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.

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.

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.

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.

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.

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 communal oviposition pheromones from the black fly Simulium vittatum.

The suite of pheromones that promote communal oviposition by Simulium vittatum, a North American black fly species, was identified and characterized using gas chromatography-mass spectrometry, electrophysiological, and behavioral bioassays. Behavioral assays demonstrated that communal oviposition was induced by egg-derived compounds that were active at short range and whose effect was enhanced through direct contact. Three compounds (cis-9-tetradecen-1-ol, 1-pentadecene, and 1-tridecene) were identified in a non-polar solvent extract of freshly deposited S. vittatum eggs that were capable of inducing the oviposition response. Electroantennography demonstrated that two of these three compounds (1-pentadecene and 1-tridecene) actively stimulated antennal neurons. Identification of the oviposition pheromones of this family may be helpful in developing control measures for nuisance black flies and for medically-important species such as Simulium damnosum sensu lato.

Identification of human semiochemicals attractive to the major vectors of onchocerciasis.

BACKGROUND: Entomological indicators are considered key metrics to document the interruption of transmission of Onchocerca volvulus, the etiological agent of human onchocerciasis. Human landing collection is the standard employed for collection of the vectors for this parasite. Recent studies reported the development of traps that have the potential for replacing humans for surveillance of O. volvulus in the vector population. However, the key chemical components of human odor that are attractive to vector black flies have not been identified. METHODOLOGY/PRINCIPAL FINDINGS: Human sweat compounds were analyzed using GC-MS analysis and compounds common to three individuals identified. These common compounds, with others previously identified as attractive to other hematophagous arthropods were evaluated for their ability to stimulate and attract the major onchocerciasis vectors in Africa (Simulium damnosum sensu lato) and Latin America (Simulium ochraceum s. l.) using electroantennography and a Y tube binary choice assay. Medium chain length carboxylic acids and aldehydes were neurostimulatory for S. damnosum s.l. while S. ochraceum s.l. was stimulated by short chain aliphatic alcohols and aldehydes. Both species were attracted to ammonium bicarbonate and acetophenone. The compounds were shown to be attractive to the relevant vector species in field studies, when incorporated into a formulation that permitted a continuous release of the compound over time and used in concert with previously developed trap platforms. CONCLUSIONS/SIGNIFICANCE: The identification of compounds attractive to the major vectors of O. volvulus will permit the development of optimized traps. Such traps may replace the use of human vector collectors for monitoring the effectiveness of onchocerciasis elimination programs and could find use as a contributing component in an integrated vector control/drug program aimed at eliminating river blindness in Africa.

Serosurveillance to monitor onchocerciasis elimination: the Ugandan experience.

Uganda is the only African country whose onchocerciasis elimination program uses a two-pronged approach of vector control and mass drug distribution. The Ugandan program relies heavily upon the use of serosurveys of children to monitor progress toward elimination. The program has tested over 39,000 individuals from 11 foci for Onchocerca volvulus exposure, using the Ov16 ELISA test. The data show that the Ov16 ELISA is a useful operational tool to monitor onchocerciasis transmission interruption in Africa at the World Health Organization (WHO) recommended threshold of < 0.1% in children. The Ugandan experience has also resulted in a re-examination of the statistical methods used to estimate the boundary of the upper 95% confidence interval for the WHO prevalence threshold when all samples tested are negative. This has resulted in the development of Bayesian and hypergeometric statistical methods that reduce the number of individuals who must be tested to meet the WHO criterion.

Evaluation of a Frequentist Hierarchical Model to Estimate Prevalence when sampling from a large geographic area using Pool Screening.

We present a frequentist Bernoulli-Beta hierarchical model to relax the constant prevalence assumption underlying the traditional prevalence estimation approach based on pooled data. This assumption is called into question when sampling from a large geographic area. Pool screening is a method that combines individual items into pools. Each pool will either test positive (at least one of the items is positive) or negative (all items are negative). Pool screening is commonly applied to the study of tropical diseases where pools consist of vectors (e.g. black flies) that can transmit the disease. The goal is to estimate the proportion of infected vectors. Intermediate estimators (model parameters) and estimators of ultimate interest (pertaining to prevalence) are evaluated by standard measures of merit, such as bias, variance and mean squared error making extensive use of expansions. Using the hierarchical model an investigator can determine the probability of the prevalence being below a prespecified threshold value, a value at which no reemergence of the disease is expected. An investigation into the least biased choice of the α parameter in the Beta (α, ß) prevalence distribution leads to the choice of α = 1.

Development of a novel trap for the collection of black flies of the Simulium ochraceum complex.

BACKGROUND: Human landing collections are currently the standard method for collecting onchocerciasis vectors in Africa and Latin America. As part of the efforts to develop a trap to replace human landing collections for the monitoring and surveillance of onchocerciasis transmission, comprehensive evaluations of several trap types were conducted to assess their ability to collect Simulium ochraceum sensu lato, one of the principal vectors of Onchocerca volvulus in Latin America. METHODOLOGY/PRINCIPAL FINDINGS: Diverse trap designs with numerous modifications and bait variations were evaluated for their abilities to collect S. Ochraceum s.l. females. These traps targeted mostly host seeking flies. A novel trap dubbed the "Esperanza window trap" showed particular promise over other designs. When baited with CO2 and BG-lure (a synthetic blend of human odor components) a pair of Esperanza window traps collected numbers of S. Ochraceum s.l. females similar to those collected by a team of vector collectors. CONCLUSIONS/SIGNIFICANCE: The Esperanza window trap, when baited with chemical lures and CO2 can be used to collect epidemiologically significant numbers of Simulium ochraceum s.l., potentially serving as a replacement for human landing collections for evaluation of the transmission of O. volvulus.

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.

Mycobacteria in terrestrial small mammals on cattle farms in Tanzania.

The control of bovine tuberculosis and atypical mycobacterioses in cattle in developing countries is important but difficult because of the existence of wildlife reservoirs. In cattle farms in Tanzania, mycobacteria were detected in 7.3% of 645 small mammals and in cow's milk. The cattle farms were divided into "reacting" and "nonreacting" farms, based on tuberculin tests, and more mycobacteria were present in insectivores collected in reacting farms as compared to nonreacting farms. More mycobacteria were also present in insectivores as compared to rodents. All mycobacteria detected by culture and PCR in the small mammals were atypical mycobacteria. Analysis of the presence of mycobacteria in relation to the reactor status of the cattle farms does not exclude transmission between small mammals and cattle but indicates that transmission to cattle from another source of infection is more likely. However, because of the high prevalence of mycobacteria in some small mammal species, these infected animals can pose a risk to humans, especially in areas with a high HIV-prevalence as is the case in Tanzania.

Temporal analysis of feeding patterns of Culex erraticus in central Alabama.

Host blood meals in seven mosquito species previously shown to be infected with eastern equine encephalitis virus at a site in the Tuskegee National Forest in southcentral Alabama were investigated. Of 1374 blood meals derived from 88 different host species collected over 6 years from these seven mosquito species, 1099 were derived from Culex erraticus. Analysis of the temporal pattern of Cx. erraticus meals using a Runs test revealed that the patterns of feeding upon avian and mammalian hosts from March to September of each year were not randomly distributed over time. Similarly, meals taken from the three most commonly targeted host species (yellow-crowned night heron, great blue heron, and white-tailed deer) were not randomly distributed. A Tukey's two-way analysis of variance test demonstrated that although the temporal pattern of meals taken from avian hosts were consistent over the years, the patterns of meals taken from the individual host species were not consistent from year to year.

The splice leader addition domain represents an essential conserved motif for heterologous gene expression in B. malayi.

Two promoters from the human filarial parasite Brugia malayi have been mapped in detail. The essential domains of both promoters lacked canonical eukaryotic core promoter motifs. However, the largest contiguous essential domain in both promoters flanked and included the splice leader addition site. These findings suggested that the region flanking the trans-splicing addition site might represent a conserved core domain in B. malayi promoters. To test this hypothesis, the putative promoters of 12 trans-spliced genes encoding ribosomal protein homologues from B. malayi were isolated and tested for activity in a B. malayi transient transfection system. Of the 12 domains examined, 11 produced detectable reporter gene activity. Mutant constructs of the six most active promoters were prepared in which the spliced leader acceptor site and the 10 nt upstream and downstream of the site were deleted. All deletion constructs exhibited >90% reduction in reporter gene activity relative to their respective wild type sequences. A conserved pyrimidine-rich tract was located directly upstream from the spliced leader splice acceptor site which contained a conserved T residue located at position -3. Mutation of the entire polypyrimidine tract or the conserved T individually resulted in the loss of over 90% of reporter gene activity. In contrast, mutation of the splice acceptor site did not significantly reduce promoter activity. These data suggest that the region surrounding the splice acceptor site in the ribosomal promoters represents a conserved essential domain which functions independently of splice leader addition.

Blood feeding patterns of potential arbovirus vectors of the genus culex targeting ectothermic hosts.

Reptiles and amphibians constitute a significant portion of vertebrate biomass in terrestrial ecosystems and may be important arbovirus reservoirs. To investigate mosquito preference for ectothermic hosts, feeding indices were calculated from data collected in Tuskegee National Forest, Alabama, USA. Four mosquito species fed upon ectothermic hosts, with Culex peccator and Cx. territans feeding primarily upon ectotherms. These two species appeared to target distinct species with little overlap in host choice. Culex peccator was a generalist in its feeding patterns within ectotherms, and Cx. territans appeared to be a more specialized feeder. Six of eleven ectotherm species fed upon by Cx. territans were fed upon more often than predicted based upon abundance. Spring peepers were highly preferred over other host species by Cx. territans. Blood meals taken from each host species varied temporally, with some hosts being targeted fairly evenly throughout the season and others being fed upon in seasonal peaks.

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.

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.

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.