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For a long time, the treatment of human African trypanosomiasis (HAT) represented for clinicians a journey through time, to the sources of colonial tropical medicine. [...]2018, the drugs available (apart from eflornithine), were commercialised during the first half of the 20th century.1 The pharmaceutical industry had no financial motivation to seek new products for a disease with a market representing a few tens of thousands of cases per year, living in rural and impoverished regions of sub-Saharan Africa. [...]at the end of the eradication process when human disease will be rare, the animal reservoir might sustain human infections, which might explain the persistence of low incidence in countries where, assuming a reproduction number lower than 1, the disease should have already disappeared.6 Could acoziborole be useful as a veterinary drug, given as mass treatment to all domesticated animals in the residual foci, once a year for 2 or 3 years, with the addition of an attractive scent for each species? Some logistical effort would be required to ensure that each animal ingests a single dose of acoziborole within a given interval, but token compensation for owners who bring animals might be useful (in two regions of the Democratic Republic of the Congo where I lived, a typical village would only hold a few dozen goats and dogs, but usually no pigs or sheep; thus, a day of work would be sufficient to treat all animals).

Clostridium difficile infection (CDI) can lead to complications, recurrence, and death. Numerous studies have assessed risk factors for these unfavourable outcomes, but systematic reviews or meta-analyses published so far were limited in scope or in quality. A systematic review was completed according to PRISMA guidelines. An electronic search in five databases was performed. Studies published until October 2013 were included if risk factors for at least one CDI outcome were assessed with multivariate analyses. 68 studies were included: 24 assessed risk factors for recurrence, 18 for complicated CDI, 8 for treatment failure, and 30 for mortality. Most studies accounted for mortality in the definition of complicated CDI. Important variables were inconsistently reported, such as previous episodes and use of antibiotics. Substantial heterogeneity and methodological limitations were noted, mainly in the sample size, the definition of the outcomes and periods of follow-up, precluding a meta-analysis. Older age, use of antibiotics after diagnosis, use of proton pump inhibitors, and strain type were the most frequent risk factors for recurrence. Older age, leucocytosis, renal failure and co-morbidities were frequent risk factors for complicated CDI. When considered alone, mortality was associated with age, co-morbidities, hypo-albuminemia, leucocytosis, acute renal failure, and infection with ribotype 027. Laboratory parameters currently used in European and American guidelines to define patients at risk of a complicated CDI are adequate. Strategies for the management of CDI should be tailored according to the age of the patient, biological markers of severity, and underlying co-morbidities.

Thirty years after the discovery of HIV-1, the early transmission, dissemination, and establishment of the virus in human populations remain unclear. Using statistical approaches applied to HIV-1 sequence data from central Africa, we show that from the 1920s Kinshasa (in what is now the Democratic Republic of Congo) was the focus of early transmission and the source of pre-1960 pandemic viruses elsewhere. Location and dating estimates were validated using the earliest HIV-1 archival sample, also from Kinshasa. The epidemic histories of HIV-1 group M and nonpandemic group O were similar until ~1960, after which group M underwent an epidemiological transition and outpaced regional population growth. Our results reconstruct the early dynamics of HIV-1 and emphasize the role of social changes and transport networks in the establishment of this virus in human populations.

Since 2002 an epidemic of Clostridium difficile-associated disease (CDAD) caused by a hypervirulent toxinotype III ribotype 027 strain has spread to many hospitals in Quebec. The strain has also been found in the United States, the United Kingdom and the Netherlands. The effects of this epidemic on mortality and duration of hospital stay remain unknown. We measured these effects among patients admitted to a hospital in Quebec during 2003 and 2004. We compared mortality and total length of hospital stay among inpatients in whom nosocomial CDAD developed and among control subjects without CDAD matched for sex, age, Charlson Comorbidity Index score and length of hospital stay up to the diagnosis of CDAD in the corresponding case. Thirty days after diagnosis 23.0% (37/161) of the patients with CDAD had died, compared with 7.0% (46/656) of the matched control subjects (p < 0.001). Twelve months after diagnosis, mortality was 37.3% (60/161) among patients with CDAD and 20.6% (135/656) among the control subjects (p < 0.001), for a cumulative attributable mortality of 16.7% (95% confidence interval 8.6%-25.2%). Each case of nosocomial CDAD led, on average, to 10.7 additional days in hospital. This study documented a high attributable mortality among elderly patients with CDAD mostly caused by a hypervirulent strain, which represents a dramatic change in the severity of this infection.

Background. Clostridium difficile infection (CDI) is associated with a high risk of recurrence (rCDI). Few studies have focused on multiple recurrences. To evaluate the potential of novel treatments targeting recurrence, we assessed the burden and severity of rCDI. Methods. This was a retrospective cohort of adults diagnosed with CDI in a hospital in Sherbrooke, Canada (1998–2013). An rCDI episode was defined by the reappearance of diarrhea leading to a treatment, with or without a positive toxin assay, within 14–60 days after the previous episode. Results. We included 1527 patients. The probability of developing a first rCDI was 25% (354/1418); a second, 38% (128/334); a third, 29% (35/121); and a fourth or more, 27% (9/33). Two or more rCDIs were observed in 9% (128/1389) of patients. The risk of a first recurrence fluctuated over time, but there was no such variation for second or further recurrences. The proportion of severe cases decreased (47% for initial episodes, 31% for first recurrences, 25% for second, 17% for third), as did the risk of complicated CDI (5.8% to 2.8%). The severity and risk of complications of first recurrences decreased over time, while oral vancomycin was used more systemically. A hospital admission was needed for 34% (148/434) of recurrences. Conclusions. This study documented the clinical and healthcare burden of rCDI: 34% of patients with rCDI needed admission, 28% developed severe CDI, and 4% developed a complication. Secular changes in the severity of recurrences could reflect variations in the predominant strain, or better management.

Anosmia and dysgeusia have been reported as potential symptoms of coronavirus disease 2019. This study aimed to confirm whether anosmia and dysgeusia are specific symptoms among those who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We conducted an age-matched case–control study in the Eastern Townships region of Quebec between Mar. 10 and Mar. 23, 2020. We included adults (age ≥ 18 yr) who tested positive for SARS-CoV-2 by reverse transcription polymerase chain reaction. Cases were matched (1:1) according to 5-year age groups with control patents selected randomly from among all patients who tested negative for SARS-CoV-2 during the same period. Demographic and laboratory information was collected from medical records. Clinical symptoms and comorbidities associated with anosmia and dysgeusia were obtained by telephone interview with a standardized questionnaire. Among 2883 people tested for SARS-CoV-2, we identified 134 positive cases (70 women [52.2%] and 64 men [47.8%]; median age 57.1 [interquartile range 41.2–64.5] yr). The symptoms independently associated with SARS-CoV-2 positivity in conditional logistic regression were anosmia or dysgeusia or both (adjusted odds ratio [OR] 62.9, 95% confidence interval [CI] 11.0–359.7), presence of myalgia (adjusted OR 7.6, 95% CI 1.9–29.9), blurred vision (adjusted OR 0.1, 95% CI 0.0–0.8) and chest pain (adjusted OR 0.1, 95% CI 0.0–0.6). We found a strong association between olfactory and gustatory symptoms and SARS-CoV-2 positivity. These symptoms should be considered as common and distinctive features of SARS-CoV-2 infection and should serve as an indication for testing and possible retesting of people whose first test result is negative.

The incidence of syphilis has increased steadily over the past 25 years. Undiagnosed cases have presumably increased in the same proportions, and rare complications are at particularly high risk of being unrecognised. A previously healthy 60-year-old man presented with rapidly progressive heart failure and severe aortic and mitral valve insufficiency, with direct valvular destruction and preservation of the aortic valve annulus and aortic root. Treponemal serology was reactive, with rapid plasma reagin titre of 1:128. The patient also had classic manifestations of tertiary syphilis: fusiform aneurysm of the aorta and meningovascular syphilis. He underwent bi-valvular and ascending aorta replacement, and the presence of Treponema pallidum was confirmed by specific immunohistochemistry and PCR in all tissues, including aortic and mitral valves, myocardium, and aorta. This case links T pallidum to infectious endocarditis with severe damage to both aortic and mitral valves, in addition to confirmed syphilitic myocarditis, a long-forgotten complication. It occurred 4 years after probable infection, long before what would be expected according to current understanding of its natural history. Syphilis serology should be considered in patients with culture-negative endocarditis as well as in those with heart failure or arrhythmias of unclear cause, especially in the presence of risk factors for syphilis. Syphilitic endocarditis and myocarditis are potentially lethal but treatable conditions.

Identifying patients at risk for adverse outcomes of Clostridium difficile infection (CDI), including recurrence and death, will become increasingly important as novel therapies emerge, which are more effective than traditional approaches but very expensive. Clinical prediction rules (CPRs) can improve the accuracy of medical decision-making. Several CPRs have been developed for CDI, but none has gained a widespread acceptance. We systematically reviewed studies describing the derivation or validation of CPRs for unfavourable outcomes of CDI, in medical databases (Medline, Embase, PubMed, Web of Science and Cochrane) and abstracts of conferences. Of 2945 titles and abstracts screened, 13 studies on the derivation of a CPR were identified: two on recurrences, five on complications (including mortality), five on mortality alone and one on response to treatment. Two studies on the validation of different severity indices were also retrieved. Most CPRs were developed as secondary analyses using cohorts assembled for other purposes. CPRs presented several methodological limitations that could explain their limited use in clinical practice. Except for leukocytosis, albumin and age, there was much heterogeneity in the variables used, and most studies were limited by small sample sizes. Eight models used a retrospective design. Only four studies reported the incidence of the outcome of interest, even if this is essential to evaluate the potential usefulness of a model in other populations. Only five studies performed multivariate analyses to adjust for confounders. The lack of weighing variables, of validation, calibration and measures of reproducibility, the weak validities and performances when assessed, and the absence of sensitivity analyses, all led to suboptimal quality and debatable utility of those CPRs. Evidence-based tools developed through appropriate prospective cohorts would be more valuable for clinicians than empirically-developed CPRs.

ObjectiveTo investigate the distribution and risk factors of hepatitis delta virus (HDV) infection in Cameroon.DesignWe tested for hepatitis B virus (HBV) surface antigen (HBsAg) and anti-HDV antibody 14 150 samples collected during a survey whose participants were representative of the Cameroonian adult population. The samples had already been tested for hepatitis C virus and HIV antibodies.ResultsOverall, 1621/14 150 (weighted prevalence=11.9%) participants were HBsAg positive, among whom 224/1621 (10.6%) were anti-HDV positive. In 2011, the estimated numbers of HBsAg positive and HDV seropositives were 1 160 799 and 122 910 in the 15–49 years age group, respectively. There were substantial regional variations in prevalence of chronic HBV infection, but even more so for HDV (from 1% to 54%). In multivariable analysis, HDV seropositivity was independently associated with living with an HDV-seropositive person (OR=8.80; 95% CI: 3.23 to 24.0), being HIV infected (OR=2.82; 95% CI: 1.32 to 6.02) and living in the South (latitude <4°N) while having rural/outdoor work (OR=15.2; 95% CI: 8.35 to 27.6, when compared with living on latitude ≥4°N and not having rural/outdoor work).ConclusionWe found evidence for effective intra-household transmission of HDV in Cameroon. We also identified large differences in prevalence between regions, with cases concentrated in forested areas close to the Equator, as described in other tropical areas. The reasons underlying these geographical variations in HDV prevalence deserve further investigation.