Search

Background\ud An increasing proportion of patients with HIV-associated cryptococcal meningitis have received antiretroviral therapy (ART) prior to presentation. There is some evidence suggesting an increased two-week mortality in those receiving ART for less than 14 days compared with those on ART for more than 14 days. However, presentation and outcomes for cryptococcal meningitis patients who have recently initiated ART, and those with virologic failure and/or non-adherence are not well described.\ud \ud Methods\ud 678 adults with first episode of cryptococcal meningitis recruited into a randomized, non-inferiority, multicentre phase 3 trial in 4 sub-Saharan countries were analysed to compare clinical presentation and 2-and 10-week mortality outcomes between ART-naive and experienced patients, and between patients receiving ART for varying durations prior to presentation.\ud \ud Results\ud Over half (56% (381/678)) the study participants diagnosed with a first episode of cryptococcal meningitis were ART-experienced. All-cause mortality was similar at 2-weeks (17% vs 20%; HR 0.85, 95%CI 0.6-1.2, p=0.35), and 10 weeks (38% vs 36%; HR 1.03, 95%CI 0.8-1.32, p=0.82) for ART-experienced vs ART-naïve patients, respectively. Among ART-experienced patients, using different cut-off points for ART duration, there were no significant differences in 2- and 10-week mortality based on duration of ART.\ud \ud Conclusion\ud In this study, there were no significant differences in mortality at 2-and 10-weeks between ART- naive and experienced patients, and between ART-experienced patients according to duration on ART.

Uncommon, or rare, yeast infections are on the rise given increasing numbers of patients who are immunocompromised or seriously ill. The major pathogens include those of the genera Geotrichum, Saprochaete, Magnusiomyces, and Trichosporon (ie, basidiomycetes) and Kodamaea, Malassezia, Pseudozyma (ie, now Moesziomyces or Dirkmeia), Rhodotorula, Saccharomyces, and Sporobolomyces (ie, ascomycetes). A considered approach to the complex, multidisciplinary management of infections that are caused by these pathogens is essential to optimising patient outcomes; however, management guidelines are either region-specific or require updating. In alignment with the One World-One Guideline initiative to incorporate regional differences, experts from diverse geographical regions analysed publications describing the epidemiology and management of the previously mentioned rare yeasts. This guideline summarises the consensus recommendations with regards to the diagnostic and therapeutic options for patients with these rare yeast infections, with the intent of providing practical assistance in clinical decision making. Because there is less clinical experience of patients with rare yeast infections and studies on these patients were not randomised, nor were groups compared, most recommendations are not robust in their validation but represent insights by use of expert opinions and in-vitro susceptibility results. In this Review, we report the key features of the epidemiology, diagnosis, antifungal susceptibility, and treatment outcomes of patients with Geotrichum, Saprochaete, Magnusiomyces, and Trichosporon spp infections.

Background Mortality from cryptoccocal meningitis remains high. The ACTA trial demonstrated that, compared with 2 weeks of amphotericin B (AmB) plus flucystosine (5FC), 1 week of AmB and 5FC was associated with lower mortality and 2 weeks of oral flucanozole (FLU) plus 5FC was non-inferior. Here, we assess the cost-effectiveness of these different treatment courses. Methods Participants were randomized in a ratio of 2:1:1:1:1 to 2 weeks of oral 5FC and FLU, 1 week of AmB and FLU, 1 week of AmB and 5FC, 2 weeks of AmB and FLU, or 2 weeks of AmB and 5FC in Malawi, Zambia, Cameroon, and Tanzania. Data on individual resource use and health outcomes were collected. Cost-effectiveness was measured as incremental costs per life-year saved, and non-parametric bootstrapping was done. Results Total costs per patient were US $1442 for 2 weeks of oral FLU and 5FC, $1763 for 1 week of AmB and FLU, $1861 for 1 week of AmB and 5FC, $2125 for 2 weeks of AmB and FLU, and $2285 for 2 weeks of AmB and 5FC. Compared to 2 weeks of AmB and 5FC, 1 week of AmB and 5FC was less costly and more effective and 2 weeks of oral FLU and 5FC was less costly and as effective. The incremental cost-effectiveness ratio for 1 week of AmB and 5FC versus oral FLU and 5FC was US $208 (95% confidence interval $91–1210) per life-year saved. Clinical Trials Registration ISRCTN45035509. Conclusions Both 1 week of AmB and 5FC and 2 weeks of Oral FLU and 5FC are cost-effective treatments., Compared to 2 weeks of amphotericin B (AmB) and flucystosine (5FC), both 1 week of AmB/5FC and 2 weeks of oral fluconazole (FLU) and 5FC save costs; 1 week of AmB/5FC reduces mortality rates more and is somewhat more costly.

Additional file 1: Table S1. Search strategy in PubMed. Table S2. Risk of bias tool. Table S3. Risk of bias on study investigating the association between HEV infection and maternofetal outcomes. Table S4. Individual characteristics of studies included in the meta-analysis prevalence of HEV infection in the global population of pregnant women. Table S5. Individual characteristics of studies included in the meta-analysis of pregnancy outcomes in HEV infection in the global population of pregnant women. Table S6. Characteristics of studies included in the meta-analysis. Figure S1. The review process. Figure S2. Funnel plot for HEV prevalence in asymptomatic pregnant women. Figure S3. Funnel plot for HEV prevalence in symptomatic pregnant women.

Cryptococcal meningitis (CM), caused by an encapsulated yeast is a leading cause of AIDS related opportunistic infection in adults in sub-Saharan Africa and a major driver of mortality, second to tuberculosis. We aimed at optimising the management of AIDS-related cryptococcal meningitis in Cameroon through interventional studies. As such, we designed and performed three studies on the role of cryptococcal antigen (CrAg) in CM diagnosis, contributed in a major phase III non-inferiority clinical trial for inductive treatment of CM in the African setting and analysed the trial participants’ tolerability of the antifungals used in the trial. We also contributed in a review on the long-term prognosis of CM and finally in an advocacy paper for CM to be recognised as a neglected tropical disease. In Cameroon, serum CrAg detection, a major risk factor for incident CM in AIDS patient is prevalent in 7.5% of patients initiating antiretroviral therapy (ART) at less than 100 CD4 cells/μL, of whom 45% have cerebrospinal fluid (CSF) evidence of asymptomatic CM. The new Biosynex CryptoPS test for CrAg detection is comparable to the IMMY lateral flow assay test and shows promise for correctly classifying patients with high serum CrAg titre, a predictor of confirmed CM. Post CrAg screening, enhanced adherence to ART and to fluconazole-based pre-emptive therapy to CrAg positive patients who present with no CM is effective in preventing incident CM within the first year of ART. In HIV patients presenting with symptoms of central nervous system disease, compared to Indian ink staining and/or culture of CSF, serum CrAg detection is highly presumptive of CM and CSF CrAg detection is diagnostic of first episode of CM. In African patients with confirmed CM, inductive therapy based on oral fluconazole-flucytosine combination or seven-day amphotericin B-flucytosine combination are as effective and more tolerated than standard fourteen-day amphotericin B-flucytosine combination. In spite advances in HIV care, mortality due to CM remains unacceptably high warranting CM to be recognised as a neglected tropical disease for which targeted resources need to be allocated to reduce HIV-related mortality. Overall, in Cameroon, putting in place of local pragmatic algorithms based on the availability of simple but highly performant diagnostic tools and sustainable recommended treatment are indispensable to decrease AIDS-associated CM-related morbidity and mortality.; Pas de résumé

Search strategy for HIV RCTs published in 2006â 2007 and 2014â 2015 in leading general medicine and infectious diseases journals. (DOCX 14Â kb)