Increasing understanding of the relationship between geographic access and gendered decision-making power for treatment-seeking for febrile children in the Chikwawa district of Malawi

Background: This study used qualitative methods to investigate the relationship between geographic access and gendered intra-household hierarchies and how these influence treatment-seeking decision-making for childhood fever within the Chikwawa district of Malawi. Previous cross-sectional survey findings in the district indicated that distance from facility and associated costs are important determinants of health facility attendance in the district. This paper uses qualitative data to add depth of understanding to these findings by exploring the relationship between distance from services, anticipated costs and cultural norms of intra-household decision-making, and to identify potential intervention opportunities to reduce challenges experienced by those in remote locations. Qualitative data collection included 12 focus group discussions and 22 critical incident interviews conducted in the local language, with primary caregivers of children who had recently experienced a febrile episode. Results: Low geographic accessibility to facilities inhibited care-seeking, sometimes by extending the ‘assessment period’ for a child’s illness episode, and led to delays in seeking formal treatment, particularly when the illness occurred at night. Although carers attempted to avoid incurring costs, cash was often needed for transport and food. Whilst in all communities fathers were normatively responsible for treatment costs, mothers generally had greater access to and control over resources and autonomy in decision-making in the matrilineal and matrilocal communities in the central part of the district, which were also closer to formal facilities. Conclusions: This study illustrates the complex interplay between geographic access and gender dynamics in shaping decisions on whether and when formal treatment is sought for febrile children in Chikwawa District. Geographic marginality and cultural norms intersect in remote areas both to increase the logistical and anticipated financial barriers to utilising services and to reduce caretakers’ autonomy to act quickly once they recognize the need for formal care. Health education campaigns should be based within communities, engaging all involved in treatment-seeking decision-making, including men and grandmothers, and should aim to promote the ability of junior women to influence the treatment-seeking process. Both mothers’ financial autonomy and fathers financial contributions are important to enable timely access to effective healthcare for children with malaria

Human cerebral malaria and Plasmodium falciparum genotypes in Malawi

<p>Abstract</p> <p>Background</p> <p>Cerebral malaria, a severe form of <it>Plasmodium falciparum </it>infection, is an important cause of mortality in sub-Saharan African children. A Taqman 24 Single Nucleotide Polymorphisms (SNP) molecular barcode assay was developed for use in laboratory parasites which estimates genotype number and identifies the predominant genotype.</p> <p>Methods</p> <p>The 24 SNP assay was used to determine predominant genotypes in blood and tissues from autopsy and clinical patients with cerebral malaria.</p> <p>Results</p> <p>Single genotypes were shared between the peripheral blood, the brain, and other tissues of cerebral malaria patients, while malaria-infected patients who died of non-malarial causes had mixed genetic signatures in tissues examined. Children with retinopathy-positive cerebral malaria had significantly less complex infections than those without retinopathy (OR = 3.7, 95% CI [1.51-9.10]).The complexity of infections significantly decreased over the malaria season in retinopathy-positive patients compared to retinopathy-negative patients.</p> <p>Conclusions</p> <p>Cerebral malaria patients harbour a single or small set of predominant parasites; patients with incidental parasitaemia sustain infections involving diverse genotypes. Limited diversity in the peripheral blood of cerebral malaria patients and correlation with tissues supports peripheral blood samples as appropriate for genome-wide association studies of parasite determinants of pathogenicity.</p

Predicting the environmental suitability and population at risk of podoconiosis in Africa

Podoconiosis is a type of tropical lymphedema that causes massive swelling of the lower limbs. The disease is associated with both economic insecurity, due to long-term morbidity-related loss of productivity, and intense social stigma. The geographical distribution and burden of podoconiosis in Africa are uncertain. We applied statistical modelling to the most comprehensive database compiled to date to predict the environmental suitability of podoconiosis in the African continent. By combining climate and environmental data and overlaying population figures, we predicted the environmental suitability and human population at risk of podoconiosis in Africa. Environmental suitability for podoconiosis was predicted in 29 African countries. In the year 2020, the total population in areas suitable for podoconiosis is estimated at 114.5 million people, (95% uncertainty interval: 109.4–123.9) with 16.9 million in areas suitable for both lymphatic filariasis and podoconiosis. Of the total 5,712 implementation units (typically second administrative-level units, such as districts) defined by the World Health Organization in Africa, 1,655 (29.0%) were found to be environmentally suitable for podoconiosis. The majority of implementation units with high environmental suitability are located in Angola (80, 4.8%), Cameroon (170, 10.3%), the DRC (244, 14.7%), Ethiopia (495, 29.9%), Kenya (217, 13.1%), Uganda (116, 7.0%) and Tanzania (112, 6.8%). Of the 1,655 environmentally suitable implementation units, 960 (58.0%) require more detailed community-level mapping. Our estimates provide key evidence of the population at risk and geographical extent of podoconiosis in Africa, which will help decision-makers to better plan more integrated intervention programmes

Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170.

We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.This is the author accepted manuscript. The final version is available from Nature Publishing Group via http://dx.doi.org/10.1038/ng.352

RA-MAP, molecular immunological landscapes in early rheumatoid arthritis and healthy vaccine recipients

Rheumatoid arthritis (RA) is a chronic inflammatory disorder with poorly defined aetiology characterised by synovial inflammation with variable disease severity and drug responsiveness. To investigate the peripheral blood immune cell landscape of early, drug naive RA, we performed comprehensive clinical and molecular profiling of 267 RA patients and 52 healthy vaccine recipients for up to 18 months to establish a high quality sample biobank including plasma, serum, peripheral blood cells, urine, genomic DNA, RNA from whole blood, lymphocyte and monocyte subsets. We have performed extensive multi-omic immune phenotyping, including genomic, metabolomic, proteomic, transcriptomic and autoantibody profiling. We anticipate that these detailed clinical and molecular data will serve as a fundamental resource offering insights into immune-mediated disease pathogenesis, progression and therapeutic response, ultimately contributing to the development and application of targeted therapies for RA.</p

Understanding Interpretations of and Responses to Childhood Fever in the Chikhwawa District of Malawi

Background Universal access to, and community uptake of malaria prevention and treatment strategies are critical to achieving current targets for malaria reduction. Each step in the treatment-seeking pathway must be considered in order to establish where opportunities for successful engagement and treatment occur. We describe local classifications of childhood febrile illnesses, present an overview of treatment-seeking, beginning with recognition of illness, and suggest how interventions could be used to target the barriers experienced. Methods Qualitative data were collected between September 2010 and February 2011. A total of 12 Focus Group Discussions and 22 Critical Incident Interviews were conducted with primary caregivers who had reported a recent febrile episode for one of their children. Findings and Conclusion The phrase ‘kutentha thupi’, or ‘hot body’ was used to describe fever, the most frequently mentioned causes of which were malungo (translated as ‘malaria’), mauka, nyankhwa and (m)tsempho. Differentiating the cause was challenging because these illnesses were described as having many similar non-specific symptoms, despite considerable differences in the perceived mechanisms of illness. Malungo was widely understood to be caused by mosquitoes. Commonly described symptoms included: fever, weakness, vomiting, diarrhoea and coughing. These symptoms matched well with the biomedical definition of malaria, although they also overlapped with symptoms of other illnesses in both the biomedical model and local illness classifications. In addition, malungo was used interchangeably to describe malaria and fever in general. Caregivers engaged in a three-phased approach to treatment seeking. Phase 1—Assessment; Phase 2—Seeking care outside the home; Phase 3—Evaluation of treatment response. Within this paper, the three-phased approach is explored to identify potential interventions to target barriers to appropriate treatment. Community engagement and health promotion, the provision of antimalarials at community level and better training health workers in the causes and treatment of non-malarial febrile illnesses may improve access to appropriate treatment and outcomes

Time to endoscopy for acute upper gastrointestinal bleeding: results from a prospective multicentre trainee-led audit

Background: Endoscopy within 24 hours of admission (early endoscopy) is a quality standard in acute upper gastrointestinal bleeding (AUGIB). We aimed to audit time to endoscopy outcomes and identify factors affecting delayed endoscopy (>24h of admission).Methods: This prospective multicentre audit enrolled patients admitted with AUGIB who underwent inpatient endoscopy between Nov-Dec 2017. Analyses were performed to identify factorsassociated with delayed endoscopy, and to compare patient outcomes, including length of stay and mortality rates, between early and delayed endoscopy groups.Results: Across 348 patients from 20 centres, the median time to endoscopy was 21.2h (IQR 12.0- 35.7), comprising median admission to referral and referral to endoscopy times of 8.1h (IQR 3.7- 18.1) and 6.7h (IQR 3.0-23.1) respectively. Early endoscopy was achieved in 58.9%, although this varied by centre (range: 31.0% - 87.5%, p=0.002). On multivariable analysis, lower Glasgow-Blatchford score, delayed referral, admissions between 7am-7pm or via the Emergency Department were independent predictors of delayed endoscopy. Early endoscopy was associated with reduced length of stay (median difference 1d; p= 0.004), but not 30-day mortality (p=0.344).Conclusions: The majority of centres did not meet national standards for time to endoscopy. Strategic initiatives involving acute care services may be necessary to improve this outcome