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Madeline Slater “Clinical and molecular studies of drug resistant malaria” Malaria is one of the most important infectious diseases worldwide, with Africa bearing the greatest burden of disease. Within the country of Uganda, malaria accounts for the greatest cause of morbidity and mortality with 25% of pediatric outpatient visits, 20% of hospital admissions, and 14% of inpatient deaths attributed to malaria. Without an effective vaccine, forces against the disease depend on post-infectious medical eradication. Chloroquine has been the first line of defense for over 50 years, but resistance to the drug is now estimated at 50% in East Africa. An alternative regimen that is safe, effective, and affordable is currently being sought with focus on combination therapy. The aim of this study is to optimize the results of an ongoing large national drug surveillance study by evaluating the impact of extended follow up and genotyping of the parasite on estimates of the efficacies of combination regimens for the treatment of uncomplicated malaria in Uganda. Through these efforts, more accurate information about drug combination efficacies can hopefully be presented to the Ugandan government in order to guide antimalarial drug treatment policy. This will be achieved by following subjects for 28 days, looking for relapse, twice the time mandated by the World Health Organization for follow up. Additionally, to assess whether recurrences are due to therapy failure vs. new infection, genotyping of the parasites in the recurrences will be performed, allowing for more accurate efficacy measurement. A separate aspect of the project will involve answering the question of whether specific mutations translate into clinical treatment failure. With technological advancements made in the technique of genotyping, it remains to be seen whether presence of the identified mutations definitively results in persistent infection. This portion of the project will be performed with blood samples, following subjects clinically, and laboratory techniques.
 
Elizabeth Partridge “Treatment compliance for tuberculosis - identifying risk factors for treatment failure” Worldwide, poor compliance for tuberculosis therapy is a major problem that can lead to treatment failure and multi-drug resistant tuberculosis (MDR-TB). A 12-week cross-sectional study will be performed to identify those factors relating to compliance for tuberculosis therapy. Risk factors for TB treatment failure will be evaluated using a standardized questionnaire. The study questionnaire will obtain information on patient demographics, medical history, treatment, and medical service evaluation. Several questions will be directed to patients receiving antiretroviral therapy. We hypothesize that the results will provide further clarification of the issues contributing to non-compliance. This information will lend itself to the design and implementation of interventions to enhance TB treatment and prevent MDR-TB.
 
Ian Rosenthal “Micronutrition and tuberculosis Susceptibility” Tuberculosis (TB) infects a third of the world population and kills more people than any other infection. Currently, we do not completely understand the determinants of TB susceptibility, including the reasons that TB deaths in Europe and North America fell by 85% over the century before anti-TB drugs or BCG vaccination were developed. TB remains common in developing countries and studies of TB immunology and epidemiology suggest that dietary micronutrient deficiency, particularly of zinc and vitamins A and D may make important contributions to these variations and TB susceptibility. The proposed project will examine the effects of micronutrient supplementation on antimycobacterial immunity of individuals in a shantytown in Lima, Peru. The study will address whether malnourished people supplemeneted with micronutrients elicit an increased immune resonse towards a TB skin test as compared to individuals with no supplementation.
 
Amod Pokhrel “Exposure to biofuel smoke and risk of tuberculosis in men and women in Nepal” Active Tuberculosis (TB) infection occurs through two routes, as activation of latent infection or directly as a primary infection. It is possible that air pollution might act at each stage of both processes, i.e., increase the chance of becoming infected (through increased coughing in the household) or increase the risk of latent or new infection converting to active status through depression of respiratory immune defence mechanisms. Three studies conducted in India and Mexico have shown an association between household indoor smoke from biofuel and TB. Based on these studies, it may be useful to investigate in more depth whether household indoor smoke from biomass cooking fuels is a significant risk factor for TB in Nepal? If such a relationship is verified, reduction in TB might thereby be achieved through introduction of improved stoves, fuels, and/or ventilation. An incidence-density-based case control study at Manipal Teaching Hospital will be conducted in Nepal, where TB remains a major public health problem today and biomass supplies the bulk of household cooking and space heating needs. In this study an exposure history to indoor smoke from various sources will be obtained through questions and indoor air quality monitoring will be conducted in the houses of twentyfive cases and controls. These measurements will provide information on present exposure, which will be used to validate the questionnaire, including confirmation of ventilation status in the kitchen and other rooms.
 
Charlotte Arrington “Association of schistosomiasis and colorectal cancer in Egypt” Schistosomiasis is caused by infection with a parasitic worm. It is the second-most prevalent parasitic infection in humans, topped only by malaria. Over 200 million people worldwide are infected. The adult worms, or schistosomes, live in the blood vessels near the liver and lay many eggs. These eggs can then become trapped in the liver and intestines. The trapped eggs cause swelling and irritation of these tissues. Because people who live in regions where the worms are present can be infected repeatedly, the chronic irritation and swelling can create a risk of cancer in these tissues.

Schistosomiasis is common in the Nile Delta region of Egypt. Additionally, the population in this area has a high rate of colorectal cancer in those less than 40 years of age. There is a well established association between one schistosome species and bladder cancer, but there is still some debate about whether the species present in Egypt can induce colon cancer. Our research group did a small study of 59 patients that showed an association between schistosomiasis and colon cancer in Egypt. Therefore, the goal of this study is to conduct a larger study to describe the epidemiology of colon cancer due to schistosomiasis in Egypt and to further explore this association.

Approximately 100-150 people with colon cancer will be indentified at the National Cancer Institute in Cairo, Egypt. Information on age, sex, residence, occupation, family history of cancer, history of schistosomiasis, tumor site and stage will be collected. Samples of the tumor and the surrounding tissue will be collected and examined for schistosome eggs. We will also perform a blood test for schistosomiasis antibody as evidence of past infection. ?????
 
Pamela Schipull “Efficacy of the ‘External Quality Assessment for AFB Smear Microscopy’ protocol in Bangladesh” Tuberculosis (TB) kills approximately 2 million people per year globally, and is responsible for nearly 36 million years of healthy life lost due to premature death and disability. Bangladesh has an annual estimated TB incidence rate of 233/10,000, and is classified by the WHO as 1 of 22 high-TB burden countries. Effective control of TB is dependent upon a network of local laboratories that provide accurate and reliable AFB microscopy testing for the diagnosis, treatment, and monitoring of TB. Serious problems can arise when the quality of local laboratory results go unmonitored, and people infected with TB are misclassified as being disease-free. Left untreated, each person with active TB will infect an average of 10 to 15 people each year. However, it is important to note that not all people infected with TB have active TB.

Many developing countries have no system for monitoring the quality of TB detection in local laboratories. In response to this need, an international guidance document for the “External Quality Assessment for AFB Smear Microscopy” was developed in 2002. It is expected that all high-burden countries will adopt this method. This operational assessment will be one of the first to examine and provide recommendations for the protocol, and is extremely relevant to the research agenda of the Bangladeshi National Tuberculosis Program.????
 
Linda Rosul “Determinants of and spatiotemporal variations in Cyclospora infection among Peruvian children” The parasite Cyclospora cayetanensis has emerged as an important cause of endemic diarrhea in developing countries and has caused newsworthy outbreaks in developed world associated with imported produce, such as basil and raspberries. Although linked to travel-related infections, it is a more serious problem in the developing world, where serious and life-threatening diarrhea, especially among children, continues to be major threat to health. Cyclospora was first identified only a decade ago and we lack a thorough understanding of how it infects people, how it survives in the environment, and how it spreads. We propose to increase that understanding in an effort to better control infection and disease.

In Peru, samples will be collected from slums in different regions of Peru, to use data from these samples to determine where Cyclospora lives and who gets infected, to optimize an large ongoing study of Cyclospora infections, and to analyze the relationship between Cyclospora infection and H. pylori, a bacterium that infects human stomachs and probably acts as a “gatekeeper” for Cyclospora and other intestinal infections. This research will take place in the context of two ongoing NIH-funded cohort studies investigating ecologic risk factors (in Tumbes, Iquitos, and Huancayo, Peru) and individual risk factors (in a shantytown near Lima) for Cyclospora infection.
 
 
 

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