patients treated with colistin monotherapy, synergism was not protective against 14-day clinical failure (aOR 0.52, 95% CI 0.26e1.04) or 14-day mortality (aOR1.09, 95% CI 0.60e1.96). Discussion: In vitro synergism between colistin and meropenem via checkerboard method did not translate into clinical benefit.

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Based on three large randomized controlled trials (RCTs) conducted in Africa, it can clearly be stated that circumcision lowers the risk of infection with the human immunodeficiency virus (HIV) and some sexually transmitted infections (STIs) among males in settings of high HIV and STI endemicity. Similar effects on STI risk may exist for females, although this may result from an indirect effect of decreasing risk of infection among male partners. It is unknown whether circumcision prevents HIV acquisition in men who have sex with men (MSM), although there might be a protective effect for men who engage mainly in insertive anal intercourse. When the effects of adult circumcision on sexual function and satisfaction of men are examined, high-quality evidence strongly supports lack of harm. Whether circumcision alters sexual satisfaction of female partners is not known as fewer and smaller studies reported conflicting results. Circumcision rarely causes serious complications if practiced by trained practitioners, in a sterile setting, and with a proper follow-up. These conclusions are limited by the lack of high-quality data from areas outside of Africa. RCTs have not been conducted to assess the effects of circumcising infants or MSM. Circumcision has well-proven benefits for people residing in areas with high prevalence of STIs, including HIV, and is not unethical for those who choose to be circumcised or have their children circumcised on religious, social, or cultural grounds. For many others, a definite pro or con recommendation, based on a risk-benefit ratio, cannot be made.

Staphylococcus aureus bloodstream (SAB) infection is a common and severe infectious disease, with a 90-day mortality of 15-30%. Despite this, fewer than 3000 people have been randomised into clinical trials of treatments for SAB infection. The limited evidence base partly results from clinical trials for SAB infections being difficult to complete at scale using traditional clinical trial methods. Here we provide the rationale and framework for an adaptive platform trial applied to SAB infections. We detail the design features of the Staphylococcus aureus Network Adaptive Platform (SNAP) trial that will enable multiple questions to be answered as efficiently as possible. The SNAP trial will commence enrolling patients across multiple countries in 2022 with an estimated target sample size of 7000 participants. This approach may serve as an exemplar to increase efficiency of clinical trials for other infectious diseases syndromes.

IntroductionTyphoid fever (TF) continues to cause considerable morbidity and mortality in Nepal, but only limited epidemiologic data is available about TF outside Kathmandu.MethodsAs part of an interventional trial, we performed a prospective cohort study of bacteremic TF patients in Dhulikhel Hospital between October 2012 and October 2014. Demographic, epidemiological, clinical, and microbiologic data were recorded.Results116 bacteremic typhoid patients were included in the study. Most were young, healthy, adults (mean age 27.9±12 years), 41.4% of whom were female. More than 70% of patients were employed in non-manual services or were university students. Salmonella Typhi accounted for 64/115 (55.7%) of all isolates, while Salmonella Paratyphi accounted for 51/115 (44.3%), of which 42 were Paratyphi A and 9 Paratyphi B. A significant proportion of TF cases occurred also during the dry season (48/116, 41.6%). The clinical presentation of Salmonella Typhi and Paratyphi infections was similar, except for a greater proportion of arthralgia in patients with Salmonella Typhi. Most Salmonella Typhi and Paratyphi isolates were resistant to nalidixic acid and susceptible to older antibiotics. One Salmonella Paratyphi isolate was resistant to ceftriaxone.ConclusionsTF remains common in the Dhulikhel area, even among those with a high level of education. Public health measures aimed at reducing the incidence of TF in the Dhulikhel area are warranted. The relative burden of TF caused by Salmonella Paratyphi is rising; a vaccine with activity against Salmonella Paratyphi is needed. Since Salmonella Paratyphi B was more prevalent in this cohort than in large cohorts of patients from Kathmandu, it is likely that there are significant regional variations in the epidemiology of TF outside Kathmandu.

Background: Nearly a year into the COVID-19 pandemic we still lack effective anti SARS-CoV-2 drugs with substantial impact on mortality rates except for dexamethasone. As the search for effective antiviral agents continues, we aimed to review data on the potential of repurposing antiparasitic drugs against viruses in general, with an emphasis on coronaviruses. Methods: We performed a review by screening in vitro and in vivo studies that assessed the antiviral activity of several antiparasitic agents: chloroquine, hydroxychloroquine, mefloquine, artesiminins, ivermectin, nitazoxanide, niclosamide, atovaquone, and albendazole. Results: For hydroxychloroquine and chloroquine we found ample in vitro evidence of antiviral activity. Cohort studies that assessed the use of hydroxychloroquine for COVID-19 reported conflicting results, but randomized controlled trials (RCTs) demonstrated no effect on mortality rates and no substantial clinical benefits of HCQ (hydroxychloroquine) used either for prevention or treatment of COVID-19. We found two clinical studies of artesiminins and two studies of nitazoxanide for treatment of viruses other than COVID-19, all of which showed mixed results. Ivermectin was evaluated in one RCT and few observational studies, demonstrating conflicting results. As the level of evidence of these data is low, the efficacy of ivermectin against COVID-19 remains to be proven. For chloroquine, hydroxychloroquine, mefloquine, artesiminins, ivermectin, nitazoxanide and niclosamide we found in vitro studies showing some effects against a wide array of viruses. We found no relevant studies for atovaquone and albendazole. Conclusions: As the search for an effective drug active against SARS-CoV-2 continues, we argue that pre-clinical research of possible antiviral effects of compounds that could have antiviral activity should be conducted. Clinical studies should be conducted when sufficient in vitro evidence exists, and drugs should be introduced into widespread clinical use only after being rigorously tested in RCTs. Such a search may prove beneficial in this pandemic, or in outbreaks yet to come.

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The relative proportion of P. malariae is on the rise. Diagnosis in routine clinical settings is inadequate due to the low sensitivity and specificity of blood smears. PCR should be considered when clinical suspicion is high. Prophylaxis failure, which caused delayed clinical presentation, was documented.