Advancing pathogen genomics in resource-limited settings.

Genomic sequencing has emerged as a powerful tool to enhance early pathogen detection and characterization with implications for public health and clinical decision making. Although widely available in developed countries, the application of pathogen genomics among low-resource, high-disease burden settings remains at an early stage. In these contexts, tailored approaches for integrating pathogen genomics within infectious disease control programs will be essential to optimize cost efficiency and public health impact. We propose a framework for embedding pathogen genomics within national surveillance plans across a spectrum of surveillance and laboratory capacities. We adopt a public health approach to genomics and examine its application to high-priority diseases relevant in resource-limited settings. For each grouping, we assess the value proposition for genomics to inform public health and clinical decision-making, alongside its contribution toward research and development of novel diagnostics, therapeutics, and vaccines.

Cost-effectiveness of sub-national geographically targeted vaccination programs: A systematic review.

Immunization is an essential component of national health plans. However, the growing number of new vaccine introductions, vaccination campaigns and increasing administrative costs create logistic and financial challenges, especially in resource-limited settings. Sub-national geographic targeting of vaccination programs is a potential strategy for governments to reduce the impact of infectious disease outbreaks while optimizing resource allocation and reducing costs, promoting sustainability of critically important national immunization plans. We conducted a systematic review of peer-reviewed literature to identify studies that investigated the cost-effectiveness of geographically targeted sub-national vaccination programs, either through routine immunization or supplementary immunization activities. A total of 16 studies were included in our review, covering nine diseases of interest: cholera, dengue, enterotoxigenic Escherichia coli (ETEC), hepatitis A, Japanese encephalitis, measles, rotavirus, Shigella and typhoid fever. All studies modelled cost-effectiveness of geographically targeted vaccination. Despite the variation in study design, disease focus and country context, studies generally found that in countries where a heterogenous burden of disease exists, sub-national geographic targeting of vaccination programs in areas of high disease burden was more cost-effective than a non-targeted strategy. Sensitivity analysis revealed that cost-effectiveness was most sensitive to variations in vaccine price, vaccine efficacy, mortality rate, administrative and operational costs, discount rate, and treatment costs. This systematic review identified several key characteristics related to geographic targeting of vaccination, including the vaccination strategy used, variations in modelling parameters and their impact on cost-effectiveness. Additional research and guidance is needed to support the appropriateness and feasibility of geographically targeted vaccination and to determine what country context would make this a viable complement to routine immunization programs.

A participatory approach to assessing refugee perceptions of health services.

OBJECTIVE: The necessity and value of beneficiary input is widely recognized by the humanitarian community. Nevertheless, limited beneficiary involvement occurs due to various barriers. This study explores the effectiveness of an innovative, participatory approach to assessing beneficiary perceptions in resource-limited settings. METHODS: A unique hybrid of qualitative and quantitative methodologies assessed perceptions of health programs within five refugee camps in Kenya and Tanzania. A database of perceptions and opinions was established through key-informant interviews, focus group discussions and free-response questionnaires among refugees, community leaders and healthcare providers. Each participant subsequently force-ranked the collected views into quasi-normal distribution according to level of agreement. Responses were analyzed using by-person factor analysis software. FINDINGS: Eighty-one individuals (96%) successfully completed the participatory exercise. The methodologies identified detailed levels of consensus, rank-ordered priorities and unique sub-population opinions. CONCLUSION: The authors illustrate benefits and feasibility of qualitative quantitative participatory methodology in assessing beneficiary perceptions of refugee services.

"Operation Helping Hands": Massachusetts health and medical response to Hurricane Katrina.

INTRODUCTION: As Hurricane Katrina bore down on New Orleans in August 2005, the city's mandatory evacuation prompted the exodus of an estimated 80% of its 485,000 residents. According to estimates from the US Centers for Disease Control and Prevention (CDC), at least 18 states subsequently hosted more than 200,000 evacuees. HYPOTHESIS/PROBLEM: In this case study, "Operation Helping Hands" (OHH), the Massachusetts health and medical response in assisting Hurricane Katrina evacuees is described. Operation Helping Hands represents the largest medical response to evacuees in recent Massachusetts history. METHODS: The data describing OHH were derived from a series of structured interviews conducted with two leading public health officials directing planning efforts, and a sample of first responders with oversight of operations at the evacuation site. Also, a literature review was conducted to identify similar experiences, common challenges, and lessons learned. RESULTS: Activities and services were provided in the following areas: (1) administration and management; (2) medical and mental health; (3) public health; and (4) social support. This study adds to the knowledge base for future evacuation and shelter planning, and presents a conceptual framework that could be used by other researchers and practitioners to describe the process and outcomes of similar operations. CONCLUSIONS: This study provides a description of the planning and implementation efforts of the largest medical evacuee experience in recent Massachusetts history, an effort that involved multiple agencies and partners. The conceptual framework can inform future evacuation and shelter initiatives at the state and national levels, and promotes the overarching public health goal of the highest attainable standard of health for all.

Aggressive behavior, related conduct problems, and variation in genes affecting dopamine turnover.

A number of dopamine-related genes have been implicated in the etiology of violent behavior and conduct problems. Of these genes, the ones that code for the enzymes that influence the turnover of dopamine (DA) have received the most attention. In this study, we investigated 12 genetic polymorphisms in four genes involved with DA functioning (COMT, MAOA and MAOB, and DbetaH) in 179 incarcerated male Russian adolescents and two groups of matched controls: boys without criminal records referred to by their teachers as (a) "troubled-behavior-free" boys, n=182; and (b) "troubled-behavior" boys, n=60. The participants were classified as (1) being incarcerated or not, (2) having the DSM-IV diagnosis of conduct disorder (CD) or not, and (3) having committed violent or nonviolent crimes (for the incarcerated individuals only). The findings indicate that, although no single genetic variant in any of the four genes differentiated individuals in the investigated groups, various linear combinations (i.e., haplotypes) and nonlinear combinations (i.e., interactions between variants within and across genes) of genetic variants resulted in informative and robust classifications for two of the three groupings. These combinations of genetic variants differentiated individuals in incarceration vs. nonincarcerated and CD vs. no-CD groups; no informative combinations were established consistently for the grouping by crime within the incarcerated individuals. This study underscores the importance of considering multiple rather than single markers within candidate genes and their additive and interactive combinations, both with themselves and with nongenetic indicators, while attempting to understand the genetic background of such complex behaviors as serious conduct problems.

Variation in the catechol-O-methyltransferase Val 158 Met polymorphism associated with conduct disorder and ADHD symptoms, among adolescent male delinquents.

OBJECTIVE: Variation in the catechol-O-methyltransferase gene (COMT) has been associated with antisocial behavior in populations with attention deficit/hyperactivity disorder (ADHD). This study examined whether COMT would predict antisocial behavior in a sample with high levels of behavior problems, not necessarily ADHD. In addition, because previous research suggests that COMT may be associated with ADHD in males, association between COMT and ADHD symptoms was examined. METHOD: This study tested whether variation in three polymorphisms of the COMT gene was predictive of symptoms of conduct disorder and ADHD, in a sample of 174 incarcerated Russian adolescent male delinquents. RESULTS: The Val allele of the ValMet polymorphism was significantly associated with conduct disorder diagnosis and symptoms, whereas the Met allele was associated with ADHD symptoms. CONCLUSION: The ValMet polymorphism of the COMT gene shows a complex relation to behavior problems, influencing conduct disorder and ADHD symptoms in opposite directions in a high-risk population.

Association between polymorphisms in the dopamine transporter gene and depression: evidence for a gene-environment interaction in a sample of juvenile detainees.

Previous research has generated examples of how genetic and environmental factors can interact to create risk for psychopathology. Using a gene-by-environment (G x E) interaction design, we tested whether three polymorphisms in the dopamine transporter gene (DAT1, also referred to as SLC6A3, located at 5p15.33) interacted with maternal parenting style to predict first-onset episodes of depression. Participants were male adolescents (N= 176) recruited from a juvenile detention center in northern Russia. As hypothesized, one of the polymorphisms (rs40184) moderated the effect of perceived maternal rejection on the onset of major depressive disorder, as well as on suicidal ideation. Further, this G x E interaction was specific to depression; it did not predict clinically significant anxiety. These results highlight the need for further research investigating the moderating effects of dopaminergic genes on depression.

Exploring interactive effects of genes and environments in etiology of individual differences in reading comprehension.

It is established that reading and reading-related processes are heritable; genes thus play an important role in the foundation of individual differences in reading. In this article, we focus on one facet of reading-comprehension. Comprehension is a higher order cognitive skill that requires many other cognitive processes for it to unfold completely and successfully. One such process is executive functioning, which has been associated with genetic variation in the catechol-O-methyltransferase (COMT) gene. Genotypes and haplotypes of four single nucleotide polymorphisms in COMT were investigated in 179 incarcerated adolescent delinquents. Four hierarchical logistic regression models predicting the presence/absence of comprehension difficulties were fitted to the data; genetic variation in COMT and the presence/absence of maternal rejection were investigated as main effects and as effects acting interactively. Three out of four interaction terms were found to be important predictors of individual differences in comprehension. These findings were supported by the results of the haplotype analyses, in which the four investigated polymorphisms were considered simultaneously.