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Background\ud Human African trypanosomiasis, or sleeping sickness, is a severe disease affecting people in the poorest parts of Africa. It is usually fatal without treatment. Conventional treatments require days of intravenous infusion, but a recently developed drug, fexinidazole, can be given orally. Another oral drug candidate, acoziborole, is undergoing clinical development and will be considered in subsequent editions. \ud \ud Objectives\ud To evaluate the effectiveness and safety of currently used drugs for treating second‐stage Trypanosoma brucei gambiense trypanosomiasis (gambiense human African trypanosomiasis, g‐HAT).\ud \ud Search methods\ud On 14 May 2021, we searched the Cochrane Infectious Diseases Group Specialized Register, the Cochrane Central Register of Controlled Trials, MEDLINE, Embase, Latin American and Caribbean Health Science Information database, BIOSIS, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform. We also searched reference lists of included studies, contacted researchers working in the field, and contacted relevant organizations.\ud \ud Selection criteria\ud Eligible studies were randomized controlled trials that included adults and children with second‐stage g‐HAT, treated with anti‐trypanosomal drugs currently in use.\ud \ud Data collection and analysis\ud Two review authors extracted data and assessed risk of bias; a third review author acted as an arbitrator if needed. The included trial only reported dichotomous outcomes, which we presented as risk ratio (RR) or risk difference (RD) with 95% confidence intervals (CI). \ud \ud Main results\ud We included one trial comparing fexinidazole to nifurtimox combined with eflornithine (NECT). This trial was conducted between October 2012 and November 2016 in the Democratic Republic of the Congo and the Central African Republic, and included 394 participants. The study reported on efficacy and safety, with up to 24 months' follow‐up. We judged the study to be at low risk of bias in all domains except blinding; as the route of administration and dosing regimens differed between treatment groups, participants and personnel were not blinded, resulting in a high risk of performance bias. \ud \ud Mortality with fexinidazole may be higher at 24 months compared to NECT. There were 9/264 deaths in the fexinidazole group and 2/130 deaths in the NECT group (RR 2.22, 95% CI 0.49 to 10.11; 394 participants; low‐certainty evidence). None of the deaths were related to treatment.\ud \ud Fexinidazole likely results in an increase in the number of people relapsing during follow‐up, with 14 participants in the fexinidazole group (14/264) and none in the NECT group (0/130) relapsing at 24 months (RD 0.05, 95% CI 0.02 to 0.08; 394 participants; moderate‐certainty evidence). \ud \ud We are uncertain whether there is any difference between the drugs regarding the incidence of serious adverse events at 24 months. (31/264 with fexinidazole and 13/130 with NECT group at 24 months). Adverse events were common with both drugs (247/264 with fexinidazole versus 121/130 with NECT), with no difference between groups (RR 1.01, 95% CI 0.95 to 1.06; 394 participants; moderate‐certainty evidence). \ud \ud Authors' conclusions\ud Oral treatment with fexinidazole is much easier to administer than conventional treatment, but deaths and relapse appear to be more common. However, the advantages or an oral option are considerable, in terms of convenience, avoiding hospitalisation and multiple intravenous infusions, thus increasing adherence.

Background\ud Prior to introducing pneumococcal conjugate vaccines (PCVs), Streptococcus pneumoniae was most commonly isolated from the middle ear fluid of children with acute otitis media (AOM). Reducing nasopharyngeal colonisation of this bacterium by PCVs may lead to a decline in AOM. The effects of PCVs deserve ongoing monitoring since studies from the post‐PCV era report a shift in causative otopathogens towards non‐vaccine serotypes and other bacteria. This updated Cochrane Review was first published in 2002 and updated in 2004, 2009, 2014, and 2019.

This is a protocol for a Cochrane Review (intervention). The objectives are as follows:\ud \ud To assess the effects of non‐steroidal anti‐inflammatory drugs (NSAIDs) for acute sore throat in children and adults.

Articles not included due to non-accessibility. (PDF 218 kb)

Articles for which data were not extracted. (PDF 163 kb)

Data extraction summary overview. (PDF 191 kb)

Norovirus (NoV) is the commonest cause of gastrointestinal disease in the United Kingdom and in many developed countries, causing diarrhea and vomiting in millions of cases worldwide annually. Transmission is most often mediated from person to person. NoV infection has, however, additionally been associated with the consumption of food, either through the consumption of food contaminated at source such as seafood, berries, and salad, or as a consequence of the foodstuff being contaminated in some way by a food handler during processing or serving. A systematic review of outbreaks attributed to NoV between January 2003 and July 2017 was conducted to assess the contribution of food handlers to the burden of NoV, and to identify foods commonly associated with NoV outbreaks. A total of 3021 articles were screened, of which 27 met the definition of confirmed foodborne outbreaks and 47 met the criteria for definite food-handler NoV outbreaks. Of all food types, shellfish were implicated in the greatest number of definite foodborne outbreaks. Food handlers contributed to definite food-handler outbreaks involving a diverse range of foodstuffs and in a wide variety of settings, including weddings and military establishments. More genotypes of NoV were found in people who were ill than in samples from food and food handlers. The potential for both food products and food handlers to contribute to the burden of NoV infection is demonstrated conclusively.

ispartof: Campbell Systematic Reviews pages:1-46 status: published

Background\ud Human African trypanosomiasis, or sleeping sickness, is a painful and protracted disease affecting people in the poorest parts of Africa and is fatal without treatment. Few drugs are currently available for second-stage sleeping sickness, with considerable adverse events and variable efficacy.\ud \ud Objectives\ud To evaluate the effectiveness and safety of drugs for treating second-stage human African trypanosomiasis.\ud \ud Search methods\ud We searched the Cochrane Infectious Diseases Group Specialized Register (May 2010), CENTRAL (The Cochrane Library Issue 3 2010) , MEDLINE (1966 to May 2010), EMBASE (1974 to May 2010), LILACS (1982 to May 2010 ), BIOSIS (1926-May 2010), mRCT (May 2010) and reference lists. We contacted researchers working in the field and organizations.\ud \ud Selection criteria\ud Randomized and quasi-randomized controlled trials.\ud Data collection and analysis\ud Two authors (VL and AK) extracted data and assessed methodological quality; a third author (JS) acted as an arbitrator. Included trials only reported dichotomous outcomes, and we present these as risk ratio (RR) with 95% confidence intervals (CI).\ud \ud Main results\ud Nine trials with 2577 participants, all with Trypansoma brucei gambiense HAT, were included. Seven trials tested currently available drugs: melarsoprol, eflornithine, nifurtimox, alone or in combination; one trial tested pentamidine, and one trial assessed the addition of prednisolone to melarsoprol. Fixed 10-day regimens of melarsoprol were found to be as effective as those of 26 days, with similar numbers of adverse events. Melarsoprol monotherapy gave fewer relapses than pentamidine or nifurtimox, but resulted in more adverse events.\ud Later trials evaluate nifurtimox combined with eflornithine (NECT), showing this gives few relapses and is well tolerated. It also has practical advantages in reducing the burden on health personnel and patients, when compared to eflornithine monotherapy.\ud \ud Authors' conclusions\ud Choice of therapy for second stage Gambiense HAT will continue to be determined by what is locally available, but eflornithine and NECT are likely to replace melarsoprol, with careful parasite resistance monitoring. We need research on reducing adverse effects of currently used drugs, testing different regimens, and experimental and clinical studies of new compounds, effective for both stages of the disease.