A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of Master of Science in Epidemiology in the field of Epidemiology and Biostatistics Johannesburg, April 2012 / Introduction: Malaria is a vector-borne parasitic disease with heterogeneous distribution in time and space. The sub-Saharan African region harbours the largest proportion of the global malaria cases and contributes over 90% to the deaths due to malaria. The present study aimed to identify trends of laboratory-confirmed malaria in both malaria endemic and non-endemic areas of South Africa over a period of ten years (January 2000 to December 2009). The association between malaria and demographic characteristics was also explored. Materials and methods This analytical cross-sectional study used secondary malaria surveillance data obtained from eight South African provinces through the National Health Laboratory Service. A population subset that utilised public health care facilities during the study period was included. Chi-square test of proportions was used to test if there were significant differences in the distribution of demographic and temporal characteristics among the laboratory-confirmed malaria cases. Annual parasite incidence of malaria was calculated to estimate malaria incidence in the population. Logistic regression models were constructed to determine the association between malaria and demographic characteristics. Results: There were 175,069 suspected malaria cases from the endemic provinces of which 26,367 (15.1%) were laboratory confirmed; 130,980 (40.2%) suspected cases were from non-endemic provinces of which 42,488 (32.4%) were diagnosed as malaria. The overall malaria positivity rate was 21.4%. There were more cases of malaria among males (62.9%) than females, among individuals aged 25-44 years (44.0%) than individuals in any other age-group and among those living in non-endemic provinces (60.8%) than those living in endemic provinces. v A linear downward trend in malaria incidence was observed over the ten-year period (p<0.001). Thus, malaria incidence declined from an overall API of 64 per 100,000 population in 2000 to 50 per 100,000 population in 2009. The incidence of malaria in both endemic and non-endemic provinces was highest in the month of January (15 per 100,000 and 24 per 100,000 respectively). The following demographic factors were found to be independently associated with increased malaria incidence: male gender (adjusted odds ratio (aOR) 1.54, CI: 1.51-1.57, p<0.001) and non-endemic province-type (aOR 2.68, CI: 2.63-2.73, p<0.001). Age was inversely associated with malaria incidence. Individuals in 45-64 and ≥ 65 year age-groups were 20% (aOR 0.80, CI: 0.77-0.82, p<0.001) and 51% (aOR 0.49, CI: 0.46-0.53, p<0.001) less likely to have malaria respectively. Conclusion: There was a high incidence of laboratory-confirmed malaria in previously malaria non-endemic parts of South Africa especially Gauteng and North West provinces in the past decade. Targeted information, education and communication (IEC) to all travelers during the annual festive and holiday seasons should be reinforced to minimize importation of malaria into non-endemic areas.

Master of Science in Epidemiology and Biostatistics / Background Malaria is one of the primary public health concerns in the world and an important cause of morbidity and mortality in sub-Saharan Africa. Malaria morbidity is associated with poverty and vulnerability as it is not easy for the poor people to access preventive treatment and protective measures. In Rwanda, malaria prevention has become a major problem against the double-barrelled burden of an overstretched health system and strained financial resources. Methods This research was a cross-sectional survey study design based on data from Rwanda collected in 2010 through the Malaria Indicator Survey as part of the Demographic and Health Survey. The primary outcome variable was an ordinal variable with these three categories; no malaria, probable malaria, and confirmed malaria cases. The outcome variable was formulated by combining rapid malaria test and confirmatory blood smear laboratory test. Statistical analysis was done using survey ordinal logistic regression modelling adjusting for random effects for direct effects and generalised structural equation modelling (G-SEM) to obtain total (direct and indirect) effects of malaria morbidity. Results The 11,865 participants had a mean age of 22 years, and two-thirds of the participants were females (67%). Household related variables (socio-economic status, health insurance, age in years) showed a significant total effect on malaria infection. Socioeconomic status had the greatest total effect which was a sum of the direct and indirect effects influenced indirectly by education, health insurance and the number of rooms for sleeping. Conclusion Poverty is still the core issue to the morbidity patterns driving the malaria epidemic in Rwanda. Access to health insurance has a high positive impact on decreasing disease as such a special focus on some regions can be an effective intervention strategy. A better understanding of the drivers of morbidity directly and/or indirectly can better target interventions to be more efficient in those affected areas. / MT2017

In this thesis, I study the role of genetic population structure in the evolution and demography of Plasmodium falciparum by focusing on the recent onset of artemisinin resistance in Southeast Asia, an alarming event for global public health. I describe the population structure of Plasmodium falciparum in the Thai-Cambodian border region, characterizing sympatric but differentiated subpopulations associated with artemisinin resistance. I show evidence that they are the product of recent founder events and seem the primary force spreading resistance. Next, I study a superset of the kelch13 mutations associated with artemisinin resistance, assessing their relationship with population structure and recent founder effects. Each resistant subpopulation possesses a distinct kelch13 allele that, in conjunction with a particular genetic background, seem to have driven recent founder effects. I examine the demography of these resistance alleles using patterns of haplotype sharing and show that the primary mode of spread consists of independent mutational events, with limited gene flow within countries in East Southeast Asia. Subsequently, I assess the origin of kelch13 mutations observed in African isolates, concluding that they are indigenous and have originated independently. These observations undermine localized resistance containment as a strategy for malaria control and suggest that population structure and founder effects may predate and facilitate the emergence of resistance. Therefore, monitoring these phenomena could warn about the development of resistance before phenotypic evidence materializes. Next, given the importance of demographic inference to inform malaria control programs and the advent of large genomic datasets, I develop a fast and scalable method to build the ancestral haplotype graph. I show that this data structure, composed of a collection of local haplotype trees, is informative about the recent genealogical history of the sequences and can be used to summarize and study shared haplotype patterns along the genome. I describe a set of algorithms with quasilinear time complexity as a first step in the development of scalable demographic inferential methods that can be applied to several thousands of sequences. I also evaluate how mixed infections affect the analysis of deep sequencing data and review the F_WS statistic, a relative measure of inbreeding and complexity of infection. In doing so, I show that the original F_WS estimator discards the diversity encoded by rare variants and provide an alternative estimator without such bias that is simpler, more intuitive and has a better resolution.

Diss. (sammanfattning) Stockholm : Univ., 2005. / Härtill 4 uppsatser.

Diss. Stockholm : Stockholms universitet, 2008. / Härtill 5 uppsatser.

Thesis (M.P.H.)--University of Michigan, 1946.

Thesis (M.P.H.)--University of Michigan, 1946.

Thesis (M.P.H.)--University of Michigan, 1946.

Thesis (M.P.H.)--University of Michigan, 1946.

Diss.med. Univ. Bern, 1999. / Am Kopf der Titelseite: Aus dem Institut für medizinische Mikrobiologie sowie dem Institut für Aus-, Weiter- und Fortbildung (IAWF), Abteilung für Unterrichtsmedien (AUM).