Social factors and public policies associated with state infant mortality rates.

Despite mounting evidence that social factors and public policies affect state infant mortality rates (IMRs), few researchers have examined variation in IMRs associated with those factors and policies. We quantified disparities in infant mortality by state social factors and public policy characteristics. We hypothesized that some social factors and public policies would be more strongly associated with infant mortality than others, and that states with similar factors and policies would form clusters with varying levels of infant mortality. We examined associations of women's economic empowerment, health and well-being, political participation, reproductive rights, and work and family-related policies with state IMRs in 2012 and 2015, using indicators created by the Institute for Women's Policy Research. Methods included generalized linear models, principal component analysis, and cluster analysis. Health and well-being predicted IMRs (2012, 2015, both p < .05), as did poverty and opportunity, and reproductive rights (2012, p < .10). Consistent with our hypothesis, states formed clusters, with the states in each cluster having similar social factors and public policies, and similar IMRs. Women's health status and insurance coverage were more predictive of state IMRs than other social factors. Improving health and insurance coverage may be an effective way to reduce state IMRs.

Mid-P confidence intervals for group testing based on the total number of positive groups.

In the estimation of proportions by group testing, unequal sized groups results in an ambiguous ordering of the sample space, which complicates the construction of exact confidence intervals. The total number of positive groups is shown to be a suitable statistic for ordering outcomes, provided its ties are broken by the MLE. We propose an interval estimation method based on this quantity, with a mid-P correction. Coverage is evaluated using group testing problems in plant disease assessment and virus transmission by insect vectors. The proposed method provides good coverage in a range of situations, and compares favorably with existing exact methods.

A taxonomy of state public health preparedness units: an empirical examination of organizational structure.

OBJECTIVE: State public health preparedness units (SPHPUs) were developed in response to federal funding to improve response to disasters: a responsibility that had not traditionally been within the purview of public health. The SPHPUs were created within the existing public health organizational structure, and their placement may have implications for how the unit functions, how communication takes place, and ultimately how well the key responsibilities are performed. This study empirically identifies a taxonomy of similarly structured SPHPUs and examines whether this structure is associated with state geographic, demographic, and threat-vulnerability characteristics. DESIGN: Data representing each SPHPU were extracted from publically available sources, including organizational charts and emergency preparedness plans for 2009. A cross-sectional segmentation analysis was conducted of variables representing structural attributes. SETTING AND PARTICIPANTS: Fifty state public health departments. MAIN OUTCOME MEASURES: Variables representing "span of control" and "hierarchal levels" were extracted from organizational charts. Structural "complexity" and "centralization" were extracted from state emergency preparedness documents and other secondary sources. RESULTS: On average, 6.6 people report to the same manager as the SPHPU director; 2.1 levels separate the SPHPU director from the state health officer; and a mean of 13.5 agencies collaborate with SPHPU during a disaster. Despite considerable variability in how SPHPUs had been structured, results of the cluster and principal component analysis identified 7 similarly structured groups. Neither the taxonomic groups nor the individual variables representing structure were found to be associated with state characteristics, including threat vulnerabilities. CONCLUSIONS: Our finding supports the hypothesis that SPHPUs are seemingly inadvertently (eg, not strategically) organized. This taxonomy provides the basis for which future research can examine how SPHPU structure relates to performance measures and preparedness strategies.

Pediatric Practice Readiness for Disaster Response.

OBJECTIVES: The American Academy of Pediatrics (AAP) calls for the inclusion of office-based pediatricians in disaster preparedness and response efforts. However, there is little research about disaster preparedness and response on the part of pediatric practices. This study describes the readiness of pediatric practices to respond to disaster and delineates factors associated with increased preparedness. METHODS: An AAP survey was distributed to members to assess the state of pediatric offices in readiness for disaster. Potential predictor variables used in chi-square analysis included community setting, primary employment setting, area of practice, and previous disaster experience. RESULTS: Three-quarters (74%) of respondents reported some degree of disaster preparedness (measured by 6 indicators including written plans and maintaining stocks of supplies), and approximately half (54%) reported response experience (measured by 3 indicators, including volunteering to serve in disaster areas). Respondents who reported disaster preparation efforts were more likely to have signed up for disaster response efforts, and vice versa. CONCLUSIONS: These results contribute information about the state of pediatric physician offices and can aid in developing strategies for augmenting the inclusion of office-based pediatricians in community preparedness and response efforts.

First detection of mycobacteria in African rodents and insectivores, using stratified pool screening.

With the rising number of patients with human immunodeficiency virus (HIV)/AIDS in developing countries, the control of mycobacteria is of growing importance. Previous studies have shown that rodents and insectivores are carriers of mycobacteria. However, it is not clear how widespread mycobacteria are in these animals and what their role is in spreading them. Therefore, the prevalence of mycobacteria in rodents and insectivores was studied in and around Morogoro, Tanzania. Live rodents were trapped, with three types of live traps, in three habitats. Pieces of organs were pooled per habitat, species, and organ type (stratified pooling); these sample pools were examined for the presence of mycobacteria by PCR, microscopy, and culture methods. The mycobacterial isolates were identified using phenotypic techniques and sequencing. In total, 708 small mammals were collected, 31 of which were shrews. By pool prevalence estimation, 2.65% of the animals were carriers of mycobacteria, with a higher prevalence in the urban areas and in Cricetomys gambianus and the insectivore Crocidura hirta. Nontuberculous mycobacteria (Mycobacterium chimaera, M. intracellulare, M. arupense, M. parascrofulaceum, and Mycobacterium spp.) were isolated from C. gambianus, Mastomys natalensis, and C. hirta. This study is the first to report findings of mycobacteria in African rodents and insectivores and the first in mycobacterial ecology to estimate the prevalence of mycobacteria after stratified pool screening. The fact that small mammals in urban areas carry more mycobacteria than those in the fields and that potentially pathogenic mycobacteria were isolated identifies a risk for other animals and humans, especially HIV/AIDS patients, that have a weakened immune system.

Characterization of the promoter of the Brugia malayi 12kDa small subunit ribosomal protein (RPS12) gene.

Unravelling gene regulatory mechanisms in human filarial parasites will require an understanding of their basic promoter structure. Only a single promoter from a human filarial parasite has been characterised in detail, the 70 kDa heat shock promoter of Brugia malayi (BmHSP70). This promoter was found to lack features found in a typical eukaryotic promoter. To determine if this was unique to the BmHSP70 promoter, a detailed analysis was undertaken of the promoter for the B. malayi small subunit 12 kDa ribosomal protein (BmRPS12) gene. The BmRPS12 promoter contained a unique tandem repeat structure. Deletion of these repeats resulted in the loss of 80% of promoter activity. Block replacement mutagenesis identified five regions outside the repeat which were essential for promoter activity. No predicted binding sites for proteins that normally associate with the typical eukaryotic core promoter domains were found in the essential domains or the repeat region. However, the repeat region contained many putative binding sites for GATAA transcription factor family proteins. Of 20 upstream domains of other ribosomal protein genes, one contained a repeat structure similar to that found in the BmRPS12 promoter, and the majority encoded putative GATAA transcription factor binding sites. This study demonstrates that the BmRPS12 promoter, like the BmHSP70 promoter, is distinct from a typical eukaryotic promoter.

Fundamental issues in mosquito surveillance for arboviral transmission.

Marked spatiotemporal variabilities in mosquito infection of arboviruses, exemplified by the transmission of West Nile virus (WNV) in America, require adaptive strategies for mosquito sampling, pool screening and data analyses. Currently there is a lack of reliable and consistent measures of risk exposure, which may compromise comparison of surveillance data. Based on quantitative reasoning, we critically examined fundamental issues regarding mosquito sampling design and estimation of transmission intensity. Two surveillance strategies were proposed, each with a distinct focus, i.e. targeted surveillance for detection of low rates of mosquito infection and extensive surveillance for evaluation of risk exposure with high levels of mosquito infection. We strongly recommend the use of indicators embodying both mosquito abundance and infection rates as measures of risk exposure. Aggregation of surveillance data over long periods of time and across broad areas obscures patterns of focal arboviral transmission. We believe that these quantitative issues, once addressed by mosquito surveillance programs, can improve the epidemiological intelligence of arbovirus transmission.

The Search for an Efficient Black Fly Trap for Xenomonitoring of Onchocerciasis.

Onchocerciasis is a neglected tropical disease that has plagued mankind for decades with pathologies that involve the eyes and the skin. The WHO and the global health community have earmarked the disease for global elimination by 2045. However, as control programmes shift focus from reduction of the burden of the disease to elimination, new tools and strategies may be needed to meet targets. Monitoring Onchocerca volvulus larvae in the black fly vectors is an important tool needed to monitor disease dynamics and certify elimination. For decades, human landing collections have been the sole means of acquiring vectors for monitoring of the disease. This procedure has been plagued with ethical concerns and sometimes the inability to harvest enough black flies needed to carry out effective monitoring. Since the 1960s, the WHO recognized the need to replace human landing collections but relatively few field studies have designed and tested alternative traps. This review article systematically discusses some of the key traps tested, their successes, and their challenges. It is the aim of the review to direct research and development focus to the most successful and promising vector traps which could potentially replace the human landing collections.

Community-directed vector control to supplement mass drug distribution for onchocerciasis elimination in the Madi mid-North focus of Northern Uganda.

BACKGROUND: Onchocerciasis a neglected tropical disease that historically has been a major cause of morbidity and an obstacle to economic development in the developing world. It is caused by infection with Onchocerca volvulus, which is transmitted by black flies of the genus Simulium. The discovery of the potent effect of Mectizan (ivermectin) on O. volvulus microfilariae and the decision by its manufacturer to donate the drug for onchocerciasis spurred the implementation of international programs to control and, more recently, eliminate this scourge. These programs rely primarily on mass distribution of ivermectin (MDA) to the afflicted populations. However, MDA alone will not be sufficient to eliminate onchocerciasis where transmission is intense and where ivermectin MDA is precluded by co-endemicity with Loa loa. Vector control will likely be required as a supplemental intervention in these situations. METHODOLOGY/PRINCIPAL FINDINGS: Because biting by the black fly vectors is often a major nuisance in onchocerciasis afflicted communities, we hypothesized that community members might be mobilized to clear the breeding sites of the vegetation that represents the primary black fly larvae attachment point. We evaluated the effect of such a community based "slash and clear" intervention in multiple communities in Northern Uganda. Slash and Clear resulted in 89-99% declines in vector biting rates. The effect lasted up to 120 days post intervention. CONCLUSIONS/SIGNIFICANCE: Slash and clear might represent an effective, inexpensive, community- based tool to supplement ivermectin distribution as a contributory method to eliminate onchocerciasis and prevent recrudescence.

Host choice and West Nile virus infection rates in blood-fed mosquitoes, including members of the Culex pipiens complex, from Memphis and Shelby County, Tennessee, 2002-2003.

The source of bloodmeals in 2,082 blood-fed mosquitoes collected from February 2002 through December 2003 in Memphis and surrounding areas of Shelby County, Tennessee were determined. Members of the genus Culex and Anopheles quadrimaculatus predominated in the collections. Members of the Cx. pipiens complex and Cx. restuans were found to feed predominately upon avian hosts, though mammalian hosts made up a substantial proportion of the bloodmeals in these species. No significant difference was seen in the host class of bloodmeals in mosquitoes identified as Cx. pipiens pipiens, Cx. p. quinquefasciatus, or hybrids between these two taxa. Anopheles quadrimaculatus and Cx. erraticus fed primarily upon mammalian hosts. Three avian species (the American Robin, the Common Grackle, and the Northern Cardinal) made up the majority of avian-derived bloodmeals, with the American Robin representing the most frequently fed upon avian host. An analysis of these host feeding data using a modification of a transmission model for Eastern Equine encephalitis virus suggested that the American Robin and Common Grackle represented the most important reservoir hosts for West Nile virus. A temporal analysis of the feeding patterns of the dominant Culex species did not support a shift in feeding behavior away from robins to mammals late in the summer. However, a significant degree of temporal variation was noted in the proportion of robin-derived bloodmeals when the data were analyzed by semi-monthly periods throughout the summers of 2002 and 2003. This pattern was consistent with the hypothesis that the mosquitoes were preferentially feeding upon nesting birds.

The length of Henle fibers in the human retina and a model of ganglion receptive field density in the visual field.

An experimental study of lateral displacement of ganglion cells (GCs) from foveal cones in six human retinas is reported. At 406-675 microm in length, as measured in radially oriented cross-sections, Henle fibers are substantially longer than previously reported. However, a new theoretical model indicates that the discrepancies in these reports are mainly due to meridional differences. The model takes into account the effects of optical degradation and peripheral ON/OFF asymmetry and predicts a central GC:cone ratio of 2.24:1. It provides estimates of cumulative counts and GC receptive field density at 0 degrees -30 degrees along the principal meridians of the visual field.

Evaluation of Community-Directed Operation of Black Fly Traps for Entomological Surveillance of Onchocerca volvulus Transmission in the Madi-Mid North Focus of Onchocerciasis in Northern Uganda.

Entomological measures of transmission are important metrics specified by the World Health Organization to document the suppression and interruption of transmission of Onchocerca volvulus, the causative agent of onchocerciasis. These metrics require testing of large numbers of vector black flies. Black fly collection has relied on human landing collections, which are inefficient and potentially hazardous. As the focus of the international community has shifted from onchocerciasis control to elimination, replacement of human landing collections has become a priority. The Esperanza window trap (EWT) has shown promise as an alternative method for collection of Simulium damnosum s.l., the primary vector of O. volvulus in Africa. Here, we report the results of a community-based trial of the EWT in northern Uganda. Traps operated by residents were compared with human landing collections in two communities over 5 months. Three traps, when operated by a single village resident, collected over four times as many S. damnosum as did the two-men collection team. No significant differences were noted among the bait formulations. The results suggest that EWTs may be effectively operated by community residents and that the trap represents a viable alternative to human landing collections for entomological surveillance of O. volvulus transmission.

Skin snips have no role in programmatic evaluations for onchocerciasis elimination: a reply to Bottomley et al.

A critique of the recommendation that skin snips be used for post-MDA surveillance of formerly endemic onchocerciasis areas is provided. After considering several fundamental aspects of the use of this methodology within the context of prolonged mass distribution of ivermectin, we argue that skin-snipping has no value for monitoring onchocerciasis elimination programs.

Identification of elements essential for transcription in Brugia malayi promoters.

Little is known concerning promoter structure in the filarial parasites. Recently, transient transfection methods have been developed for the human filarial parasite Brugia malayi. These methods have been employed to localize the promoter for the 70kDa heat shock protein (BmHSP70) to a region extending 394nt upstream from the initiating codon of the BmHSP70 open reading frame. Replacement mutagenesis was used to define the elements necessary for BmHSP70 promoter activity in detail. Four domains, ranging in size from six to 22 nucleotides, were found to be necessary for full promoter activity. The two most distal domains encoded a binding site for the heat shock transcription factor and a putative binding site for the GAGA transcription factor, motifs that are found in many other HSP70 promoters. However, none of the essential domains contained sequences typical of cis elements that are usually found in the core domain of a eukaryotic promoter. The largest essential domain was located at positions -53 to -32, and included the splice leader addition site. These data suggest that the regulatory domains of the BmHSP70 promoter were similar to those found in other eukaryotes, but that the core promoter domain exhibited features that appeared to be distinct from those found in most other well-characterized eukaryotic promoters. An analysis of two additional promoters of B.malayi highly transcribed genes suggests that they also lack features commonly found in most eukaryotic core promoters, suggesting that the unique features of the BmHSP70 core promoter are not confined to this gene.

Important experimental parameters for determining infection rates in arthropod vectors using pool screening approaches.

Measuring transmission of a vector-borne infection is essential to understanding infection dynamics. When infection prevalence in the vector population is low, transmission is often measured by pool screening (also referred to as group testing). Several investigators have developed statistical methods to recover infection prevalence estimates from pool screen data. These are based on models that contain certain assumptions, and a pool screening approach must be designed to take these into account if accurate estimates of infection prevalence are to be obtained. Here we describe these assumptions and discuss appropriate sampling protocols. The sources of error inherent in pool screening are described, and we show that, under most conditions in which one would want to use group testing, most of the error results from sampling and not the pooling process. Issues involved in developing a sampling protocol, including the total number of insects to be screened and optimal pool size, are explored. The meaning of confidence intervals associated with prevalence estimates and the appropriate interpretation of these intervals are discussed.

Large-scale entomologic assessment of Onchocerca volvulus transmission by poolscreen PCR in Mexico.

To study the impact of mass Mectizan treatment on Onchocerca volvulus transmission in Mexico, entomological surveys were carried out in the endemic foci of Oaxaca, Southern Chiapas, and Northern Chiapas. Collected flies were screened by polymerase chain reaction (PCR) for O. volvulus parasites. The prevalence of infected and infective flies was estimated using the PoolScreen algorithm and with a novel probability-based method. O. volvulus infective larvae were not detected in flies from 6/13 communities. In 7/13 communities, infective flies were detected, with prevalences ranging from 1.6/10,000 to 29.0/10,000 and seasonal transmission potentials ranging from 0.4 to 3.3. Infected and infective flies were found in a community in Northern Chiapas, suggesting that, according to World Health Organization criteria, autochthonous transmission exists in this focus. These data suggest that O. volvulus transmission in Mexico has been suppressed or brought to a level that may be insufficient to sustain the parasite population.

Elevated fluctuating asymmetry in eastern mosquitofish (Gambusia holbrooki) from a river receiving paper mill effluent.

The present study investigated whether fluctuating asymmetry can serve as a useful biomarker of environmental stress in the eastern mosquitofish (Gambusia holbrooki). Fluctuating asymmetry was measured in sexually mature females sampled from two Florida, USA, coastal streams: The Fenholloway River, which is dominated by effluent from a paper mill, and Spring Creek, a tributary to the Fenholloway River (Taylor County, FL, USA) that does not receive paper mill effluent. Nine morphometric (lengths of the A and B scales, fifth pectoral fin ray, supraorbital canal, and preorbital canal and the sixth gill raker on the first brachial arch; orbit diameter; distance from the dorsal-ventral midpoint of the eye socket to the base of the pectoral fin; and distance from the postorbital canal to the operculum) and five meristic traits (numbers of scales in the lateral line, radii on the A and B scales, pectoral fin rays, and gill rakers on the first brachial arch) were included. For each of the three indexes of fluctuating asymmetry that were used, the majority of the traits showed a higher level of fluctuating asymmetry in fish from the Fenholloway River than in fish from Spring Creek. For two of the indexes, the difference was significant. Comparisons of mean values for fluctuating asymmetry (over all traits) for each fish and the means of a composite index of asymmetry both indicated that fish from the Fenholloway River had significantly greater overall fluctuating asymmetry than those from Spring Creek. Results of the present study are consistent with the hypothesis that environmental stress increased the level of fluctuating asymmetry in fish from the Fenholloway River. Thus, fluctuating asymmetry appears to be a useful biomarker for stress-induced developmental instability in the eastern mosquitofish.

A dynamic transmission model of eastern equine encephalitis virus.

Eastern equine encephalitis virus (EEEV) is one of several arthropod-borne viruses (arboviruses) endemic to the United States. Interactions between arthropod (mosquito) vectors and avian amplification host populations play a significant role in the dynamics of arboviral transmission. Recent data have suggested the hypothesis that an increased rate of successful feeding on young-of-the-year (YOY) birds might play a role in the dynamics of EEEV transmission. To test this hypothesis, we developed a model to explore the effect of the interactions of the vectors and avian host populations on EEEV transmission. Sensitivity analyses conducted using this model revealed eleven parameters that were capable of disproportionately affecting the predicted level of EEEV infection in the vertebrate reservoir and vector populations. Of these, four parameters were related to the interaction of the vector with young-of-the-year birds. Furthermore, adult birds could not substitute for young-of-the-year in initiating and maintaining a predicted enzootic outbreak of EEEV. Taken together, the model predicted that young-of-the-year birds play a key role in establishing and maintaining enzootic outbreaks of EEEV.

Blood pressure reactivity to psychological stress predicts hypertension in the CARDIA study.

BACKGROUND: A longstanding but controversial hypothesis is that individuals who exhibit frequent, large increases in blood pressure (BP) during psychological stress are at risk for developing essential hypertension. We tested whether BP changes during psychological stress predict incident hypertension in young adults. METHODS AND RESULTS: We used survival analysis to predict hypertensive status during 13 years of follow-up in a sample of >4100 normotensive black and white men and women (age at entry, 18 to 30 years) enrolled in the CARDIA study. BP responses to 3 psychological challenges--cold pressor, star tracing, and video game tasks--were measured. Hypertensive status was defined as use of antihypertensive medication or measured BP > or =140/90 mm Hg. After adjustment for race, gender, covariates (education, body mass index, age, and resting pressure), and their significant interactions, the larger the BP responses were to each of the 3 tasks, the earlier hypertension occurred (P<0.0001 to <0.01). The systolic BP effect for the cold pressor task was apparent for women and for whites in race- and gender-specific models, whereas the diastolic BP effect for the video game was apparent for men. CONCLUSIONS: Young adults who show a large BP response to psychological stress may be at risk for hypertension as they approach midlife.

Wolbachia endosymbiont levels in severe and mild strains of Onchocerca volvulus.

Epidemiological, clinical and genetic data have all suggested that the filarial parasite Onchocerca volvulus, the causative agent of onchocerciasis (or river blindness) exists as two strains in West Africa. The severe strain induces severe ocular disease in a large proportion of the infected population, while the mild strain induces little ocular disease. Although DNA probes based upon a non-coding repeat sequence family can distinguish the two strains, the underlying basis for this difference in pathogenicity is not understood. Recently, several studies have implicated products produced by the Wolbachia endosymbiotic bacterium of O. volvulus in the pathogenesis of onchocerciasis. This suggested the hypothesis that differences in the Wolbachia endosymbiont population might be responsible for the pathogenic differences noted in the two strains. To test this hypothesis, quantitative PCR assays were used to measure the amount of Wolbachia DNA per nuclear genome in a collection of well characterized samples of mild and severe strain O. volvulus. The median ratio of Wolbachia DNA to nuclear DNA was significantly greater in severe strain parasites than in mild strain parasites. These data support the hypothesis that the pathogenic differences seen in severe and mild strain O. volvulus may be a function of their relative Wolbachia burden and provide additional support to the hypothesis that Wolbachia products may play a central role in the pathogenesis of ocular onchocerciasis.