[Show abstract][Hide abstract] ABSTRACT: Subcortical auditory nuclei were traditionally viewed as non-plastic in adulthood so that acoustic information could be stably conveyed to higher auditory areas. Studies in a variety of species, including humans, now suggest that prolonged acoustic training can drive long-lasting brainstem plasticity. The neurobiological mechanisms for such changes are not well understood in natural behavioral contexts due to a relative dearth of in vivo animal models in which to study this. Here, we demonstrate in a mouse model that a natural life experience with increased demands on the auditory system - motherhood - is associated with improved temporal processing in the subcortical auditory pathway. We measured the auditory brainstem response to test whether mothers and pup-naïve virgin mice differed in temporal responses to both broadband and tone stimuli, including ultrasonic frequencies found in mouse pup vocalizations. Mothers had shorter latencies for early ABR peaks, indicating plasticity in the auditory nerve and the cochlear nucleus. Shorter interpeak latency between waves IV and V also suggest plasticity in the inferior colliculus. Hormone manipulations revealed that these cannot be explained solely by estrogen levels experienced during pregnancy and parturition in mothers. In contrast, we found that pup-care experience, independent of pregnancy and parturition, contributes to shortening auditory brainstem response latencies. These results suggest that acoustic experience in the maternal context imparts plasticity on early auditory processing that lasts beyond pup weaning. In addition to establishing an animal model for exploring adult auditory brainstem plasticity in a neuroethological context, our results have broader implications for models of perceptual, behavioral and neural changes that arise during maternity, where subcortical sensorineural plasticity has not previously been considered.
PLoS ONE 01/2014; 9(7):e101630. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Population vaccination coverage is often estimated by simple point estimation or by survival analysis methods; the latter requires knowledge of age at the time of vaccination. For situations when such data cannot be determined, we explore two versions of a logistic model. The first is a logistic growth model; the second model reparameterizes the numerator of the first to naturally constrain parameter estimates. Due to computational challenges in estimation of constrained parameters, we explore three methods of estimation for each model (nonlinear least squares, maximum likelihood estimation, and Bayesian estimation). Simulation results show that all methods of estimation produce comparable estimates and model results, but also that all three are sensitive to data configurations at times yielding unstable estimates. We apply all three methods to the 2003 Kenya Demographic and Health Surveys to estimate the sample vaccination coverage of the combined diphtheria, pertussis, and tetanus vaccine series. While all three methods of estimation have attractive properties as well as limitations, we find Bayesian estimation appealing in its ability to restrict parameter estimates through prior distributions, its relative stability in comparison to maximum likelihood estimation and nonlinear least squares, and associated inference that does not rely on asymptotic distributions of parameter estimates.
139st APHA Annual Meeting and Exposition 2011; 11/2011
[Show abstract][Hide abstract] ABSTRACT: Successful elimination of lymphatic filariasis (LF) requires accurate identification of residual foci of transmission and stringent surveillance strategies to combat potential resurgence. This is challenging in areas where the day-biting Aedes polynesiensis is endemic, such as Samoa, since in previous studies no geographical clustering of infection has been demonstrated. Another challenge for this low prevalence phase is the choice of diagnostic assay as testing for circulating filarial antigen (CFA) or microfilariae (Mf) alone may not have adequate sensitivity. This could be solved by using the commercially available filariasis Cellabs enzyme linked immunosorbent assay (CELISA) to measure antibody. In the current study five Samoan villages were chosen based on previous epidemiological assessments to represent a range of infection prevalences. CFA, Mf, and antibody levels in children ≤ 10 years had been recorded and results linked to household of residence and/or primary school of attendance. To ascertain the location of exposure, two scenarios based on potential foci of transmission around communities and schools were explored. Both scenarios revealed significant spatial clusters of households with infected individuals and a relationship to antibody positive children when they were included in the spatial analysis. Fasitoo-Tai had the highest LF prevalence and largest geographical spatial clusters for both scenarios. In Falefa, spatial clusters were detected only for the primary school scenario. In Tafua, which spanned an area of 19.5 km(2), no spatial clusters were detected. Lastly, in Siufaga, the village with the lowest LF prevalence, significant clustering of infected individuals was observed and, for the primary school scenario, this was geographically related to exposure. These promising findings are the first published evidence of spatial clustering of LF in a day-biting Ae. polynesiensis endemic area.
[Show abstract][Hide abstract] ABSTRACT: Seven rounds of mass drug administration (MDA) have been administered in Leogane, Haiti, an area hyperendemic for lymphatic filariasis (LF). Sentinel site surveys showed that the prevalence of microfilaremia was reduced to <1% from levels as high as 15.5%, suggesting that transmission had been reduced. A separate 30-cluster survey of 2- to 4-year-old children was conducted to determine if MDA interrupted transmission. Antigen and antifilarial antibody prevalence were 14.3% and 19.7%, respectively. Follow-up surveys were done in 6 villages, including those selected for the cluster survey, to assess risk factors related to continued LF transmission and to pinpoint hotspots of transmission. One hundred houses were mapped in each village using GPS-enabled PDAs, and then 30 houses and 10 alternates were chosen for testing. All individuals in selected houses were asked to participate in a short survey about participation in MDA, history of residence in Leogane and general knowledge of LF. Survey teams returned to the houses at night to collect blood for antigen testing, microfilaremia and Bm14 antibody testing and collected mosquitoes from these communities in parallel. Antigen prevalence was highly variable among the 6 villages, with the highest being 38.2% (Dampus) and the lowest being 2.9% (Corail Lemaire); overall antigen prevalence was 18.5%. Initial cluster surveys of 2- to 4-year-old children were not related to community antigen prevalence. Nearest neighbor analysis found evidence of clustering of infection suggesting that LF infection was focal in distribution. Antigen prevalence among individuals who were systematically noncompliant with the MDAs, i.e. they had never participated, was significantly higher than among compliant individuals (p<0.05). A logistic regression model found that of the factors examined for association with infection, only noncompliance was significantly associated with infection. Thus, continuing transmission of LF seems to be linked to rates of systematic noncompliance.
[Show abstract][Hide abstract] ABSTRACT: Mutations in the dihydrofolate reductase (dhfr) and dihydropteroate synthase (dhps) genes of Plasmodium falciparum are associated with resistance to anti-folate drugs, most notably sulphadoxine-pyrimethamine (SP). Molecular studies document the prevalence of these mutations in parasite populations across the African continent. However, there is no systematic review examining the collective epidemiological significance of these studies. This meta-analysis attempts to: 1) summarize genotype frequency data that are critical for molecular surveillance of anti-folate resistance and 2) identify the specific challenges facing the development of future molecular databases.
This review consists of 220 studies published prior to 2009 that report the frequency of select dhfr and dhps mutations in 31 African countries. Maps were created to summarize the location and prevalence of the highly resistant dhfr triple mutant (N51I, C59R, S108N) genotype and dhps double mutant (A437G and K540E) genotype in Africa. A hierarchical mixed effects logistic regression was used to examine the influence of various factors on reported mutant genotype frequency. These factors include: year and location of study, age and clinical status of sampled population, and reporting conventions for mixed genotype data.
A database consisting of dhfr and dhps mutant genotype frequencies from all African studies that met selection criteria was created for this analysis. The map illustrates particularly high prevalence of both the dhfr triple and dhps double mutant genotypes along the Kenya-Tanzania border and Malawi. The regression model shows a statistically significant increase in the prevalence of both the dhfr triple and dhps double mutant genotypes in Africa.
Increasing prevalence of the dhfr triple mutant and dhps double mutant genotypes in Africa are consistent with the loss of efficacy of SP for treatment of clinical malaria in most parts of this continent. Continued assessment of the effectiveness of SP for the treatment of clinical malaria and intermittent preventive treatment in pregnancy is needed. The creation of a centralized resistance data network, such as the one proposed by the WorldWide Antimalarial Resistance Network (WWARN), will become a valuable resource for planning timely actions to combat drug resistant malaria.
[Show abstract][Hide abstract] ABSTRACT: Aedes polynesiensis and Ae. aegypti breeding site productivity in two American Samoa villages were analyzed during a dry season survey and compared with a wet season survey. Both surveys identified similar container types producing greater numbers of pupae, with buckets, drums, and tires responsible for > 50% of Aedes pupae during the dry season. The prevalence of containers with Ae. polynesiensis and the density of Ae. polynesiensis in discarded appliances, drums, and discarded plastic ice cream containers were significantly greater during the dry season. Aedes aegypti pupal densities were significantly greater in the dry season in ice cream containers and tires. Significant clustering of the most productive container types by household was only found for appliances. The high productivity for Ae. polynesiensis and Ae. aegypti pupae during the wet and dry seasons suggests that dengue and lymphatic filariasis transmission can occur throughout the year, consistent with the reporting of dengue cases.
The American journal of tropical medicine and hygiene 12/2009; 81(6):1013-9. · 2.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Entomologic monitoring of filarial infections, xenomonitoring, may have advantages in certain epidemiologic situations to assess the presence of infections in humans. Hemalum staining and dissection and polymerase chain reaction (PCR) were compared to determine the filarial infection status of Aedes (Stegomyia) mosquitoes in American Samoa. The overall prevalences of Wuchereria bancrofti and Dirofilaria immitis infections in Ae. polynesiensis were, respectively, 0.16% and 1.06% by dissection and 0.69% and 1.77% by PCR. Human filarial worm DNA rates in Aedes aegypti and Aedes upolensis were 1.16% and 0.38%, respectively. The results suggest that W. bancrofti transmission to humans may be continuing at low levels in some villages despite recent completion of 5 years of mass drug administration. PCR testing of mosquitoes collected using the BG-Sentinel traps represents a promising alternative to landing catches for assessing the transmission of filariasis in areas where Ae. polynesiensis and related species are the primary vectors.
The American journal of tropical medicine and hygiene 06/2009; 80(5):774-81. · 2.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine implicated in the pathogenesis of a number of human diseases including inflammatory neurological diseases. Its role in the pathogenesis of cerebral malaria is unknown. Cerebral malaria is a life-threatening complication of falciparum malaria with approximately 20%-30% of patients dying despite appropriate anti-malarial treatment. The reason for this cerebral malaria mortality is still unknown although host proinflammatory factors have been shown to be evidently important. The current study investigated the role of circulating MIF in the pathogenesis and outcomes of cerebral malaria.
Three categories of subjects contributed to this study: healthy controls subjects, mild malaria patients, and cerebral malaria patients. The cerebral malaria patients were further grouped into cerebral malaria survivors and cerebral malaria non-survivors. MIF levels in the peripheral blood plasma, obtained at the time of enrollment, were measured using standard ELISA methods. In logistic regression on cerebral malaria patients, log MIF levels were found to be significantly associated with fatal outcome (odds ratio 4.0; 95%CI 1.6, 9.8; p = 0.003). In multinomial logistic regression log MIF levels were found to be significantly associated with patient category (p = 0.004).
This study suggests that elevated levels of MIF in the peripheral blood of cerebral malaria patients may be associated with fatal outcomes.
[Show abstract][Hide abstract] ABSTRACT: Sample size and power calculations are often based on a two-group comparison. However, in some instances the group membership cannot be ascertained until after the sample has been collected. In this situation, the respective sizes of each group may not be the same as those prespeci-fied due to binomial variability, which results in a difference in power from that expected. Here we suggest that investigators calculate an "expected power" taking into account the binomial variability of the group member-ship, and adjust the sample size accordingly when planning such studies. We explore different scenarios where such an adjustment may or may not be necessary for both continuous and binary responses. In general, the number of additional subjects required depends only slightly on the values of the (standardized) difference in the two group means or proportions, but more importantly on the respective sizes of the group membership. We present tables with adjusted sample sizes for a variety of scenarios that can be read-ily used by investigators at the study design stage. The proposed approach is motivated by a genetic study of cerebral malaria and a sleep apnea study.