Microarrays for public health: genomic epidemiology of tuberculosis

In response to a large local school-based outbreak of tuberculosis, we have been evaluating the utility of microarray bacterial genomic analysis in outbreak management. After initial comparison of the isolate from the index case with Mycobacterium tuberculosis H37Rv, it was possible to design robust PCRs directed towards strain-specific deletions. Rapid PCR analysis of isolates proved valuable in determining whether or not other isolates were compatible with the outbreak strain and further microarray studies revealed genetic markers that could be used to discriminate between locally circulating strains.We suggest that this approach forms the basis for developing rapid local genotyping schemes applicable to M. tuberculosis and that application to other pathogens warrants consideration.     

Drug-resistant malaria: molecular mechanisms and implications for public health

Resistance to antimalarial drugs has often threatened malaria elimination efforts and historically has led to the short-term resurgence of malaria incidences and deaths. With concentrated malaria eradication efforts currently underway, monitoring drug resistance in clinical settings complemented by in vitro drug susceptibility assays and analysis of resistance markers, becomes critical to the implementation of an effective antimalarial drug policy. Understanding of the factors, which lead to the development and spread of drug resistance, is necessary to design optimal prevention and treatment strategies. This review attempts to summarize the unique factors presented by malarial parasites that lead to the emergence and spread of drug resistance, and gives an overview of known resistance mechanisms to currently used antimalarial drugs.     

Biomarkers in molecular epidemiology studies for health risk prediction

The field of molecular epidemiology is very promising, as sophisticated techniques are being developed to address etiology, genetic susceptibility and mechanisms for induction of disease. The use of biomarkers plays a key role in these investigations because the information can be used to predict the development of disease and to implement disease prevention programs. However, as emphasized by Frederica P. Perera, the field is strewn with studies either that failed to use validated biomarkers or whose designs did not adequately consider the biology of the endpoints, and the availability of validated biomarkers of health risk is still limited. In this review, we have briefly described the usefulness of certain biomarkers for the documentation of exposure and early biological effects, with special concern for the prediction of cancer. An emphasis is placed on understanding the biological and health significance of biomarkers. By building reliable biomarker databases, a promising future is the integration of information from the genome programs to expand the scientific frontiers on etiology, health risk prediction and prevention of environmental disease.     

Molecular epidemiology: potential impacts on the assessment of public health

In trying to decide what type of scientific paper I could prepare as a tribute to Jim Neel, I thought back over the discussions that we had over some 25 years. Sometimes these discussions were on specific topics such as how to extrapolate from mutation data in mice to those for humans following radiation or chemical exposures. On other occasions, our discussions were of a more philosophical nature, particularly on where the field of epidemiology might or needed to go. For example, what types of data are needed for assessing the public health impact of exposure to environmental agents. Perhaps because I enjoyed these discussions so much, I have chosen to take a look from a current perspective at the field of molecular epidemiology. Jim Neel would have loved to have entered into this discussion; he would have enhanced it in is own inimitable way.     

Methods for a public health response to birth defects clusters

Few resources are available to guide public health officials in investigations of reported birth defects clusters. The majority of published resources focus on the investigation of cancer and infectious disease clusters and do not address clinical and epidemiologic concerns specific to birth defects research. This document aims to address these concerns, discuss the needs of the affected community, and provide suggestions for the development of a standardized protocol to be used as a guide in the investigation of birth defects clusters. We suggest that health departments and birth defects registries that may receive reports of birth defects clusters establish a protocol for responding that includes the following steps: develop a proactive plan for future birth defects cluster reports (step I), receive report of a birth defects cluster (step II), verify diagnoses and complete case ascertainment (step III), compare the observed rate to a reference rate (step IV), ascertain exposures among cases from available records (step V), interview case mothers (step VI), initiate further epidemiologic study-selection of controls (step VII), and communicate results to the community (step VIII). Specific criteria for continuing or terminating an investigation should be established before receiving cluster reports. The recommendations in this report should be carefully considered to ensure that the specific needs of the region, agency and affected community are met.     

Modeling inhalational tularemia: deliberate release and public health response

Two epidemic modeling studies of inhalational tularemia were identified in the published literature, both demonstrating the high number of potential casualties that could result from a deliberate aerosolized release of the causative agent in an urban setting. However, neither study analyzed the natural history of inhalational tularemia nor modeled the relative merits of different mitigation strategies. We first analyzed publicly available human/primate experimental data and reports of naturally acquired inhalational tularemia cases to better understand the epidemiology of the disease. We then simulated an aerosolized release of the causative agent, using airborne dispersion modeling to demonstrate the potential number of casualties and the extent of their spatial distribution. Finally, we developed a public health intervention model that compares 2 mitigation strategies: targeting antibiotics at symptomatic individuals with or without mass distribution of antibiotics to potentially infected individuals. An antibiotic stockpile that is sufficient to capture all areas where symptomatic individuals were infected is likely to save more lives than treating symptomatic individuals alone, providing antibiotics can be distributed rapidly and their uptake is high. However, with smaller stockpiles, a strategy of treating symptomatic individuals alone is likely to save many more lives than additional mass distribution of antibiotics to potentially infected individuals. The spatial distribution of symptomatic individuals is unlikely to coincide exactly with the path of the dispersion cloud if such individuals are infected near their work locations but then seek treatment close to their homes. The optimal mitigation strategy will depend critically on the size of the release relative to the stockpile level and the effectiveness of treatment relative to the speed at which antibiotics can be distributed.     

The epidemiology and public health importance of toxocariasis: A zoonosis of global importance

Toxocariasis, caused by infection with larvae of Toxocara canis, and to a lesser extent by Toxocara cati and other ascaridoid species, manifests in humans in a range of clinical syndromes. These include visceral and ocular larva migrans, neurotoxocariasis and covert or common toxocariasis. Toxocara canis is one of the most widespread public health and economically important zoonotic parasitic infections humans share with dogs, cats and wild canids, particularly foxes. This neglected disease has been shown through seroprevalence studies to be especially prevalent among children from socio-economically disadvantaged populations both in the tropics and sub-tropics and in industrialised nations. Human infection occurs by the accidental ingestion of embryonated eggs or larvae from a range of wild and domestic paratenic hosts. Most infections remain asymptomatic. Clinically overt infections may go undiagnosed, as diagnostic tests are expensive and can require serological, molecular and/or imaging tests, which may not be affordable or available. Treatment in humans varies according to symptoms and location of the larvae. Anthelmintics, including albendazole, thiabendazole and mebendazole may be given together with anti-inflammatory corticosteroids. The development of molecular tools should lead to new and improved strategies for the treatment, diagnosis and control of toxocariasis and the role of other ascaridoid species in the epidemiology of Toxocara spp. Molecular technologies may also help to reveal the public health importance of T. canis, providing new evidence to support the implementation of national control initiatives which have yet to be developed for Toxocara spp. A number of countries have implemented reproductive control programs in owned and stray dogs to reduce the number of young dogs in the population. These programs would positively impact upon T. canis transmission since the parasite is most fecund and prevalent in puppies. Other control measures for T. canis include the regular and frequent anthelmintic treatment of dogs and cats, starting at an early age, education and enforcement of laws for the disposal of canine faeces, dog legislation and personal hygiene. The existence of wild definitive and paratenic hosts complicates the control of T. canis. Increasing human and dog populations, population movements and climate change will all serve to increase the importance of this zoonosis. This review examines the transmission, diagnosis and clinical syndromes of toxocariasis, its public health importance, epidemiology, control and current research needs.