J. M. Ong'echa

J. M. Ong'echa
Kenya Medical Research Institute | KEMRI · Centre for Global Health Research

PhD

About

125
Publications
9,417
Reads
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2,124
Citations
Additional affiliations
September 2002 - December 2007
University of Pittsburgh
Position
  • PostDoc Position
Description
  • Worked on the immunologic and genetic basis of severe malaria anemia in children
January 2002 - present
Kenya Medical Research Institute
Position
  • Researcher
Description
  • I oversee all the field and laboratory studies related to our investigations on the immunologic and genetic basis of severe malaria anemia. In addition, I co-ordinate several clinical trials on anti-malaria drugs.

Publications

Publications (125)
Article
Full-text available
Background Individuals living in endemic areas acquire immunity to malaria following repeated parasite exposure. We sought to assess the controlled human malaria infection (CHMI) model as a means of studying naturally acquired immunity in Kenyan adults with varying malaria exposure. Methods We analysed data from 142 Kenyan adults from three locati...
Article
Full-text available
Children diagnosed with endemic Burkitt lymphoma (eBL) are deficient in interferon-γ (IFN-γ) responses to Epstein–Barr Nuclear Antigen1 (EBNA1), the viral protein that defines the latency I pattern in this B cell tumor. However, the contributions of immune-regulatory cytokines and phenotypes of the EBNA1-specific T cells have not been characterized...
Article
Full-text available
Background: Human infection studies (HIS) that involve deliberately infecting healthy volunteers with a pathogen raise important ethical issues, including the need to ensure that benefits and burdens are understood and appropriately accounted for. Building on earlier work, we embedded social science research within an ongoing malaria human infecti...
Article
Full-text available
Endemic Burkitt lymphoma (eBL) is an aggressive pediatric B cell lymphoma, common in Equatorial Africa. Co-infections with Epstein-Barr virus (EBV) and Plasmodium falciparum, coupled with c-myc translocation are involved in eBL etiology. Infection-induced immune evasion mechanisms to avoid T cell cytotoxicity may increase the role of Natural killer...
Article
Full-text available
Herpesvirus infections shape the human natural killer (NK) cell compartment. While Epstein-Barr virus (EBV) expands immature NKG2A⁺ NK cells, human cytomegalovirus (CMV) drives accumulation of adaptive NKG2C⁺ NK cells. Kaposi sarcoma-associated herpesvirus (KSHV) is a close relative of EBV, and both are associated with lymphomas, including primary...
Article
Full-text available
Non-typhoidal Salmonella (NTS) is a major global health concern that often causes bloodstream infections in areas of the world affected by malnutrition and comorbidities such as HIV and malaria. Developing a strategy to control the emergence and spread of highly invasive and antimicrobial resistant NTS isolates requires a comprehensive analysis of...
Preprint
Full-text available
Endemic Burkitt lymphoma (eBL) is an aggressive pediatric B cell lymphoma, common in Equatorial Africa. Co-infections with Epstein-Barr virus (EBV) and Plasmodium falciparum, coupled with c-myc translocation are involved in eBL etiology. Infection-induced immune evasion mechanisms to avoid T cell cytotoxicity may increase the role of Natural killer...
Conference Paper
Introduction: The tumor microenvironment and the interaction between immune checkpoint inhibitors (ICIs) and tumor cells are essential to understand for designing future immunotherapy strategies. In this study, we aim to characterize the tumor microenvironment (TME) in children diagnosed with endemic Burkitt lymphoma (eBL), the most common pediatri...
Conference Paper
Full-text available
Endemic Burkitt lymphoma (eBL), the most common pediatric cancer in equatorial Africa, has long been associated with two etiologic agents: Epstein-Barr virus (EBV) and Plasmodium falciparum malaria. On the other hand, Natural Killer (NK) cells are essential in the clearance of infected cells as well as play a critical role in tumor immunosurveillan...
Article
Objective: To assess the baseline types of HPV infection among HIV-positive and HIV-negative women in western Kenya undergoing cryotherapy or loop electrosurgical excision procedure (LEEP) for cervical intraepithelial neoplasia. Methods: A prospective observational study was conducted of baseline HPV characteristics women undergoing visual inspe...
Article
Full-text available
Endemic Burkitt lymphoma (eBL), the most prevalent pediatric cancer in sub-Saharan Africa, is associated with malaria and Epstein Barr virus (EBV). In order to better understand the role of EBV in eBL, we improved viral DNA enrichment methods and generated a total of 98 new EBV genomes from both eBL cases (N=58) and healthy controls (N=40) residing...
Article
Full-text available
Natural Killer (NK) cells play an essential role in antiviral and anti-tumoral immune responses. In peripheral blood, NK cells are commonly classified into two major subsets: CD56brightCD16neg and CD56dimCD16pos despite the characterization of a CD56negCD16pos subset 25 years ago. Since then, several studies have described the prevalence of an CD56...
Article
Full-text available
Background: Endemic Burkitt's lymphoma (eBL) is associated with Epstein-Barr virus (EBV) and Plasmodium falciparum (Pf) malaria co-infections. However, the role of Kaposi sarcoma-associated herpesvirus (KSHV), also endemic in Africa, has not been evaluated as a co-factor in eBL pathogenesis. Methods: Multiplexed seroprofiles for EBV, malaria and...
Article
Full-text available
Malaria remains a major public health burden despite approval for implementation of a partially effective pre-erythrocytic malaria vaccine. There is an urgent need to accelerate development of a more effective multi-stage vaccine. Adults in malaria endemic areas may have substantial immunity provided by responses to the blood stages of malaria para...
Article
Full-text available
Cyclooxygenase-2 [(COX-2) or prostaglandin endoperoxide H2 synthase-2 (PTGS-2)] induces the production of prostaglandins as part of the host-immune response to infections. Although a number of studies have demonstrated the effects of COX-2 promoter variants on autoimmune and inflammatory diseases, their role in malaria remains undefined. As such, w...
Article
Full-text available
Burkitt lymphoma (BL) is an aggressive, MYC-driven lymphoma comprising 3 distinct clinical subtypes: sporadic BLs that occur worldwide, endemic BLs that occur predominantly in sub-Saharan Africa, and immunodeficiency-associated BLs that occur primarily in the setting of HIV. In this study, we comprehensively delineated the genomic basis of BL throu...
Article
Full-text available
Background: Severe malarial anemia (SMA) is a leading cause of malaria-related morbidity and mortality in children. The genetic factors that influence development of SMA and inefficient erythropoiesis, a central pathogenic feature of SMA, are only partially understood. Methods: We performed a pilot Genome-wide Association Study (GWAS) on childre...
Preprint
Full-text available
Endemic Burkitt lymphoma (eBL), the most prevalent pediatric cancer in sub-Saharan Africa, is associated with malaria and Epstein Barr virus (EBV). In order to better understand the role of EBV in eBL, we improved viral DNA enrichment methods and generated a total of 98 new EBV genomes from both eBL cases (N=58) and healthy controls (N=40) residing...
Article
Full-text available
Background: Severe malarial anaemia (SMA) is a leading cause of childhood mortality in holoendemic Plasmodium falciparum regions. Methods: To gain an improved understanding of SMA pathogenesis, whole genome and transcriptome profiling was performed in Kenyan children (n=144, 3-36months) with discrete non-SMA and SMA phenotypes. Leukocyte associa...
Article
Full-text available
Background: Leukocyte-associated immunoglobulin like receptor-1 (LAIR1) is a transmembrane inhibitory receptor that influences susceptibility to a myriad of inflammatory diseases. Our recent investigations of severe malarial anaemia (SMA) pathogenesis in Kenyan children discovered that novel LAIR1 genetic variants which were associated with decrea...
Article
e17015 Background: Cervical cancer, a malignancy caused by human papillomavirus (HPV) infection, is the most common malignancy in women living in sub-Saharan African countries including Kenya. HIV co-infection accelerates the natural course of cervical cancer. To determine the specific HPV type distribution in HIV-infected women compared to HIV-uni...
Article
Full-text available
Background Cervical cancer is caused by oncogenic human papillomaviruses (HPV) and is one of the most common malignancies in women living in sub-Saharan Africa. Women infected with the human immunodeficiency virus (HIV) have a higher incidence of cervical cancer, but the full impact on HPV detection is not well understood, and associations of biolo...
Article
Full-text available
Background Both malaria and mental disorders are associated with immune changes. We have previously reported the associations between malaria and mental disorders. We now report associations between malaria, mental disorders and immunity. Methods A household survey of malaria, mental disorders and immunity was conducted in a health and demographic...
Article
Full-text available
Key Points Terminally differentiated CD56neg NK cells expand in children after chronic malaria exposure and in those diagnosed with eBL. NK cells in eBL patients express high levels of MIP-1β in lieu of TNF-α, and normal NK cell profiles appear to be restored in eBL survivors.
Article
Full-text available
Natural killer (NK) cells are critical for restricting viral infections and mediating tumor immunosurveillance. Epstein-Barr virus (EBV) and Plasmodium falciparum malaria are known risk factors for endemic Burkitt lymphoma (eBL), the most common childhood cancer in equatorial Africa. To date, the composition and function of NK cells have not been e...
Article
Full-text available
Background Burkitt lymphoma (BL) is characterized by overexpression of the c-myc oncogene, which in the vast majority of cases is a consequence of an IGH/MYC translocation. While myc is the seminal event, BL is a complex amalgam of genetic and epigenetic changes causing dysregulation of both coding and non-coding transcripts. Emerging evidence sugg...
Article
Full-text available
Cellular and humoral constituents of the immune system differ significantly between children and adults, yet very little is known about the impact of early-life pathogen exposure on this immunologic transition. We examined CD4+ and CD8+ T cell subsets defined by CCR7 and CD45RA expression in two longitudinal pediatric cohorts experiencing divergent...
Article
Full-text available
Endemic Burkitt lymphoma (eBL) is the most common pediatric cancer in malaria-endemic equatorial Africa and nearly always contains Epstein-Barrvirus (EBV), unlike sporadic Burkitt lymphoma (sBL) that occurs with a lower incidence in developed countries. Given these differences and the variable clinical presentation and outcomes, we sought to furthe...
Article
Full-text available
In Plasmodium falciparum holoendemic transmission regions of western Kenya, life-threatening pediatric malaria manifests primarily as severe malarial anemia (SMA, Hb≤6.0 g/dL with any density parasitemia). To determine the role that CD4+ T-cell-driven inflammatory responses have in the pathogenesis of SMA, peripheral CD4+ T-cell populations and the...
Article
Full-text available
Background: Naturally-acquired immunity to Plasmodium falciparum malaria develops after several episodes of infection. Fc gamma receptors (FcγRs) bind to immunoglobulin G (IgG) antibodies and mediate phagocytosis of opsonized microbes, thereby, linking humoral and cellular immunity. FcγR polymorphisms influence binding affinity to IgGs and consequ...
Article
Full-text available
Background Improved understanding of the molecular mechanisms involved in pediatric severe malarial anemia (SMA) pathogenesis is a crucial step in the design of novel therapeutics. Identification of host genetic susceptibility factors in immune regulatory genes offers an important tool for deciphering malaria pathogenesis. The IL-23/IL-17 immune pa...
Data
Representative flow cytometry plots of cytokine production and the gating strategy used to set the cut-offs for cytokine-positive and–negative cells. (A) Representative forward versus side scatter gating strategy for the peripheral blood stimulation for the study participants. Dot plot (B) CD4+CD45RA+ T cells, (C) CD4+CD45RA+IFN-γ+ T cells, (D) CD4...
Data
Representative flow cytometry plots showing the gating strategy using isotypic controls and matched IL-17 antibodies to set the cut-offs for cytokine-positive and -negative cells. Isotypic controls 1–3 have their matched IL-17-positive cell cut-offs below them. (TIF)
Data
Characteristics of the study participants stratified by age. Data analysis performed by Mann-Whitney U tests except for gender and sickle cell trait that we compared using χ2 tests. Data are presented as median (IQR); except for gender and sickle cell trait that are presented as n (%). (DOCX)
Data
Representative flow cytometry plots showing the gating strategy using isotypic controls and matched IFN-γ antibodies to set the cut-offs for cytokine-positive and -negative cells. Isotypic controls 1–3 have their matched IFN-γ-positive cell cut-offs below them. (TIF)
Article
Full-text available
Endemic Burkitt lymphoma (eBL) is an aggressive B cell lymphoma and is associated with Epstein-Barr virus (EBV) and Plasmodium falciparum malaria co-infections. Central to BL oncogenesis is the over-expression of the MYC proto-oncogene which is caused by a translocation of an Ig enhancer in approximation to the myc gene. While whole genome/transcri...
Data
Normalized expression counts of Human and EBV miRNAs expressed in eBL tumor.
Data
Pearson correlation scatter plots showing a positive correlation between qRT-PCR miR-10a-5p expression levels and miRNA-seq miR-10a-5p expression levels.
Data
Key patient characteristics and small RNA sequence mapping information.
Data
Hierarchical clustering of all the host and viral miRNAs expressed in the eBL tumor cells.
Data
PCA plots of eBL tumors sites. The sample names were colored per their groups (red represents the jaw tumors and black represented the abdominal tumors). The tumor samples don't show well-defined grouping based on tumor site in the PCA analysis.
Data
Pearson correlation scatter plots showing the relationship between hsa-miR-10a-5p expression and its target gene expression in eBL patients. The blue points represent the eBL patients with the jaw tumors and the red points represents eBL patients with the abdominal tumors.
Data
Validated target genes of miR-10a-5p and miRNA-target mRNA expression correlation coefficients.
Data
Bioinformatic workflow for host and viral miRNA analysis pipeline (processed raw reads and identified counts of known human and ebv miRNAs in high-throughput sequencing data).
Data
Gene ontologies enriched (Biological processes, Cellular components and Molecular functions) by the validated target genes of miR-10a-5p.
Data
miRNA differential expression analysis results.
Article
Endemic Burkitt lymphoma (eBL) is the most common pediatric cancer in malaria-endemic equatorial Africa and nearly always contains Epstein-Barrvirus (EBV), unlike sporadic Burkitt lymphoma (sBL) that occurs with a lower incidence in developed countries. Given these differences and the variable clinical presentation and outcomes, we sought to furthe...
Article
Full-text available
Background: Despite a reduction in the global burden of malaria, the disease remains responsible for 214 million cases and 438,000 deaths annually with 88% of the mortality occurring in sub-Saharan Africa. Malaria control largely depends on effective chemotherapy. However, the historic and current emergence and spread of multi-drug resistant paras...
Article
Full-text available
Deficiencies in Epstein-Barr virus (EBV)-specific T cell immunosurveillance appear to precede the development of endemic Burkitt lymphoma (eBL), a malaria-associated pediatric cancer common in sub-Saharan Africa. However, T cell contributions to eBL disease progression and survival have not been characterized. Our objective was to investigate regul...
Data
Gating strategies. Gating strategy for identification of T cells from singlets, live CD3+ T cells (using ViViD live/dead exclusion dye with CD14 and CD19 dump channel), and CD4+ versus CD8+ cells (A). Within the CD4+ gate, identification of CD25+Foxp3+ Treg cells using CD25 and Foxp3 Fluorescence Minus One (FMO) stains (B). Identification of CD4+ I...
Data
Overall frequencies of CD45RA and CCR7 expressing T cell subsets do not differ between non-survivors, survivors, and healthy controls. (A) Gating strategy to identify CD8+ CD45RA and CCR7 subsets. Frequencies of CD8+ and CD4+ CD45RA-CCR7+, CD45RA+CCR7+, CD45RA-CCR7-, CD45RA+CCR7- cells (B, C). ● Non-survivors; ■ Survivors; ▲Healthy controls (TIF)
Data
No differences with malaria parasitemia or tumor stage. (A) Among those that produced CD4+ IFN-γ in response