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3. Clinical epidemiology of malaria under differing levels of transmission

Author

Mwangi, Tabitha Wanja

Subjects
616.936200967623, Africa
Abstract

Malaria is a major public health problem in Africa. A key issue in studies of epidemiology, treatment, immunity and community-based interventions is the definition of clinical disease due to malaria. However this remains problematic due to both the phenomenon of asymptomatic background parasitisation in endemic areas, and differences in the pattern and amount of clinical disease with differing levels of transmission. This thesis describes attempts to define and quantify malarial disease in two communities in coastal Kenya with similar ethnic, geographical and socio-economic backgrounds but which differ in the level of malaria transmission. A sample of 1,500 people of all age groups from two areas within Kilifi District, with differing transmission were observed for two years. The main objective of this study was to define and quantify non-severe malaria within the two areas of differing malaria transmissions. The thesis is divided into nine chapters, the first three being an introduction to malaria and study design and the other seven chapters being analysis of data and discussion of various results. Chapter two is a literature review of the epidemiology. of severe and non-severe clinical malaria in Africa. It discusses the pathophysiology and clinical presentation of both nonsevere and severe malaria and the difficulties involved in its malaria diagnosis. Effects of age and transmission on severe malaria and mortality are reviewed. Finally, other factors that affect malaria morbidity are discussed. Chapter three is a discussion of the overall design and methodology. The study area is discussed in terms of location, population, topography, climate and entomological factors related to malaria transmission. A description is made of the study population, their occupation, socio-economic status, health seeking practices and main causes of paediatric admissions at the Kilifi District hospital. The study design is described in detail including the selection of the study population, aging of the study participants and weekly follow-up. Chapter four is a discussion of basic descriptive parameters of the study population. Age patterns of the general population in the two study areas are described. The study participants that attended the study clinic are then described in terms of their age, sex, symptoms and clinical signs at presentation and the overall diagnosis made at the clinic. A total of six cross-sectional surveys were conducted in the course of the study and the parasite prevalence by age in the two areas were compared. The effect of regular treatments on parasite prevalence rates are discussed. Other physiological parameters such as body temperature, haemoglobin and C-reactive protein levels are described and the differences among people of different age groups in the study areas discussed. Chapter five details the approach to defining non-severe malaria for epidemiological studies in Kilifi. Logistic regression methods were used to derive malaria attributable fractions of fevers and to derive various parasite density cut-offs as malaria case definitions in the two study areas in Kilifi. These definitions were then used to quantify malaria from data of two years of longitudinal follow-up and the rates of malaria and fever by age in the two study areas. Fin ally, there is a comparison of the rates of malaria treatments provided at the study clinic and that provided at a rural health facility in Ngerenya. The main finding in this chapter was the age differences in non-severe clinical malaria disease presentation with a higher incidence of malaria in the area with lower malaria transmission. Chapter six is an attempt to derive algorithms for clinical malaria diagnosis from data of patients that presented to the clinic with a history of fever. Using clinical symptoms and sIgns three age groups. The four algorithms in each age group were compared with those derived from other African studies and the 'best' algorithms compared in terms of their ability to predict malaria for treatment using hypothetical situations. The difficulties of using clinical algorithms to define malaria for treatment in endemic areas are discussed. Chapter seven discusses the data on children admitted into the Kilifi District hospital from the two study areas with differing transmission. Two sets of data are described; malaria admissions among those recruited into the longitudinal study and from the wider study area. The admissions were discussed in terms of age, haemoglobin, parasitaemia and associations with clinical criteria that have been used in several African countries to define severe malaria. Despite there being more admissions from Ngerenya (the lower transmission area) than Chonyi ( the higher transmission area), those from Chonyi were associated with clinical criteria carrying an increased risk of death compared with those from Ngerenya. Appendix XI is a systematic review of several studies conducted in areas of differing malaria transmission in Africa that attempted to quantify malaria. Difficulties of comparing data from studies with different methodologies are discussed and comparisons of malaria rates in areas of differing endemicity described. In conclusion, it appears that the incidence of clinical malaria is rises with increasing malaria endemicity up to high-moderate transmission, after which there is no further rise with increasing endemicity. Appendix XII is a paper soon to be published in the 'Transactions of the Royal Society of Tropical Medicine and Hygiene that describes the effects of untreated bednets on malaria "infection and imelidence. Only data from Ngerenya was used and the conclusion was that untreated bednets in good condition were capable of reducing malaria infection and disease compared to use of no nets at all or worn untreated nets.

Published
2003
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14. Defining childhood severe falciparum malaria for intervention studies

Author

Bejon, Philip, Berkley, James A., Mwangi, Tabitha, Ogada, Edna, Mwangi, Isaiah, Maitland, Kathryn, Williams, Thomas, G. Scott, J. Anthony, English, Mike, Lowe, Brett S., Peshu, Norbert, Newton, Charles R.J.C., and Marsh, Kevin

Subjects
Malaria -- Prevention, Malaria -- Diagnosis, Children -- Diseases, Children -- Prevention, Medical research, Medicine, Experimental, Methodology
Abstract

ABSTRACT Background Clinical trials of interventions designed to prevent severe falciparum malaria in children require a clear endpoint. The internationally accepted definition of severe malaria is sensitive, and appropriate for [...]

Published
2007

15. The haptoglobin 2-2 genotype is associated with a reduced incidence of Plasmodium falciparum malaria in children of the coast of Kenya

Author

Atkinson, Sarah H., Mwangi, Tabitha W., Yoga, Sohie M., Ogada, Edna, Macharia, Alex W., Marsh, Kevin, Prentice, Andrew M., and Williams, Thomas N.

Subjects
Haptoglobin -- Genetic aspects, Haptoglobin -- Research, Malaria -- Risk factors, Malaria -- Prevention, Malaria -- Research, Children -- Diseases, Children -- Risk factors, Children -- Prevention, Children -- Research, Health, Health care industry
Published
2007

16. The effect of [[alpha].sup.+]-thalassaemia on the incidence of malaria and other diseases in children living on the coast of Kenya

Author

Wambua, Sammy, Mwangi, Tabitha W., Kortok, Moses, Uyoga, Sophie M., Macharia, Alex W., Mwacharo, Jedidah K., Weatherall, David J., Snow, Robert W., Marsh, Kevin, and Williams, Thomas N.

Subjects
Thalassemia -- Case studies, Thalassemia -- Physiological aspects, Malaria -- Physiological aspects, Malaria -- Genetic aspects, Children -- Diseases
Abstract

ABSTRACT Background The [alpha]-thalassaemias are the commonest genetic disorders of humans. It is generally believed that this high frequency reflects selection through a survival advantage against death from malaria; nevertheless, [...]

Published
2006

22. Acquisition of naturally occurring antibody responses to recombinant protein domains of Plasmodium falciparum erythrocyte membrane protein 1

Author

Pinches Robert, Kortok Moses, Mwangi Tabitha W, Christodoulou Zoe, Mackintosh Claire L, Williams Thomas N, Marsh Kevin, and Newbold Christopher I

Subjects
Arctic medicine. Tropical medicine, RC955-962, Infectious and parasitic diseases, RC109-216
Abstract

Abstract Background Antibodies targeting variant antigens expressed on the surface of Plasmodium falciparum infected erythrocytes have been associated with protection from clinical malaria. The precise target for these antibodies is unknown. The best characterized and most likely target is the erythrocyte surface-expressed variant protein family Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1). Methods Using recombinant proteins corresponding to five domains of the expressed A4 var gene, A4 PfEMP1, the naturally occurring antibody response was assessed, by ELISA, to each domain in serum samples obtained from individuals resident in two communities of differing malaria transmission intensity on the Kenyan coast. Using flow cytometry, the correlation in individual responses to each domain with responses to intact A4-infected erythrocytes expressing A4 PfEMP1 on their surface as well as responses to two alternative parasite clones and one clinical isolate was assessed. Results Marked variability in the prevalence of responses between each domain and between each transmission area was observed, as wasa strong correlation between age and reactivity with some but not all domains. Individual responses to each domain varied strikingly, with some individuals showing reactivity to all domains and others with no reactivity to any, this was apparent at all age groups. Evidence for possible cross-reactivity in responses to the domain DBL4γ was found. Conclusion Individuals acquire antibodies to surface expressed domains of a highly variant protein. The finding of potential cross-reactivity in responses to one of these domains is an important initial finding in the consideration of potential vaccine targets.

Published
2008
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23. Prevalence and correlates of home delivery amongst HIV-infected women attending care at a rural public health facility in Coastal Kenya

Author

Leerstoel Baar, Development and Treatment of Psychosocial Problems, Chea, Stevenson K., Mwangi, Tabitha W., Ndirangu, Kennedy K., Abdullahi, Osman A., Munywoki, Patrick K., Abubakar, Amina, Hassan, Amin S., Leerstoel Baar, Development and Treatment of Psychosocial Problems, Chea, Stevenson K., Mwangi, Tabitha W., Ndirangu, Kennedy K., Abdullahi, Osman A., Munywoki, Patrick K., Abubakar, Amina, and Hassan, Amin S.

Published
2018

27. An outbreak of cholera in western Kenya, 2015: a case control study

Author

Oyugi, Elvis O., primary, Boru, Waqo, additional, Obonyo, Mark, additional, Githuku, Jane, additional, Onyango, Dickens, additional, Wandeba, Alfred, additional, Omesa, Eunice, additional, Mwangi, Tabitha, additional, Kigen, Hudson, additional, Muiruri, Joshua, additional, and Gura, Zeinab, additional

Published
2017
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28. Reproducible Statistics course for the future, from Stata to R

Author

Mwai, Kennedy, Thairu, Amos, Mwangi, Tabitha, and Fegan, Greg

Abstract

Reproducibility being laudable and frequently called for, we should be instilling this practice in students before they set out to do research. The maturity and extensive reproducibility abilities of Git, R and RStudio based materials make an excellent choice for professional statistical skills training. The most commonly used statistical softwares namely SAS, SPSS and STATA can cost over US$500 for a single license and over US$5,000 for a discounted twenty user access and can be challenging to create reproducible courses for universities and training institutions. Currently, it has been observed that the trend is changing and R popularity is rising. This talk will focus on the success of converting a two weeks statistical methodology for the design and analysis of epidemiological studies (SMDAES) course from Stata based to R based reproducible course using RMarkdown or LaTeX, Git and GitHub, R and RStudio server. We present the importance of using Git ,R and RStudio as tools for statistical workshops and institution trainings over commercial based tools.The talk shows the success of teamwork on Git while creating the course materials.

Published
2015
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29. Identifying children with excess malaria episodes after adjusting for variation in exposure: identification from a longitudinal study using statistical count models

Author

Ndungu, Francis Maina, primary, Marsh, Kevin, additional, Fegan, Gregory, additional, Wambua, Juliana, additional, Nyangweso, George, additional, Ogada, Edna, additional, Mwangi, Tabitha, additional, Nyundo, Chris, additional, Macharia, Alex, additional, Uyoga, Sophie, additional, Williams, Thomas N, additional, and Bejon, Philip, additional

Published
2015
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30. The Induction and Persistence of T Cell IFN-γ Responses after Vaccination or Natural Exposure Is Suppressed by Plasmodium falciparum1

Author

Bejon, Philip, Mwacharo, Jedidah, Kai, Oscar, Todryk, Stephen, Keating, Sheila, Lowe, Brett, Lang, Trudie, Mwangi, Tabitha W., Gilbert, Sarah C., Peshu, Norbert, Marsh, Kevin, and Hill, Adrian V. S.

Subjects
Analysis of Variance, Infant, Lymphocyte Activation, Parasitemia, Article, Interferon-gamma, Logistic Models, Double-Blind Method, T-Lymphocyte Subsets, Child, Preschool, parasitic diseases, Malaria Vaccines, Multivariate Analysis, Humans, Regression Analysis, Malaria, Falciparum, Child, Cells, Cultured
Abstract

Epidemiological observations suggest that T cell immunity may be suppressed in malaria-endemic areas. In vitro studies, animal models, and limited data in humans link immunosuppression with malaria, malnutrition, and other parasitic infections. However, there are no data to determine whether malaria-induced immunosuppression is significant in the long-term, or relative data comparing it with other factors in malaria-endemic areas, so as to measure the impact of malaria, other parasitic disease, nutritional status, age. and location on the acquisition and longevity of IFN-gamma responses in children in Kenya. We studied these factors in two cohorts of 1- to 6-year-old children in a malaria-endemic area. T cell responses were induced by vaccination in one cohort, and acquired as a result of natural exposure in a second cohort. Serial ELISPOT assays conducted over a 1-year period measured the induction and kinetics of IFN-gamma production in response to the malaria Ag thrombospondin-related adhesion protein. Induced responses in both cohorts and the longevity of response in the vaccinated cohort were fitted to potential explanatory variables. Parasitemia was prospectively associated with reduced IFN-gamma-producing T cells in both cohorts (by 15-25%), and both parasitemia and episodes of febrile malaria were associated with 19 and 31% greater attrition of T cell responses, respectively. Malaria may reduce the efficacy vaccinations such as bacillus Calmette-Guérin and investigational T cell-inducing vaccines, and may delay the acquisition of immunity following natural exposure to malaria and other pathogens.

Published
2007

39. Breadth and Magnitude of Antibody Responses to MultiplePlasmodium falciparumMerozoite Antigens Are Associated with Protection from Clinical Malaria

Author

Osier, Faith H. A., primary, Fegan, Gregory, additional, Polley, Spencer D., additional, Murungi, Linda, additional, Verra, Federica, additional, Tetteh, Kevin K. A., additional, Lowe, Brett, additional, Mwangi, Tabitha, additional, Bull, Peter C., additional, Thomas, Alan W., additional, Cavanagh, David R., additional, McBride, Jana S., additional, Lanar, David E., additional, Mackinnon, Margaret J., additional, Conway, David J., additional, and Marsh, Kevin, additional

Published
2008
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42. The Induction and Persistence of T Cell IFN-γ Responses after Vaccination or Natural Exposure Is Suppressed by Plasmodium falciparum

Author

Bejon, Philip, primary, Mwacharo, Jedidah, additional, Kai, Oscar, additional, Todryk, Stephen, additional, Keating, Sheila, additional, Lowe, Brett, additional, Lang, Trudie, additional, Mwangi, Tabitha W., additional, Gilbert, Sarah C., additional, Peshu, Norbert, additional, Marsh, Kevin, additional, and Hill, Adrian V. S., additional

Published
2007
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44. A Phase 2b Randomised Trial of the Candidate Malaria Vaccines FP9 ME-TRAP and MVA ME-TRAP among Children in Kenya

Author

Bejon, Philip, primary, Mwacharo, Jedidah, additional, Kai, Oscar, additional, Mwangi, Tabitha, additional, Milligan, Paul, additional, Todryk, Stephen, additional, Keating, Sheila, additional, Lang, Trudie, additional, Lowe, Brett, additional, Gikonyo, Caroline, additional, Molyneux, Catherine, additional, Fegan, Greg, additional, Gilbert, Sarah C, additional, Peshu, Norbert, additional, Marsh, Kevin, additional, and Hill, Adrian V. S, additional

Published
2006
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47. CELLULAR REACTIVITY TO THE P. FALCIPARUM PROTEIN TRAP IN ADULT KENYANS: NOVEL EPITOPES, COMPLEX CYTOKINE PATTERNS, AND THE IMPACT OF NATURAL ANTIGENIC VARIATION

Author

FLANAGAN, KATIE L., primary, SHEU, ERIC, additional, HART, KEITH, additional, MARSH, KEVIN, additional, PLEBANSKI, MAGDALENA, additional, KORTOK, MOSES, additional, MWANGI, TABITHA, additional, HILL, ADRIAN V. S., additional, ODHIAMBO, KENNEDY, additional, LOWE, BRETT, additional, GELDER, COLIN, additional, and ROBSON, KATHRYN J., additional

Published
2006
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49. Negative epistasis between the malaria-protective effects of α+-thalassemia and the sickle cell trait

Author

Williams, Thomas N, primary, Mwangi, Tabitha W, additional, Wambua, Sammy, additional, Peto, Timothy E A, additional, Weatherall, David J, additional, Gupta, Sunetra, additional, Recker, Mario, additional, Penman, Bridget S, additional, Uyoga, Sophie, additional, Macharia, Alex, additional, Mwacharo, Jedidah K, additional, Snow, Robert W, additional, and Marsh, Kevin, additional

Published
2005
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