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Increased rates of sexually transmitted infections (STIs) are reported among men who have sex with men (MSM) and new interventions are needed. We aimed to assess whether post-exposure prophylaxis (PEP) with doxycycline could reduce the incidence of chlamydia or syphilis (or both) and whether the meningococcal group B vaccine (4CMenB) could reduce the incidence of gonorrhoea in this population. ANRS 174 DOXYVAC is a multicentre, open-label, randomised trial with a 2 × 2 factorial design conducted at ten hospital sites in Paris, France. Eligible participants were MSM aged 18 years or older, HIV negative, had a history of bacterial STIs within the 12 months before enrolment, and who were already included in the ANRS PREVENIR study (a cohort of MSM using pre-exposure prophylaxis with tenofovir and emtricitabine for HIV prevention). Participants were randomly assigned (2:1) to doxycycline PEP (two pills of 100 mg each orally within 72 h after condomless sex, with no more than three doses of 200 mg per week) or no PEP groups and were also randomly assigned (1:1) to the 4CMenB vaccine (GlaxoSmithKline, Paris, France; two intramuscular injections at enrolment and at 2 months) or no vaccine groups, using a computer-generated randomisation list with a permuted fixed block size of four. Follow-up occurred for at least 12 months (with visits every 3 months) up to 24 months. The coprimary outcomes were the risk of a first episode of chlamydia or syphilis (or both) after the enrolment visit at baseline for the doxycycline intervention and the risk of a first episode of gonorrhoea starting at month 3 (ie, 1 month after the second vaccine dose) for the vaccine intervention, analysed in the modified intention-to-treat population (defined as all randomly assigned participants who had at least one follow-up visit). This trial is registered with ClinicalTrials.gov, NCT04597424 (ongoing). Between Jan 19, 2021, and Sept 19, 2022, 556 participants were randomly assigned. 545 (98%) participants were included in the modified intention-to-treat analysis for the doxycycline PEP and no PEP groups and 544 (98%) were included for the 4CMenB vaccine and no vaccine groups. The median follow-up was 14 months (IQR 9–18). The median age was 40 years (34–48) and all 545 participants were male. There was no interaction between the two interventions (p≥0·1) for the primary outcome. The incidence of a first episode of chlamydia or syphilis (or both) was 8·8 per 100 person-years (35 events in 362 participants) in the doxycycline PEP group and 53·2 per 100 person-years (80 events in 183 participants) in the no PEP group (adjusted hazard ratio [aHR] 0·17 [95% CI 0·12–0·26]; p<0·0001). The incidence of a first episode of gonorrhoea, starting from month 3 was 58·3 per 100 person-years (103 events in 274 participants) in the 4CmenB vaccine group and 77·1 per 100 person-years (122 events in 270 participants) in the no vaccine group (aHR 0·78 [95% CI 0·60–1·01]; p=0·061). There were no deaths during the study. One drug-related serious adverse event (fixed-drug eruption) occurred in the doxycycline PEP group. Six (2%) participants in the doxycycline group discontinued doxycycline PEP because of gastrointestinal adverse events. Doxycycline PEP strongly reduced the incidence of chlamydia and syphilis in MSM, but we did not show efficacy of the 4CmenB vaccine for gonorrhoea. Doxycycline PEP should be assessed in other populations, such as heterosexual men and women, and its effect on antimicrobial resistance carefully monitored. ANRS Maladies Infectieuses Emergentes. For the French translation of the abstract see Supplementary Materials section.

Rabies is a neglected zoonotic disease with a global burden of approximately 59,000 human deaths a year. Once clinical symptoms appear, rabies is almost invariably fatal; however, with timely and appropriate post-exposure prophylaxis (PEP) consisting of wound washing, vaccine, and in some cases rabies immunoglobulin (RIG), the disease is almost entirely preventable. Access to PEP is limited in many countries, and when available, is often very expensive. We distributed a standardized assessment tool electronically to a convenience sample of 25 low- and middle-income countries in Asia and Africa to collect information on rabies PEP procurement, forecasting, distribution, monitoring and reporting. Information was collected from national rabies focal points, focal points at the World Health Organization (WHO) country offices, and others involved in procurement, logistics and distribution of PEP. Because RIG was limited in availability or unavailable in many countries, the assessment focused on vaccine. Data were collected between January 2017 and May 2018. We received responses from key informants in 23 countries: 11 countries in Asia and 12 countries in Africa. In 9 of 23 (39%) countries, rabies vaccine was provided for free in the public sector and was consistently available. In 10 (43%) countries, all or some patients were required to pay for the vaccine in the public sector, with the cost of a single dose ranging from US$ 6.60 to US$ 20/dose. The primary reason for the high cost of the vaccine for patients was a lack of funding at the central level to subsidize vaccine costs. In the remaining 4 (17%) countries, vaccine was provided for free but was often unavailable so patients were required to purchase it instead. The majority of countries used the intramuscular route for vaccine administration and only 5 countries exclusively used the dose-sparing intradermal (ID) route. Half (11/22; 50%) of all countries assessed had a standardized distribution system for PEP, separate from the systems used for routine childhood vaccines, and almost half used separate storage facilities at both central and health facility levels. Approximately half (9/22; 41%) of all countries assessed reported having regular weekly, monthly or quarterly reporting on rabies vaccination. While all countries in our assessment had rabies vaccines available in the public sector to some extent, barriers to access include the high cost of the vaccine to the government as well as to patients. Countries should be encouraged to use ID administration as this would provide access to rabies vaccine for many more people with the same number of vaccine vials. In addition, standardized monitoring and reporting of vaccine utilization should be encouraged, in order to improve data on PEP needs.

Introduction Post‐exposure prophylaxis (PEP) remains underutilized despite being the only prevention option currently available that covers risk after an exposure. We sought to evaluate uptake and patterns of use of PEP among men and women in rural Uganda and Kenya. Methods We analysed PEP uptake from three randomized trials enrolling persons aged ≥15 years with HIV risk from antenatal clinics, outpatient departments and community settings from April through August 2021 (NCT04810650). In each trial, participants were randomized to a person‐centred, dynamic choice HIV prevention (DCP) model or standard‐of‐care (SoC) arm. DCP offered choice of biomedical product (oral pre‐exposure prophylaxis [PrEP] or PEP) with an option to switch over time; service location (clinic vs. out‐of‐clinic); testing option (rapid blood‐based test or oral HIV self‐test). The SoC offered HIV prevention services as per in‐country guidelines. In both arms, PEP comprised a 28‐day oral Tenofovir/Lamivudine/Dolutegravir course with HIV testing at start and end of the 28‐day period. We described patterns of and predictors of self‐reported PEP use over the 12 months of follow‐up. Results A total of 1232 participants were enrolled, balanced by arm and country. Of the 1147 (93%) who completed at least one survey on self‐reported use of biomedical prevention, the median follow‐up time was 12 months [IQR: 11, 12]. Overall, a total of 104 courses of PEP were dispensed to 59 participants. PEP use was significantly higher among persons enrolled in the DCP arm (relative risk [RR] = 3.30; 95% CI: 1.58−6.91), from Uganda (RR = 3.17; 95% CI: 1.53−6.59), reporting alcohol use (RR = 2.20; 95% CI: 1.30−3.72) and men (RR = 2.08; 95% CI: 1.11−3.91). Of the 59 PEP users, 14 (24%) transitioned to PrEP and 28(47%) used PEP on more than one occasion. Multiple uses of PEP were more common among persons from Uganda versus Kenya (RR = 4.43; 95% CI: 1.10−17.80) and persons enrolled from the community (RR = 4.45; 95% CI: 1.89−10.45) versus clinic. There were no seroconversions reported among PEP users. No serious adverse events were reported. Conclusions PEP reaches groups such as men and those who use alcohol who are more likely to benefit from this short‐term prevention modality than PrEP. There is a need to make PEP accessible within a context of person‐centred delivery to optimize its benefits.

Tens of thousands of people die from dog-mediated rabies annually. Deaths can be prevented through post-exposure prophylaxis for people who have been bitten, and the disease eliminated through dog vaccination. Current post-exposure prophylaxis use saves many lives, but availability remains poor in many rabies-endemic countries due to high costs, poor access, and supply. We developed epidemiological and economic models to investigate the effect of an investment in post-exposure prophylaxis by Gavi, the Vaccine Alliance. We modelled post-exposure prophylaxis use according to the status quo, with improved access using WHO-recommended intradermal vaccination, with and without rabies immunoglobulin, and with and without dog vaccination. We took the health provider perspective, including only direct costs. We predict more than 1 million deaths will occur in the 67 rabies-endemic countries considered from 2020 to 2035, under the status quo. Current post-exposure prophylaxis use prevents approximately 56 000 deaths annually. Expanded access to, and free provision of, post-exposure prophylaxis would prevent an additional 489 000 deaths between 2020 and 2035. Under this switch to efficient intradermal post-exposure prophylaxis regimens, total projected vaccine needs remain similar (about 73 million vials) yet 17·4 million more people are vaccinated, making this an extremely cost-effective method, with costs of US$635 per death averted and $33 per disability-adjusted life-years averted. Scaling up dog vaccination programmes could eliminate dog-mediated rabies over this time period; improved post-exposure prophylaxis access remains cost-effective under this scenario, especially in combination with patient risk assessments to reduce unnecessary post-exposure prophylaxis use. Investing in post-exposure vaccines would be an extremely cost-effective intervention that could substantially reduce disease burden and catalyse dog vaccination efforts to eliminate dog-mediated rabies. World Health Organization.

IntroductionDoxycycline postexposure prophylaxis (doxy-PEP) can prevent sexually transmitted infections (STIs) among men who have sex with men (MSM) and transgender women (TGW). STI rates are high among MSM and TGW in China, and implementation strategies are needed to optimise doxy-PEP services. Pay-it-forward and social network distribution approaches may increase uptake of STI services and could increase the uptake of doxy-PEP. We present the protocol for a randomised controlled trial evaluating the effectiveness of pay-it-forward strategies with and without adjunctive social network distribution among MSM and TGW in China.Methods and analysisA total of 399 MSM and TGW will be recruited at seven sites in China and randomly allocated in a 1:1:1 ratio to (1) self-pay, (2) pay-it-forward alone or (3) pay-it-forward with adjunctive social network distribution of doxy-PEP. Participants assigned to the self-pay arm can purchase a doxy-PEP packet out-of-pocket. Participants in the pay-it-forward arm will be offered a free doxy-PEP packet and the opportunity to donate to support doxy-PEP for future participants. Participants in the pay-it-forward arm with social network distribution will receive the pay-it-forward intervention as well as additional free doxy-PEP packets to distribute to peers. Those randomised to the self-pay and the pay-it-forward with social network distribution arms (ie, index participants) will receive and distribute referral cards to recruit additional peers (ie, alter participants). Alter participants recruited through the control arm will be referred to the clinic to purchase doxy-PEP. Alter participants recruited through the pay-it-forward with adjunctive social network distribution arm will receive doxy-PEP directly from referring index participants. Both index and alter participants in each arm will be asked to complete a follow-up survey 3 and 6 months after enrolment. The primary outcome will be the proportion of participants who report using doxy-PEP within 72-hours of condomless anal or oral sex on one or more occasions during follow-up.Ethics and disseminationEthical approval was obtained from the ethics review committee of the Dermatology Hospital of Southern Medical University (Approval number: 2023109). The findings will be disseminated in peer-reviewed publications.Trial registration numberThe study has been registered with the Chinese Clinical Trial Registry (trial ID ChiCTR2300074903). Date of registration: 18 August 2023.

Doxycycline post-exposure prophylaxis (doxy-PEP) reduces bacterial sexually transmitted infections among men who have sex with men and transgender women. Although poised for widespread clinical implementation, the impact of doxy-PEP on antimicrobial resistance remains a primary concern as its effects on the gut microbiome and resistome, or the antimicrobial resistance genes (ARGs) present in the gut microbiome, are unknown. To investigate these effects, we studied participants from the DoxyPEP trial, a randomized clinical trial comparing doxy-PEP use, a one-time doxycycline 200-mg dose taken after condomless sex (DP arm, n  = 100), to standard of care (SOC arm, n  = 50) among men who have sex with men and transgender women. From self-collected rectal swabs at enrollment (day-0) and after 6 months (month-6), we performed metagenomic DNA sequencing (DNA-seq) or metatranscriptomic RNA sequencing (RNA-seq). DNA-seq data were analyzable from 127 samples derived from 89 participants, and RNA-seq data were analyzable from 86 samples derived from 70 participants. We compared the bacterial microbiome and resistome between the two study arms and over time. The median number of doxycycline doses taken since enrollment by participants with DNA-seq data was zero (interquartile range (IQR): 0–7 doses) for the SOC arm and 42 (IQR: 27–64 doses) for the DP arm. Tetracycline ARGs were detected in all day-0 DNA-seq samples and in 85% of day-0 RNA-seq samples. The proportional mass of tetracycline ARGs in the resistome increased between day-0 and month-6 in DP participants from 46% to 51% in the metagenome ( P  = 2.3 × 10 −2 ) and from 4% to 15% in the metatranscriptome ( P  = 4.5 × 10 −6 ), but no statistically significant increases in other ARG classes were observed. Exposure to a higher number of doxycycline doses correlated with proportional enrichment of tetracycline ARGs in the metagenome (Spearman’s ρ  = 0.23, P  = 9.0 × 10 −3 ) and metatranscriptome (Spearman’s ρ  = 0.55, P  = 3.7 × 10 −8 ). Bacterial microbiome alpha diversity, beta diversity and total bacterial mass did not differ between day-0 and month-6 samples from DP participants when assessed by either DNA-seq or RNA-seq. In an abundance-based correlation analysis, we observed an increase over time in the strength of the correlation between tetracycline ARGs and specific bacterial taxa, including some common human pathogens. In sum, doxy-PEP use over a 6-month period was associated with an increase in the proportion of tetracycline ARGs comprising the gut resistome and an increase in the expression of tetracycline ARGs. At 6 months of doxy-PEP use, no residual differences were observed in alpha and beta diversity or taxonomic composition of the gut microbiome. As doxy-PEP is implemented as a public health strategy, further studies and population-level surveillance of doxycycline-resistant pathogens are needed to understand the implications of these findings. ClinicalTrials.gov registration number: NCT03980223 . In participants from a randomized controlled trial, doxy-PEP use over 6 months minimally affected the gut microbiome’s taxonomic composition but increased the abundance and active expression of tetracycline antibiotic resistance genes.

There are approximately 35,000 human deaths from rabies in Asia annually. Rabies can be prevented through timely post-exposure prophylaxis (PEP) consisting of wound washing, rabies vaccine, and in some cases, rabies immunoglobulin (RIG). However, access to rabies PEP often remains limited to urban areas and is cost-prohibitive. There is little information on procurement, distribution, monitoring, and reporting of rabies PEP. We interviewed key informants in the public sector from various levels in Bangladesh, Bhutan, Cambodia, and Sri Lanka between March 2017 and May 2018 using a descriptive assessment tool to obtain information on procurement, distribution, monitoring, and reporting of rabies PEP. These four countries in Asia were chosen to showcase a range of rabies PEP systems. National rabies focal points were interviewed in each country and focal points helped identify additional key informants at lower levels. A total of 22 key informants were interviewed at various levels (central level to health facility level) including national rabies focal points in each country. Each country has a unique system for managing rabies PEP procurement, distribution, monitoring, and reporting. There are varying levels of PEP access for those with potential rabies exposures. Rabies PEP is available in select health facilities throughout the country in Bangladesh, Bhutan, and Sri Lanka. In Cambodia, rabies PEP is limited to two urban centers. The availability of RIG in all four countries is limited. In these four countries, most aspects of the rabies PEP distribution system operate independently of systems for other vaccines. However, in Bhutan, rabies PEP and Expanded Programme on Immunization (EPI) vaccines share cold chain space in some locations at the lowest level. All countries have a monitoring system in place, but there is limited reporting of data, particularly to the central level. Systems to procure, deliver, monitor, and report on rabies PEP are variable across countries. Sharing information on practices more widely among countries can help programs to increase access to this life-saving treatment.

•Prompt post-exposure vaccination is extremely effective in preventing human rabies.•Intradermal post-exposure vaccination is easily adopted by health workers in Tanzania.•High costs of PEP to government affect the supply chain and limit its availability.•Limited PEP supply results in higher out-of-pocket payments and increased risks.•Investment to facilitate free PEP provision would reduce rabies deaths. Rabies is preventable through prompt administration of post-exposure prophylaxis (PEP) to exposed persons, but PEP access is limited in many rabies-endemic countries. We investigated how access to PEP can be improved to better prevent human rabies. Using data from different settings in Tanzania, including contact tracing (2,367 probable rabies exposures identified) and large-scale mobile phone-based surveillance (24,999 patient records), we estimated the incidence of rabies exposures and bite-injuries, and examined health seeking and health outcomes in relation to PEP access. We used surveys and qualitative interviews with stakeholders within the health system to further characterise PEP supply and triangulate these findings. Incidence of bite-injury patients was related to dog population sizes, with higher incidence in districts with lower human:dog ratios and urban centres. A substantial percentage (25%) of probable rabies exposures did not seek care due to costs and limited appreciation of risk. Upon seeking care a further 15% of probable rabies exposed persons did not obtain PEP due to shortages, cost barriers or misadvice. Of those that initiated PEP, 46% did not complete the course. If no PEP was administered, the risk of developing rabies following a probable rabies exposure was high (0.165), with bites to the head carrying most risk. Decentralized and free PEP increased the probability that patients received PEP and reduced delays in initiating PEP. No major difficulties were encountered by health workers whilst switching to dose-sparing ID administration of PEP. Health infrastructure also includes sufficient cold chain capacity to support improved PEP provision. However, high costs to governments and patients currently limits the supply chain and PEP access. The cost barrier was exacerbated by decentralization of budgets, with priority given to purchase of cheaper medicines for other conditions. Reactive procurement resulted in limited and unresponsive PEP supply, increasing costs and risks to bite victims. PEP access could be improved and rabies deaths reduced through ring-fenced procurement, switching to dose-sparing ID regimens and free provision of PEP.

Introduction Knowledge of HIV status relies on accurate HIV testing, and is the first step towards access to HIV treatment and prevention programmes. Globally, HIV‐status unawareness represents a significant challenge for achieving zero new HIV infections and deaths. In order to enhance knowledge of HIV status, the World Health Organisation (WHO) recommends a testing strategy that includes the use of HIV‐specific antibody point‐of‐care tests (POCT). These POCTs do not detect acute HIV infection, the stage of disease when viral load is highest but HIV antibodies are undetectable. Complicating things further, in the presence of antiretroviral therapy (ART) for pre‐exposure prophylaxis (PrEP) or post‐exposure prophylaxis (PEP), other currently available testing technologies, such as viral load detection for diagnosis of acute HIV infection, may yield false‐negative results. In this scoping review, we evaluate the evidence and discuss alternative HIV testing algorithms that may mitigate diagnostic dilemmas in the setting of increased utilization of ART for immediate treatment and prevention of HIV infection. Discussion Missed acute HIV infection prevents people living with HIV (PLHIV) from accessing early treatment, increases likelihood of onward transmission, and allows for inappropriate initiation or continuation of PrEP, which may result in HIV drug resistance. While immediate ART is recommended for all PLHIV, studies have shown that starting ART in the setting of acute HIV infection may result in a delayed or complete absence of development of HIV‐specific antibodies, posing a diagnostic challenge that is particularly pertinent to resource‐limited, high HIV burden settings where HIV‐antibody POCTs are standard of care. Similarly, ART used as PrEP or PEP may supress HIV RNA viral load, complicating current HIV testing algorithms in resource‐wealthy settings where viral detection is included. As rollout of PrEP continues, HIV testing algorithms may need to be modified. Conclusions With increasing use of PrEP and ART in acute infection we anticipate diagnostic challenges using currently available HIV testing strategies. Research and surveillance are needed to determine the most appropriate assays and optimal testing algorithms that are accurate, affordable and sustainable.

ObjectivesWe 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).MethodsCross-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.Results875 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%.ConclusionsApproximately 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.