enhances the utility of both PEP and PrEP services. We offer theoretical insights into the reasons behind these PEP-PrEP transitions and evolve the Canadian model into a cohesive framework for implementation.

Rabies post-exposure prophylaxis in the emergency department.

STUDY OBJECTIVES: Rabies is a zoonotic single-stranded RNA lyssavirus that can cause acute infections of the central nervous system (CNS) including encephalomyelitis, encephalitis, and meningoencephalitis that is progressively fatal. Rabies is more common in developing countries, but approximately 23,000 people in the United States (US) are estimated to have been exposed or to have received post exposure prophylaxis (PEP) yearly. Nebraska Medicine follows the Advisory Committee on Immunization Practices (ACIP) guidelines for the vaccination series, as well as the 20 units/kg administration of immunoglobulin (RIG). Nebraska Medicine Medical Center (NMC) and Bellevue Medical Center (BMC) treat the scheduling of the complete rabies vaccine series differently. At both campuses, patients receive their immunoglobulin and first vaccine in the Emergency Department (ED). At NMC, patients are scheduled to receive the remainder of their vaccination series at the outpatient infusion center by the ED pharmacist. At BMC, the subsequent vaccinations are given as "Nurse Only" return visits to the ED. The objective of this study was to compare patient compliance of two different processes for follow-up rabies vaccine series completion. This project's primary aim was to determine the rate of patient compliance for follow up rabies vaccine doses. The secondary aims of this project were to determine if there was a difference in patient follow-up compliance between the two campuses, patient specific factors that impact compliance, and potential cost savings if a dose rounding protocol for RIG was utilized. METHODS: This retrospective chart review was completed as a quality improvement project. Data from patients who had received either rabies immunoglobulin and/or a rabies vaccine, were >18 years of age, and were not admitted were collected for a 3-year period from July 1, 2019, to June 30, 2022. Data were abstracted from the patient's EMR (electronic medical records) using a SQL (Structured query language) query of pre-identified data elements. When unable to abstract with SQL query, data elements were manually abstracted. All data abstracted was collated and descriptive analysis performed. RESULTS: A total of 723 individual encounters were identified during the study period. After combining rabies series for each individual patient, 173 unique patients remained. After exclusions were applied, 143 patients were included: 104 patients from NMC, and 39 from BMC. For the primary outcome, appropriate completion between the two campuses was 78.3%. When comparing the two campuses, completion rates were higher at NMC (82% vs. 69%), although not statistically significant (p = 0.12). Appropriate completion of vaccine series was statistically significant for both payor and exposure type. Application of a dose rounding policy with those >45 kg, rounding to the nearest vial, as well as rounding down if at the midpoint interval, 56 fewer vials would have been used between the two campuses. This would have resulted in a potential cost savings of $57,928.64 over the study period.

Feasibility of post-exposure-prophylaxis with single-dose rifampicin and identification of high prevalent clusters in villages' hyperendemic for leprosy in Senegal.

INTRODUCTION: Senegal is a leprosy low-endemic country with nine villages known to be hyperendemic with a leprosy incidence rate above 1,000 per million inhabitants. We aim to implement a door-to-door screening strategy associated with the administration of a single-dose-rifampicin (SDR) as post-exposure prophylaxis (PEP) to household and social contacts in these villages and to identify spatial clustering and assess the risk of leprosy in population according to the physical distance to the nearest index-case. METHODS: From October/2020 to February/2022 active door-to-door screening for leprosy was conducted in nine villages. Using an open-source application, we recorded screening results, demographic and geographic coordinate's data. Using Poisson model we analysed clustering and estimated risk of contracting leprosy in contacts according to the distance to the nearest new leprosy patient. RESULTS: In nine villages, among 9086 contacts listed, we examined 7115. Among 6554 eligible contacts, 97.8% took SDR. We found 39(0.64%) new leprosy cases among 6,124 examined in six villages. Among new cases, 21(53.8%) were children, 10(25.6%) were multibacillary and 05(12.8%) had grade 2 disability. The prevalent risk ratio and 95% confidence intervale(95%CI) adjusted by village were 4.2(95%CI 1.7-10.1), 0.97(95%CI 0.2-4.4), 0.87(95%CI 0.2-25), 0.89(95%CI 0.3-2.6) and 0.70(95%CI 0.2-2.5) for the contacts living in the same household of an index case, 1-25m, 26-50m, 51-75m and 76-100m compared to those living at more than 100m respectively. We identified nine high prevalent clusters including 27/39(69%) of new cases in 490/7,850(6%) inhabitants, with relative risks of 46.6(p-value = 0.01), and 7.3, 42.8, 8.2, 12.5, 11.4, 23.5, 22.3, and 14.6 (non-significant p-values). CONCLUSIONS: Our strategy has proved the feasibility of active screening for leprosy in contacts and the introduction of PEP for leprosy under programmatic conditions. Only individuals living in the same household as the leprosy patient had a significant risk of contracting leprosy. We documented nine clusters of leprosy that could benefit from tailored control activities while optimizing resources.

The PEP++ study protocol: a cluster-randomised controlled trial on the effectiveness of an enhanced regimen of post-exposure prophylaxis for close contacts of persons affected by leprosy to prevent disease transmission.

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.

[Presentations for HIV post-exposure prophylaxis in emergency departments: guideline and recommendations]. / HIV-Postexpositionsprophylaxe in der Notaufnahme: Vorgehen, Tipps & Tricks.

Patients often present to emergency departments after potential or confirmed exposure to human immunodeficiency virus (HIV) asking for recommendations concerning the initiation of post-exposure prophylaxis (PEP). These presentations may occur after occupational as well as non-occupational exposure. PEP entails taking a triple antiretroviral therapy for 28-30 days. If taken early (ideally within 2 h, but no later than 72 h) and as indicated, HIV infection can be prevented with a high level of probability. Since these presentations occur around the clock, they require basic expertise on the part of the emergency department staff regarding its indication and its side effects as well as standardized procedures in the emergency department to not delay initiation. Patients should present to an infectious disease outpatient clinic or practice specialized in HIV in order to have the indication reviewed by a specialist and, if necessary, adapted to complex cases with the aim of making individual case decisions. This review article aims to summarize core statements of the 2022 German-Austrian guideline on HIV post-exposure prophylaxis and to give emergency department staff necessary knowledge to safely and correctly begin PEP.

JYNNEOS™ effectiveness as post-exposure prophylaxis against mpox: Challenges using real-world outbreak data.

BACKGROUND: JYNNEOSTM vaccine has been used as post-exposure prophylaxis (PEP) during a mpox outbreak in New York City (NYC). Data on effectiveness are limited. METHODS: Effectiveness of a single dose of JYNNEOSTM vaccine administered subcutaneously ≤ 14 days as PEP for preventing mpox disease was assessed among individuals exposed to case-patients from May 22, 2022-August 24, 2022. Individuals were evaluated for mpox through 21 days post-exposure. An observational study was conducted emulating a sequence of nested "target" randomized trials starting each day after exposure. Results were adjusted for exposure risk and race/ethnicity. Analyses were conducted separately based on last (PEPL) and first (PEPF) exposure date. We evaluated the potential to overestimate PEP effectiveness when using conventional analytic methods due to exposed individuals developing illness before they can obtain PEP (immortal time bias) compared to the target trial. RESULTS: Median time from last exposure to symptom onset (incubation period) among cases that did not receive PEPL was 7 days (range 1-16). Time to PEPL receipt was 7 days (range 0-14). Among 549 individuals, adjusted PEPL and PEPF effectiveness was 19 % (95 % Confidence Interval [CI], -54 % to 57 %) and -7% (95 % CI, -144 % to 53 %) using the target trial emulation, respectively, and 78 % (95 % CI, 50 % to 91 %) and 73 % (95 % CI, 31 % to 91 %) using conventional analysis. CONCLUSIONS: Determining PEP effectiveness using real-world data during an outbreak is challenging. Time to PEP in NYC coupled with the observed incubation period resulted in overestimated PEP effectiveness using a conventional method. The target trial emulation, while yielding wide confidence intervals due to small sample size, avoided immortal time bias. While results from these evaluations cannot be used as reliable estimates of PEP effectiveness, we present important methodologic considerations for future evaluations.

Concordance of emergency department physicians' decisions on HIV post-exposure prophylaxis with national guidelines: results from a retrospective cohort study.

BACKGROUND: Post-exposure prophylaxis (PEP) is an effective tool to prevent infection with HIV. Patients seeking PEP after potential HIV exposure usually present to the emergency department (ED). Our study sought to determine the concordance of ED physicians' decisions on HIV-PEP with national guidelines (primary objective) and to assess the clinical relevance of drug-drug interactions (DDIs) between the HIV-PEP regimen and patients' concomitant medication (secondary objective). METHODS: We conducted a retrospective cohort study at the ED of Hannover Medical School, Germany. Between 1 January 2018 and 31 December 2019, 113 of 11 246 screened patients presented to the ED after potential HIV exposure and were enrolled in the study. RESULTS: The median age of the patients (82.3% male) was 30 y (IQR 25-35.5), 85.8% of potential HIV exposures were characterised as sexual and 85.0% presented within 72 h. ED physicians' decisions on HIV-PEP were concordant with national guidelines in 93.8%. No clinically relevant DDIs were detected. CONCLUSIONS: ED physicians' decisions on HIV-PEP were highly concordant with national guidelines. Approximately 1% of patient presentations to the ED were related to HIV exposure; therefore, training ED physicians on HIV transmission risk assessment and indications/contraindications for HIV-PEP is paramount.

A novel mRNA rabies vaccine as a promising candidate for rabies post-exposure prophylaxis protects animals from different rabies viruses.

Rabies, caused by the rabies virus (RABV), is the most fatal zoonotic disease. It is a neglected tropical disease which remains a major public health problem, causing approximately 59,000 deaths worldwide annually. Despite the existence of effective vaccines, the high incidence of human rabies is mainly linked to tedious vaccine immunisation procedures and the overall high cost of post-exposure prophylaxis. Therefore, it is necessary to develop an effective vaccine that has a simple procedure and is affordable to prevent rabies infection in humans. RABV belongs to the genus Lyssavirus and family Rhabdoviridae. Previous phylogenetic analyses have identified seven major clades of RABV in China (China I-VII), confirmed by analysing nucleotide sequences from both the G and N proteins. This study evaluated the immunogenicity and protective capacity of SYS6008, an mRNA rabies vaccine expressing rabies virus glycoprotein, in mice and cynomolgus macaques. We demonstrated that SYS6008 induced sufficient levels of rabies neutralising antibody (RVNA) in mice. In addition, SYS6008 elicited strong and durable RVNA responses in vaccinated cynomolgus macaques. In the pre-exposure prophylaxis murine model, one or two injections of SYS6008 at 1/10 or 1/30 of dosage provided protection against a challenge with a 30-fold LD50 of rabies virus (China I and II clades). We also demonstrated that in the post-exposure prophylaxis murine model, which was exposed to lethal rabies virus (China I-VII clades) before vaccination, one or two injections of SYS6008 at both 1/10 and 1/30 dosages provided better protection against rabies virus challenge than the immunization by five injections of commercial vaccines at the same dosage. In addition, we proved that SYS6008-induced RVNAs could neutralise RABV from the China I-VII clades. Finally, 1/10 of the dosage of SYS6008 was able to stimulate significant RABV-G specificity in the T cell response. Furthermore, we found that SYS6008 induced high cellular immunity, including RABV-G-specific T cell responses and memory B cells. Our results imply that the SYS6008 rabies vaccine, with a much simpler vaccination procedure, better immunogenicity, and enhanced protective capacity, could be a candidate vaccine for post-exposure prophylaxis of rabies infections.

Neuroimmunology of rabies: New insights into an ancient disease.

Rabies is an ancient neuroinvasive viral (genus Lyssavirus, family Rhabdoviridae) disease affecting approximately 59,000 people worldwide. The central nervous system (CNS) is targeted, and rabies has a case fatality rate of almost 100% in humans and animals. Rabies is entirely preventable through proper vaccination, and thus, the highest incidence is typically observed in developing countries, mainly in Africa and Asia. However, there are still cases in European countries and the United States. Recently, demographic, increasing income levels, and the coronavirus disease 2019 (COVID-19) pandemic have caused a massive raising in the animal population, enhancing the need for preventive measures (e.g., vaccination, surveillance, and animal control programs), postexposure prophylaxis, and a better understanding of rabies pathophysiology to identify therapeutic targets, since there is no effective treatment after the onset of clinical manifestations. Here, we review the neuroimmune biology and mechanisms of rabies. Its pathogenesis involves a complex and poorly understood modulation of immune and brain functions associated with metabolic, synaptic, and neuronal impairments, resulting in fatal outcomes without significant histopathological lesions in the CNS. In this context, the neuroimmunological and neurochemical aspects of excitatory/inhibitory signaling (e.g., GABA/glutamate crosstalk) are likely related to the clinical manifestations of rabies infection. Uncovering new links between immunopathological mechanisms and neurochemical imbalance will be essential to identify novel potential therapeutic targets to reduce rabies morbidity and mortality.

High post-exposure prophylaxis (PEP) uptake among household contacts of pertussis patients enrolled in a PEP effectiveness evaluation - United States, 2015-2017.

BACKGROUND: Post-exposure prophylaxis (PEP) for pertussis is recommended for household contacts of pertussis cases in the United States within 21 days of exposure, but data on PEP effectiveness for prevention of secondary cases in the setting of widespread pertussis vaccination are limited. We implemented a multi-state evaluation of azithromycin PEP use and effectiveness among household contacts. METHODS: Culture- or PCR-confirmed pertussis cases were identified through surveillance. Household contacts were interviewed within 7 days of case report and again 14-21 days later. Interviewers collected information on exposure, demographics, vaccine history, prior pertussis diagnosis, underlying conditions, PEP receipt, pertussis symptoms, and pertussis testing. A subset of household contacts provided nasopharyngeal and blood specimens during interviews. RESULTS: Of 299 household contacts who completed both interviews, 12 (4%) reported not receiving PEP. There was no evidence of higher prevalence of cough or pertussis symptoms among contacts who did not receive PEP. Of 168 household contacts who provided at least one nasopharyngeal specimen, four (2.4%) were culture or PCR positive for B. pertussis; three of these received PEP prior to their positive test result. Of 156 contacts with serologic results, 14 (9%) had blood specimens that were positive for IgG anti-pertussis toxin (PT) antibodies; all had received PEP. CONCLUSIONS: Very high PEP uptake was observed among household contacts of pertussis patients. Although the number of contacts who did not receive PEP was small, there was no difference in prevalence of pertussis symptoms or positive laboratory results among these contacts compared with those who did receive PEP.

Highlights From CROI, the Conference on Retroviruses and Opportunistic Infections-Postexposure Prophylaxis for Sexually Transmitted Infections, a New Protease Inhibitor for COVID-19, Goals for Preventing HIV Transmission, and More.

This Medical News Q&A discusses research highlights from the recent Conference on Retroviruses and Opportunistic Infections.

Strategies to inTerrupt RAbies Transmission for the Elimination Goal by 2030 In China (STRATEGIC): a modelling study.

BACKGROUND: A global plan has been set to end human deaths from dog-mediated rabies by 2030 ("Zero-by-30"), but whether it could be achieved in some countries, such as China, remains unclear. Although elimination strategies through post-exposure prophylaxis (PEP) use, dog vaccination, and patient risk assessments with integrated bite case management (IBCM) were proposed to be cost-effective, evidence is still lacking in China. We aim to evaluate the future burdens of dog-mediated human rabies deaths in the next decade and provide quantitative evidence on the cost-effectiveness of different rabies-control strategies in China. METHODS: Based on data from China's national human rabies surveillance system, we used decision-analytic modelling to estimate dog-mediated human rabies death trends in China till 2035. We simulated and compared the expected consequences and costs of different combination strategies of the status quo, improved access to PEP, mass dog vaccination, and use of IBCM. RESULTS: The predicted human rabies deaths in 2030 in China will be 308 (95%UI: 214-411) and remain stable in the next decade under the status quo. The strategy of improved PEP access alone could only decrease deaths to 212 (95%UI: 147-284) in 2028, remaining unchanged till 2035. In contrast, scaling up dog vaccination to coverage of 70% could eliminate rabies deaths by 2033 and prevent approximately 3,265 (95%UI: 2,477-3,687) extra deaths compared to the status quo during 2024-2035. Moreover, with the addition of IBCM, the "One Health" approach through mass dog vaccination could avoid unnecessary PEP use and substantially reduce total cost from 12.53 (95%UI: 11.71-13.34) to 8.73 (95%UI: 8.09-9.85) billion US dollars. Even if increasing the total costs of IBCM from 100 thousand to 652.10 million US dollars during 2024-2035, the combined strategy of mass dog vaccination and use of IBCM will still dominate, suggesting the robustness of our results. CONCLUSIONS: The combined strategy of mass dog vaccination and IBCM requires collaboration between health and livestock/veterinary sectors, and it could eliminate Chinese rabies deaths as early as 2033, with more deaths averted and less cost, indicating that adding IBCM could reduce unnecessary use of PEP and make the "One Health" rabies-control strategy most cost-effective.