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Collins Ouma - One of the best experts on this subject based on the ideXlab platform.
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haplotype of non synonymous mutations within il 23r is associated with susceptibility to severe malaria anemia in a p falciparum Holoendemic transmission area of kenya
BMC Infectious Diseases, 2017Co-Authors: Evans Raballah, Collins Ouma, Elly O Munde, Winnie A Okeyo, John M Ongecha, Douglas J PerkinsAbstract: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 pathway is important for both immunity and erythropoiesis via its effects through IL-23 receptors (IL-23R). However, the impact of IL-23R variants on SMA has not been fully elucidated. Since variation within the coding region of IL-23R may influence the pathogenesis of SMA, the association between IL-23R rs1884444 (G/T), rs7530511 (C/T), and SMA (Hb < 6.0 g/dL) was examined in children (n = 369, aged 6–36 months) with P. falciparum malaria in a Holoendemic P. falciparum transmission area. Logistic regression analysis, controlling for confounding factor of anemia, revealed that individual genotypes of IL-23R rs1884444 (G/T) [GT; OR = 1.34, 95% CI = 0.78–2.31, P = 0.304 and TT; OR = 2.02, 95% CI = 0.53–7.74, P = 0.286] and IL-23R rs7530511 (C/T) [CT; OR = 2.6, 95% CI = 0.59–11.86, P = 0.202 and TT; OR = 1.66, 95% CI = 0.84–3.27, P = 0.142] were not associated with susceptibility to SMA. However, carriage of IL-23R rs1884444T/rs7530511T (TT) haplotype, consisting of both mutant alleles, was associated with increased susceptibility to SMA (OR = 1.12, 95% CI = 1.07–4.19, P = 0.030). Results presented here demonstrate that a haplotype of non-synonymous IL-23R variants increase susceptibility to SMA in children of a Holoendemic P. falciparum transmission area.
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access to artemisinin based combination therapy act and quinine in malaria Holoendemic regions of western kenya
Malaria Journal, 2014Co-Authors: Carren A Watsierah, Collins OumaAbstract:Background: Artemisinin-based combination therapy (ACT) has been adopted as the most effective treatment against malaria in many endemic countries like Kenya while quinine has remained the second line. The objective of the current study was to assess access to Kenya’s policy recommended anti-malarials, ACT and quinine in the public, private and not-for-profit drug outlets in western Kenya. Methods: A cross-sectional survey using purposive sampling of 288 outlets (126 public, 96 private, 66 not-for-profit) was conducted in western Kenya in two regions with varying Plasmodium falciparum endemicities. Information on access (availability, price, affordability) on ACT and quinine was collected using the WHO and Healthcare Associated Infection (HAI) standardized methodologies for availability, prices and affordability of drugs. From a Ministry of Health database, the following were included in the analyses: one (1) main public hospital, followed by random selection of five hospitals under this main facility. Eight other public outlets under each of the hospitals were selected, to a total of 96. Matching number of private outlets (n = 96), all (66) not-for-profit outlets and additional 30 public health facilities were sampled to get the required sample size of 288. Results: More public 111 (88.1%) and not-for-profit 27 (40.9%) outlets stocked subsidized ACT (artemether-lumefantrine, AL). Other artemisinin-based combinations were widely available for both children 93 (96.9%) and adults 82 (85.0%) in private outlets. Frequent stock-outs were in public in 106 (84%), reporting three times or more stock-outs in three months. Subsidized ACT (AL) was sold at median price of USD 0.94 and 0.75 in private and not-for-profit outlets respectively. The costs was higher than recommended price of USD 0.5 and requiring up to 0.20-0.25 days of disposable income for households in lowest economic status. Conclusion: There is low availability of subsidized ACT (AL) and higher frequency of stock-outs in government facilities, while private sector sells AL at higher prices, thus making it less affordable to many households. These factors determine the adherence to the dosing schedules during the treatment course and thus the evaluation of the subsidy policy, its implementation and role in malaria burden in this region is compulsory.
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knowledge and behaviour as determinants of anti malarial drug use in a peri urban population from malaria Holoendemic region of western kenya
Malaria Journal, 2011Co-Authors: Carren A Watsierah, Walter G Z O Jura, Evans Raballah, Dan Kaseje, Benard Abongo, Collins OumaAbstract:Background The appropriate use of anti-malarial drugs determines therapeutic efficacy and the emergence and spread of drug-resistant malaria. Strategies for improving drug compliance require accurate information about current practices at the consumer level. This is to ascertain that the currently applied new combination therapy to malaria treatment will achieve sustained cure rates and protection against parasite resistance. Therefore, this cross-sectional study was designed to determine knowledge and behaviour of the consumers in households (n = 397) in peri-urban location in a malaria Holoendemic region of western Kenya.
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factors determining anti malarial drug use in a peri urban population from malaria Holoendemic region of western kenya
Malaria Journal, 2010Co-Authors: Carren A Watsierah, Walter G Z O Jura, Benard Abongo, Collins Ouma, Henry OyugiAbstract:Background Interventions to reverse trends in malaria-related morbidity and mortality in Kenya focus on preventive strategies and drug efficacy. However, the pattern of use of anti-malarials in malaria-endemic populations, such as in western Kenya, is still poorly understood. It is critical to understand the patterns of anti-malarial drug use to ascertain that the currently applied new combination therapy to malaria treatment, will achieve sustained cure rates and protection against parasite resistance. Therefore, this cross-sectional study was designed to determine the patterns of use of anti-malarial drugs in households (n = 397) in peri-urban location of Manyatta-B sub-location in Kisumu in western Kenya.
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clinical predictors of severe malarial anaemia in a Holoendemic plasmodium falciparum transmission area
British Journal of Haematology, 2010Co-Authors: Enrico M. Novelli, Collins Ouma, James B. Hittner, Gregory C. Davenport, Tom Were, Stephen K Obaro, Sandra S. Kaplan, John M OngechaAbstract:Summary Severe malarial anaemia (SMA) is a common complication of Plasmodium falciparum infections, resulting in mortality rates that may exceed 30% in paediatric populations residing in Holoendemic transmission areas. One strategy for reducing the morbidity and mortality associated with SMA is to identify clinical predictors that can be readily recognized by caregivers for prompt therapeutic interventions. To determine clinical predictors of SMA, Kenyan children (3–36 months, n = 671) presenting with acute illness at a rural hospital in Siaya District were recruited. Demographic, clinical, laboratory and haematological parameters were measured upon enrolment. As human immunodeficiency virus-1 and bacteraemia promote reduced haemoglobin (Hb) concentrations, children with these infections were excluded from the analyses. Children with P. falciparum mono-infections (n = 355) were stratified into three groups: uncomplicated malaria (Hb ≥ 110 g/l); non-SMA (60 ≤ Hb < 109), and SMA (Hb < 60 g/l). SMA was characterized by a younger age, monocytosis, thrombocytopenia, reticulocytosis, reduced erythropoiesis, elevated pigment-containing monocytes (PCM), respiratory distress, conjunctival and palmar pallor, splenomegaly, signs of malnutrition, and protracted fever and emesis. Logistic regression analysis demonstrated that age, reticulocyte count, presence of PCM and conjunctival and palmar pallor were significant predictors of SMA. Recognition of these clinical signs in children residing in resource-poor settings may help to guide the identification and management of SMA.
Rosemary Rochford - One of the best experts on this subject based on the ideXlab platform.
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aid expression in peripheral blood of children living in a malaria Holoendemic region is associated with changes in b cell subsets and epstein barr virus
International Journal of Cancer, 2015Co-Authors: Joel R Wilmore, Odada P. Sumba, Amolo S. Asito, Erwan Piriou, Ignacio Sanz, Rosemary RochfordAbstract:: The development of endemic Burkitt's lymphoma (eBL) is closely associated with Epstein-Barr virus (EBV) infection and Holoendemic malaria infections. The role of EBV in the development of malignancy has been studied in depth, but there is still little known about the mechanisms by which malaria affects Burkitt's lymphomagenesis. Activation induced cytidine deaminase (AID) expression is necessary for the introduction of c-myc translocations that are characteristic of BL, but a link between AID and EBV or malaria is unclear. To determine whether frequency of malaria exposure leads to increased AID expression in peripheral blood mononuclear cells (PBMC) we examined two cohorts of children in western Kenya with endemic and sporadic malaria transmission dynamics. High frequency of malaria exposure led to increased expression of AID, which coincided with decreases in the IgM(+) memory B cells. In the children from the malaria endemic region, the presence of a detectible EBV viral load was associated with higher AID expression compared to children with undetectable EBV, but this effect was not seen in children with sporadic exposure to malaria. This study demonstrates that intensity of malaria transmission correlates with AID expression levels in the presence of EBV suggesting that malaria and EBV infection have a synergistic effect on the development of c-myc translocations and BL.
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The Many Roles of Malaria in the Etiology of Endemic Burkitt Lymphoma
Burkitt’s Lymphoma, 2012Co-Authors: Rosemary Rochford, Amolo S. AsitoAbstract:The weight of both epidemiologic and molecular studies confirms that malaria is an etiologic cofactor in endemic Burkitt’s lymphoma (eBL). This chapter will review the literature on the epidemiologic association of eBL with areas of Africa and Papua New Guinea where malaria transmission is Holoendemic as well as studies revealing potential mechanisms by which malaria could contribute to the increased incidence of eBL.
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decline in ebv specific ifn t cell responses in kenyan infants from a malaria Holoendemic region of kenya
Infectious Agents and Cancer, 2012Co-Authors: Ann M. Moormann, Odada P. Sumba, Amolo S. Asito, Erwan Piriou, Rosemary RochfordAbstract:Background Endemic Burkitt’s lymphoma, the most prevalent childhood cancer in Equatorial Africa, is a rapidly growing B-cell malignancy that is ultimately fatal if untreated. Two co-factors are linked to the etiology of this pediatric cancer: Epstein-Barr virus (EBV) infection, and sustained and intense exposure to Plasmodium falciparum malaria (Holoendemic malaria). In this study, we wanted to test the hypothesis that P. falciparum infections during early infancy results in elevated EBV viral load which results in diminished EBV-specific T-cell immune responses over time.
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serological evidence for long term epstein barr virus reactivation in children living in a Holoendemic malaria region of kenya
Journal of Medical Virology, 2009Co-Authors: Erwan Piriou, Ann M. Moormann, Kiprotich Chelimo, Robert Ploutzsnyder, Rhonda Kimmel, Jaap M Middeldorp, Peter Sumba Odada, Rosemary RochfordAbstract:To study the long term the effects of chronic exposure to P. falciparum malaria on Epstein– Barr virus (EBV) reactivation in children, EBVspecific antibody levels were measured in a cross-sectional survey of two groups of Kenyan children with divergent malaria exposure, varying in age from 1 to 14 years. A total of 169 children were analyzed within three age groups (1–4 years, 5–9 years and 10–14 years). Using a Luminex assay, elevated levels of IgG to EBV lytic and latent antigens were observed in children from the Holoendemic malaria area; these remained elevated for each age group studied. In comparison, children from the sporadic malaria area had lower levels of EBV-specific IgG antibodies and these levels declined across age groups. These data suggest that chronic exposure to malaria may lead to long-term EBV reactivation. J. Med. Virol. 81:1088–1093,
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exposure to Holoendemic malaria results in suppression of epstein barr virus specific t cell immunosurveillance in kenyan children
The Journal of Infectious Diseases, 2007Co-Authors: Ann M. Moormann, Rosemary Rochford, Kiprotich Chelimo, Peter Odada Sumba, Daniel J Tisch, James W. KazuraAbstract:BACKGROUND: Malaria and Epstein-Barr virus (EBV) infection are cofactors in the pathogenesis of endemic Burkitt lymphoma (eBL). The mechanisms by which these pathogens predispose to eBL are not known. METHODS: Healthy Kenyan children with divergent malaria exposure were measured for responses to EBV latent and lytic antigens by interferon (IFN)- gamma enzyme-linked immunospot (ELISPOT) assay and interleukin (IL)-10 ELISA. Phytohemagglutinin (PHA), purified protein derivative (PPD), and T cell epitope peptides derived from merozoite surface protein (MSP)-1, a malaria blood-stage antigen, were also evaluated. RESULTS: Children 5-9 years old living in an area Holoendemic for malaria had significantly fewer EBV-specific IFN- gamma responses than did children of the same age living in an area with unstable malaria transmission. This effect was not observed for children 9 years old. In contrast, IFN- gamma responses to PHA, PPD, and Plasmodium falciparum MSP-1 peptides did not significantly differ by age. IL-10 responses to EBV lytic antigens, PPD, and PHA correlated inversely with malaria exposure regardless of age. CONCLUSIONS: Children living in malaria-Holoendemic areas have diminished EBV-specific T cell immunosurveillance between the ages of 5 and 9 years, which coincides with the peak age incidence of eBL.
Jose A Stoute - One of the best experts on this subject based on the ideXlab platform.
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use of mosquito preventive measures is associated with increased rbc cr1 levels in a malaria Holoendemic area of western kenya
American Journal of Tropical Medicine and Hygiene, 2015Co-Authors: Christine King, Ping Du, Walter Otieno, Jose A StouteAbstract:Abstract. Malaria is responsible for close to 1 million deaths each year, mostly among African children. Red blood cells (RBCs) of children with severe malarial anemia show loss of complement regulatory proteins such as complement receptor 1 (CR1). We carried out this study to identify socio-economic, environmental, and biological factors associated with the loss of RBC CR1. A cross-sectional study was conducted in a malaria Holoendemic area of western Kenya. Twelve socioeconomic, environmental, and biological factors were examined for a relationship with RBC CR1 level using bivariate linear regression followed by creation of a multivariate linear regression model. A significant positive relationship between RBC CR1 level and use of mosquito countermeasures was found. However, there was no evidence of a significant relationship between RBC CR1 level and malaria infection or parasitemia level. Reducing mosquito exposure may aid in the prevention of severe malarial anemia by reducing the number of infections and thus preserving RBC CR1.
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association between sickle cell trait and low density parasitaemia in a p falciparum malaria Holoendemic region of western kenya
International Journal of Tropical Disease & Health, 2012Co-Authors: Walter Otieno, Benson B Estambale, Joash R Aluoch, Stacey M O Gondi, Jose A StouteAbstract:Aims: The frequency of the mutant gene for sickle cell is widely distributed in the subSaharan Africa, the Middle East, and the Indian subcontinent. There is epidemiologic evidence that sickle cell trait confers a survival advantage against malaria and that the selection pressure due to malaria has resulted in high frequencies of the mutant gene in areas of high malaria transmission. We carried out a study to look at the relationship between sickle cell trait, age, haemoglobin level, and malaria parasite density. Methods: We carried out a cross-sectional study between the months of October and December, 2004 in Kombewa Division of Kisumu West District, a P. falciparum malaria
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Reduced Immune Complex Binding Capacity and Increased Complement Susceptibility of Red Cells from Children with Severe Malaria-Associated Anemia
Molecular Medicine, 2008Co-Authors: Boaz O. Owuor, Collins O. Odhiambo, Walter O. Otieno, Christine Adhiambo, Dominic W. Makawiti, Jose A StouteAbstract:Plasmodium falciparum malaria causes 1–2 million deaths per year. Most deaths occur as a result of complications such as severe anemia and cerebral malaria (CM) (coma). Red cells of children with severe malaria-associated anemia (SMA) have acquired deficiencies in the complement regulatory proteins complement receptor 1 (CR1, CD35) and decay accelerating factor (DAF, CD55). We investigated whether these deficiencies affect the ability of erythrocytes to bind immune complexes (ICs) and regulate complement activation. We recruited 75 children with SMA (Hb ≤ 6 g/dL) from the Holoendemic malaria region of the Lake Victoria basin, western Kenya, and 74 age- and gender-matched uncomplicated malaria controls. In addition, we recruited 32 children with CM and 52 age- and gender-matched controls. Deficiencies in red cell CR1 and CD55 in children with SMA were accompanied by a marked decline in IC binding capacity and increased C3b deposition in vivo and ex vivo. Importantly, these changes were specific because they were not seen in red cells of children with CM or their controls. These data suggest that the declines in red cell CR1 and CD55 seen in children with SMA are of physiologic significance and may predispose erythrocytes to complement-mediated damage and phagocytosis in vivo.
Jean-françois Trape - One of the best experts on this subject based on the ideXlab platform.
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high annual and seasonal variations in malaria transmission by anophelines and vector species composition in dielmo a Holoendemic area in senegal
American Journal of Tropical Medicine and Hygiene, 1997Co-Authors: Didier Fontenille, Christophe Rogier, Lassana Konate, Nafissatou Diagne, Laurence Lochouarn, Cheikh Sokhna, Jeanjacques Lemasson, M Diatta, Farba B K Faye, Jean-françois TrapeAbstract:We conducted a three-year entomologic study in Dielmo, a village of 250 inhabitants in a Holoendemic area for malaria in Senegal. Anophelines were captured on human bait and by pyrethrum spray collections. The mosquitoes belonging to the Anopheles gambiae complex were identified using the polymerase chain reaction. Malaria vectors captured were An. funestus, An. arabiensis, and An. gambiae. Anopheles funestus was the most abundant mosquito captured the first year, An. arabiensis in the following years. The annual entomologic inoculation rates calculated by enzyme-linked immunosorbent assay were 238, 89, and 150 for the first, second, and third years, respectively. Each year there was a peak of transmission at the end of the rainy season, but transmission occurred year round. The heterogeneity of transmission was found at four different levels: 1) the relative vector proportion according to the place and method of capture, 2) the human biting rate and relative proportion of vectors by month and year, 3) the infection rate of each vector by year, and 4) the number of infected bites for all vectors, and for each species, for the year. Our data show that even in areas of intense and perennial transmission, there exist large longitudinal variations and strong heterogeneity in entomologic parameters of malaria transmission. It is important to take these into account for the study of the variations in clinical and biological parameters of human malaria, and to evaluate this relationship, a very thorough investigation of transmission is necessary. The interpretation of malaria parameters such as parasit- emia, morbidity, mortality, and associated immune responses depends on having precise information and close follow-up of variations in malaria transmi~sion.'~~ It is very well known that the transmission of malaria in Africa is not homoge- neo~s.~ The vector species and density, the Plasmodium spe- cies, the number of infective bites per human per year (also called the annual entomologic inoculation rate (EX)), and the monthly Em, are changeable. Many studies have com- pared transmission between villages in the same area:-8 but few have shown that significant differences may also occur within the same location over a several year follow-up study. Such variations have to be taken into account in longitudinal studies on the development of malaria immunity, but so far these have been studied very little. A longitudinal study be- gan in 1990 to evaluate malaria infections and the mecha- nisms of protective immunity in a population living in Diel- mo, a village in a Holoendemic area of Senegal. During a four-month follow-up of the entire population conducted during the 1990 rainy season, the cumulative prevalence of P. falciparum, P. malariae, and P. ovale were 98.6%, 50.5%, and 40.3%, respe~tively.~ The preliminary studies showed that the transmission was continuous throughout the year and that the vectors were Anopheles funestus and mos- quitoes of the An. gambiae complex.'0*'' Three species of this complex were noted in the study area: An. gambiae, An. arabiensis, and An. melas. Malaria transmission by these different vectors was stud- ied from 1992 to 1995 using the polymerase chain reaction (PCR), which identifies the species of the An. gambiae com- plex.'* In this paper, we have investigated the relative fre- quencies of the different vector species (An. funestus, An. gambiae, An. arabiensis, andAn. melas) collected within the study area according to the time, season, place, kd method of capture, and
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pattern of immunoglobulin isotype response to plasmodium falciparum blood stage antigens in individuals living in a Holoendemic area of senegal dielmo west africa
American Journal of Tropical Medicine and Hygiene, 1996Co-Authors: Georgette Aribot, Jean-louis Sarthou, Jean-françois Trape, Christophe Rogier, Aissatou Toure Balde, Pierre Druilhe, Christian RoussilhonAbstract:: Three cross-sectional studies were conducted in a representative cohort of individuals living continuously in an area Holoendemic for malaria in Senegal. Plasma from 145 children and adults were tested. The pattern of antimalarial immunoglobulin class (IgM and IgG) and subclass (IgG1 to IgG4) antibody distribution was determined by enzyme-linked immunosorbent assay using a crude blood-stage antigen of Plasmodium falciparum-infected red blood cells. Adults had higher levels of specific antibodies than children, and IgM, IgG2, and IgG3 accounted for the highest difference (2.9, 6.5, and 4.5 times, respectively). Differences in antibody levels were significant for IgG1 to IgG4 between the lowest and the highest transmission season. No particular isotype distribution pattern could be found associated with any given parasitemia level. The relationship between the optical density (OD) values of each isotype and the risk of clinical malaria attack was tested using a Poisson regression model. Only the IgG3 OD increases were found associated with a significantly reduced risk of malaria attack. These seroepidemiologic data suggest that whereas the total IgG-specific activity is not indicative of any given level of protection against malaria, the level of IgG3 was significantly associated with the relative susceptibility to clinical P. falciparum malaria attacks.
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the dielmo project a longitudinal study of natural malaria infection and the mechanisms of protective immunity in a community living in a Holoendemic area of senegal
American Journal of Tropical Medicine and Hygiene, 1994Co-Authors: Jean-françois Trape, Christophe Rogier, Lassana Konate, Nafissatou Diagne, Hilaire Bouganali, Bruno Canque, Fabrice Legros, Assane Badji, Gora Ndiaye, Papa NdiayeAbstract:Abstract The Dielmo project, initiated in 1990, consisted of long-term investigations on host-parasite relationships and the mechanisms of protective immunity in the 247 residents of a Senegalese village in which malaria is Holoendemic. Anopheles gambiae s.l. and An. funestus constituted more than 98% of 11,685 anophelines collected and were present all year round. Inoculation rates of Plasmodium falciparum, P. malariae, and P. ovale averaged respectively 0.51, 0.10, and 0.04 infective bites per person per night. During a four-month period of intensive parasitologic and clinical monitoring, Plasmodium falciparum, P. malariae, and P. ovale were observed in 72.0%, 21.1% and 6.0%, respectively, of the 8,539 thick smears examined. Individual longitudinal data revealed that 98.6% of the villagers harbored trophozoites of P. falciparum at least once during the period of the study. Infections by P. malariae and P. ovale were both observed in individuals of all age groups and their cumulative prevalences reached 50.5% and 40.3%, respectively. Malaria was responsible for 162 (60.9%) of 266 febrile episodes; 159 of these attacks were due to P. falciparum, three to P. ovale, and none to P. malariae. The incidence of malaria attacks was 40 times higher in children 0–4 years of age than in adults more than 40 years old. Our findings suggest that sterile immunity and clinical protection are never fully achieved in humans continuously exposed since birth to intense transmission.
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Lymphocyte response in vitro toPlasmodium falciparum merozoite antigens in donors from a Holoendemic area
Parasitology Research, 1993Co-Authors: A Dieye, Pascal Launois, Jean-françois Trape, Christophe Rogier, Anthony A. Holder, H. -g. Heidrich, Jean-louis SarthouAbstract:Crude merozoite antigens from Plasmodium falciparum were used to evaluate the profilerative response of peripheral mononuclear cells (PBMCs) from 114 inhabitants of the village of Dielmo (Senegal, West Africa) exposed continuously to malaria transmission. The high or low responses to merozoite antigens obtained in lymphocyte stimulation assays were correlated with the presence or absence of parasites, IFN-γ production and HLA phenotype. The high responders produced high levels of IFN-γ, in contrast to the low responders, most of whom did not secrete IFN-γ (23/27). Among others, the two HLA phenotypes HLA-B51 and HLA-DR1 were significantly associated with a high response ( P
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analysis of the antibody response to merozoite antigens in a malaria Holoendemic area
Dakar médical, 1993Co-Authors: A Dieye, Jean-louis Sarthou, Jean-françois Trape, Christophe Rogier, A Baldetoure, Georgette Aribot, Christian Roussilhon, H. -g. HeidrichAbstract:: In the aim to determine the possible role of HLA-antigens in malaria infection, sera from 50 HLA-typed donors from Dielmo (Senegal) were tested in immunoblotting (using crude merozoites as antigen) and immunoprecipitation (using detergent-extracts from surface-iodinated merozoite as antigen). The donors were previously tested on lymphocyte proliferation in vitro and gamma-interferon production and grouped into two classes: high responders and low responders. In immunoblotting and immunoprecipitation experiments, no specific differences were found in the antibody reactivity with native merozoite antigen in individuals with high (HR) or low (LR) in vitro proliferative T cell responses. In other words, both groups of responders, high and low, showed antibodies in their sera against a wide range of different parasite antigens; although between individual donors striking differences were found. Individual donors had developed different levels of antibodies, or no antibodies at all, against individual natural antigens. These differences, however, could not be correlated with HR or LR. The band patterns obtained were compared with HLA-antigens of donors phenotypes. Results showed that there was no correlation found between the different merozoite antigens recognized by sera of the different donors or groups of donors (HR and LR) and the donors' HLA-phenotypes. The fact that donors with HLA-B51 all recognized (MSP1(42) and donors with DR1 recognized MSP1(19), was not a convincing correlation.
Kiprotich Chelimo - One of the best experts on this subject based on the ideXlab platform.
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decreased growth rate of p falciparum blood stage parasitemia with age in a Holoendemic population
The Journal of Infectious Diseases, 2014Co-Authors: Mykola Pinkevych, John M Vulule, Ann M. Moormann, James W. Kazura, Kiprotich Chelimo, Janka Petravic, Miles P DavenportAbstract:In malaria Holoendemic settings, decreased parasitemia and clinical disease is associated with age and cumulative exposure. The relative contribution of acquired immunity against various stages of the parasite life cycle is not well understood. In particular, it is not known whether changes in infection dynamics can be best explained by decreasing rates of infection, or by decreased growth rates of parasites in blood. Here, we analyze the dynamics of Plasmodium falciparum infection after treatment in a cohort of 197 healthy study participants of different ages. We use both polymerase chain reaction (PCR) and microscopy detection of parasitemia in order to understand parasite growth rates and infection rates over time. The more sensitive PCR assay detects parasites earlier than microscopy, and demonstrates a higher overall prevalence of infection than microscopy alone. The delay between PCR and microscopy detection is significantly longer in adults compared with children, consistent with slower parasite growth with age. We estimated the parasite multiplication rate from delay to PCR and microscopy detections of parasitemia. We find that both the delay between PCR and microscopy infection as well as the differing reinfection dynamics in different age groups are best explained by a slowing of parasite growth with age.
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density dependent blood stage plasmodium falciparum suppresses malaria super infection in a malaria Holoendemic population
American Journal of Tropical Medicine and Hygiene, 2013Co-Authors: Mykola Pinkevych, John M Vulule, Ann M. Moormann, James W. Kazura, Kiprotich Chelimo, Janka Petravic, Miles P DavenportAbstract:Recent studies of Plasmodium berghei malaria in mice show that high blood-stage parasitemia levels inhibit the development of subsequent liver-stage infections. Whether a similar inhibitory effect on liver-stage Plasmodium falciparum by blood-stage infection occurs in humans is unknown. We have analyzed data from a treatment-time-to-infection cohort of children < 10 years of age residing in a malaria Holoendemic area of Kenya where people experience a new blood-stage infection approximately every 2 weeks. We hypothesized that if high parasitemia blocked the liver stage, then high levels of parasitemia should be followed by a “skipped” peak of parasitemia. Statistical analysis of “natural infection” field data and stochastic simulation of infection dynamics show that the data are consistent with high P. falciparum parasitemia inhibiting liver-stage parasite development in humans.
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Holoendemic malaria exposure is associated with altered epstein barr virus specific cd8 t cell differentiation
Journal of Virology, 2013Co-Authors: Pratip K Chattopadhyay, John M Vulule, Kiprotich Chelimo, Peter Odada Sumba, Paula B Embury, David H Mulama, Emma Gostick, Kristin Ladell, Tess M Brodie, Mario RoedererAbstract:Coinfection with Plasmodium falciparum malaria and Epstein-Barr virus (EBV) is a major risk factor for endemic Burkitt lymphoma (eBL), still one of the most prevalent pediatric cancers in equatorial Africa. Although malaria infection has been associated with immunosuppression, the precise mechanisms that contribute to EBV-associated lymphomagenesis remain unclear. In this study, we used polychromatic flow cytometry to characterize CD8+ T-cell subsets specific for EBV-derived lytic (BMFL1 and BRLF1) and latent (LMP1, LMP2, and EBNA3C) antigens in individuals with divergent malaria exposure. No malaria-associated differences in EBV-specific CD8+ T-cell frequencies were observed. However, based on a multidimensional analysis of CD45RO, CD27, CCR7, CD127, CD57, and PD-1 expression, we found that individuals living in regions with intense and perennial (Holoendemic) malaria transmission harbored more differentiated EBV-specific CD8+ T-cell populations that contained fewer central memory cells than individuals living in regions with little or no (hypoendemic) malaria. This profile shift was most marked for EBV-specific CD8+ T-cell populations that targeted latent antigens. Importantly, malaria exposure did not skew the phenotypic properties of either cytomegalovirus (CMV)-specific CD8+ T cells or the global CD8+ memory T-cell pool. These observations define a malaria-associated aberration localized to the EBV-specific CD8+ T-cell compartment that illuminates the etiology of eBL.
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serological evidence for long term epstein barr virus reactivation in children living in a Holoendemic malaria region of kenya
Journal of Medical Virology, 2009Co-Authors: Erwan Piriou, Ann M. Moormann, Kiprotich Chelimo, Robert Ploutzsnyder, Rhonda Kimmel, Jaap M Middeldorp, Peter Sumba Odada, Rosemary RochfordAbstract:To study the long term the effects of chronic exposure to P. falciparum malaria on Epstein– Barr virus (EBV) reactivation in children, EBVspecific antibody levels were measured in a cross-sectional survey of two groups of Kenyan children with divergent malaria exposure, varying in age from 1 to 14 years. A total of 169 children were analyzed within three age groups (1–4 years, 5–9 years and 10–14 years). Using a Luminex assay, elevated levels of IgG to EBV lytic and latent antigens were observed in children from the Holoendemic malaria area; these remained elevated for each age group studied. In comparison, children from the sporadic malaria area had lower levels of EBV-specific IgG antibodies and these levels declined across age groups. These data suggest that chronic exposure to malaria may lead to long-term EBV reactivation. J. Med. Virol. 81:1088–1093,
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exposure to Holoendemic malaria results in suppression of epstein barr virus specific t cell immunosurveillance in kenyan children
The Journal of Infectious Diseases, 2007Co-Authors: Ann M. Moormann, Rosemary Rochford, Kiprotich Chelimo, Peter Odada Sumba, Daniel J Tisch, James W. KazuraAbstract:BACKGROUND: Malaria and Epstein-Barr virus (EBV) infection are cofactors in the pathogenesis of endemic Burkitt lymphoma (eBL). The mechanisms by which these pathogens predispose to eBL are not known. METHODS: Healthy Kenyan children with divergent malaria exposure were measured for responses to EBV latent and lytic antigens by interferon (IFN)- gamma enzyme-linked immunospot (ELISPOT) assay and interleukin (IL)-10 ELISA. Phytohemagglutinin (PHA), purified protein derivative (PPD), and T cell epitope peptides derived from merozoite surface protein (MSP)-1, a malaria blood-stage antigen, were also evaluated. RESULTS: Children 5-9 years old living in an area Holoendemic for malaria had significantly fewer EBV-specific IFN- gamma responses than did children of the same age living in an area with unstable malaria transmission. This effect was not observed for children 9 years old. In contrast, IFN- gamma responses to PHA, PPD, and Plasmodium falciparum MSP-1 peptides did not significantly differ by age. IL-10 responses to EBV lytic antigens, PPD, and PHA correlated inversely with malaria exposure regardless of age. CONCLUSIONS: Children living in malaria-Holoendemic areas have diminished EBV-specific T cell immunosurveillance between the ages of 5 and 9 years, which coincides with the peak age incidence of eBL.