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Performing health surveys in developing countries and humanitarian emergencies can be challenging work because the resources in these settings are often quite limited and information needs to be gathered quickly. The Expanded Program on Immunization (EPI) sampling method provides one way of selecting subjects for a survey. It involves having field workers proceed on a random walk guided by a path of nearest household neighbours until they have met their quota for interviews. Due to its simplicity, the EPI sampling method has been utilized by many surveys. However, some concerns have been raised over the quality of estimates resulting from such samples because of possible selection bias inherent to the sampling procedure. We present an algorithm for obtaining the probability of selecting a household from a cluster under several variations of the EPI sampling plan. These probabilities are used to assess the sampling plans and compute estimator properties. In addition to the typical estimator for a proportion, we also investigate the Horvitz-Thompson (HT) estimator, an estimator that assigns weights to individual responses. We conduct our study on computer-generated populations having different settlement types, different prevalence rates for the characteristic of interest and different spatial distributions of the characteristic of interest. Our results indicate that within a cluster, selection probabilities can vary largely from household to household. The largest probability was over 10 times greater than the smallest probability in 78% of the scenarios that were tested. Despite this, the properties of the estimator with equally weighted observations (EQW) were similar to what would be expected from simple random sampling (SRS) given that cases of the characteristic of interest were evenly distributed throughout the cluster area. When this was not true, we found absolute biases as large as 0.20. While the HT estimator was always unbiased, the trade off was a substantial increase in the variability of the estimator where the design effect relative to SRS reached a high of 92. Overall, the HT estimator did not perform better than the EQW estimator under EPI sampling, and it involves calculations that may be difficult to do for actual surveys. Although we recommend continuing to use the EQW estimator, caution should be taken when cases of the characteristic of interest are potentially concentrated in certain regions of the cluster. In these situations, alternative sampling methods should be sought. / Thesis / Master of Science (MSc)

The Expanded Program on Immunization Sampling Method (known simply as EPI sampling) is a two-stage sampling procedure originally intended for quick estimation of disease prevalence in large geographical regions. The method was developed in the 1970s and all the subsequent assessments of its performance have been conducted by simulation. In her master's thesis, Reyes (2016) studied in detail the second-stage sampling of the method by developing formulas for the exact calculation of the household inclusion probabilities when sectors are used to identify the initial household to generate the EPI samples. The inclusion probabilities were used in turn to obtain exact mean, bias, variance and mean square error of any estimator of disease prevalence in the population. Thus, no extensive simulations are required and the results are exact rather than just estimates. This thesis is an extension of Reyes' (2016) work. The extension is two-fold; (a) employing strips rather than sectors because they narrow the geographic area for field workers and to use strips to select the first household for the EPI sample at the secondary stage, and (b) carrying out an analysis on simulated population and sampling plans, using both stages of the EPI method. Analyzing the simulated populations showed that equal weight estimator that samples primary units with replacement with probability proportional to size (EW1) should be used when the target characteristic is thought to be spread randomly throughout the population, and the Horvitz-Thompson estimator that samples primary units systematically with replacement (HTSYS) should be used when the disease is believed to spread from a central location or through pocketing. Comparing the strip and sector sampling methods at the secondary stage using their effective areas leads to a comparative basis in which the inclusion probabilities are identical for both methods. / Thesis / Master of Science (MSc)

Le paludisme est l’une des maladies infectieuses la plus fréquente au monde avec 40% de la population mondiale exposée. En dépit des stratégies actuelles de lutte notamment la prise en charge rapide des cas, l’utilisation de matériaux imprégnés et la pulvérisation intra domiciliaire d’insecticide, le paludisme reste une des premières causes de morbidité et de mortalité notamment en Afrique subsaharienne. Cette partie du monde totalise à elle seule plus de 90% des cas de décès par paludisme dont 88% chez les enfants de moins de moins de 5 ans. En absence de vaccin utilisable en santé publique, il y a donc un besoin urgent de trouver une stratégie efficiente et simple de contrôle du paludisme. Le traitement préventif intermittent (TPI) définie comme l’administration d’un antipaludique à dose curative à des intervalles de temps prédéfinis réduit l’incidence du paludisme et apparaît aujourd’hui comme une des stratégies les plus prometteuses. Cette stratégie couplée au Programme Elargi de Vaccination (PEV) chez les enfants de moins de 1 an réduit l’incidence du paludisme de 30%. Des résultats plus importants sont obtenus chez les enfants de 0 à 5 ans voire de 0 à 10 ans lorsque la stratégie est appliquée en ciblant la saison de transmission. Nos travaux de recherche au Mali ont porté sur :- l’impact de la mise en œuvre du TPI couplé à la vaccination du PEV (TPin) sur i) la résistance P. falciparum à la Sulfadoxine pyrimethamine (SP), ii) la couverture des vaccins du PEV, iii) le taux de mortalité des enfants âgés de 4 à 18 mois.- l’efficacité du TPI chez les enfants ciblant la saison de transmission (TPIe) dans un contexte de faible et de forte couverture en des Moustiquaires Imprégnés d’Insecticides (MII). Nos résultats ont montré qu’après une année de mise en œuvre à l’échelle du district sanitaire, le TPIn a entrainé une augmentation de la couverture des vaccins du PEV. Cette couverture était de 53% en zone de non-intervention contre 69.5% en zone d’intervention (p<0.01). Il y a eu une réduction de la mortalité globale de 27% (RR= 0,73, IC95% : 0,55-0,97, p=0,029) chez les enfants âgés de 4 à 18 mois. Les fréquences des marqueurs moléculaires de la résistance de P. falciparum à SP en début et en fin la mise en œuvre et entre la zone d’intervention et la zone de non –intervention après une année de mise en œuvre étaient similaires. Deux doses de SP données en TPI à 8 semaines d’ intervalle durant la saison de transmission réduit le taux d’incidence du paludisme pendant la saison de transmission de 69,4% chez les enfants de moins de 5 ans et de 63,4% chez les enfants de 5-10 ans dans un contexte de très faible utilisation de MII (<5%). Dans une autre étude que nous avons menée, le TPI avec SP + Amodiaquine (AQ) donné en 3 occasions à un mois d’ intervalle pendant la saison de transmission a réduit le taux d’ incidence du paludisme clinique non compliqué de 82% (IC à 95%: 78%– 85%; P<0.001) et les formes graves de paludisme de 87% (IC à 95% 42% – 99%, P=0.001) chez les enfants âgés de 3 à 59 mois en dépit un taux d’utilisation des MII de plus de 99%. Nous n’avons pas documenté d’événement indésirable grave lié à l’utilisation de la SP ou de la SP + AQ en TPI durant ces deux études. Nos résultats étayent la recommandation du TPI, ciblant la saison de transmission ou couplée au PEV, pour la lutte antipaludique chez les enfants. / Malaria is one of the most common infectious diseases in the world and 40% of the world population is exposed to malaria. Despite the current control strategies such as rapid diagnosis and treatment of disease cases, use of insecticide impregnated materials and indoor residuals spraying with insecticides, malaria remained a main cause of morbidity and mortality particularly in sub Saharan Africa. More than 90% of the deaths due to malaria occurred in this region and 88% of these deaths occurred in children aged less than 5 years of age. In absence of vaccine that can be used in public health, there is an urgent need for a simple and efficient control strategy. Malaria intermittent preventive treatment (IPT) defined as the administration of curative dose of anti-malarial drug at predefined time intervals, appears as one of the most promising strategies. Given through the Expanded Program of Immunization (EPI), the strategy reduced the incidence of malaria by 30%. More drastic reductions were obtained in children aged 0-5 years and even 0-10 years when the malaria transmission season was targeted for the administration of the strategy. Our research work in Mali has assessed the following:- The impact of implementation of IPT administrated through EPI (IPTi) on: i) the resistance of P. falciparum to Sulfadoxine pyrimethamine (SP); ii) EPI vaccine coverage, and iii) mortality of children of 4-18 months of age. - The efficacy of IPT in children targeting the malaria transmission season (IPTe) in a context of low and high coverage of insecticide impregnated nets (ITN).We have found that the implementation of IPTi at the district level has resulted in an augmentation of the EPI vaccine coverage. The EPI vaccine coverage was 53% in the non-intervention zone compared to 69.5% in the intervention zone (p<0,01). There was a reduction in all cause mortality of 27% (RR= 0.73, 95% CI : 0.55-0.97, p=0.029) in children aged 4-18 months. The frequencies of molecular markers of the resistance of P. falciparum to SP were similar at the beginning and the end of the one year implementation period and between the intervention and non-intervention zones.Two doses of SP given at 8 weeks interval during the transmission season, reduced the incidence of malaria episodes during the transmission season by 69.4% in children aged less than 5 years and by 63.4% in children aged 5-10 years in a context of very low ITN use (<5%). In another study that we have conducted, IPT with SP + Amodiaquine (AQ) given at three occasions at one month interval during the transmission season reduced the incidence rate of clinical malaria by 82% (95% CI: 78%– 85%; P<0.001), and the incidence of severe and complicated malaria by 87% (95% IC 42% – 99%, P=0.001) in children aged 3 to 59 months of age despite an ITN use of greater than 99%.There was no serious adverse event related to the use of SP or SP+AQ in IPT during the two studies. Our results support the recommendation of IPT targeting the transmission season and IPT given through the EPI for malaria control in children.