Developmental Regulation of Genes Encoding Universal Stress Proteins in Schistosoma mansoni

The draft nuclear genome sequence of the snail-transmitted, dimorphic, parasitic, platyhelminth Schistosoma mansoni revealed eight genes encoding proteins that contain the Universal Stress Protein (USP) domain. Schistosoma mansoni is a causative agent of human schistosomiasis, a severe and debilitating Neglected Tropical Disease (NTD) of poverty, which is endemic in at least 76 countries. The availability of the genome sequences of Schistosoma species presents opportunities for bioinformatics and genomics analyses of associated gene families that could be targets for understanding schistosomiasis ecology, intervention, prevention and control. Proteins with the USP domain are known to provide bacteria, archaea, fungi, protists and plants with the ability to respond to diverse environmental stresses. In this research investigation, the functional annotations of the USP genes and predicted nucleotide and protein sequences were initially verified. Subsequently, sequence clusters and distinctive features of the sequences were determined. A total of twelve ligand binding sites were predicted based on alignment to the ATP-binding universal stress protein from Methanocaldococcus jannaschii. In addition, six USP sequences showed the presence of ATP-binding motif residues indicating that they may be regulated by ATP. Public domain gene expression data and RT-PCR assays confirmed that all the S. mansoni USP genes were transcribed in at least one of the developmental life cycle stages of the helminth. Six of these genes were up-regulated in the miracidium, a free-swimming stage that is critical for transmission to the snail intermediate host. It is possible that during the intra-snail stages, S. mansoni gene transcripts for universal stress proteins are low abundant and are induced to perform specialized functions triggered by environmental stressors such as oxidative stress due to hydrogen peroxide that is present in the snail hemocytes. This report serves to catalyze the formation of a network of researchers to understand the function and regulation of the universal stress proteins encoded in genomes of schistosomes and their snail intermediate hosts

Original Article The incidence, intensity and host morbidity of human parasitic protozoan infections in gastrointestinal disorder outpatients in Buea Sub Division,

Background: Numerous protozoans inhibit the gastrointestinal tract of humans with the majority being either non-pathogenic commensals or of a type that may result in mild disease. However, some of these organisms can cause severe diseases under certain circumstances while others may become highly virulent and invasive causing potentially lethal systemic disease. This study investigated the prevalence, intensity and host morbidity of human intestinal protozoan infections in individuals living in the Buea Sub-Division, Cameroon. Methodology: Random sampling was used to collect stool samples from 356 patients in a cross-sectional study. All samples were examined by formol-ether concentration and direct smear techniques. Data collected was analyzed and differences in proportions were determined using the Chi square (χ 2) test, Fisher’s exact test, or analysis of variance where appropriate. Results: It was found that 28.1 % (100/356) of the sampled population were infected with protozoans. Females showed a higher infection rate (29.7%; 56/182) than males (26.4%; 46/174) and there was a significantly (P < 0.001) higher prevalence in rural areas (38.7%; 55/142) than in urban areas (21.0%; 45/214). The 6 to 12 years age group had a significantly (P < 0.05) higher infection rate (42.9%; 30/70). The total prevalence of intestinal protozoans was as follows: E. histolytica (24.4%), E. coli (11.2%) and G. lamblia (0.6%). The most prevalent morbidity effects associated with intestinal protozoan infections were abdominal pains, dysentery and body weakness. Conclusions: Since human intestinal parasitic infections are high in the study area, mass treatment of people with intestinal protozoans i

Pre-treatment drug resistance and HIV-1 genetic diversity in the rural and urban settings of Northwest-Cameroon.

BackgroundWith the scale-up of antiretroviral therapy (ART), pre-treatment drug resistance (PDR) appears ≥10% amongst ART-initiators in many developing countries, including Cameroon. Northwest region-Cameroon having the second epidemiological burden of HIV infection, generating data on PDR in these geographical settings, will enhance evidence-based decision-making.ObjectivesWe sought to ascertain levels of PDR and HIV-1 clade dispersal in rural and urban settings, and their potential association with subtype distribution and CD4-staging.MethodsA cross-sectional study was conducted from February to May 2017 among patients recently diagnosed with HIV-infection and initiating ART at the Bamenda regional Hospital (urban setting) and the Mbingo Baptist hospital (rural setting). Protease and reverse transcriptase sequencing was performed using an in-house protocol and pre-treatment drug resistance mutations were interpreted using Stanford HIVdb.v8.3. Phylogeny was performed for subtype assignation.ResultsA total of 61 patient sequences were generated from ART initiators (median age: 37 years old; 57.4% female; median CD4 cell count: 184 [IQR: 35-387] in urban vs. 161 [IQR: 96-322] cells/mm3 in rural). Overall, the level of PDR was 9.8% (6/61). Of note, burden of PDR was almost doubled in urban (12.9% [4/31]) compared to rural setting 6.7% (2/30), p = 0.352). Fifteen (15) PDR mutations were found among four patients the urban settings [6 resistance mutations to NRTIs:[M41L (2), E44D (1), K65R (1), K70E (1), M184V/I (2), K219R (1)] and 6 resistance mutations to NNRTIs: K103N (1), E138A/G (2), V179E (1), M230L (1), K238T (1), P225H (1)] against two (02) mutations found in two patients in the rural setting[2 resistant mutations to NNRTIs: E138A (1) and Y188H (1)]. The rural setting showed more genetic diversity (8 subtypes) than the urban setting (5 subtypes), with CRF02_AG being the most prevalent clade (72.1% [44/61]). Of note, level of PDR was similar between patients infected with CRF02_AG and non-CRF02_AG infected (9.1% [4/44]) vs. 11.8% [2/17]), p = 1.000). Moreover, PDR appeared higher in patients with CD4 cell count ConclusionsPDR is at a moderate rate in the Northwest region of Cameroon, with higher burden within urban populations. CRF02_AG is the most predominant clade in both urban and rural settings. No effect of HIV molecular epidemiology and CD4-staging on the presence of PDR in patients living in these settings was found. Our findings suggest close monitoring, NNRTI-sparing regimens or sequencing for patients initiating ART, especially in urban settings

Back to the basics: Clinical assessment yields robust mortality prediction and increased feasibility in low resource settings

IntroductionMortality prediction aids clinical decision-making and is necessary for trauma quality improvement initiatives. Conventional injury severity scores are often not feasible in low-resource settings. We hypothesize that clinician assessment will be more feasible and have comparable discrimination of mortality compared to conventional scores in low and middle-income countries (LMICs).MethodsBetween 2017 and 2019, injury data were collected from all injured patients as part of a prospective, four-hospital trauma registry in Cameroon. Clinicians used physical exam at presentation to assign a highest estimated abbreviated injury scale (HEAIS) for each patient. Discrimination of hospital mortality was evaluated using receiver operating characteristic curves. Discrimination of HEAIS was compared with conventional scores. Data missingness for each score was reported.ResultsOf 9,635 presenting with injuries, there were 206 in-hospital deaths (2.2%). Compared to 97.5% of patients with HEAIS scores, only 33.2% had sufficient data to calculate a Revised Trauma Score (RTS) and 24.8% had data to calculate a Kampala Trauma Score (KTS). Data from 2,328 patients with all scores was used to compare models. Although statistically inferior to the prediction generated by RTS (AUC 0.92-0.98) and KTS (AUC 0.93-0.99), HEAIS provided excellent overall discrimination of mortality (AUC 0.84-0.92). Among 9,269 patients with HEAIS scores was strongly predictive of mortality (AUC 0.93-0.96).ConclusionClinical assessment of injury severity using HEAIS strongly predicts hospital mortality and far exceeds conventional scores in feasibility. In contexts where traditional scoring systems are not feasible, utilization of HEAIS could facilitate improved data quality and expand access to quality improvement programming

Population genetic structure of Schistosoma mansoni and Schistosoma haematobium from across six sub-Saharan African countries: Implications for epidemiology, evolution and control

We conducted the first meta-analysis of ten Schistosoma haematobium (one published and nine unpublished) and eight Schistosoma mansoni (two published and six unpublished) microsatellite datasets collected from individual schistosome-infected school-children across six sub-Saharan Africa countries. High levels of genetic diversity were documented in both S. haematobium and S. mansoni. In S. haematobium populations, allelic richness did not differ significantly between the ten schools, despite widely varying prevalences and intensities of infection, but higher levels of heterozygote deficiency were seen in East than in West Africa. In contrast, S. mansoni populations were more diverse in East than West African schools, but heterozygosity levels did not vary significantly with geography. Genetic structure in both S. haematobium and S. mansoni populations was documented, at both a regional and continental scale. Such structuring might be expected to slow the spread to new areas of anti-schistosomal drug resistance should it develop. There was, however, limited evidence of genetic structure at the individual host level, which might be predicted to promote the development or establishment of drug resistance, particularly if it were a recessive trait. Our results are discussed in terms of their potential implications for the epidemiology and evolution of schistosomes as well as their subsequent control across sub-Saharan Africa