Trust and Expectations of Researchers and Public Health Departments for the Use of HIV Molecular Epidemiology.

Background: Molecular epidemiology (ME) is a technique used to study the dynamics of pathogen transmission through a population. When used to study HIV infections, ME generates powerful information about how HIV is transmitted, including epidemiologic patterns of linkage and, potentially, transmission direction. Thus, ME raises challenging questions about the most responsible way to protect individual privacy while acquiring and using these data to advance public health and inform HIV intervention strategies. Here, we report on stakeholders' expectations for how researchers and public health agencies might use HIV ME. Methods: We conducted in-depth semistructured interviews with 40 key stakeholders to find out how these individuals respond to the proposed risks and benefits of HIV ME. Transcripts were coded and analyzed using Atlas.ti. Expectations were assessed through analysis of responses to hypothetical scenarios designed to help interviewees think through the implications of this emerging technique in the contexts of research and public health. Results: Our analysis reveals a wide range of imagined responsibilities, capabilities, and trustworthiness of researchers and public health agencies. Specifically, many respondents expect researchers and public health agencies to use HIV ME carefully and maintain transparency about how data will be used. Informed consent was discussed as an important opportunity for notification of privacy risks. Furthermore, some respondents wished that public health agencies were held to the same form of oversight and accountability represented by informed consent in research. Conclusions: To prevent HIV ME from becoming a barrier to testing or a source of public mistrust, the sense of vulnerability expressed by some respondents must be addressed. In research, informed consent is an obvious opportunity for this. Without giving specimen donors a similar opportunity to opt out, public health agencies may find it difficult to adopt HIV ME without deterring testing and treatment.

Improving the quality and workflow of bacterial genome sequencing and analysis: paving the way for a Switzerland-wide molecular epidemiological surveillance platform.

Facing multidrug resistant (MDR) bacterial pathogens is one of the most important challenges for our society. The spread of highly virulent and resistant pathogens can be described using molecular typing technologies; in particular, whole genome sequencing (WGS) data can be used for molecular typing purposes with high resolution. WGS data analysis can explain the spatiotemporal patterns of pathogen transmission. However, the transmission between compartments (human, animal, food, environment) is very complex. Interoperable and curated metadata are a key requirement for fully understanding this complexity. In addition, high quality sequence data are a key element between centres using WGS data for diagnostic and epidemiological applications. We aim to describe steps to improve WGS data analysis and to implement a molecular surveillance platform allowing integration of high resolution WGS typing data and epidemiological data.

Epidemiología molecular de Bartonella Henselae en gatos callejeros y de albergue en Zaragoza, España / Molecular epidemiology of Bertonella Henselae in stray and sheltered cats of Zaragoza, Spain

Fundamentos: Bartonella henselae produce la enfermedad del arañazo del gato en las personas y se considera infradiagnosticada. El objetivo fue detectar y cuantificar la carga de ácido desoxiribonucleico (ADN) de B. henselae en muestras de sangre y orales de gatos callejeros y de albergue de Zaragoza, España y analizar su relación con factores epidemiológicos y clínicos. Métodos: Se estudiaron 47 gatos. El ADN de B. henselae,se detectó mediante reacción en cadena de la polimerasa en tiempo real (qPCR) en sangre y muestras orales. Se usó el paquete estadístico SPSS para analizar la positividad de las muestras pareadas y su relación con factores epidemiológicos (edad, sexo, origen, mes de muestreo, presencia de pulgas/garrapatas) y clínicos (estado de salud y presencia de lesiones orales). Se realizó un análisis de regresión logística para conocer la asociación entre la presencia en sangre y cavidad oral y el resto de las variables. Resultados: el 23,40% de las muestras de sangre y el 27,65% de las orales portaba el ADN de B. henselae. Se observó débil correlación de la positividad de las muestras pareadas (kappa= 0,33; p <0,05). No se detectó asociación estadística (p>0,05) entre la presencia de ADN de B. henselae en las muestras y los factores epidemiológicos y clínicos. Los gatos con lesiones orales portaban una carga más elevada de ADN (3,12/1x106 células) en la boca que los que no tenían lesiones (2,58 /1por106 células), (p=0,032). Conclusiones: La detección de ADN de B. henselae en sangre no parece estar relacionada con su presencia en cavidad oral y viceversa. Los gatos positivos con lesiones orales pueden significar mayor riesgo de infección por B. henselae para las personas que los manejan (AU)

Background: Bartonella henselae is responsible for the Cat Scratch Disease in humans, being it underdiagnosed. This study aims to detect and quantify the load of B. henselae DNA in oral and whole blood samples from stray and shelthered cats from Zaragoza (Spain), and analyze associations with epidemiological and clinical factors. Methods: 47 cats entered in the estudy. Real time PCR was used to detect B. henselae DNA in blood and oral samples. The SPSS software was applied to the statistical analysis of positivity of paired samples and its relationship with variables as age, sex, origin, month of sampling and fleas/ticks observation in fur and clinical factors (health status and observation of oral lesions). Logistic Regression was used. Results: a 23.40% of blood samples and the 27.65% of the oral swabs carried the B. henselae DNA. A fair agreement between paired samples was observed (kappa value = 0.33, p<0.05). Bacterial DNA detected in oral and blood samples were not significantly associated to any of the epidemiological and clinical factors. Positive cats having oral lesions carried higher loads (3,12 / 1x106 cells) of bacterial DNA in their oral cavity than those without lesions (2,58/1x106 cells) being p = 0.032. Conclusions: Carriage of the B. henselae DNA in the blood samples appears not to be related with carriage of the DNA of the bacteria in mouth and vice versa. Positive cats having oral lesions carry a higher load of B. henselae DNA and may suppose a higher risk of transmission to people handling them (AU)

Vigilancia microbiológica del sarampión y la rubéola en España. Red de laboratorios / Microbiological surveillance of measles and rubella in Spain. Laboratory network

El laboratorio es un elemento imprescindible en la vigilancia del sarampión y la rubéola, ya que los casos han de ser adecuadamente confirmados para poder estimar la incidencia de forma precisa, las cepas han de ser caracterizadas genéticamente para conocer el patrón de circulación de los virus y estudiar de forma completa los brotes y las cadenas de transmisión y la susceptibilidad de la población debe de ser determinada mediante encuestas de seroprevalencia. El diagnóstico de laboratorio de las infecciones agudas por estos agentes se basa en la detección de la respuesta inmune específica de clase IgM, que debe de complementarse con la detección del genoma del virus en exudado faríngeo y/u orina para poder alcanzar un rendimiento diagnóstico óptimo, especialmente si la recogida de las muestras es muy temprana. El genotipado de la cepa se realiza por secuenciación genómica de acuerdo a protocolos de referencia de la OMS. La vigilancia de laboratorio de sarampión y rubéola en España se estructura en forma de red, con laboratorios autonómicos de capacidades diferentes y un Laboratorio Nacional de Referencia (LNR), que es el Centro Nacional de Microbiología, que garantiza la disponibilidad de las técnicas en todo el territorio nacional, vela por la calidad de los resultados y representa a la Red Nacional en la Red Europea de laboratorios. El LNR está actualmente implantando nuevas herramientas de caracterización molecular basadas en regiones hipervariables del genoma para la caracterización de las cepas a nivel subgenotípico y su aplicación a la vigilancia (AU)

The Laboratory is a fundamental component on the surveillance of measles and rubella. Cases need to be properly confirmed to ensure an accurate estimation of the incidence. Strains should be genetically characterized to know the transmission pattern of these viruses and frequently, outbreaks and transmission chains can be totally discriminated only after that. Finally, the susceptibility of the population is estimated on the basis of sero-prevalence surveys. Detection of specific IgM response is the base of the laboratory diagnosis of these diseases. It should be completed with genomic detection by RT-PCR to reach an optimal efficiency, especially when sampling is performed early in the course of the disease. Genotyping is performed by genomic sequencing according to reference protocols of the WHO. Laboratory surveillance of measles and rubella in Spain is organized as a net of regional laboratories with different capabilities. The National Center of Microbiology as National Reference Laboratory (NRL), supports regional laboratories ensuring the availability of all required techniques in the whole country and watching for the quality of the results. The NRL is currently working in the implementation of new molecular techniques based on the analysis of genomic hypervariable regions for the strain characterization at sub-genotypic levels and use them in the surveillance (AU)

Estudios de epidemiología molecular en población inmigrante en España / Molecular epidemiology studies on the immigrant population in Spain

Fundamentos: La epidemiología molecular es una nueva disciplina que permite la integración de la información sobre la variabilidad genética de patógenos infecciosos con su difusión en la población y subgrupos de la misma incluyendo, por ejemplo, las mutaciones de resistencia a antibióticos y antivirales. El objetivo es conocer qué posibles diferencias existe en las características genéticas de los agentes infecciosos que afectan a las poblaciones inmigrante y autóctoctona en España.. Métodos: Se revisaron artículos originales publicados entre 1998- 2013, con las palabras clave "epidemiología molecular", "tipado molecular", "secuenciación", "inmigrante", "España". Resultados: De un total de 267 artículos identificados inicialmente, 50 pasaron los diferentes filtros establecidos. De ellos, 36 analizan las infecciones por Mycobacterium tuberculosis y VIH, seguidos de los que analizan infecciones por Staphylococcus aureus (3) y el Virus de la Hepatitis B (3). Conclusiones: Los objetivos principales de estos trabajos fueron el tipado del patógeno y la determinación de la frecuencia de mutaciones de resistencia. Los estudios más frecuentes correspondieron a cohortes retrospectivas, seguidos por los estudios ecológicos y los ensayos clínicos. En general los estudios son descriptivos y su ámbito por el tipo y tamaño de muestra es bastante restringido. En varios se determina que las cepas o variantes del patógeno encontradas en inmigrantes tienen su origen más probable en sus países de origen, si bien otros también ponen de manifiesto la transmisión desde la población autóctona a la inmigrante (AU)

Background: Molecular epidemiology is a new scientific discipline which allows to integrate information on the genetic variation of infectious pathogens with their diffusion in a population and its subgroups including, for instance, resistance mutations to antibiotics and antiretrovirals. We present the results of an analysis of scientific publications that analyze the health status of the immigrant population in Spain from a molecular epidemiology perspective. Methods:We reviewed original articles published in 1998-2014 with he keywords "molecular epidemiology", "molecular typing", "sequencing", "immigrant", and "Spain". Results: Froma total of 267 articles identified initially, only 50 passed through the established filters. Most of them (36) analyzed infections by Mycobacterium tuberculosis (3) and HIV (3), followed at a large distance by Staphylococcus aureus and hepatitis B virus. The main goal of these works was the typing of the pathogen and to determine the frequency of resistance mutations. Conclusion: Is difficult to generalize the conclusions from the analyzed articles because most of them have a purely descriptive and quite restricted scope, considering the type and size of the samples studied. Several studies are focused on the most likely origin for the strains or variants of the pathogen but others also reveal transmissions from the local to the immigrant populations (AU)

Data sharing in large research consortia: experiences and recommendations from ENGAGE.

Data sharing is essential for the conduct of cutting-edge research and is increasingly required by funders concerned with maximising the scientific yield from research data collections. International research consortia are encouraged to share data intra-consortia, inter-consortia and with the wider scientific community. Little is reported regarding the factors that hinder or facilitate data sharing in these different situations. This paper provides results from a survey conducted in the European Network for Genetic and Genomic Epidemiology (ENGAGE) that collected information from its participating institutions about their data-sharing experiences. The questionnaire queried about potential hurdles to data sharing, concerns about data sharing, lessons learned and recommendations for future collaborations. Overall, the survey results reveal that data sharing functioned well in ENGAGE and highlight areas that posed the most frequent hurdles for data sharing. Further challenges arise for international data sharing beyond the consortium. These challenges are described and steps to help address these are outlined.

Establishment and operation of a biorepository for molecular epidemiologic studies in Costa Rica.

BACKGROUND: The Proyecto Epidemiológico Guanacaste (PEG) has conducted several large studies related to human papillomavirus (HPV) and cervical cancer in Guanacaste, Costa Rica in a long-standing collaboration with the U.S. National Cancer Institute. To improve molecular epidemiology efforts and save costs, we have gradually transferred technology to Costa Rica, culminating in state-of-the-art laboratories and a biorepository to support a phase III clinical trial investigating the efficacy of HPV 16/18 vaccine. OBJECTIVE: Here, we describe the rationale and lessons learned in transferring molecular epidemiologic and biorepository technology to a developing country. RESULTS: At the outset of the PEG in the early 1990s, we shipped all specimens to repositories and laboratories in the United States, which created multiple problems. Since then, by intensive personal interactions between experts from the United States and Costa Rica, we have successfully transferred liquid-based cytology, HPV DNA testing and serology, chlamydia and gonorrhea testing, PCR-safe tissue processing, and viable cryopreservation. To accommodate the vaccine trial, a state-of-the-art repository opened in mid-2004. Approximately 15,000 to 50,000 samples are housed in the repository on any given day, and >500,000 specimens have been shipped, many using a custom-made dry shipper that permits exporting >20,000 specimens at a time. Quality control of shipments received by the NCI biorepository has revealed an error rate of <0.2%. Recently, the PEG repository has incorporated other activities; for example, large-scale aliquotting and long-term, cost-efficient storage of frozen specimens returned from the United States. Using Internet-based specimen tracking software has proven to be efficient even across borders. CONCLUSION: For long-standing collaborations, it makes sense to transfer the molecular epidemiology expertise toward the source of specimens. The successes of the PEG molecular epidemiology laboratories and biorepository prove that the physical and informatics infrastructures of a modern biorepository can be transferred to a resource-limited and weather-challenged region. Technology transfer is an important and feasible goal of international collaborations.

The interface of genetics and public health: research and educational challenges.

As the target date for the sequencing of the human genome approaches, there is growing recognition that public health practice, research, and education will be impacted by new genetic technologies and information and that a multidisciplinary approach is required. Research in the emerging field of public health genetics encompasses a broad range of disciplines and will increasingly involve the interactions among the investigators in these fields. An overview of these areas of research is provided, with illustrative examples. Education in public health genetics needs to address a variety of audiences, including public health graduate students and practitioners, students from related disciplines, and health care professionals. Two new graduate programs at the Universities of Michigan and Washington and training opportunities for public health professionals are described. These educational efforts must be ongoing so that the potential of genetic technology and information can be appropriately used to benefit the health of all.

Toward an integrated approach to molecular epidemiology.

The emergence of "molecular epidemiology" as a scientific approach within the fields of epidemiology and toxicology has led to spirited discussion within the biomedical community, particularly in the area of cancer research. At scientific meetings and in peer-reviewed journals, numerous issues have been raised not only with regard to the practice of molecular epidemiology, but also with regard to its role in traditional epidemiology, toxicology, and risk assessment. Furthermore, the utility of information gleaned from such studies and the implications for public health have been the subject of considerable debate. Conceptual differences in how one views the function of epidemiologic and laboratory research may be reflected in discussions on the merits of molecular epidemiology. This commentary reviews some of the prevailing attitudes toward molecular epidemiology, with the goal of identifying areas of concern and suggesting means of achieving harmonization. The need for cross-training of epidemiologists and laboratory scientists is discussed, and suggestions are made for building successful collaborative relations across disciplines.

[A view of the representation of the Pan-American Health Organization in Mexico with respect to support for molecular epidemiology]. / Una visión de la representación de la Organización Panamericana de la Salud en México respecto al apoyo de la epidemiología molecular.

In spite of the fact that epidemiology has the same commitments that in the past, in terms of political orientation, the changes of the epidemiological patterns offer new challenges. The scientific and technological development gives new tools for a better knowledge of the behaviour of diseases in populations. This is the case of molecular biology, which provides with the option of identifying risk factors in individuals and in populations. Several developing countries including Mexico, have satisfactory epidemiology programs and research groups in molecular biology contributing to the better epidemiological understanding. IMETAF is a collaborative network to reinforce infrastructure, support projects and personnel training. The World Health Organization, the Panamerican Health Organization and consequently, the Mexico Representation of the mentioned Organizations, contribute to the development of modern technology related to epidemiological tasks.

Applying management strategies in molecular epidemiology field studies.

In conducting field studies of human exposure, we have encountered significant methodological challenges. The management strategy our group developed to conduct two recent studies of environmental health utilizes a collaborative study design process and innovative protocol management tools, and emphasizes community outreach. We present here the phases of planning, development and realization of two studies--one conducted in an environmentally contaminated area, and another in an occupational setting. We show how the use of this management strategy increases the efficiency of field operations and improves variability assessment.

Mechanisms of carcinogenesis and molecular epidemiology.

Molecular epidemiology supplies information on various stages of the multistep process of carcinogenesis and allows identification of biological markers that may indicate an increased risk of cancer. These markers have an established position in occupational and environmental epidemiology.