Spatially resolved single-cell atlas unveils a distinct cellular signature of fatal lung COVID-19 in a Malawian population.

Postmortem single-cell studies have transformed understanding of lower respiratory tract diseases (LRTDs), including coronavirus disease 2019 (COVID-19), but there are minimal data from African settings where HIV, malaria and other environmental exposures may affect disease pathobiology and treatment targets. In this study, we used histology and high-dimensional imaging to characterize fatal lung disease in Malawian adults with (n = 9) and without (n = 7) COVID-19, and we generated single-cell transcriptomics data from lung, blood and nasal cells. Data integration with other cohorts showed a conserved COVID-19 histopathological signature, driven by contrasting immune and inflammatory mechanisms: in US, European and Asian cohorts, by type I/III interferon (IFN) responses, particularly in blood-derived monocytes, and in the Malawian cohort, by response to IFN-γ in lung-resident macrophages.

Reflections on 20 years of the Wilms Africa project: Lessons learned and the way forward.

Wilms tumour (WT) is one of the common and curable childhood cancer types included in the Global Initiative for Childhood Cancer (GICC) to monitor progress. Local evidence is key to finding effective and sustainable solutions to local challenges to improve care and survival. Local evidence generated by the Wilms Africa project is summarised with recommendations for the future.

Effectiveness of a Wilms tumour treatment guideline adapted to local circumstances in sub-Saharan Africa: A report from Wilms Africa Phase II-CANCaRe Africa.

Background: Wilms tumour (WT) is one of the cancer types targeted by the Global Initiative for Childhood Cancer (GICC). The objective of this study was to describe the outcomes of Wilms Africa Phase II in sub-Saharan Africa.

Methods: Wilms Africa Phase II used a comprehensive WT treatment protocol in a multi-centre, prospective study conducted in eight hospitals in Ethiopia (2), Ghana (2), Malawi, Cameroon, Zimbabwe and Uganda.

Human leukocyte antigen-DQA1*04:01 and rs2040406 variants are associated with elevated risk of childhood Burkitt lymphoma.

Burkitt lymphoma (BL) is responsible for many childhood cancers in sub-Saharan Africa, where it is linked to recurrent or chronic infection by Epstein-Barr virus or Plasmodium falciparum. However, whether human leukocyte antigen (HLA) polymorphisms, which regulate immune response, are associated with BL has not been well investigated, which limits our understanding of BL etiology. Here we investigate this association among 4,645 children aged 0-15 years, 800 with BL, enrolled in Uganda, Tanzania, Kenya, and Malawi.

Genotypes and Risk of Childhood Burkitt Lymphoma in East Africa.

Interferon lambda 4 (IFN-λ4) is a novel type-III interferon that can be expressed only by carriers of the genetic variant rs368234815-dG within the first exon of the gene. Genetic inability to produce IFN-λ4 (in carriers of the rs368234815-TT/TT genotype) has been associated with improved clearance of hepatitis C virus (HCV) infection. The IFN-λ4-expressing rs368234815-dG allele (-dG) is most common (up to 78%) in West sub-Saharan Africa (SSA), compared to 35% of Europeans and 5% of individuals from East Asia.

Minimally Invasive Postmortem Intestinal Tissue Sampling in Malnourished and Acutely Ill Children Is Feasible and Informative.

Background: Intestinal disorders such as environmental enteric dysfunction (EED) are prevalent in low- and middle-income countries (LMICs) and important contributors to childhood undernutrition and mortality. Autopsies are rarely performed in LMICs but minimally invasive tissue sampling is increasingly deployed as a more feasible and acceptable procedure, although protocols have been devoid of intestinal sampling to date. We sought to determine (1) the feasibility of postmortem intestinal sampling, (2) whether autolysis precludes enteric biopsies' utility, and (3) histopathologic features among children who died during hospitalization with acute illness or undernutrition.

Localised release of matrix metallopeptidase 8 in fatal cerebral malaria.

Objective: Cerebral malaria (CM) is a complication of malaria, in which progressive brain swelling is associated with sequestration of parasites and impaired barrier function of the cerebral microvascular endothelium. To test the hypothesis that localised release of matrix metallopeptidase 8 (MMP8) within the retina is implicated in microvascular leak in CM, we examined its expression and association with extravascular fibrinogen leak in a case-control study of post-mortem retinal samples from 13 Malawian children who met the clinical case definition of CM during life. Cases were seven children who were found on post-mortem examination to have 'true-CM' (parasite sequestration in brain blood vessels), whilst controls were six children who had alternative causes of death ('faux-CM', no parasite sequestration in blood vessels).

Assessment of Mixed Infection in Endemic Burkitt Lymphoma: A Case-Control Study in Malawi.

Background: Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in Africa and is linked to () malaria infection, one of the most common and deadly childhood infections in Africa; however, the role of genetic diversity is unclear. A potential role of genetic diversity in eBL has been suggested by a correlation of age-specific patterns of eBL with the complexity of infection in Ghana, Uganda, and Tanzania, as well as a finding of significantly higher genetic diversity, based on a sensitive molecular barcode assay, in eBL cases than matched controls in Malawi. We examined this hypothesis by measuring diversity in serine repeat antigen-5 (), an antigenic target of blood-stage immunity to malaria, among 200 eBL cases and 140 controls, all polymerase chain reaction (PCR)-positive, in Malawi.

HLA-DRB1 alleles and cervical cancer: A meta-analysis of 36 case-control studies.

Background: Human leukocyte antigens (HLA) are encoded by closely linked genetic loci, and are important in cervical carcinogenesis. The association between HLA-DRB1 alleles with cervical cancer has been studied extensively, but results reported thus far have been inconsistent. Hence, we performed a meta-analysis to precisely assess this association.

Improvement of overall survival in the Collaborative Wilms Tumour Africa Project.

Introduction: The Collaborative Wilms Tumour (WT) Africa Project implemented an adapted WT treatment guideline in six centres in sub-Saharan Africa. The primary objectives were to describe abandonment of treatment, death during treatment, event-free survival (EFS) and relapse following implementation. An exploratory objective was to compare outcomes with the baseline evaluation, a historical cohort preceding implementation.

Association of TP53 rs1042522 with cervical cancer in the sub-Saharan African population: a meta-analysis.

Objective: TP53 plays a crucial role in preventing cancer development. Previous studies in sub-Saharan Africa (SSA) reported inconclusive findings for the association of the TP53 rs1042522 C > G variant with cervical cancer. We therefore performed a meta-analysis to summarise this association in the SSA population.

Impact of Maternal HIV Infection and Placental Malaria on the Transplacental Transfer of Influenza Antibodies in Mother-Infant Pairs in Malawi, 2013-2014.

Background: Maternal influenza vaccination protects infants against influenza virus infection. Impaired transplacental transfer of influenza antibodies may reduce this protection.

Methods: We conducted a cross-sectional study of influenza vaccine-naïve pregnant women recruited at delivery from Blantyre (urban, low malaria transmission) and Chikwawa (rural, high malaria transmission) in Southern Malawi.

Comparison of CD8 T Cell Accumulation in the Brain During Human and Murine Cerebral Malaria.

CD8 T cells have been shown to play a critical role in the pathogenesis of experimental cerebral malaria (ECM) in mice, but their role in development of human cerebral malaria (HCM) remains unclear. Thus, in this study we have provided the first direct contrast of the accumulation of CD8 T cells in the brain during HCM and ECM. HCM cases were from children who died of cerebral malaria at Queen Elizabeth Central Hospital (Malawi) between 2003 and 2010.

The Medical Education Partnership Initiative (MEPI): Innovations and Lessons for Health Professions Training and Research in Africa.

MEPI was a $130 million competitively awarded grant by President's Emergency Plan for AIDS Relief (PEPFAR) and National Institutes of Health (NIH) to 13 Medical Schools in 12 Sub-Saharan African countries and a Coordinating Centre (CC). Implementation was led by Principal investigators (PIs) from the grantee institutions supported by Health Resources and Services Administration (HRSA), NIH and the CC from September, 2010 to August, 2015. The goals were to increase the capacity of the awardees to produce more and better doctors, strengthen locally relevant research, promote retention of the graduates within their countries and ensure sustainability.

Evaluating the use of pathology in improving diagnosis in rural Malawi.

Introduction: Limited data exists on histologically confirmed cancers and tuberculosis in rural Malawi, despite the high burden of both conditions. One of the main reasons for the limited data is the lack of access to pathology services for diagnosis. We reviewed histopathology results of patients in Neno District, one of the poorest rural districts in Malawi, from May 2011 to July 2017, with an emphasis on cancers and tuberculosis.

Survival of children with a Wilms tumor in Blantyre, Malawi.

Wilms tumor (WT) has a survival rate above 90% in high income countries. Reported survival rates in sub-Saharan Africa are much lower and long-term outcome is not well known as follow-up is challenging. In Blantyre, Malawi, an adapted WT treatment guideline with preoperative chemotherapy, supportive care, and strategies to enable children and parents to complete treatment was introduced in 2006.

Neurovascular sequestration in paediatric malaria is visible clinically in the retina.

Retinal vessel changes and retinal whitening, distinctive features of malarial retinopathy, can be directly observed during routine eye examination in children with cerebral malaria. We investigated their clinical significance and underlying mechanisms through linked clinical, clinicopathological and image analysis studies. Orange vessels and severe foveal whitening (clinical examination, n = 817, OR, 95% CI: 2.

Co-causation of reduced newborn size by maternal undernutrition, infections, and inflammation.

More than 20 million babies are born with low birthweight annually. Small newborns have an increased risk for mortality, growth failure, and other adverse outcomes. Numerous antenatal risk factors for small newborn size have been identified, but individual interventions addressing them have not markedly improved the health outcomes of interest.

Periapical infection may affect birth outcomes via systemic inflammation.

Objectives: Maternal dental periapical infections are associated with preterm birth and intrauterine growth restriction. This study investigates whether the association is mediated through bacterial spread from periapical lesions to placenta (direct pathway) or systemic inflammatory reaction (indirect pathway).

Materials And Methods: We compared birth outcomes in Malawian mothers with and without periapical infection.

The Role of Human Immunodeficiency Virus-Associated Vasculopathy in the Etiology of Stroke.

Background: Human immunodeficiency virus (HIV) infection is a recognized risk factor for stroke among young populations, but the exact mechanisms are poorly understood. We studied the clinical, radiologic, and histologic features of HIV-related ischemic stroke to gain insight into the disease mechanisms.

Methods: We conducted a prospective, in-depth analysis of adult ischemic stroke patients presenting to Queen Elizabeth Central Hospital, Blantyre, Malawi, in 2011.

Extranodal natural killer/T-cell lymphoma in Malawi: a report of three cases.

Background: Extranodal NK/T-cell lymphoma (ENKTCL) reports from sub-Saharan Africa (SSA) are remarkably rare, despite early childhood acquisition and high prevalence of the causative infectious agent, Epstein-Barr virus (EBV), and frequent occurrence of other lymphoproliferative disorders causally associated with EBV.

Case Presentations: At a national teaching hospital in Malawi, three patients of African descent were seen with ENKTCL between 2013 and 2014. Patients were aged between 29 and 60 years, two with craniofacial involvement and one with a primary abdominal tumor, and all were HIV-negative.