Tackling antimicrobial resistance in neonatal sepsis.

Comment - No abstract available

Effectiveness of melarsoprol and eflornithine as first-line regimens for gambiense sleeping sickness in nine Médecins Sans Frontières programmes.

This paper describes the effectiveness of first-line regimens for stage 2 human African trypanosomiasis (HAT) due to Trypanosoma brucei gambiense infection in nine Médecins Sans Frontières HAT treatment programmes in Angola, Republic of Congo, Sudan and Uganda. Regimens included eflornithine and standard- and short-course melarsoprol. Outcomes for 10461 naïve stage 2 patients fitting a standardised case definition and allocated to one of the above regimens were analysed by intention-to-treat analysis. Effectiveness was quantified by the case fatality rate (CFR) during treatment, the proportion probably and definitely cured and the Kaplan-Meier probability of relapse-free survival at 12 months and 24 months post admission. The CFR was similar for the standard- and short-course melarsoprol regimens (4.9% and 4.2%, respectively). The CFR for eflornithine was 1.2%. Kaplan-Meier survival probabilities varied from 71.4-91.8% at 1 year and 56.5-87.9% at 2 years for standard-course melarsoprol, to 73.0-91.1% at 1 year for short-course melarsoprol, and 79.9-97.4% at 1 year and 68.6-93.7% at 2 years for eflornithine. With the exception of one programme, survival at 12 months was >90% for eflornithine, whilst for melarsoprol it was <90% except in two sites. Eflornithine is recommended where feasible, especially in areas with low melarsoprol effectiveness

Neglected Diseases in the News: A Content Analysis of Recent International Media Coverage Focussing on Leishmaniasis and Trypanosomiasis

In recent years, there has been a flurry of activity to reverse the neglect that has characterised NTDs, mostly focussed on drug development. The drug gap may be explained by market failure, yet other forces also conspire to cause the neglect of NTDs. One problem is the low visibility of these diseases. By comparison, the high-profile “big three” infectious diseases of AIDS, tuberculosis, and malaria have received increased donor attention and funding with greater visibility. Efforts to remove the “neglect” from NTDs must involve raising their profile. This study, focussing on three of the most neglected diseases, aims to provide a context of the current media situation—the what, where, and why of NTD coverage—to support future advocacy work

Clinical and hospitalisation predictors of COVID-19 in the first month of the pandemic, Portugal

COVID-19 mainly presents as a respiratory disease with flu-like symptoms, however, recent findings suggest that non-respiratory symptoms can occur early in the infection and cluster together in different groups in different regions. We collected surveillance data among COVID-19 suspected cases tested in mainland Portugal during the first wave of the pandemic, March-April 2020. A multivariable logistic-regression analysis was performed to ascertain the effects of age, sex, prior medical condition and symptoms on the likelihood of testing positive and hospitalisation. Of 25,926 COVID-19 suspected cases included in this study, 5,298 (20%) tested positive. Symptoms were grouped into ten clusters, of which two main ones: one with cough and fever and another with the remainder. There was a higher odds of a positive test with increasing age, myalgia and headache. The odds of being hospitalised increased with age, presence of fever, dyspnoea, or having a prior medical condition although these results varied by region. Presence of cough and other respiratory symptoms did not predict COVID-19 compared to non-COVID respiratory disease patients in any region. Dyspnoea was a strong determinant of hospitalisation, as well as fever and the presence of a prior medical condition, whereas these results varied by region.The author(s) received no specific funding for this work

Household transmission of invasive group A Streptococcus infections in England: a population-based study, 2009, 2011 to 13

Invasive group A s treptococcal infection has a 15% case fatality rate and a risk of secondary transmission. This retrospective study us ed two national data sources from England ; enhanced surveillance ( 2009) and a case management system ( 2011 - 13) to identify clusters of sever e group A streptococcal disease . 2 4 household pairs were identified. The median onset interval between cases was 2 days (range 0 - 28) with simultaneous onset in 8 pairs . The attack rate during the 30 days after first exposure to a primary case was 4 52 0 per 100000 person - years at risk (95% CI 2 900 - 673 0 ) a 19 40 ( 12 40 - 28 80 ) fold elevation over the background incidence . The theoretical number needed to treat ( NNT ) to prevent one secondary case using antibiotic prophylaxis was 2 71 ( 194 - 454 ) overall, 50 for mother - neonate pairs ( 2 7 - 3 93 ) and 8 2 for couples aged 75 years and over ( 46 - 417 ). Whilst a dramatic increased risk of infection was noted in all household contacts, increased ris k was greatest for mother - neonate pairs and couples aged 75 and over , suggesting targeted prophylaxis c ould be considered. Offering prophylaxis is challenging due to the short time interval between cases emphasising the importance of immediate notification and assessment of contacts

Partial Failure of Milk Pasteurization as a Risk for the Transmission of Campylobacter From Cattle to Humans

Background. Cattle are the second most common source of human campylobacteriosis. However, routes to account for this scale of transmission have not been identified. In contrast to chicken, red meat is not heavily contaminated at point of sale. Although effective pasteurization prevents milk-borne infection, apparently sporadic infections may include undetected outbreaks from raw or perhaps incompletely pasteurized milk.Methods. A rise in Campylobacter gastroenteritis in an isolated population was investigated using whole-genome sequencing (WGS), an epidemiological study, and environmental investigations.Results. A single strain was identified in 20 cases, clearly distinguishable from other local strains and a reference population by WGS. A case-case analysis showed association of infection with the outbreak strain and milk from a single dairy (odds ratio, 8; Fisher exact test P value = .023). Despite temperature records indicating effective pasteurization, mechanical faults likely to lead to incomplete pasteurization of part of the milk were identified by further testing and examination of internal components of dairy equipment.Conclusions. Here, milk distribution concentrated on a small area, including school-aged children with low background incidence of campylobacteriosis, facilitated outbreak identification. Low-level contamination of widely distributed milk would not produce as detectable an outbreak signal. Such hidden outbreaks may contribute to the substantial burden of apparently sporadic Campylobacter from cattle where transmission routes are not certain. The effective discrimination of outbreak isolates from a reference population using WGS shows that integrating these data and approaches into surveillance could support the detection as well as investigation of such outbreaks

Pentamidine Dosage: A Base/Salt Confusion

Pentamidine has a long history in the treatment of human African trypanosomiasis (HAT) and leishmaniasis. Early guidelines on the dosage of pentamidine were based on the base-moiety of the two different formulations available. Confusion on the dosage of pentamidine arose from a different labelling of the two available products, either based on the salt or base moiety available in the preparation. We provide an overview of the various guidelines concerning HAT and leishmaniasis over the past decades and show the confusion in the calculation of the dosage of pentamidine in these guidelines and the subsequent published reports on clinical trials and reviews. At present, only pentamidine isethionate is available, but the advised dosage for HAT and leishmaniasis is (historically) based on the amount of pentamidine base. In the treatment of leishmaniasis this is probably resulting in a subtherapeutic treatment. There is thus a need for a new, more transparent and concise guideline concerning the dosage of pentamidine, at least in the treatment of HAT and leishmaniasi

Paromomycin for the Treatment of Visceral Leishmaniasis in Sudan: A Randomized, Open-Label, Dose-Finding Study

Visceral leishmaniasis (VL) is a parasitic disease transmitted through the bite of sandflies. The WHO estimates 500,000 new cases of VL each year, with more than 90% of cases occurring in Southeast Asia, East Africa, and South America. If left untreated, VL can be fatal. We had previously conducted a large multi-center study in Sudan, East Africa, to assess the efficacy of paromomycin (PM) alone or in combination with sodium stibogluconate. Clinical studies in India have shown that 15 mg/kg/day PM for 21 days was an effective cure. However, the same treatment regimen was not efficacious in two study sites in Sudan. Here, our aim was to assess two high-dose regimens of PM in Sudan: 15 mg/kg/day for 28 days and 20 mg/kg/day for 21 days. The results suggest that, at these total doses, PM is more efficacious than when given daily at 15 mg/kg for 21 days, and that high doses are required to treat VL in Sudan. Efficacy of 20 mg/kg/day PM for 21 days is currently being evaluated in a prospective, comparative phase III trial in East Africa

In-hospital safety in field conditions of Nifurtimox Eflornithine Combination Therapy (NECT) for T. B. Gambiense Sleeping Sickness

Trypanosoma brucei (T.b.) gambiense Human African trypanosomiasis (HAT; sleeping sickness) is a fatal disease. Until 2009, available treatments for 2(nd) stage HAT were complicated to use, expensive (eflornithine monotherapy), or toxic, and insufficiently effective in certain areas (melarsoprol). Recently, nifurtimox-eflornithine combination therapy (NECT) demonstrated good safety and efficacy in a randomised controlled trial (RCT) and was added to the World Health Organisation (WHO) essential medicines list (EML). Documentation of its safety profile in field conditions will support its wider use

Safety and Efficacy of miltefosine alone and in combination with sodium stibogluconate and liposomal amphotericin B for the treatment of primary visceral leishmaniasis in East Africa: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Treatment options for Visceral Leishmaniasis (VL) in East Africa are far from satisfactory due to cost, toxicity, prolonged treatment duration or emergence of parasite resistance. Hence there is a need to explore alternative treatment protocols such as miltefosine alone or in combinations including miltefosine, sodium stibogluconate (SSG) or liposomal amphotericin B. The aim of this trial is to identify regimen(s) which are sufficiently promising for future trials in East Africa.</p> <p>Methods/Design</p> <p>A phase II randomized, parallel arm, open-labelled trial is being conducted to assess the efficacy of each of the three regimens: liposomal amphotericin B with SSG, Liposomal amphotericin B with miltefosine and miltefosine alone. The primary endpoint is cure at day 28 with secondary endpoint at day 210 (6 months). Initial cure is a single composite measure based on parasitologic evaluation (bone marrow, spleen or lymph node aspirate) and clinical assessment. Repeated interim analyses have been planned after recruitment of 15 patients in each arm with a maximum sample size of 63 for each. These will follow group-sequential methods (the triangular test) to identify when a regimen is inadequate (<75% efficacy) or adequate (>90% efficacy). We describe a method to ensure consistency of the sequential analysis of day 28 cure with the non-sequential analysis of day 210 cure.</p> <p>Discussion</p> <p>A regimen with adequate efficacy would be a candidate for treatment of VL with reasonable costs. The design allows repeated testing throughout the trial recruitment period while maintaining good statistical properties (Type I & II error rates) and reducing the expected sample sizes.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01067443">NCT01067443</a></p