Prevalence and mortality rate of sepsis among adults admitted to hospitals in sub-Saharan Africa: a systematic review and meta-analysis.

Due to abundant pathogen diversity and mounting antimicrobial resistance, sepsis is more common in sub-Saharan Africa (sSA). However, there is a lack of consistent reports regarding the prevalence of adult sepsis in the region. Therefore, this study aimed to determine pooled estimates of sepsis prevalence and associated mortality among adults admitted to hospitals in sSA. Medline (through PubMed), Scopus, Embase, and Web of Science were systematically searched for studies of sepsis in sSA published before 13th February 2023. A random-effects meta-analysis of hospital-wide and intensive care unit (ICU)-based sepsis prevalence was performed with a 95% confidence interval (CI). Subgroup analysis was conducted considering geographic region and sepsis diagnostic criteria. Funnel plots and Egger's test were used to assess publication bias. The protocol was submitted to the Prospective Register for Systematic Reviews (PROSPERO) with an identifier (CRD42023396719). Overall, 14 observational studies, published between 2009 and 2022, from eight different sSA countries comprising 31,653 adult patients (5723 with sepsis) were included in the review. Nine studies that were conducted in a hospital-wide setting showed a pooled prevalence and mortality of 17% (95% CI: 12-21%) and 15% (95% CI: 17-35%), respectively. Five studies in the ICUs presented a pooled prevalence and mortality of 31% (95% CI: 24-38%) and 46% (95% CI: 39-54%), respectively. Based on the sub-group analysis, the pooled hospital-wide prevalence of sepsis in East and Southern Africa was 18% (95% CI: 11-25%), and 20% (95% CI: 2-42%), respectively. The pooled prevalence in the ICU was 14% (95% CI: 4-23%) and 13% (95% CI: 5-20%) for East and Southern Africa, respectively. The hospital-wide and ICU-based sepsis prevalence and mortality are high in sSA. Addressing the burden of adult sepsis should be a priority for healthcare systems in sub-Saharan Africa.

[Neurogenetics of schizophrenia: findings from studies based on data sharing and global partnerships]. / Neurogenetik der Schizophrenie: Erkenntnisse aus Studien basierend auf Datenaustausch und globalen Partnerschaften.

Schizophrenic psychoses are the result of a multifactorial process in which not only environmental influences but also genetic factors play an important role. These factors are based on a complex mode of inheritance that involves a large number of genetic variants. In the last three decades, biological psychiatric research has focused closely on molecular genetic aspects of the hereditary basis of schizophrenic psychoses. In particular, international consortia are combining cohorts from individual researchers, creating continuously increasing sample sizes and thus increased statistical power. As part of the Psychiatric Genomics Consortium (PGC), genome-wide association studies with tens of thousands of patients and controls have for the first time found robustly replicable markers for schizophrenic psychoses. Through intensive phenotyping, first approaches to a transdiagnostic clinical reclassification of severe mental illnesses have been established in the longitudinal PsyCourse study of the UMG Göttingen and the LMU Munich, allowing new biologically validated disease subgroups with prognostic value to be identified. For the first time environmental factors could even be examined in an African cohort that contribute to the development of the psychosis. In the coming years, the enormous technical progress in the area of genomic high-throughput technologies (next-generation sequencing) is expected to provide new knowledge not only about the influence of frequently occurring single nucleotide polymorphisms but also about rare variants. For the successful use of this technological revolution an exchange of data between research groups is essential.

Evaluation of the therapeutic efficacy of praziquantel against schistosomes in seven countries with ongoing large-scale deworming programs.

The World Health Organization (WHO) recommends periodic assessment of the therapeutic efficacy of praziquantel (PZQ) to detect reduced efficacy that may arise from drug resistance in schistosomes. In this multi-country study (2014), we assessed the therapeutic efficacy of a single oral dose of PZQ (40 mg/kg) against Schistosoma mansoni (Brazil, Cameroon, Ethiopia, Mali, Madagascar and Tanzania), S. haematobium (Cameroon, Ethiopia, Mali, Tanzania and Zanzibar) and S. japonicum (the Philippines) infections in school-aged children, across a total of 12 different trials. Each trial was performed according to the standardized methodology for evaluating PZQ efficacy as described by the WHO. Overall, therapeutic efficacy, measured as the reduction in arithmetic mean of schistosome egg counts following drug administration (egg reduction rate; ERR), was high for all three schistosome species (S. mansoni: 93.4% (95%CI: 88.8-96.8); S. haematobium: 97.7% (95%CI: 96.5-98.7) and S. japonicum: 90.0% (95%CI: 68.4-99.3). At the trial level, therapeutic efficacy was satisfactory (point estimate ERR ≥90%) for all three Schistosoma species with the exception of S. mansoni in Cameroon where the ERR was 88.5% (95%CI: 79.0-95.1). Furthermore, we observed that in some trials individual drug response could vary significantly (wide 95%CI) and that few non-responsive individuals could significantly impact ERR point estimates. In conclusion, these results do not suggest any established reduced efficacy of the standard PZQ treatment to any of the three schistosome species within these countries. Nevertheless, the substantial degree of variation in individual responses to treatment in some countries underpins the need for future monitoring. The reported ERR values serve as reference values to compare with outcomes of future PZQ efficacy studies to ensure early detection of reduced efficacies that could occur as drug pressure continues increase. Finally, this study highlights that 95%CI should be considered in WHO guidelines to classify the therapeutic efficacy of PZQ.

NS1 DNA vaccination protects against Zika infection through T cell-mediated immunity in immunocompetent mice.

The causal association of Zika virus (ZIKV) with microcephaly, congenital malformations in infants, and Guillain-Barré syndrome in adults highlights the need for effective vaccines. Thus far, efforts to develop ZIKV vaccines have focused on the viral envelope. ZIKV NS1 as a vaccine immunogen has not been fully explored, although it can circumvent the risk of antibody-dependent enhancement of ZIKV infection, associated with envelope antibodies. Here, we describe a novel DNA vaccine encoding a secreted ZIKV NS1, that confers rapid protection from systemic ZIKV infection in immunocompetent mice. We identify novel NS1 T cell epitopes in vivo and show that functional NS1-specific T cell responses are critical for protection against ZIKV infection. We demonstrate that vaccine-induced anti-NS1 antibodies fail to confer protection in the absence of a functional T cell response. This highlights the importance of using NS1 as a target for T cell-based ZIKV vaccines.

Efficacy of different albendazole and mebendazole regimens against heavy-intensity Trichuris trichiura infections in school children, Jimma Town, Ethiopia.

Recent studies have shown that the efficacy of benzimidazole drugs is influenced by the intensity of trichuriasis. Therefore, the objective of this study was to determine the efficacy of albendazole (ALB) and mebendazole (MBZ) administered randomly for 1 (ALB×1 and MBZ×1) or 2 days (ALB×2 and MBZ×2) to 385 school children with heavy-intensity trichuriasis (mean faecal egg counts (FEC) >1000 eggs per gram of stool (epg)) in Jimma Town, Ethiopia. The efficacies (95% confidence intervals) by means of reduction in faecal egg counts (FECs) were 29·3% (-9·9-56·2), 60·0% (48·5-70·9), 73·5% (64·2-81·3), and 87·1% (81·4-91·2) for ALB×1, MBZ×1, ALB×2, and MBZ×2, respectively. These observations highlight that assessment of the anthelmintic efficacy of existing or new compounds against Trichuris trichiura should be assessed under varying levels of infection intensity.

The impact of baseline faecal egg counts on the efficacy of single-dose albendazole against Trichuris trichiura.

There is considerable variation in the efficacy of single-dose albendazole (400mg) against Trichuris trichiura across human trials. Factors contributing to this variation have not yet been identified. We assessed the impact of mean baseline faecal egg counts (FEC) on the efficacy of single-dose albendazole against T. trichiura in five previously conducted trials. Our results suggest that efficacy measured by reduction in mean FECs decreased significantly (p<0.0001) when mean baseline FECs increased, highlighting that this parameter should be considered as an important confounding factor for drug efficacy.

Human papillomavirus type distribution among women with cervical pathology - a study over 4 years at Jimma Hospital, southwest Ethiopia.

Over the period 1998-2001 women attending Jimma hospital (southwest Ethiopia) with cervical dysplasia were screened for human papillomavirus (HPV), identifying a prevalence of 67.1% in this population. High-risk HPV types 16 (55.7%), 18 (8.2%), 56 (8.2%), 45 (4.1%), 39 (2.5%), 52 (1.6%), 31 (1.6%), 35 (1.6%), 58 (0.8%), 33 (0.8%), 59 (0.8%) caused severe pathology as single/multiple infection. Strategies need to be envisioned for vaccinating children, young women prior to first sexual contact and preventive screening of HPV high-risk types.