Malaria is a disease that causes great burden in public health worldwide. It was estimated that in 2011 there were 3.3 billion people at risk of acquiring malaria. According to data from the Ministry of Public Health of Ecuador, malaria incidence has shown a 99.9% steady decrease since year 2000. This study evaluated the effect of timely treatment on circulating gametocyte and malaria incidence rates. All cases reported in the province of Esmeraldas, Ecuador from July 2012 to March 2015 and to the national headquarters between February 2012 and December 2014 were studied. The effect of early treatment on: 1) follow-up gametocytemia at an individual level (cases reported in Esmeraldas); and, 2) incidence rates at a population level (within Esmeraldas and within Ecuador) was evaluated using a retrospective cohort and an ecologic study design, respectively. A total of 193 cases from the province of Esmeraldas were included in the retrospective cohort study. Patients were classified into three groups depending on time to treatment (i.e. how many days elapsed from symptoms onset to treatment) as follows: 1) early treatment for those treated within 2 days; 2) late treatment for those treated between 3 to 7 days; and, 3) extremely late for those receiving treatment after 7 days. A consistent association between time to treatment and follow-up gametocytemia was found in different regression models including logistic (adjusted OR = 0.20 and 0.28 for early and late treatment, respectively, p < 0.05), linear (parameter estimate = 0.018, p < 0.05) Poisson log linear (parameter estimate 0.103, p < 0.05), and negative binomial (parameter estimate = 0.111, p < 0.05). Extremely late patients had higher follow-up gametocytemia levels during follow-up visits 1 and 2. A survival analysis showed that extremely late treated patients tend to clear gametocytes later than the other two treatment arms (p > 0.05). Finally, there was a positive association between time to treatment and a period of transmisibiltiy, which was estimated based on the potential number of days that a patient has gametocytemia (p < 0.05). Population-level associations between time to treatment and malaria incidence rates were assessed through a two-tiered ecologic study: nationwide for Ecuador and provincewide for Esmeraldas.. A parish-level anlaysis of malaria among all parishes in the province of Esmeraldas revealed that malaria transmission differs widely within each population-level treatment arm classification group. A repeated measures negative binomial regression showed that there is a positive association between malaria incidence rate in subsequent periods and mean time to treatment, follow-up gametocytemia and a negative association with malaria incidence rate in the previous period (p < 0.05 for all associations). The nationwide analysis confirmed that there is wide variation in malaria incidence rate within each population-level treatment arm classification group. Although the World Health Organization (WHO) recommends timely malaria treatment there seems to be lack of peer-reviewed published evidence evaluating the association of time to malaria treatment with follow-up gametocytemia and incidence rates, especially in Latin America. This study has important public health implications. Firstly, there seems to be no clear definition for early malaria treatment. In this study, consistent evidence of the association between time to treatment and, specifically, early malaria treatment (i.e. malaria within 2 days of symptoms onset) with follow-up gametocytemia and period of transmissibliity is provided. Evidence provided here can serve as a basis for future research in other countreis facing similar conditions. Additionally, this information can serve to better inform public health policy, especially regarding the definition of early treatment and, thus, setting goals to accomplish early treatment among malaria infected patients. Noteworthy, Esmeraldas and Ecuador face significant challenges not only to achieve but to maintain malaria elimination, if achieved. These challenges arise from favorable local environmental conditions and to certain vulnerabilities like proximity to neibhoring areas with high malaria incidence, susceptibility to receive migration, specially refugees fleeing armed conflict, socio-economic disadvantages and remoteness of some parishes were malaria remains active. Moreover, the integration of the current national malaria control program into the organizational strucutre of the Ministry of Health may impose additional challenges like: 1) differential prioritization of other diseases, 2) lack of clear guidance about the role of the current malaria-dedicated personnel in the MoH strucutre; and, 3) lack of specification about on whom would accountability for malaria control rely. All these vulnerabilities should be properly addressed if malaria elimination is to be achieved in Ecuador. Finally, further research is required to confirm whether these trends and association are replicable across different populations, countries and continents. If these associations are similar or even stronger in other populations, then better malaria control programs informed in evidence-based definition of early malaria treatment could certainly be planned and implemented to achieve malaria elimination and control in other regions of the world.

Master of Public Health - MPH / Introduction:Highest-risk malaria areas in South Africa share borders with Mozambique, Swaziland and Zimbabwe. Ongoing migration between these neighbouring areas impacts on malaria control interventions. For example, 30% of the adult population in Bushbuckridge originate from Mozambique. Despite these dynamics, no studies were found which investigated knowledge,attitudes and behaviours towards malaria in Bushbuckridge. Methods:This study was undertaken as a descriptive cross-sectional survey. A field-piloted structured questionnaire was administered to 602 randomly selected households, where only one household member was interviewed. Interviewees were heads of households, but in their absence, responsible adults above 18 years were included.Results:Of 602 respondents, 93% (n=559, 95% CI: 90.4 – 94.7%) had heard about malaria, mainly from health facilities (29%, n=175) and radios (20%,n=119). Most respondents correctly associated malaria with mosquito bites. There were no differences in knowledge of the causes of malaria between males and females, whereas age and educational level influenced malaria knowledge.Younger and more educated respondents were more knowledgeable than their older and less educated counterparts. Despite 91% of respondents (n=546, 95% CI: 88.0 – 92.8%) knowing that malaria can kill if untreated; only 48% could identify one or two symptoms of malaria. Most (99%, n=595, 95% CI: 97.5 – 99.5%) of the respondents would seek treatment at health facilities,82% (n=488) of whom would do so within 24 hours of onset of malaria symptoms.Discussion and conclusion : Most respondents showed a fair amount of knowledge on the causes of malaria, but not enough people were able to correctly identify the key symptoms of malaria. Health facility and radio were the main sources of malaria information. Most respondents sought treatment at health care facilities, contrary to most African countries where treatment is first sought at non-public health facilities.Word count: 288

Le paludisme, qui est la maladie à transmission vectorielle la plus répandue, provoque depuis quelques années de plus en plus d’épidémies liées à des anomalies climatiques. Dans de nombreux pays endémiques comme l’Ouganda, les changements climatiques représentent une préoccupation importante pour la santé publique. Des débats existent toutefois quant à l’évolution future du paludisme car la majorité des études de prédictions ne considèrent pas les effets de certains facteurs anthropiques qui influencent la transmission (ex. les interventions de contrôle antivectorielles). Ainsi, les objectifs de cette thèse étaient donc 1) d’estimer les associations entre le risque du paludisme, des variables de l’environnement (comme les précipitations, la température, l’humidité et la végétation) et les interventions antivectorielles (moustiquaires imprégnées d’insecticide longue durée, MILD, et pulvérisation intra-domiciliaire, PID) pour 2) prédire la distribution du paludisme selon des scénarios de climat futur. À cette fin, les associations ont été étudiées à partir (i) des données d’une cohorte d’enfants de trois sous régions d’Ouganda à partir de modèles mixtes linéaires généralisés basés sur une distribution log-binomiale; (ii) des données de surveillance passive du paludisme dans la population générale de six sous régions, à partir de modèles mixtes linéaires généralisés basés sur une distribution binomiale négative. Les associations étudiées au sein de la population générale ont ensuite été utilisées pour projeter le risque futur selon 14 simulations climatiques et deux scénarios d’émission de gaz à effet de serre (RCP4.5 et RCP8.5). Pour le premier objectif, les résultats de l’analyse des données de la cohorte infantile ont mis en évidence une variabilité sous régionale dans la forme (linéaire et non linéaire), la direction et l'ampleur des associations entre les variables de l’environnement et le risque de paludisme. L'ajustement du modèle de régression pour la PID a modifié l'ampleur et/ou la direction des associations environnement-paludisme, suggérant un effet d'interaction. À partir des données de la population générale, l’analyse groupée des six sous régions a montré que les interventions réduisaient le risque de paludisme d'environ 35 % avec les MILD et de 63 % avec la PID; des interactions significatives ont été observées entre certaines variables environnementales et les interventions de lutte antivectorielle. À l’échelle sous régionale, une variabilité de la forme des relations environnement-paludisme (linéarité, non linéarité, direction) et de l'influence des interventions a aussi été observée. Les prédictions du risque de paludisme avec les changements climatiques suggèrent des tendances à la hausse des cas de paludisme en absence d’interventions à l’horizon 2050, bien qu’une grande variabilité dans les prédictions existent selon le modèle de climat considéré (médianes et min-max de la période historique vs RCP 4.5 : 16 785, 9 902 - 74 382 vs 21 289, 11 796 - 70 606). En considérant l’effet des interventions, une réduction du nombre de cas annuels médian de 35%, 63% et à 76% est prédite avec les MILD seules, la PID seule et la combinaison de MILD et PID, respectivement. Cette thèse a donc permis de clarifier l’influence des MILD et de la PID sur les relations entre variables de l’environnement et le paludisme et de démontrer l’importance de considérer les mesures de contrôle antivectorielle dans les analyses du risque épidémiologique de paludisme et dans les prédictions du risque avec les changements climatiques. / Malaria, which is the most widespread vector-borne disease, has in recent years caused more and more epidemics linked to climatic anomalies. In several malaria endemic countries such as Uganda, climate change is a major public health concern. Debates exist, however, about the future evolution of malaria in relation to climate as the majority of prediction studies do not consider the effects of certain anthropogenic factors that influence transmission (e.g. vector control interventions). Therefore, the objectives of this thesis were 1) to estimate the associations between malaria risk, environmental variables (such as precipitation, temperature, humidity which are related to climate and vegetation) and vector interventions (long-lasting insecticide-treated bed nets - LLINs, and indoor residential spraying - IRS), and to 2) predict malaria distribution under future climate scenarios. The associations were studied with (i) data from a cohort of children from three sub-regions of Uganda using generalized linear mixed models based on a log-binomial distribution; (ii) data from passive surveillance of malaria in the general population of six sub-regions, using generalized linear mixed models based on a negative binomial distribution. The associations studied in the general population were then used to predict future risk under 14 climate simulations and two greenhouse gas emission scenarios (RCP4.5 and RCP8.5). For the first objective, the results of the analysis of the infant cohort data highlighted a sub-regional variability in the form (linear and nonlinear), the direction and the magnitude of the associations between the environmental variables. and the risk of malaria. Adjusting the regression model for IRS changed the magnitude and/or direction of environment-malaria associations, suggesting an interaction effect. Using data from the general population, the pooled analysis of the six sub-regions showed that the interventions reduced malaria risk by approximately 35% with LLINs and by 63% with IRS; significant interactions were observed between some environmental variables and vector control interventions. At the sub-regional scale, variability in the form of environment-malaria relationships (linearity, non-linearity, direction) and in the influence of interventions was also observed. Predictions of malaria risk with climate change suggest upward trends in malaria cases in the absence of interventions by 2050, although great variability in the predictions exists depending on the climate model considered (medians and min-max of the historical period vs RCP 4.5: 16,785, 9,902 - 74,382 vs 21,289, 11,796 - 70,606). Considering the effect of interventions, a reduction in the median number of annual cases of 35%, 63% and 76% is predicted for LLINs alone, IRS alone and the combination of LLINs and IRS, respectively. This thesis examined the influence of LLINs and IRS on the relationships between environmental variables and malaria and demonstrates the importance of considering vector control measures in analyzes of the epidemiological risk of malaria and in its prediction with climate change.

Malaria is a major public health problem in under developed countries especially countries undergoing war or conflict due to breakdown of health system and exposure of the vulnerable population through displacement. The knowledge, practice and attitude (KAP) of community members have direct influences on malaria preventive measures. A quantitative, explorative and descriptive study was conducted among rural communities of Mundri East County using interview schedules to ascertain malaria related knowledge, practices and attitude and the common factors hindering the malaria control measures at house hold level. Data were collected from 68 respondents from the randomly selected household through personal interviews using a pre-tested interview schedule which was analysed using the SPSS version 15 computer soft ware program. Most of the respondents demonstrated some understanding of malaria as a disease, its transmission, prevention and treatment, although there is a need to improve this through the preferable and acceptable community channels as well as the methods of accessing the modern and scientifically proved and acceptable methods. Given the relatively moderate acceptability of malaria control measures used by the participants in Mundri East County, there is need to conduct further research on the practical implemented measure including the local herbs used for preventive and treatment of malaria Understanding the factors that inhibits or promotes the malaria control measures at community level is necessary for better planning and implementation of malaria intervention programme, which keeps complex and sensitive matters such as educational background, religious and cultural beliefs, and political affiliations in mind. / Health Studies / M.A. (Public Health)

With parts of SA in a malaria endemic area, a preventative way of fighting malaria is with the use of pesticides such as 1,1,1–Trichloro–2,2–bis(pclorophenyl) ethane, also known as DDT. DDT is listed under the persistent organic pollutants (POPs) and considered an endocrine disruptive compound (EDC) under the Stockholm Convention. SA registered an exemption to use DDT as means to fight malaria. DDT and its isomers are, however, known EDCs. Combined with their ability to persist in the environment while not being target specific motivates further studies into possible detrimental effects. The present study aimed to establish if ED was present by comparing the male reproductive organs from snails from an area currently sprayed with DDT (for malaria control) to an area not sprayed with DDT in the Limpopo Province. A possible endpoint (the penis sheath/preputium length ratio or PSPLR) was identified for the freshwater snail Bulinus tropicus. B. tropicus and sediment samples were collected from DDT–sprayed and nonsprayed areas located close together. The snails were dissected and various morphometric parameters measured. Sediments from the sites where the snails were collected were analysed for DDT using GC–MS. Statistical analysis showed significant differences in PSPLR (and therefore possible ED) between snails from the two areas. The difference in PSPLR values was mainly due to a relatively shorter preputium for the snails from the DDT–sprayed area. Even though the sediment samples showed that DDT was present in most of the DDT–sprayed sites and not in the non–DDT sprayed sites, causality of the possible ED could not be established from this field study. This study indicated the possibility of using the PSPLR as endpoint for ED. Recommendations are made for further development of the PSPLR and B. tropicus as biological indicators for endocrine disruption, but causality must first be established. / Thesis (M.Sc (Environmental Science))--North-West University, Potchefstroom Campus, 2011.

With parts of SA in a malaria endemic area, a preventative way of fighting malaria is with the use of pesticides such as 1,1,1–Trichloro–2,2–bis(pclorophenyl) ethane, also known as DDT. DDT is listed under the persistent organic pollutants (POPs) and considered an endocrine disruptive compound (EDC) under the Stockholm Convention. SA registered an exemption to use DDT as means to fight malaria. DDT and its isomers are, however, known EDCs. Combined with their ability to persist in the environment while not being target specific motivates further studies into possible detrimental effects. The present study aimed to establish if ED was present by comparing the male reproductive organs from snails from an area currently sprayed with DDT (for malaria control) to an area not sprayed with DDT in the Limpopo Province. A possible endpoint (the penis sheath/preputium length ratio or PSPLR) was identified for the freshwater snail Bulinus tropicus. B. tropicus and sediment samples were collected from DDT–sprayed and nonsprayed areas located close together. The snails were dissected and various morphometric parameters measured. Sediments from the sites where the snails were collected were analysed for DDT using GC–MS. Statistical analysis showed significant differences in PSPLR (and therefore possible ED) between snails from the two areas. The difference in PSPLR values was mainly due to a relatively shorter preputium for the snails from the DDT–sprayed area. Even though the sediment samples showed that DDT was present in most of the DDT–sprayed sites and not in the non–DDT sprayed sites, causality of the possible ED could not be established from this field study. This study indicated the possibility of using the PSPLR as endpoint for ED. Recommendations are made for further development of the PSPLR and B. tropicus as biological indicators for endocrine disruption, but causality must first be established. / Thesis (M.Sc (Environmental Science))--North-West University, Potchefstroom Campus, 2011.

Malaria is a major public health problem in under developed countries especially countries undergoing war or conflict due to breakdown of health system and exposure of the vulnerable population through displacement. The knowledge, practice and attitude (KAP) of community members have direct influences on malaria preventive measures. A quantitative, explorative and descriptive study was conducted among rural communities of Mundri East County using interview schedules to ascertain malaria related knowledge, practices and attitude and the common factors hindering the malaria control measures at house hold level. Data were collected from 68 respondents from the randomly selected household through personal interviews using a pre-tested interview schedule which was analysed using the SPSS version 15 computer soft ware program. Most of the respondents demonstrated some understanding of malaria as a disease, its transmission, prevention and treatment, although there is a need to improve this through the preferable and acceptable community channels as well as the methods of accessing the modern and scientifically proved and acceptable methods. Given the relatively moderate acceptability of malaria control measures used by the participants in Mundri East County, there is need to conduct further research on the practical implemented measure including the local herbs used for preventive and treatment of malaria Understanding the factors that inhibits or promotes the malaria control measures at community level is necessary for better planning and implementation of malaria intervention programme, which keeps complex and sensitive matters such as educational background, religious and cultural beliefs, and political affiliations in mind. / Health Studies / M.A. (Public Health)

Ph.D. / The toxicant dichlorodiphenyl-trichloroethane, commonly known as DDT, is a broad spectrum insecticide and is currently banned in most countries due to its toxic effects. However, in some countries restricted use of DDT has been authorized as an effective vector control within malarial control programmes. South Africa is one such country, where spraying of DDT occurs in three provinces including the Limpopo Province, KwaZulu Natal and Mpumalanga. Specifically in the Limpopo Province, spraying of DDT has been ongoing for almost 56 years within the eastern malaria belt of the province. Despite this long term spraying there is still a scarcity of data regarding DDT and its effects on indigenous aquatic organisms in South Africa. Any research regarding DDT will therefore be of the utmost value. It was in this context that the present study was initiated, which primarily aimed to assess the extent of contamination within DDT sprayed areas in South Africa and the associated effects on indigenous species, whilst identifying techniques that could be used in future monitoring of these areas. This assessment was done in the Luvuvhu River catchment at three reference sites and four exposure sites situated within the areas where indoor residual spraying of DDT is done annually. At these sites the extent of DDT contamination within the water, sediment and biota (using the bioindicator pecies C. gariepinus from only the lentic sites) in the Luvuvhu river was evaluated. The results showed that DDT concentrations were well above recommended levels in all three of the measured phases, with the highest concentrations predominantly observed at the Xikundu weir. This site was particularly impacted by DDT due to a combination of its close proximity to the DDT sprayed areas, concentration accumulation from upstream sources and environmental conditions that accentuated contamination. These elevated levels of DDT did, however, not induce significant quantifiable effects in the bioindicator C. gariepinus or in the fish and macro-invertebrate community structures. Specifically, the effects in the catfish, C. gariepinus, were assessed using a range of biomarkers specific to the endocrine disrupting effects of DDT, including indirect measures of vitellogenin (calcium, zinc, magnesium and alkali-labile phosphate (ALP) that are all present on the VTG molecule in high abundances), gonad-somatic index (GSI), condition factor (CF), analysis of covariance (ANCOVA) manipulated gonads, protein carbonyls (PC) and intersex. Although none of these biomarkers could be significantly correlated with the DDT contaminations, DDT was shown to induce a slight sub-organismal effect by slightly inducing the synthesis of ALP and Ca as well as reducing the gonad mass (shown by GSI and adjusted gonad mass biomarkers) and body condition. In contrast, the fish and macroinvertebrate communities showed no conclusive relationship with DDT contamination, using a variety of methodologies, including informal assessments, univariate diversity indices, multivariate statistics, abundance models, fish response assessment index (FRAI) as well as average score per taxon (ASPT) and Ephemeroptera, Plecoptera and Trichoptera (EPT) richness. In conclusion, it was shown that DDT concentrations within the Luvuvhu River only induced effects at the lower levels of complexity, which highlights the importance of the utilisation of biomarkers to measure more subtle long-term effects as compared to the usage of community level effects.