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Objective: Adoption of pre-exposure prophylaxis (PrEP) to prevent HIV infection has been slow. The purpose of this study was to evaluate knowledge, attitudes and referral practices for PrEP among non-prescribing providers, who may play key role. Methods: We performed a cross-sectional survey on PrEP knowledge, attitudes, and referral practices among 66 non-prescribing HIV prevention providers (1st August to 31st December, 2016), in Philadelphia, followed by qualitative interviews with 12 of them (5th April to 10th May, 2017). Results: Participants had a mean age of 36 years, with 62% females. Majority were HIV case managers and rapid testers. For half of the respondents, PrEP eligibility screening was part of rapid HIV testing at their organization, 40% never had PrEP training and only 27% indicated personally screening clients for eligibility. Qualitative data revealed that participants held positive attitudes about PrEP and perceived organizational support, but had concerns about potential negative impacts and barriers to routine HIV screening. Conclusion: Results highlight the importance of training non-prescribing HIV prevention providers about PrEP, addressing their concerns, and incorporating PrEP screening and referral into routine HIV testing. [ABSTRACT FROM AUTHOR]

High HIV incidence rates have been observed among pregnant and breastfeeding women in sub-Saharan Africa. Oral pre-exposure prophylaxis (PrEP) can effectively reduce HIV acquisition in women during these periods; however, understanding of its acceptability and feasibility in antenatal and postpartum populations remains limited. To address this gap, we conducted in-depth interviews with 90 study participants in Malawi and Zambia: 39 HIV-negative pregnant/breastfeeding women, 14 male partners, 19 healthcare workers, and 18 policymakers. Inductive and deductive approaches were used to identify themes related to PrEP. As a public health intervention, PrEP was not well-known among patients and healthcare workers; however, when it was described to participants, most expressed positive views. Concerns about safety and adherence were raised, highlighting two critical areas for community outreach. The feasibility of introducing PrEP into antenatal services was also a concern, especially if introduced within already strained health systems. Support for PrEP varied among policymakers in Malawi and Zambia, reflecting the ongoing policy discussions in their respective countries. Implementing PrEP during the pregnancy and breastfeeding periods will require addressing barriers at the individual, facility, and policy levels. Multi- level approaches should be considered in the design of new PrEP programs for antenatal and postpartum populations. [ABSTRACT FROM AUTHOR]

Objective: We assessed the impact of intravenous (IV) infusion versus intramuscular (IM) oxytocin on postpartum blood loss and rates of postpartum hemorrhage (PPH) when administered during the third stage of labor. While oxytocin is recommended for prevention of PPH, few double-blind studies have compared outcomes by routes of administration. Methods: A double-blind, placebo-controlled randomized trial was conducted at a hospital in Argentina. Participants were assigned to receive 10 IU oxytocin via IV infusion or IM injection and a matching saline ampoule for the other route after vaginal birth. Blood loss was measured using a calibrated receptacle for a 1-hour minimum. Shock index (SI) was also calculated, based on vital signs measurements, and additional interventions were recorded. Primary outcomes included: the frequency of blood loss ≥500ml and mean blood loss. Results: 239 (IV infusion) and 241 (IM) women were enrolled with comparable baseline characteristics. Mean blood loss was 43ml less in the IV infusion group (p = 0.161). Rates of blood loss ≥500ml were similar (IV infusion = 21%; IM = 24%, p = 0.362). Women in the IV infusion group received significantly fewer additional uterotonics (5%), than women in the IM group (12%, p = 0.007). Women with PPH in the IM group experienced a larger increase in SI after delivery, which may have influenced recourse to additional interventions. Conclusions: The route of oxytocin administration for PPH prevention did not significantly impact measured blood loss after vaginal birth. However, differences were observed in recourse to additional uterotonics, favoring IV infusion over IM. In settings where IV lines are routinely placed, oxytocin infusion may be preferable to IM injection. [ABSTRACT FROM AUTHOR]

Adoptive T cell therapy (ACT) has become a treatment option for viral reactivations in patients undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT). Animal models have shown that pathogen-specific central memory T cells (TCM) are protective even at low numbers and show long-term survival, extensive proliferation and high plasticity after adoptive transfer. Concomitantly, our own recent clinical data demonstrate that minimal doses of purified (not in-vitro- expanded) human CMV epitope-specific T cells can be sufficient to clear viremia. However, it remains to be determined if human virus-specific TCM show the same promising features for ACT as their murine counterparts. Using a peptide specific proliferation assay (PSPA) we studied the human Adenovirus- (AdV), Cytomegalovirus- (CMV) and Epstein-Barr virus- (EBV) specific TCM repertoires and determined their functional and proliferative capacities in vitro. TCM products were generated from buffy coats, as well as from non-mobilized and mobilized apheresis products either by flow cytometry-based cell sorting or magnetic cell enrichment using reversible Fab-Streptamers. Adjusted to virus serology and human leukocyte antigen (HLA)-typing, donor samples were analyzed with MHC multimer- and intracellular cytokine staining (ICS) before and after PSPA. TCM cultures showed strong proliferation of a plethora of functional virus-specific T cells. Using PSPA, we could unveil tiniest virus epitope-specific TCM populations, which had remained undetectable in conventional ex-vivo-staining. Furthermore, we could confirm these characteristics for mobilized apheresis- and GMP-grade Fab-Streptamer-purified TCM products. Consequently, we conclude that TCM bare high potential for prophylactic low-dose ACT. In addition, use of Fab-Streptamer-purified TCM allows circumventing regulatory restrictions typically found in conventional ACT product generation. These GMP-compatible TCM can now be used as a broad-spectrum antiviral T cell prophylaxis in alloHSCT patients and PSPA is going to be an indispensable tool for advanced TCM characterization during concomitant immune monitoring. [ABSTRACT FROM AUTHOR]

The World Health Organization, the World Organization for Animal Health, and the Food and Agriculture Organization have resolved to eliminate human rabies deaths due to dog bites by 2030, and the Vaccine Alliance (Gavi) has added human rabies vaccines to their investments for 2021–2025. Implementing these goals cost-effectively and sustainably requires understanding the complex connections between dog rabies vaccination and human risk and response. The objective of this paper is to estimate how dog rabies vaccinations affect human rabies deaths, mediated through dog rabies cases, dog bite reporting, and post-exposure human rabies vaccination. To approach this objective, we apply multivariate regression analysis over five rabies-related outcomes: (a) dog vaccinations, (b) dog rabies cases, (c) reported human exposures, (d) human post-exposure prophylaxis (PEP) use, and (e) human rabies cases. Analysis uses aggregate annual data over 1995–2005 for seven Latin American countries that experienced dramatic declines in canine and human rabies. Among other results, we estimate the following. (i) A 10% increase in dog vaccinations decreases dog rabies cases by 2.3%. (ii) Reported exposures decline as concurrent dog rabies cases decline, but these declines are more than offset by increases in reported exposures per dog rabies case, which may result from higher rabies awareness due to anti-rabies campaigns. (iii) A 10% increase in PEP use decreases human deaths by 7%, but a 10% increase in dog vaccination induces a 2.8% decrease in PEP use. The net effect is that a 10% increase in dog vaccination reduces human deaths by 12.4% overall, although marginal effectiveness declines as dog rabies incidence declines. (iv) Increases in income and public health expenditures increase PEP demand. The findings highlight the importance of mass dog vaccination, heightened awareness, treatment access, and clinical algorithms to reduce both false negatives leading to death and false positives leading to costly unnecessary PEP prescriptions. [ABSTRACT FROM AUTHOR]

In pediatric burns the use of systemic antibiotic prophylaxis is a standard procedure in some burn centers, though its beneficial effect on the infectious complications is debated. The present meta-analysis aimed at determining whether systemic antibiotic prophylaxis prevents infectious complications in pediatric patients with burn injuries. We searched the PubMed, EMBASE, and Cochrane Library databases from inception to August 2019. We included 6 studies, in which event rates of infectious complications were reported in children with burn injuries receiving or not receiving systemic antibiotic prophylaxis. We found that the overall odds ratio (OR) of developing an infection (including local and systemic) was not different between the groups (OR = 1.35; 95% CI, 0.44, 4.18). The chances for systemic infectious complications alone were also not different between antibiotic-treated and non-treated patients (OR = 0.74; 95% CI, 0.38, 1.45). Based on the age, affected total body surface area, and country income level, we did not find any subgroup that benefited from the prophylaxis. Our findings provide quantitative evidence for the inefficacy of systemic antibiotic prophylaxis in preventing infections in pediatric burns. To validate our conclusion, multinational, randomized trials in a diverse population of children with burn injuries are warranted. [ABSTRACT FROM AUTHOR]

Introduction: Developing guidelines to inform the use of antiretroviral pre-exposure prophylaxis (PrEP) for HIV prevention in resource-limited settings must necessarily be informed by considering the resources and infrastructure needed for PrEP delivery. We describe an approach that identifies subpopulations of cisgender men who have sex with men (MSM) and transgender women (TGW) to prioritize for the rollout of PrEP in resource-limited settings. Methods: We use data from the iPrEx study, a multi-national phase III study of PrEP for HIV prevention in MSM/TGW, to build statistical models that identify subpopulations at high risk of HIV acquisition without PrEP, and with high expected PrEP benefit. We then evaluate empirically the population impact of policies recommending PrEP to these subpopulations, and contrast these with existing policies. Results: A policy recommending PrEP to a high risk subpopulation of MSM/TGW reporting condomless receptive anal intercourse over the last 3 months (estimated 3.3% 1-year HIV incidence) yields an estimated 1.95% absolute reduction in 1-year HIV incidence at the population level, and 3.83% reduction over 2 years. Importantly, such a policy requires rolling PrEP out to just 59.7% of MSM/TGW in the iPrEx population. We find that this policy is identical to that which prioritizes MSM/TGW with high expected PrEP benefit. It is estimated to achieve nearly the same reduction in HIV incidence as the PrEP guideline put forth by the US Centers for Disease Control, which relies on the measurement of more behavioral risk factors and which would recommend PrEP to a larger subset of the MSM/TGW population (86% vs. 60%). Conclusions: These findings may be used to focus future mathematical modelling studies of PrEP in resource-limited settings on prioritizing PrEP for high-risk subpopulations of MSM/TGW. The statistical approach we took could be employed to develop PrEP policies for other at-risk populations and resource-limited settings. [ABSTRACT FROM AUTHOR]

Background: In Peru, there is an ongoing high-incidence HIV epidemic among men who have sex with men (MSM) and transgender women (TW). Sexual concurrency, or having sex with a partner in between two acts of sex with another partner, may be a key factor in onward HIV transmission. In this study, we quantify concurrency, evaluate factors associated with concurrency, and assess condom use with concurrent partners among MSM and TW in Peru. Methods: We conducted a secondary analysis of data from the 2011 Peruvian Biobehavioral Survey. Pearson’s Chi-squared test was used to identify individual-level characteristics associated with concurrency. We estimated the association between participant characteristics, concurrent partnerships, partnership type (stable vs. non-stable), and CLAI within the context of concurrent partnerships using multivariate and repeated-measure Poisson regression. Results: 3-month cumulative prevalence of concurrency was higher among TW compared to MSM (30.7% vs 25.2%, p = 0.014). Among those with concurrent stable and non-stable partners, 45% used condoms with both partners (95% CI: 40%-50%) and 30% preferentially had CLAI with the stable partner only (95%CI: 26%-35%). Factors associated with CLAI within the context of concurrent partnerships varied between MSM and TW. Conclusions: Although concurrency is common among TW and MSM in Peru, patterns of concurrency and differential condom use may vary between TW and MSM. Future research may explore differential condom use with stable and non-stable partners to better understand behavioral factors that may alter vulnerability to HIV in TW compared to MSM. [ABSTRACT FROM AUTHOR]

Background: Young women account for a disproportionate fraction of new HIV infections in Africa and are a priority population for HIV prevention, including implementation of preexposure prophylaxis (PrEP). The overarching goal of this project was to demonstrate the feasibility of integrating PrEP delivery within routine family planning (FP) clinics to serve as a platform to efficiently reach at-risk adolescent girls and young women (AGYW) for PrEP in HIV high-burden settings.Methods and Findings: The PrEP Implementation in Young Women and Adolescents (PrIYA) program is a real-world implementation program to demonstrate integration of PrEP delivery for at-risk AGYW in FP clinics in Kisumu, Kenya. Between November 2017 and June 2018, women aged 15 to 45 from the general population seeking FP services at 8 public health clinics were universally screened for HIV behavioral risk factors and offered PrEP following national PrEP guidelines. We evaluated PrEP uptake and continuation, and robust Poisson regression methods were used to identify correlates of uptake and early continuation of PrEP, with age included as a one-knot linear spline. Overall, 1,271 HIV-uninfected women accessing routine FP clinics were screened for PrEP; the median age was 25 years (interquartile range [IQR]: 22-29), 627 (49%) were <24 years old, 1,026 (82%) were married, more than one-third (34%) had partners of unknown HIV status, and the vast majority (n = 1,200 [94%]) reported recent condom-less sex. Of 1,271 women screened, 278 (22%) initiated PrEP, and 114 (41%) returned for at least one refill visit after initiation. PrEP uptake was independently associated with reported male-partner HIV status (HIV-positive 94%, unknown 35%, HIV-negative 8%; p < 0.001) and marital status (28% unmarried versus married 21%; p = 0.04), and a higher proportion of women ≥24 years (26%; 191/740) initiated PrEP compared to 16% (87/531) of young women <24 years (p < 0.001). There was a moderate and statistically non-significant unadjusted increase in PrEP uptake among women using oral contraception pills (OCPs) compared to women using injectable or long-acting reversible contraception methods (OCP 28% versus injectable/implants/intrauterine devices [IUDs] 18%; p = 0.06). Among women with at least one post-PrEP initiation follow-up visit (n = 278), no HIV infection was documented during the project period. Overall, continuation of PrEP use at 1, 3, and 6 months post initiation was 41%, 24%, and 15%, respectively. The likelihood for early continuation of PrEP use (i.e., return for at least one PrEP refill within 45 days post initiation) was strongly associated with reported male-partner HIV status (HIV-positive 67%, -negative 39%, unknown 31%; overall effect p = 0.001), and a higher proportion of women ≥24 years old continued PrEP at 1 month compared with young women <24 years old (47% versus 29%; p = 0.002). For women ≥24 years old, the likelihood to continue PrEP use at 1 month post initiation increased by 3% for each additional year of a woman's age (adjusted prevalence ratio [PR]: 1.03; 95% confidence interval [CI]: 1.01-1.05; p = 0.01). In contrast, for women <24 years old, the likelihood of continuing PrEP for each additional year of a woman's age was high in magnitude (approximately 6%) but statistically non-significant (adjusted PR: 1.06; 95% CI: 0.97-1.16; p = 0.18). Frequently reported reasons for discontinuing PrEP were low perceived risk of HIV (25%), knowledge that partner was HIV negative (24%), experiencing side effects (20%), and pill burden (17%). Study limitations include lack of qualitative work to provide insights into women's decision-making on PrEP uptake and continuation, the small number of measured covariates imposed by the program data, and a nonrandomized design limiting definitive ascertainment of the robustness of a PrEP-dedicated nurse-led implementation strategy.Conclusions: In this real-world PrEP implementation program in Kenya, integration of universal screening and counseling for PrEP in FP clinics was feasible, making this platform a potential "one-stop" location for FP and PrEP. There was a high drop-off in PrEP continuation, but a subset of women continued PrEP use at least through 1 month, possibly indicating further reflection or decision-making on PrEP use. Greater efforts to support PrEP normalization and persistence for African women are needed to help women navigate their decisions about HIV prevention preferences as their reproductive goals and HIV vulnerability evolve. [ABSTRACT FROM AUTHOR]

Vaccines remain one of the main tools to control infectious diseases in domestic livestock. Although a plethora of veterinary vaccines are on the market and routinely applied to protect animals against infection with particular pathogens, the disease in question often continues to persist, sometimes at high prevalence. The limited effectiveness of certain vaccines in the field leaves open questions regarding the required properties that an effective vaccine should have, as well as the most efficient vaccination strategy for achieving the intended goal of vaccination programmes. To date a systematic approach for studying the combined effects of different types of vaccines and vaccination strategies is lacking. In this paper, we develop a theoretical framework for modelling the epidemiological consequences of vaccination with imperfect vaccines of various types, administered using different strategies to herds with different replacement rates and heterogeneity in vaccine responsiveness. Applying the model to the Porcine Reproductive and Respiratory Syndrome (PRRS), which despite routine vaccination remains one of the most significant endemic swine diseases worldwide, we then examine the influence of these diverse factors alone and in combination, on within-herd virus transmission. We derive threshold conditions for preventing infection invasion in the case of imperfect vaccines inducing limited sterilizing immunity. The model developed in this study has practical implications for the development of vaccines and vaccination programmes in livestock populations not only for PRRS, but also for other viral infections primarily transmitted by direct contact. [ABSTRACT FROM AUTHOR]

Background: Given the slow uptake of PrEP among cisgender men who have sex with men (MSM) in high-income countries, efforts to roll-out PrEP in low- and middle-income countries (LMIC) should address barriers to PrEP use to facilitate its more rapid uptake. To inform PrEP programs in LMIC, we examined patterns of perceived barriers to PrEP use among HIV-negative MSM in Tijuana, Mexico. Methods: From 03/2016-09/2017, 364 MSM completed interviewer-administered surveys assessing perceived barriers to PrEP use across 4 domains: PrEP attribute, individual, interpersonal, and structural. Latent class analysis was performed to identify distinct classes with respect to perceived barriers to PrEP use. Multinomial logistic regression was used to identify factors associated with class membership. Results: We identified three classes characterized by (1) high levels of perceived barriers across domains (12%), (2) low levels of perceived barriers across domains (43%), and (3) perceived PrEP attribute barriers (i.e., side-effects and cost) (45%). Membership in the high level of perceived barriers class (vs. the low level of perceived barriers class) was positively associated with having a history of incarceration (AOR: 2.44; 95% CI: 1.04, 5.73) and negatively associated with more social support (AOR: 0.99; 95% CI: 0.98, 1.00). Membership in the perceived PrEP attribute barriers class was positively associated with having seen a healthcare provider in the past year (AOR: 2.78; 95% CI: 1.41, 5.45) and negatively associated with having any HIV-positive or status unknown partners (AOR: 0.56; 95% CI: 0.31, 1.01). Conclusions: Since most participants were in either the low level of perceived barriers class or the perceived PrEP attribute barriers class, future PrEP uptake may be high among MSM in Tijuana. However, these findings suggest that achieving sufficient PrEP uptake and adherence among MSM in Tijuana may require a range of comprehensive HIV prevention interventions. [ABSTRACT FROM AUTHOR]

Introduction: Efficacy of daily emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) for PrEP is strongly dependent on the adherence. We examined the concordance between indirect adherence measures and protective drug levels among participants retained through 48 weeks in the PrEP Brasil Study. Methods: PrEP Brasil was a prospective, multicenter, open-label demonstration project evaluating PrEP provision for men who have sex with men (MSM) and transgender women (TGW) at higher risk for HIV infection within the setting of Brazilian Public Health System. Three indirect adherence measures were obtained at week 48: medication possession ratio (MPR), pill count and self-report (30-days recall). Tenofovir diphosphate (TFV-DP) concentration in Dried Blood Spot (DBS) was measured at week 48. Areas under (AUC) the receiver operating characteristics (ROC) curve were used to evaluate the concordance between achieving protective drug levels (TFV-DP≥700fmol/punch) and the indirect adherence measures. Youden's index and distance to corner were used to determine the optimal cutoff points for each indirect adherence measure. We calculated sensitivity, specificity, negative (NPV) and positive (PPV) predictive values for the found cutoff points. Finally, Delong test was used to compare AUCs. Results and discussion: From April, 2014 to July, 2016, 450 participants initiated PrEP, 375(83.3%) were retained through 48 weeks. Of these, 74% (277/375) had TFV-DP ≥700fmol/punch. All adherence measures discriminated between participants with and without protective drug levels (AUC>0.5). High indirect adherence measure was predictive of protective drug levels (PPV>0.8) while low indirect adherence measure was not predictive of lack of protective drug levels (NPV<0.5). No significant differences were found between the adherence methods (p = 0.44). Conclusions: Low-burden measurements such as MPR and self-report can be used to predict PrEP adherence in a public health context in Brazil for MSM and TGW retained through 48 weeks. Clinical Trial Number: . [ABSTRACT FROM AUTHOR]

Background: Additional forms of pre-exposure prophylaxis are needed to prevent HIV-1 infection. 3BNC117 and 10–1074 are broadly neutralizing anti-HIV-1 antibodies that target non-overlapping epitopes on the HIV-1 envelope. We investigated the safety, tolerability, pharmacokinetics, and immunogenicity of the intravenous administration of the combination of 3BNC117 and 10–1074 in healthy adults. Methods: This randomized, double-blind, placebo-controlled, single center, phase 1 study enrolled healthy adults aged 18–65 years to receive one infusion of 3BNC117 immediately followed by 10–1074 at 10 mg/kg, three infusions of 3BNC117 followed by 10–1074 at 3 mg/kg or 10 mg/kg every 8 weeks, or placebo infusions. The primary outcomes were safety and pharmacokinetics. This trial is registered with ClinicalTrials.gov, number NCT02824536. Findings: Twenty-four participants were enrolled in a 3:1 ratio to receive the study products or placebo. The combination of 3BNC117 and 10–1074 was safe and generally well tolerated. There were no serious adverse events considered related to the infusions. The mean elimination half-lives of 3BNC117 and 10–1074 were 16.4 ± 4.6 days and 23.0 ± 5.4 days, respectively, similar to what was observed in previous studies in which each antibody was administered alone. Anti-drug antibody responses were rare and without evidence of related adverse events or impact on elimination kinetics. Interpretation: Single and repeated doses of the combination of 3BNC117 and 10–1074 were well tolerated in healthy adults. These data support the further development of the combination of 3BNC117 and 10–1074 as a long-acting injectable form of pre-exposure prophylaxis for the prevention of HIV-1 infection. [ABSTRACT FROM AUTHOR]

An effective surveillance system is critical for the elimination of canine rabies in Latin America. Brazil has made substantial progress towards canine rabies elimination, but outbreaks still occurred in the last decade in two states. Brazil uses a health information system (SINAN) to record patients seeking post-exposure prophylaxis (PEP) following contact with an animal suspected of having rabies. This study evaluated: (i) whether SINAN can be reliably used for rabies surveillance; (ii) if patients in Brazil are receiving appropriate PEP and (iii) the benefits of implementing the latest World Health Organization (WHO) recommendations on PEP. Analysing SINAN records from 2008 to 2017 reveals an average of 506,148 bite-injury patients/year [range: 437k -545k] in the country, equivalent to an incidence of 255 bite-injuries/100,000 people/year [range: 231–280]. The number of reports of bites from suspect rabid dogs generally increased over time. In most states, records from SINAN indicating a suspect rabid dog do not correlate with confirmed dog rabies cases reported to the Regional Information System for Epidemiological Surveillance of Rabies (SIRVERA) maintained by the Pan American Health Organization (PAHO). Analyses showed that in 2017, only 45% of patients received appropriate PEP as indicated by the Brazilian Ministry of Health guidance. Implementation of the latest WHO guidance using an abridged intradermal post-exposure vaccination regimen including one precautionary dose for dog bites prior to observation would reduce the volume of vaccine required by up to 64%, with potential for annual savings of over USD 6 million from reduced vaccine use. Our results highlight the need to improve the implementation of SINAN, including training of health workers responsible for delivering PEP using an Integrated Bite Case Management approach so that SINAN can serve as a reliable surveillance tool for canine rabies elimination. [ABSTRACT FROM AUTHOR]

Background: Antimicrobial resistance has become a global health emergency and is contributed to by inappropriate antibiotic use in community clinical settings. The aim of this study was to evaluate the antimicrobial use pattern in infants from birth until 18 months of age in Indonesia. Methods: A post-hoc analysis was conducted in 1621 participants from the RV3BB Phase IIb trial conducted in Indonesia from January 2013 through July 2016. Any health events were documented in the trial as adverse events. Concomitant medication surveillance recorded all medications, including antibiotics during the 18 months of follow-up. Information included the frequency, duration of usage, formulation, classes, and their indications, including prophylactic antibiotic and perinatal use. Results: Of 1621 participants, 551 (33.99%) received at least one antibiotic for treatment of infections during the 18 months observation period. Additionally, during the perinatal period, prophylactic antibiotics were used in 1244 (76.74%) participants and antibiotics consumed in 235 mothers of participants (14.50%). A total of 956 antibiotic consumptions were recorded for 18 months follow up, 67 (7.01%) as part of antimicrobial combinations. The average duration of antibiotic course was 4.92 days. Penicillin and sulfonamides were the most common antibiotic classes consumed (38.81% and 24.48%, respectively). Conclusions: Despite the low community consumption rate, the overuse of antibiotic in URTIs and non-bloody diarrhea in our setting represents a major opportunity for antimicrobial stewardship, particularly in early life. [ABSTRACT FROM AUTHOR]

Marleen Temmerman and colleagues describe a model of care for people who have experienced sexual violence, set in Kenya. [ABSTRACT FROM AUTHOR]

Background & aims: Bacterial infections, in particular a spontaneous bacterial peritonitis (SBP), are a major threat in patients with liver cirrhosis. Recently, it has been shown that the impact on mortality might be underestimated by established risk-scores. Onset of infection was suggested to define a distinct stage of cirrhosis. However, it remains unclear whether all stages of decompensated cirrhosis are equally affected. Moreover, if there is such a distinct stage, it must be determined whether it is reversible after the infection has resolved. In this study we aimed to further analyze the impact of a current as well as a resolved SBP in different stages of decompensated liver cirrhosis. Methods: A number of 579 patients with liver cirrhosis and ascites were included. MELD-score was used to determine the stage of liver disease. Low (<15), intermediate (15–25) and high (>25) MELD-groups were compared. Patients were followed up for 90 days. Primary endpoint was overall mortality. Statistical analyses were performed using the log-rank test, Cox regression and competing risk analysis. Results: Mortality was significantly higher in patients with nosocomial-acquired SBP (nSBP) compared to patients without SBP (p<0.001;HR = 2.05). However, the most prominent difference in mortality was documented in the intermediate MELD-group (nSBP: p = 0.02;HR = 2.10). Importantly, mortality in nSBP patients remained increased even after the initial nSBP episode had resolved (p<0.01;HR = 1.90). Again, this was only significant in those with intermediate MELD-scores (p = 0.02;HR = 2.28). While a current as well as a resolved nSBP were significantly linked to a higher mortality, neither of them did increase the likelihood for liver transplantation. Conclusions: Development of nSBP is independently associated with increased mortality supporting the concept of a distinct status of cirrhosis. Importantly, the prognosis remains unfavorable even after resolution of nSBP. This could be particularly relevant for patients with intermediate MELD-scores, who have limited chances for a donor liver. [ABSTRACT FROM AUTHOR]

Background: Infection in acute pancreatitis (AP) is associated with nutritional therapies including naso-gastric (NG), naso-jejunal (NJ), and total parenteral nutrition (TPN). To examine infections among NG, NJ, TPN, and no nutritional support (NNS) in treating patients with AP. Methods: The investigators completed comprehensive search in the Cochrane library, EMBASE, PubMed, Web of Science, and ClinicalTrials.gov without restriction on language and publication date before January 21, 2019. They also searched the reference lists of relevant studies for randomized controlled trials (RCTs) comparing NG, NJ, TPN, and NNS among patients with AP. Quantitative synthesis was conducted in a contrast-based network meta-analysis. To clarify effects, a network meta-analysis was conducted to calculate the surface under the cumulative ranking curve (SUCRA). Beside of overall infections, the event rates of infected pancreatic necrosis, bacteremia, line infection, pneumonia, urinary tract infection, and other types of infections were measured. Results: The network meta-analysis of 16 RCTs showed that NJ had significantly lower overall infection rates compared with TPN (risk ratio: 0.59; 95% confidence interval: 0.38, 0.90); and NG had a larger effect size and higher rank probability compared with NJ, TPN, and NNS (mean rank = 1.7; SUCRA = 75.8). TPN was the least preferred (mean rank = 3.2; SUCRA = 26.6). Conclusions: NG and NJ may be preferred therapies for treating patients with AP. Clinicians may consider NG as a first-line treatment for patients with AP (including severe AP) and even in patients receiving prophylactic antibiotics. In addition, we found that NNS should be avoided when treating patients with severe AP. [ABSTRACT FROM AUTHOR]

Introduction: Despite vaccination, there were more than 100,000 annual cases of varicella in the United States in 2013–2014. Individuals at highest risk of developing severe or complicated varicella include immunocompromised people, preterm infants, and pregnant women. Varicella zoster immune globulin (human) (VARIZIG) is recommended by the CDC for postexposure prophylaxis to prevent or attenuate varicella-zoster virus infection in high-risk individuals. Contemporary information on administration of VARIZIG is limited. Methods: This open-label, expanded-access program provided VARIZIG to physician-identified, high-risk participants exposed to varicella. Participants included immunocompromised children/adults, infants (preterm, newborns whose mothers had varicella onset within 5 days before or 2 days after delivery, and those aged <1 year), and pregnant women. VARIZIG (125 IU/10 kg [up to 625 IU]) was administered intramuscularly, ideally within 96 hours, but up to 10 days, postexposure. Incidence of varicella rash and severity (>100 pox, pneumonia, or encephalitis) were assessed up to 42 days after administration. Results: The varicella outcome population (n = 507) included 263 immunocompromised participants (32 adults, 231 children), 137 pregnant women, 105 infants, and 2 healthy adults with no history of varicella. Varicella incidence was 4.5% in immunocompromised participants, 7.3% in pregnant women, and 11.5% in infants. The incidence of varicella was similar when comparing VARIZIG administration ≤ 96 hours vs > 96 hours (up to 10 days) postexposure in the entire population (6.2% vs. 9.4%, respectively), and also in each subgroup. Of 34 participants with varicella, 5 developed > 100 pox and 1 developed pneumonia and encephalitis. There were no product-related deaths and only 1 serious adverse event (serum sickness) considered probably related to VARIZIG. Conclusion: Postexposure administration of VARIZIG was associated with low rates of varicella in high-risk participants, regardless of when administered within 10 days postexposure. VARIZIG was well-tolerated and safe in high-risk participants. [ABSTRACT FROM AUTHOR]

The objective of the study was to find out the prophylactic efficacy of Quercetin in ameliorating the hypoxia induced vascular leakage in lungs of rats. Male SD rats received different doses of quercetin @ 25mg, 50mg, 100mg and 200mg/Kg BW, 1h prior to hypobaric hypoxia exposure (7,620m, for 6h). Quercetin 50 mg/kg BW supplemented orally 1h prior to hypoxia exposure was considered to be the optimum dose, due to significant reduction (p<0.001) in lung water content and lung transvascular leakage compared to control (hypoxia, 6h). Further, biochemical analysis (ROS, MDA, GSH, GPx, LDH, and albumin) and differential expressions of proteins (IKK-α/β, NFĸB, Nrf-2,TNF-α, ICAM-1, VCAM, P-selectin, Hif-1α, VEGF, TNF-α, TGF-β, INF-γ and IL-4) were determined by western blotting and ELISA. Changes in lung parenchyma were assessed by histopathology. Quercetin (50 mg/kg BW) prophylaxis under hypoxia showed significant reduction in oxidative stress (ROS and MDA), concomitant increase in antioxidants (GSH, GPx and SOD) followed by decreased LDH and albumin extravasation in BAL fluid over hypoxia. Quercetin prophylaxis significantly down regulated hypoxia induced increase in IKKα/β and NFĸB expressions leading to reduction in the levels of pro-inflammatory cytokines (TNF-α and INF-γ) followed by up regulation of anti-inflammatory cytokines (IL-4 and INF-γ) in lungs. Further, hypoxia mediated increase in HIF-1α was stabilized and VEGF levels in lungs were significantly down regulated by quercetin supplementation, leading to reduction in vascular leakage in lungs of rats under hypoxia. However, Quercetin has also enacted as Nrf-2 activator which significantly boosted up the synthesis of GSH under hypoxic condition compared to hypoxia. Histopathological observations further confirmed that quercetin preconditioning has an inhibitory effect on progression of oxidative stress and inflammation via attenuation of NFκB and stabilization HIF-1α in lungs of rats under hypoxia.These studies indicated that quercetin prophylaxis abrogates the possibility of hypobaric hypoxia induced pulmonary edema in rats. [ABSTRACT FROM AUTHOR]

Background: Expanded HIV prevention options are needed to increase uptake of HIV prevention among women, especially in generalized epidemics. As the dapivirine vaginal ring moves forward through regulatory review and open-label extension studies, the potential public health impact and cost-effectiveness of this new prevention method are not fully known. We used mathematical modeling to explore the impact and cost-effectiveness of the ring in different implementation scenarios alongside scale-up of other HIV prevention interventions. Given the knowledge gaps about key factors influencing the ring’s implementation, including potential uptake and delivery costs, we engaged in a stakeholder consultation process to elicit plausible parameter ranges and explored scenarios to identify the possible range of impact, cost, and cost-effectiveness. Methods and findings: We used the Goals model to simulate scenarios of oral and ring pre-exposure prophylaxis (PrEP) implementation among female sex workers and among other women ≤21 years or >21 years with multiple male partners, in Kenya, South Africa, Uganda, and Zimbabwe. In these scenarios, we varied antiretroviral therapy (ART) coverage, dapivirine ring coverage and ring effectiveness (encompassing efficacy and adherence) by risk group. Following discussions with stakeholders, the maximum level of PrEP coverage (oral and/or ring) considered in each country was equal to modern contraception use minus condom use in the two age groups. We assessed results for 18 years, from 2018 to 2035. In South Africa, for example, the HIV infections averted by PrEP (ring plus oral PrEP) ranged from 310,000 under the highest-impact scenario (including ART held constant at 2017 levels, high ring coverage, and 85% ring effectiveness) to 55,000 under the lowest-impact scenario (including ART reaching the UNAIDS 90-90-90 targets by 2020, low ring coverage, and 30% ring effectiveness). This represented a range of 6.4% to 2.2% of new HIV infections averted. Given our assumptions, the addition of the ring results in 11% to 132% more impact than oral PrEP alone. The cost per HIV infection averted for the ring ranged from US$13,000 to US$121,000. Conclusions: This analysis offers a wide range of scenarios given the considerable uncertainty over ring uptake, consistency of use, and effectiveness, as well as HIV testing, prevention, and treatment use over the next two decades. This could help inform donors and implementers as they decide where to allocate resources in order to maximize the impact of the dapivirine ring in light of funding and implementation constraints. Better understanding of the cost and potential uptake of the intervention would improve our ability to estimate its cost-effectiveness and assess where it can have the most impact. [ABSTRACT FROM AUTHOR]

Introduction: ARV-based pre-exposure prophylaxis (PrEP) has the potential to avert many new HIV infections, yet little is known about how to reach women at high risk for HIV infection and motivate them to initiate PrEP. Clinical trials have succeeded in recruiting at-risk participants, evidenced by control arm HIV incidence ≥3% (defined by the World Health Organization as “substantial risk”). We examined experiences from HIV prevention trials to document recruitment strategies and identify practical, potentially effective strategies for reaching women in real-world PrEP delivery. Methods: We conducted semi-structured qualitative phone interviews with 31 staff from five countries who had worked on one or more of seven ARV-based HIV prevention clinical trials. Questions explored recruitment strategies used to reach women at risk of HIV and to successfully communicate about PrEP (inclusive of oral and vaginal formulations). We structurally coded data in NVivo and analyzed codes to derive themes. We conducted results interpretation webinars with research and programmatic stakeholders to validate findings and develop recommendations. Results: Clinical trial researchers employed a range of recruitment strategies to recruit at-risk women. They recommended engaging the local community and potential PrEP users via community events, meetings with gatekeepers, and use of community advisory boards; and they encouraged interpersonal communication like presentations in waiting rooms and door-to-door recruitment to address personal concerns and prevent misinformation. Participants also stressed the importance of addressing the challenges that already exist within the health system to create a more enabling environment and delivering positive messages through a variety of communication channels to normalize PrEP. Conclusions: Findings from this study provide important insights into potentially effective ways for countries currently rolling out oral PrEP to reach at-risk women with information about PrEP and promote uptake. [ABSTRACT FROM AUTHOR]

Introduction: Our objective was to assess whether clusters of centers with similar peritoneal dialysis (PD) catheter related practices were associated with differences in the risk of technique failure. Methods: Patients on incident PD in French centers contributing to the French Language PD Registry from 2012 to 2016 were included in a retrospective analysis of prospectively collected data. Centers with similar catheter cares practices were gathered in clusters in a hierarchical analysis. Clusters of centers associated with technique failure were evaluated using Cox and Fine and Gray models. A mixed effect Cox model was used to assess the influence of a center effect, as explained by the clusters. Results: Data from 2727 catheters placed in 64 centers in France were analyzed. Five clusters of centers were identified. After adjustment for patient-level characteristics, the fourth cluster was associated with a lower risk of technique failure (cause specific-HR 0.70, 95%CI 0.54–0.90. The variance of the center effect decreased by 5% after adjusting for patient characteristics and by 26% after adjusting for patient characteristics and clusters of centers in the mixed effect Cox model. Favorable outcomes were observed in clusters with a greater proportion of community hospitals, where catheters were placed via open surgery, first dressing done 6 to 15 days after catheter placement, and local prophylactic antibiotics was applied on exit-site. Conclusion: Several patterns of PD catheter related practices have been identified in France, associated with differences in the risk of technique failure. Combinations of favorable practices are suggested in this study. [ABSTRACT FROM AUTHOR]

South Africa ranks third among 22 high burden countries in the world. TB which remains a leading cause of death causes one in five adult deaths in South Africa. An in-depth understanding of knowledge, attitudes and practices of young people towards TB is required to implement meaningful interventions. We analysed young men and women (18–24 years)'s TB knowledge including TB/HIV coinfections, testing rates and factors associated with them. A cross sectional cluster-based household survey was conducted in two provinces. Participants completed computer-assisted self-interviews on TB knowledge, testing history and TB/HIV coinfections. A participant was regarded as knowledgeable of TB if s/he correctly answered the WHO-adopted TB knowledge questions. We built three multivariate regression models in Stata 13.0 to assess factors associated with knowing TB alone, testing alone and both knowing and testing for TB. 1955 participants were interviewed (89.9% response rate). Their median age was 20 years (IQR19-22). Sixteen percent (16.2%) of the participants were social grant recipients, 55% were enrolled in a school/college and 5% lived in substandard houses. A total of 72% had knowledge of TB, 21% underwent screening tests for TB and 14.7% knew and tested for TB. Factors associated with TB knowledge were being female, younger, a student, social grant recipient, not transacting sex and having positive attitudes towards people living with HIV (PLWH). Factors associated with TB testing were being a student, receiving a social grant, living in OR Tambo district, HIV knowledge and having a family member with TB history. Factors associated with both TB knowledge and testing were being female, a student, using the print media, living in OR Tambo district and having a family member with a TB history. The study demonstrates the importance of demographic factors (gender, economic status, family TB history, and location) and HIV factors in explaining TB knowledge and testing. We recommend extending community TB testing services to increase testing. [ABSTRACT FROM AUTHOR]

Background: In western countries, men who have sex with men (MSM) are most affected by HIV and increasingly likely to engage in risky sexual behaviour. MSM who experience a potential sexual exposure to HIV (PEPSE) and receive a preventative regimen of anti-HIV treatment are at particularly high risk of acquiring HIV and could potentially benefit from targeted risk reduction behavioural interventions such as motivational interviewing (MI). Purpose: The aim of this trial was to examine the impact of augmented MI (MI plus information provision and behavioural skills building), over and above routine care, on reducing risky sexual behaviour in MSM prescribed PEPSE. Secondary aims of the research were to examine whether the intervention reduced sexually transmitted infections (STI) and further requests for PEP. Methods: A parallel-group pragmatic randomised controlled trial was conducted with 175 MSM recruited from five sexual health (SH) clinics in the south east of England. The intervention was two fixed-duration sessions of telephone administered augmented MI. A manual guided the selection of individualised persuasive communication strategies based on underlying change mechanisms specified by the Information, Motivation and Behavioural Skills (IMB) model. Primary outcomes were the number of receptive and active anal intercourse (AI) partners, the use of condoms every time during receptive and active AI and the use of condoms sometimes during receptive and active AI. Results: There were no significant impacts on sexual risk behaviour or any of the psychological measures, and no discernible reduction in requests for repeat PEP or rates of STIs within a year. Conclusion: Our behavioural intervention of augmented MI did not affect risky sexual behaviour, rates of further PEP and STIs, and psychological factors, in MSM prescribed PEPSE. Trial registration numbers: UKCRN ID:11436; . [ABSTRACT FROM AUTHOR]

Background: Pre-exposure prophylaxis (PrEP) is an effective and safe intervention approved for use to prevent HIV transmission. PrEP scale-up strategies and clinical practice are currently being informed by modeling studies, which have estimated the impact of PrEP in adult and adolescent MSM populations separately. This partitioning may miss important effects or yield biased estimates by excluding dependencies between populations. Methods: We combined two published models of HIV transmission among adults and adolescent MSM. We simulated an HIV epidemic among MSM aged 13–39 without PrEP, with PrEP for adult MSM ages (19–39) and with the addition of PrEP for adolescents ages (16–18), comparing percent of incident infections averted (impact), the number of person-years on PrEP per infection averted (efficiency), and changes in prevalence. Results: PrEP use among eligible 19–39 year old MSM averted 29.0% of infections and reduced HIV prevalence from 23.2% to 17.0% over ten years in the population as a whole. Despite being ineligible for PrEP in this scenario, prevalence among sexually active 18 year-olds declined from 6.0% to 4.3% due to reduced transmissions across age cohorts. The addition of PrEP for adolescents ages 16–18 had a small impact on the overall epidemic, further reducing overall prevalence from 17.0% to 16.8%; however prevalence among the sexually active 18 year-olds further declined from 4.3% to 3.8%. Conclusions: PrEP use among adults may significantly reduce HIV prevalence among MSM and may also have significant downstream effects on HIV incidence among adolescents; PrEP targeting adolescents remains an important intervention for HIV prevention. [ABSTRACT FROM AUTHOR]

Background: To improve the care and treatment of HIV-exposed children, early infant diagnosis (EID) using dried blood spot (DBS) sampling has been performed in Senegal since 2007, making molecular diagnosis accessible for patients living in decentralized settings. This study aimed to determine the evolution of the HIV transmission rate in children from 2008 to 2015 and to analyze associated factors, particularly the mother’s treatment status and/or child’s prophylaxis status and the feeding mode. Methods: The data were analyzed using EID reports from the reference laboratory. Information related to sociodemographic characteristics, HIV profiles, the mother’s treatment status, the child’s prophylaxis status, and the feeding mode was included. Descriptive statistics were calculated, and bivariate and multivariate logistic regression analyses were performed. Results: During the study period, a total of 5418 samples (5020 DBS and 398 buffy coat) from 168 primary prevention of HIV mother-to-child transmission (PMTCT) intervention sites in Senegal were tested. The samples were collected from 4443 children with a median age of 8 weeks (1–140 weeks) and a sex ratio (M/F) of 1.1 (2309/2095). One-third (35.2%; N = 1564) of the children were tested before 6 weeks of age. Twenty percent (N = 885) underwent molecular diagnostic testing more than once. An increased number of mothers receiving treatment (57.4%; N = 2550) and children receiving prophylaxis (52.1%; N = 2315) for protection against HIV infection during breastfeeding was found over the study period. The transmission rate decreased from 14.8% (95% confidence interval (CI): 11.4–18.3) in 2008 to 4.1% (95% CI: 2.5–7.5) in 2015 (p < 0.001). However, multivariate logistic regression analysis revealed that independent predictors of HIV mother-to-child transmission included lack of mother’s treatment (adjusted odd ratio (aOR) = 3.8, 95% CI: 1.9–7.7; p˂0.001), lack of child’s prophylaxis (aOR = 7.8, 95% CI: 1.7–35.7; p = 0.009), infant age at diagnosis (aOR = 2.2, 95% CI: 1.1–4.3 for ≤6 weeks versus 12–24 weeks; p = 0.025) and protective effect of breastfeeding on ART against formula feeding (aOR = 0.4, 95% CI: 0.2, 0.7; p = 0.005). Conclusion: This study demonstrates the effectiveness of PMTCT interventions in Senegal but indicates also that increased efforts should be continued to reduce the MTCT rate to less than 2%. [ABSTRACT FROM AUTHOR]

Introduction: Antibiotics are among the most commonly misused of all drugs, which results in antibiotic resistance and waste of resources and it has not been studied in Ethiopia. Therefore, this study was carried out to assess antibiotic use–related problems and their costs among patients hospitalized at the surgical ward of Jimma University Medical Center. Methods: Hospital-based prospective observational study was used to assess the prevalence, cost, and determinants of antibiotic use–related problems; multiple stepwise backward logistic regression analysis was done for a P value of < 0.25 to look for predictors of antibiotic use-related problems. Written informed consent was obtained and confidentiality was secured. Results: Among 300 participants, antibiotic use–related problems (ABURPs) were found in 69.3% of the study participants. The direct total cost attributed to these problems was approximated to a minimum of 2230.15 US$. Independent predictors for antibiotic use–related problems were: indication for antibiotic use like: use of antibiotic for prophylaxis; p < 0.0001, antibiotic use for both therapeutic & prophylaxis; p < 0.0001, CDC wound class I and II; p = 0.016 and; p = 0.002 respectively, overall poly-pharmacy and greater than 2 antibiotic exposure during hospital stay; p = 0.019and p = 0.006 respectively and hospital stay for ≥21 days; p = 0.007. Conclusion: The prevalence of antibiotic use-related problems was high and resulted in extra cost. Antibiotic use for prophylaxis, prophylaxis, and treatment, poly-pharmacy, greater than 2 antibiotic exposures during the hospital stay, CDC wound class I and II, and duration of hospital stay of ≥ 21 days was found to be independent predictors of antibiotic use–related problems. [ABSTRACT FROM AUTHOR]

Background: The intentional use of drugs to have sex–chemsex–among men who have sex with men (MSM) might contribute to the high sexually transmitted infections (STI) prevalence in this group. Limited data is available on chemsex outside major cities. The current study investigated the use of a wide variety of drugs during sex among MSM living outside major cities in the Netherlands and their associations with STI. Methods: In 2018, 350 MSM were recruited at STI clinics and 250 MSM completed an online questionnaire. Questionnaire data were linked to clients’ most recent STI laboratory test results. Chemsex was defined as using cocaine, crystal meth, designer drugs, GHB/GBL, ketamine, speed, or XTC/MDMA during sex in the preceding six months. The use of other drugs was also assessed. Determinants (chemsex, specific drugs, number of drugs, combining, and frequency) potentially associated with STI were assessed using multivariable logistic regression analyses adjusting for sociodemographic characteristics and sexual history. Results: Chemsex was reported by 35% (95%CI: 29–41) of the 250 participants. XTC/MDMA (27%; 68/250) and GHB/GBL (26%; 64/250) were the most used drugs. STI positivity was 33% (29/87) in MSM engaging in chemsex and 12% (12/163) in MSM not engaging in chemsex (p<0.001). Half of MSM engaging in chemsex (45/87) used three of more different chemsex drugs; STI positivity in this group was 44% (20/45). The only factor independently associated with STI was the use of three or more chemsex drugs (aOR: 4.13, 95%CI: 1.77–9.62). Conclusion: This study shows that chemsex is prevalent among MSM visiting the STI clinic outside major cities in the Netherlands, suggesting that health services in both urban and non-urban areas should be aware of and informed on chemsex. MSM who used multiple drugs are at particular risk for STI, indicating a special need for STI prevention and care in this group. [ABSTRACT FROM AUTHOR]

The Gram-positive α-hemolytic Streptococcus suis is a major pathogen in the swine industry and an emerging zoonotic agent that can cause several systemic issues in both pigs and humans. A total of 35 S. suis serotypes (SS) have been identified and genotyped into > 700 sequence types (ST) by multilocus sequence typing (MLST). Eurasian ST1 isolates are the most virulent of all S. suis SS2 strains while North American ST25 and ST28 strains display moderate to low/no virulence phenotypes, respectively. Notably, S. suis 90–1330 is an avirulent Canadian SS2-ST28 isolate producing a lantibiotic bacteriocin with potential prophylactic applications. To investigate the suitability of this strain for such purposes, we sequenced its complete genome using the Illumina and PacBio platforms. The S. suis 90–1330 bacteriocin was found encoded in a locus cargoed in what appears to be an integrative and conjugative element (ICE). This bacteriocin locus was also found to be widely distributed across several streptococcal species and in a few Staphylococcus aureus strains. Because the locus also confers protection from the bacteriocin, the potential prophylactic benefits of using this strain may prove limited due to the spread of the resistance to its effects. Furthermore, the S. suis 90–1330 genome was found to code for genes involved in blood survival, suggesting that strain may not be a benign as previously thought. [ABSTRACT FROM AUTHOR]

Objective: To compare the diagnostic performance of BD MAX and GenomEra PCR assays for a rapid PCR detection of vaginal carriage of group B streptococci at delivery. Methods: This is a retrospective laboratory analysis of vaginal swab samples taken intrapartum from a randomly selected cohort of pregnant women giving birth at a single childbirth and maternity unit. Results: Ninety-one culture-positive and 279 culture-negative vaginal samples were included from a cohort of 902 women. One-hundred-and-two specimens were found positive with the BD MAX and 84 with the GenomEra PCR assay. No statistically significant difference was observed compared to culture, sensitivity of BD MAX 84.6% (77/91) [95%CI 75.5–91.3] and of GenomEra 71.4% (65/91) [95%CI 61.0–80.4]. When compared to a combined reference standard, no statistically significant differences were seen between culture, BD MAX and GenomEra PCR assays. The sensitivities were 82.7% (91/110) [95%CI 74.3–89.3], 87.3% (96/110) [95%CI 79.6–92.9], and 79.1% (87/110) [95%CI 70.3–86.3], respectively. Conclusion: Both PCR assays performed comparably to culture of the intrapartum vaginal samples. In particular, the GenomEra assay is potentially an easy and rapid on-site PCR test for intrapartum detection of vaginal carriage of group B streptococci at a maternity ward to identify women who should receive intrapartum antibiotic prophylaxis. [ABSTRACT FROM AUTHOR]

Background: In the UK, approximately 4,200 men who have sex with men (MSM) are living with HIV but remain undiagnosed. Maximising the number of high-risk people testing for HIV is key to ensuring prompt treatment and preventing onward infection. This study assessed how different HIV test characteristics affect the choice of testing option, including remote testing (HIV self-testing or HIV self-sampling), in the UK, a country with universal access to healthcare.Methods and Findings: Between 3 April and 11 May 2017, a cross-sectional online-questionnaire-based discrete choice experiment (DCE) was conducted in which respondents who expressed an interest in online material used by MSM were asked to imagine that they were at risk of HIV infection and to choose between different hypothetical HIV testing options, including the option not to test. A variety of different testing options with different defining characteristics were described so that the independent preference for each characteristic could be valued. The characteristics included where each test is taken, the sampling method, how the test is obtained, whether infections other than HIV are tested for, test accuracy, the cost of the test, the infection window period, and how long it takes to receive the test result. Participants were recruited and completed the instrument online, in order to include those not currently engaged with healthcare services. The main analysis was conducted using a latent class model (LCM), with results displayed as odds ratios (ORs) and probabilities. The ORs indicate the strength of preference for one characteristic relative to another (base) characteristic. In total, 620 respondents answered the DCE questions. Most respondents reported that they were white (93%) and were either gay or bisexual (99%). The LCM showed that there were 2 classes within the respondent sample that appeared to have different preferences for the testing options. The first group, which was likely to contain 86% of respondents, had a strong preference for face-to-face tests by healthcare professionals (HCPs) compared to remote testing (OR 6.4; 95% CI 5.6, 7.4) and viewed not testing as less preferable than remote testing (OR 0.10; 95% CI 0.09, 0.11). In the second group, which was likely to include 14% of participants, not testing was viewed as less desirable than remote testing (OR 0.56; 95% CI 0.53, 0.59) as were tests by HCPs compared to remote testing (OR 0.23; 95% CI 0.15, 0.36). In both classes, free remote tests instead of each test costing £30 was the test characteristic with the largest impact on the choice of testing option. Participants in the second group were more likely to have never previously tested and to be non-white than participants in the first group. The main study limitations were that the sample was recruited solely via social media, the study advert was viewed only by people expressing an interest in online material used by MSM, and the choices in the experiment were hypothetical rather than observed in the real world.Conclusions: Our results suggest that preferences in the context we examined are broadly dichotomous. One group, containing the majority of MSM, appears comfortable testing for HIV but prefers face-to-face testing by HCPs rather than remote testing. The other group is much smaller, but contains MSM who are more likely to be at high infection risk. For these people, the availability of remote testing has the potential to significantly increase net testing rates, particularly if provided for free. [ABSTRACT FROM AUTHOR]

Women remain highly vulnerable to HIV infection in sub-Saharan Africa, with female sex workers (FSWs) facing some of the highest rates of HIV. Oral pre-exposure prophylaxis (PrEP) has the potential to reduce new infections among populations at highest risk and end-user perspectives of actual use in ‘real-world’ settings are critical to informing PrEP implementation. This paper presents findings from serial in-depth interviews (IDIs) conducted with FSW participants during the course of the Treatment And Prevention for Sex workers (TAPS) Demonstration Project in South Africa, exploring the lived experiences and perceptions of taking up and using PrEP. This research provides insight into risks and responsibilities facing FSWs perceived as prominent drivers in taking up and using PrEP, how PrEP was adopted to mitigate risk or ameliorate realities, and the characteristics of PrEP most valued, all of which are critical to consider in scale-up. Overall, distrust in the existence and/or efficacy of PrEP affected the motivation of women to come to the clinic and to maintain use. As one of the first reports of PrEP use among FSWs outside of a clinical trial setting, this research shows that it will be important to ensure accurate, relevant, and widespread messaging in communities to generate demand and support for PrEP. [ABSTRACT FROM AUTHOR]

Background: With the introduction of new interventions to prevent leprosy, such as post-exposure prophylaxis (PEP) given to contacts of leprosy patients, it is necessary to update our understanding of knowledge and perception of leprosy among the populations where these interventions will be introduced, in order to tailor communication optimally to the current situation. This study is a baseline study of the PEP++ project and aimed to assess the knowledge, attitudes and practices regarding leprosy in Fatehpur, India. Methodology: The study used a community-based cross-sectional design with a mixed-methods approach. We assessed knowledge, attitudes, and practices with the KAP measure, and stigma with the Explanatory Model Interview Catalogue community stigma scale (EMIC-CSS) and the Social Distance Scale (SDS). In addition, semi-structured interviews and focus group discussions were conducted with all participant groups. The quantitative data were analysed using stepwise multivariate regression. The qualitative data were analysed using open, inductive coding and content analysis. Findings: A total of 446 participants were included in the study: 100 persons affected by leprosy, 111 close contacts, 185 community members and 50 health care workers. In addition, 24 in-depth interviews were conducted and 35 people were included in focus group discussions. 12.5% of the participants had adequate knowledge of leprosy, while 22% had poor knowledge. Knowledge on cause (answered correctly by 10% of the participants), mode of transmission (5%) and symptoms of leprosy (16%) was especially poor. The mean EMIC-CSS score was 15.3 (95%CI 14.6–16.0) and mean SDS score 7.2 (95%CI 6.6–7.8). Better knowledge of leprosy was associated with lower levels of social distance towards persons affected by leprosy. Conclusion: This study revealed poor knowledge regarding leprosy and high levels of stigma and fear and desire to keep social distance towards persons affected by leprosy. Community education that takes cultural beliefs, knowledge gaps and fears into consideration could improve knowledge, reduce misconceptions and positively influence the perception of leprosy. [ABSTRACT FROM AUTHOR]

Background: Intrapartum antibiotic prophylaxis (IAP) to reduce the likelihood of neonatal early-onset group B streptococcal infection (EOGBS) has coincided with major reductions in incidence. While the decline has been largely ascribed to IAP following either universal screening or a risk-based approach to identify mothers whose babies may most benefit from IAP, there is lack of high quality evidence to support this view. Aims: To describe management of maternal GBS colonisation in one local health district using universal screening and assess rates of EOGBS over time. Methods: A retrospective cohort study was undertaken to describe compliance with GBS management, to determine the incidence of EOGBS and association between rates and maternal screening. Linking routinely collected maternity and pathology data, we explored temporal trends using logistic regression and covariates for potential effect modifiers. Results: Our cohort included 62,281 women who had 92,055 pregnancies resulting in 93,584 live born babies. Screening occurred in 76% of pregnancies; 69% had a result recorded, 21.5% of those were positive for GBS. Prophylaxis was used by 79% of this group. Eighteen babies developed EOGBS, estimated incidence/1000 live births in 2006 and 2016 was 0.35 (95% CI, 0.07 to 0.63) and 0.1 (95% CI, 0 to 0.2) respectively. Seven of 10 term babies with EOGBS were born to mothers who screened negative. Data were unable to provide evidence of difference in rates of EOGBS between screened and unscreened pregnancies. We estimated the difference in EOGBS incidence from crude and weighted models to be 0 (95% CI, -0. 2 to 0.17) and -0.01 (95% CI, -0.13 to 0.10) /1000 live births respectively. Conclusion: No change was detected in rates of EOGBS over time and no difference in EOGBS in babies of screened and unscreened populations. Screening and prophylaxis rates were modest. Limitations of universal screening suggest alternatives be considered. [ABSTRACT FROM AUTHOR]

Introduction: Single-tablet combination emtricitabine/tenofovir is highly effective as HIV pre-exposure prophylaxis (PrEP). Scale-up efforts have targeted men who have sex with men (MSM), but patterns of racial disparities in PrEP use have begun to emerge. African, Caribbean and Black (ACB) communities in Canada and USA are also disproportionately affected by HIV, and there is lack of guidance regarding PrEP implementation in this priority population. Methods: ACB men from Toronto, Canada were recruited in community settings by peers. Participants completed a detailed socio-behavioural questionnaire. Biological samples were collected and tested for sexually transmitted infections. Willingness to accept PrEP was assessed in relation to actual and self-perceived risk of acquiring HIV, as well as demographic and behavioural variables. Results: 424 ACB men were included in the analysis. ACB MSM were more likely to accept PrEP than ACB men only reporting sex with women (MSW; 50.0% vs. 23.6%). The most common reasons for PrEP non-acceptance were concerns regarding side-effects and low self-perceived risk. PrEP acceptance was lowest among younger men (12.5%) and those born in Canada (15.2%). Men with a high self-perceived HIV risk were more likely to accept PrEP (41.3% vs. 22.7% of men with a low self-perceived risk), but only 25.4% of men who were defined as being at high-risk, self-identified themselves as such. Conclusions: Most ACB MSW were unlikely to accept PrEP, largely due to low self-perceived HIV risk, but PrEP acceptance among ACB MSM was similar to other contemporaneous Toronto MSM communities. PrEP acceptance was particularly low among younger ACB men and those born in Canada. Tailored strategies will be needed to effectively implement PrEP in Toronto ACB communities. [ABSTRACT FROM AUTHOR]

The article discusses about approaches towards the diagnosis and treatment of leprosy in Cambodia. It looks at the retrospective active case finding (RACF) program in the country for tracing leprosy patients, screening of the patients' contacts for leprosy, and providing a single dose of rifampicin (SDR) as post exposure prophylaxis (PEP) to the contacts.

Brain metastases are prevalent in various types of cancer and are often terminal, given the low efficacy of available therapies. Therefore, preventing them is of utmost clinical relevance, and prophylactic treatments are perhaps the most efficient strategy. Here, we show that systemic prophylactic administration of a toll-like receptor (TLR) 9 agonist, CpG-C, is effective against brain metastases. Acute and chronic systemic administration of CpG-C reduced tumor cell seeding and growth in the brain in three tumor models in mice, including metastasis of human and mouse lung cancer, and spontaneous melanoma-derived brain metastasis. Studying mechanisms underlying the therapeutic effects of CpG-C, we found that in the brain, unlike in the periphery, natural killer (NK) cells and monocytes are not involved in controlling metastasis. Next, we demonstrated that the systemically administered CpG-C is taken up by endothelial cells, astrocytes, and microglia, without affecting blood-brain barrier (BBB) integrity and tumor brain extravasation. In vitro assays pointed to microglia, but not astrocytes, as mediators of CpG- C effects through increased tumor killing and phagocytosis, mediated by direct microglia-tumor contact. In vivo, CpG-C–activated microglia displayed elevated mRNA expression levels of apoptosis-inducing and phagocytosis-related genes. Intravital imaging showed that CpG-C–activated microglia cells contact, kill, and phagocytize tumor cells in the early stages of tumor brain invasion more than nonactivated microglia. Blocking in vivo activation of microglia with minocycline, and depletion of microglia with a colony-stimulating factor 1 inhibitor, indicated that microglia mediate the antitumor effects of CpG-C. Overall, the results suggest prophylactic CpG-C treatment as a new intervention against brain metastasis, through an essential activation of microglia. [ABSTRACT FROM AUTHOR]

Objective: Pneumocystis pneumonia (PCP) is one of the most common opportunistic infections. In systemic autoimmune disease patients receiving immunosuppressive treatments, low lymphocyte count, old age and coexisting lung disease have been known as risk factors for the occurrence of PCP. However, factors relevant to prognosis of PCP have not been fully studied. Methods: A total of 95 sequential patients who developed PCP during immunosuppressive treatment for systemic autoimmune diseases was identified from five Japanese centres. We retrospectively assessed baseline characteristics, immunosuppressive treatment prior to the onset of PCP, treatment for PCP and survival. Univariate and multivariate analyses were performed to identify prognostic factors. Results: Forty-two deaths (44.2%) were observed in this study. Age at the diagnosis of PCP was higher in non-survivors than in survivors (74 years vs. 64 years, p = 0.008). Non-survivors more frequently had lung involvement than did survivors (47.6% vs. 13.2%, p<0.001). Median lymphocyte count at the diagnosis of PCP was lower in non-survivors than in survivors (499/μl vs. 874/μl, p = 0.002). Multivariate analysis identified lower lymphocyte count, older age and coexisting lung disease at the diagnosis of PCP as independent risk factors for death. Those risk factors for death were similar to the known risk factors for the occurrence of PCP. Conclusion: Although PCP can occur even in patients without these risk factors, our data demonstrate that the overall prognosis of PCP in such patients is good. Given that the standard prophylactic treatment against PCP has safety issues, the risk-stratified use of prophylactic treatment may be advisable. [ABSTRACT FROM AUTHOR]

Objective: Cotrimoxazole prevents opportunistic infections including falciparum malaria in HIV-infected individuals but there are concerns of cross-resistance to other antifolate drugs such as sulphadoxine-pyrimethamine (SP). In this study, we investigated the prevalence of antifolate-resistance mutations in Plasmodium falciparum that are associated with SP resistance in HIV-infected individuals on antiretroviral treatment randomized to discontinue (STOP-CTX), or continue (CTX) cotrimoxazole in Western Kenya. Design: Samples were obtained from an unblinded, non-inferiority randomized controlled trial where participants were recruited on a rolling basis for the first six months of the study, then followed-up for 12 months with samples collected at enrollment, quarterly, and during sick visits. Method: Plasmodium DNA was extracted from blood specimens. Initial screening to determine the presence of Plasmodium spp. was performed by quantitative reverse transcriptase real-time PCR, followed by genotyping for the presence of SP-resistance associated mutations by Sanger sequencing. Results: The prevalence of mutant haplotypes associated with SP-resistant parasites in pfdhfr (51I/59R/108N) and pfdhps (437G/540E) genes were significantly higher (P = 0.0006 and P = 0.027, respectively) in STOP-CTX compared to CTX arm. The prevalence of quintuple haplotype (51I/59R/108N/437G/540E) was 51.8% in STOP-CTX vs. 6.3% (P = 0.0007) in CTX arm. There was a steady increase in mutant haplotypes in both genes in STOP-CTX arm overtime through the study period, reaching statistical significance (P < 0.0001). Conclusion: The frequencies of mutations in pfdhfr and pfdhps genes were higher in STOP-CTX arm compared to CTX arm, suggesting cotrimoxazole effectively controls and selects against SP-resistant parasites. Trial registration: ClinicalTrials.gov [ABSTRACT FROM AUTHOR]

Background: Seasonal epidemics of bacterial meningitis in the African Meningitis Belt carry a high burden of disease and mortality. Reactive mass vaccination is used as a control measure during epidemics, but the time taken to gain immunity from the vaccine reduces the flexibility and effectiveness of these campaigns. Targeted reactive antibiotic prophylaxis could be used to supplement reactive mass vaccination and further reduce the incidence of meningitis, and the potential effectiveness and efficiency of these strategies should be explored. Methods and findings: Data from an outbreak of meningococcal meningitis in Niger, caused primarily by Neisseria meningitidis serogroup C, is used to estimate clustering of meningitis cases at the household and village level. In addition, reactive antibiotic prophylaxis and reactive vaccination strategies are simulated to estimate their potential effectiveness and efficiency, with a focus on the threshold and spatial unit used to declare an epidemic and initiate the intervention. There is village-level clustering of suspected meningitis cases after an epidemic has been declared in a health area. Risk of suspected meningitis among household contacts of a suspected meningitis case is no higher than among members of the same village. Village-wide antibiotic prophylaxis can target subsequent cases in villages: across of range of parameters pertaining to how the intervention is performed, up to 220/672 suspected cases during the season are potentially preventable. On the other hand, household prophylaxis targets very few cases. In general, the village-wide strategy is not very sensitive to the method used to declare an epidemic. Finally, village-wide antibiotic prophylaxis is potentially more efficient than mass vaccination of all individuals at the beginning of the season, and than the equivalent reactive vaccination strategy. Conclusions: Village-wide antibiotic prophylaxis should be considered and tested further as a response against outbreaks of meningococcal meningitis in the Meningitis Belt, as a supplement to reactive mass vaccination. [ABSTRACT FROM AUTHOR]

Background: Gay, bisexual, and other men who have sex with men (GBM) have the highest proportion of incident HIV infection. Pre-exposure prophylaxis (PrEP) use and screening for sexually transmitted infections (STIs) are primary HIV prevention strategies, however, uptake remains low. Social capital, collective resources generated through social connections, are associated with lower HIV risk and infection. We investigated social capital in association with PrEP indicators among GBM. Methods: Analyses included (N = 376) GBM from the 2014 National HIV Behavioral Surveillance (NHBS) in New Orleans. Multiple regression methods assessed the association between one item within each of eight domains from the Onyx and Bullen Social Capital Scale and: awareness and willingness to use PrEP. Analyses are adjusted for age, race, education, sexual intercourse with women, and health insurance. Results: Forty percent of GBM were 18–29 years, 52 percent White. Sixty percent were willing to use PrEP. Social capital was above 50 percent across 7 of 8 indicators. Community group participation (vs no participation) was associated with higher likelihoods of PrEP awareness (adjusted Prevalence Ratio [aPR] = 1.41, 95% Confidence Interval [CI] = 1.02, 1.95). None of the seven remaining social capital indicators were significantly associated with any of the PrEP outcomes. Conclusions: Community groups and organizations could be targeted for interventions to increase uptake of HIV prevention strategies among GBM in New Orleans [ABSTRACT FROM AUTHOR]

Clinical and model studies indicate that low nitric oxide (NO) bioavailability due in part to profound hypoargininemia contributes to cerebral malaria (CM) pathogenesis. Protection against CM pathogenesis may be achieved by altering the diet before infection with Plasmodium falciparum infection (nutraceutical) or by administering adjunctive therapy that decreases CM mortality (adjunctive therapy). This hypothesis was tested by administering citrulline or arginine in experimental CM (eCM). We report that citrulline injected as prophylaxis immediately post infection (PI) protected virtually all mice by ameliorating (i) hypoargininemia, (ii) urea cycle impairment, and (iii) disruption of blood brain barrier. Citrulline prophylaxis inhibited plasma arginase activity. Parasitemia was similar in citrulline- and vehicle control-groups, indicating that protection from pathogenesis was not due to decreased parasitemia. Both citrulline and arginine administered from day 1 PI in the drinking water significantly protected mice from eCM. These observations collectively indicate that increasing dietary citrulline or arginine decreases eCM mortality. Citrulline injected ip on day 4 PI with quinine-injected ip on day 6 PI partially protected mice from eCM; citrulline plus scavenging of superoxide with pegylated superoxide dismutase and pegylated catalase protected all recipients from eCM. These findings indicate that ameliorating hypoargininemia with citrulline plus superoxide scavenging decreases eCM mortality. [ABSTRACT FROM AUTHOR]

Background: Inappropriate and excessive use of surgical antibiotic prophylaxis are associated with the emergence of antibiotic resistance. Antibiotic prophylaxis malpractices are common in obstetrics and gynecology settings and antibiotic stewardship is used to correct such malpractice. Objective: To evaluate the impact of antibiotic stewardship interventions on compliance with surgical antibiotic prophylaxis practice in obstetrics and gynecology surgeries. Method: A prospective pre- and post-intervention study was conducted in two tertiary hospitals between May and December 2016. The duration of the each period was 3 months. Antibiotic stewardship interventions including development of a protocol, educational meeting and audit and feedback were implemented. Data were collected using the patient records and analyzed with SPSS version 23. Results: A total of 226 and 238 surgical procedures were included in the pre- and post-intervention periods respectively. Age, length of stay and estimated blood loss were similar between the two groups. However, specialty and surgical procedures varied significantly. There was a significant increase in compliance with timing (from 14.2% to 43.3%) and duration (from 0% to 21.8%) of surgical antibiotic prophylaxis after the interventions. The interventions significantly reduced the prescription of third generation cephalosporin (-8.6%), redundant antibiotic (-19.1%), antibiotic utilization (-3.8 DDD/procedure) and cost of antibiotic prophylaxis (-$4.2/procedure). There was no significant difference in the rate of surgical site infection between the two periods. Post-intervention group (OR: 5.60; 95% CI: 3.31–9.47), elective surgery (OR: 4.62; 95% CI: 2.51–8.47) and hospital attended (OR: 9.89; 95% CI: 5.66–17.26) were significant predictors of compliance with timing while elective surgery (OR: 12.49; 95% CI: 2.85–54.71) and compliance with timing (OR: 58.55; 95% CI: 12.66–270.75) were significantly associated with compliance to duration of surgical antibiotic prophylaxis. Conclusion: The interventions improve compliance with surgical antibiotic prophylaxis and reduce antibiotic utilization and cost. However, there is opportunity for further improvement, particularly in non-elective surgical procedures. [ABSTRACT FROM AUTHOR]

Background: Men who have sex with men (MSM) are at high risk for anal cancer, primarily related to human papillomavirus genotype 16 (HPV16) infections. At 8.5 per 100,000 per year, the incidence rate of anal cancer among MSM is similar to that of cervical cancer among adult women in the Netherlands. However, MSM are not included in most HPV vaccination programs. We explored the potential effectiveness of prophylactic immunization in reducing anogenital HPV16 transmission among MSM in the Netherlands.Methods and Findings: We developed a range of mathematical models for penile-anal HPV16 transmission, varying in sexual contact structure and natural history of infection, to provide robust and plausible predictions about the effectiveness of targeted vaccination. Models were informed by an observational cohort study among MSM in Amsterdam, 2010-2013. Parameters on sexual behavior and HPV16 infections were obtained by fitting the models to data from 461 HIV-negative study participants, considered representative of the local MSM population. We assumed 85% efficacy of vaccination against future HPV16 infections as reported for HIV-negative MSM, and age-specific uptake rates similar to those for hepatitis B vaccination among MSM in the Netherlands. Targeted vaccination was contrasted with vaccination of 12-year-old boys at 40% uptake in base-case scenarios, and we also considered the effectiveness of a combined strategy. Offering vaccine to MSM without age restrictions resulted in a model-averaged 27.3% reduction (90% prediction interval [PI] 11.9%-37.5%) in prevalence of anal HPV16 infections, assuming similar uptake among MSM as achieved for hepatitis B vaccination. The predicted reduction improved to 46.1% (90% PI 21.8%-62.4%) if uptake rates among MSM were doubled. The reductions in HPV16 infection prevalence were mostly achieved within 30 years of a targeted immunization campaign, during which they exceeded those induced by vaccinating 40% of preadolescent boys, if started simultaneously. The reduction in anal HPV16 prevalence amounted to 74.8% (90% PI 59.8%-93.0%) under a combined vaccination strategy. HPV16 prevalence reductions mostly exceeded vaccine coverage projections among MSM, illustrating the efficiency of prophylactic immunization even when the HPV vaccine is given after sexual debut. Mode of protection was identified as the key limitation to potential effectiveness of targeted vaccination, as the projected reductions were strongly reduced if we assumed no protection against future infections in recipients with prevalent infection or infection-derived immunity at the time of immunization. Unverified limitations of our study include the sparsity of data to inform the models, the omission of oral sex in transmission to the penile or anal site, and the restriction that our modeling results apply primarily to HIV-negative MSM.Conclusions: Our findings suggest that targeted vaccination may generate considerable reductions in anogenital HPV16 infections among MSM, and has the potential to accelerate anal cancer prevention, especially when combined with sex-neutral vaccination in preadolescence. [ABSTRACT FROM AUTHOR]

Background: The long-term treatment outcome of visceral leishmaniasis (VL) patients with HIV co-infection is complicated by a high rate of relapse, especially when the CD4 count is low. Although use of secondary prophylaxis is recommended, it is not routinely practiced and data on its effectiveness and safety are limited. Methods: A prospective cohort study was conducted in Northwest Ethiopia from August 2014 to August 2017 (NCT02011958). HIV-VL patients were followed for up to 12 months. Patients with CD4 cell counts below 200/μL at the end of VL treatment received pentamidine prophylaxis starting one month after parasitological cure, while those with CD4 count ≥200 cells/μL were followed without secondary prophylaxis. Compliance, safety and relapse-free survival, using Kaplan-Meier analysis methods to account for variable time at risk, were summarised. Risk factors for relapse or death were analysed. Results: Fifty-four HIV patients were followed. The probability of relapse-free survival at one year was 50% (95% confidence interval [CI]: 35–63%): 53% (30–71%) in 22 patients with CD4 ≥200 cells/μL without pentamidine prophylaxis and 46% (26–63%) in 29 with CD4 <200 cells/μL who started pentamidine. Three patients with CD4 <200 cells/μL did not start pentamidine. Amongst those with CD4 ≥200 cells/μL, VL relapse was an independent risk factor for subsequent relapse or death (adjusted rate ratio: 5.42, 95% CI: 1.1–25.8). Except for one case of renal failure which was considered possibly related to pentamidine, there were no drug-related safety concerns. Conclusion: The relapse-free survival rate for VL patients with HIV was low. Relapse-free survival of patients with CD4 count <200cells/μL given pentamidine secondary prophylaxis appeared to be comparable to patients with a CD4 count ≥200 cells/μL not given prophylaxis. Patients with relapsed VL are at higher risk for subsequent relapse and should be considered a priority for secondary prophylaxis, irrespective of their CD4 count. [ABSTRACT FROM AUTHOR]

Purpose: To analyze risk factors for recurrent toxoplasmic retinochoroiditis. Design: Single center prospective case series. Population and Methods: A total of 230 patients with toxoplasmic retinochoroiditis were prospectively followed to assess recurrences. All patients were treated with a specific drug regime for toxoplasmosis in each episode of active retinochoroiditis. Individuals with chronic diseases and pregnant women were excluded. Survival analysis by extended Cox regression model (Prentice-Williams-Peterson counting process model) was performed to evaluate the time between recurrences according to some potential risk factors: age, number of retinochoroidal lesions at initial evaluation, sex and interferon gamma +874 T/A gene polymorphism. Hazard Ratios (HR) and 95% confidence intervals (CI) were provided to interpret the risk effects. Results: One hundred sixty-two recurrence episodes were observed in 104 (45.2%) patients during follow-up that lasted from 269 to 1976 days. Mean age at presentation was 32.8 years (Standard deviation = 11.38). The risk of recurrence during follow up was influenced by age (HR = 1.02, 95% CI = 1.01–1.04) and number of retinochoroidal lesions at the beginning of the study (HR = 1.60, 95% CI = 1.07–2.40). Heterozygosis for IFN-γ gene polymorphism at position +874 T/A was also associated with recurrence (HR = 1.49, 95% CI = 1.04–2.14). Conclusion: The risk of ocular toxoplasmosis recurrence after an active episode increased with age and was significantly higher in individuals with primary lesions, which suggests that individuals with this characteristic and the elderly could benefit from recurrence prophylactic strategies with antimicrobials. Results suggest an association between IFN-γ gene polymorphism at position +874T/A and recurrence. [ABSTRACT FROM AUTHOR]

Background: Despite the importance of platelet transfusions in treatment of hematologic cancer patients, the optimal platelet count threshold for prophylactic transfusion is unknown in sub-Saharan Africa. Methods: We followed patients admitted to the Uganda Cancer Institute with a hematological malignancy in 3 sequential 4-month time-periods using incrementally lower thresholds for prophylactic platelet transfusion: platelet counts ≤ 30 x 109/L in period 1, ≤ 20 x 109/L in period 2, and ≤ 10 x 109/L in period 3. Clinically significant bleeding was defined as WHO grade ≥ 2 bleeding. We used generalized estimating equations (GEE) to compare the frequency of clinically significant bleeding and platelet transfusions by study period, adjusting for age, sex, cancer type, chemotherapy, baseline platelet count, and baseline hemoglobin. Results: Overall, 188 patients were enrolled. The median age was 22 years (range 1–80). Platelet transfusions were given to 42% of patients in period 1, 55% in period 2, and 45% in period 3. These transfusions occurred on 8% of days in period 1, 12% in period 2, and 8% in period 3. In adjusted models, period 3 had significantly fewer transfusions than period 1 (RR = 0.6, 95% CI 0.4–0.9; p = 0.01) and period 2 (RR = 0.5, 95% CI 0.4–0.7; p<0.001). Eighteen patients (30%) had clinically significant bleeding on at least one day in period 1, 23 (30%) in period 2, and 15 (23%) in period 3. Clinically significant bleeding occurred on 8% of patient-days in period 1, 9% in period 2, and 5% in period 3 (adjusted p = 0.41). Thirteen (21%) patients died in period 1, 15 (22%) in period 2, and 11 (19%) in period 3 (adjusted p = 0.96). Conclusion: Lowering the threshold for platelet transfusion led to fewer transfusions and did not change the incidence of clinically significant bleeding or mortality, suggesting that a threshold of 10 x 109/L platelets, used in resource-rich countries, may be implemented as a safe level for transfusions in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]

Currently, there is no effective vaccine to halt HIV transmission. However, pre-exposure prophylaxis (PrEP) with the drug combination Truvada can substantially decrease HIV transmission in individuals at risk. Despite its benefits, Truvada-based PrEP is expensive and needs to be taken once-daily, which often leads to inadequate adherence and incomplete protection. These deficits may be overcome by next-generation PrEP regimen, including currently investigated long-acting formulations, or patent-expired drugs. However, poor translatability of animal- and ex vivo/in vitro experiments, and the necessity to conduct long-term (several years) human trials involving considerable sample sizes (N>1000 individuals) are major obstacles to rationalize drug-candidate selection. We developed a prophylaxis modelling tool that mechanistically considers the mode-of-action of all available drugs. We used the tool to screen antivirals for their prophylactic utility and identify lower bound effective concentrations that can guide dose selection in PrEP trials. While in vitro measurable drug potency usually guides PrEP trial design, we found that it may over-predict PrEP potency for all drug classes except reverse transcriptase inhibitors. While most drugs displayed graded concentration-prophylaxis profiles, protease inhibitors tended to switch between none- and complete protection. While several treatment-approved drugs could be ruled out as PrEP candidates based on lack-of-prophylactic efficacy, darunavir, efavirenz, nevirapine, etravirine and rilpivirine could more potently prevent infection than existing PrEP regimen (Truvada). Notably, some drugs from this candidate set are patent-expired and currently neglected for PrEP repurposing. A next step is to further trim this candidate set by ruling out compounds with ominous safety profiles, to assess different administration schemes in silico and to test the remaining candidates in human trials. [ABSTRACT FROM AUTHOR]

Background: Human cytomegalovirus (HCMV) can be managed by monitoring HCMV DNA in the blood and giving valganciclovir when viral load exceeds a defined value. We hypothesised that such pre-emptive therapy should occur earlier than the standard 3000 genomes/ml (2520 IU/ml) when a seropositive donor transmitted virus to a seronegative recipient (D+R-) following solid organ transplantation (SOT). Methods: Our local protocol was changed so that D+R- SOT patients commenced valganciclovir once the viral load exceeded 200 genomes/ml; 168 IU/ml (new protocol). The decision point remained at 3000 genomes/ml (old protocol) for the other two patient subgroups (D+R+, D-R+). Virological outcomes were assessed three years later, when 74 D+R- patients treated under the old protocol could be compared with 67 treated afterwards. The primary outcomes were changes in peak viral load, duration of viraemia and duration of treatment in the D+R- group. The secondary outcome was the proportion of D+R- patients who developed subsequent viraemia episodes. Findings: In the D+R- patients, the median values of peak viral load (30,774 to 11,135 genomes/ml, p<0.0215) were significantly reduced on the new protocol compared to the old, but the duration of viraemia and duration of treatment were not. Early treatment increased subsequent episodes of viraemia from 33/58 (57%) to 36/49 (73%) of patients (p< 0.0743) with a significant increase (p = 0.0072) in those episodes that required treatment (16/58; 27% versus 26/49; 53%). Median peak viral load increased significantly (2,103 to 3,934 genomes/ml, p<0.0249) in the D+R+ but not in the D-R+ patient subgroups. There was no change in duration of viraemia or duration of treatment for any patient subgroup. Interpretation: Pre-emptive therapy initiated at the first sign of viraemia post-transplant significantly reduced the peak viral load but increased later episodes of viraemia, consistent with the hypothesis of reduced antigenic stimulation of the immune system. [ABSTRACT FROM AUTHOR]