Summary

OBJECTIVES

To summarise age- and intensity-stratified associations between human hookworm infection and anaemia and to quantify the impact of treatment with the benzimidazoles, albendazole and mebendazole, on haemoglobin and anaemia in non-pregnant populations.

METHODS

Electronic databases (MEDLINE, EMBASE, PubMed) were searched for relevant studies published between 1980 and 2009, regardless of language, and researchers contacted about potential data. Haemoglobin concentration (Hb) was compared between uninfected individuals and individuals harbouring hookworm infections of different intensities, expressed as standardised mean differences (SMD) and 95% confidence intervals (CI). Meta-analysis of randomised control trials (RCTs) investigated the impact of treatment on Hb and anaemia.

RESULTS

Twenty-three cross-sectional studies, six pre- and post-intervention studies and 14 trials were included. Among cross-sectional studies, moderate- and heavy-intensity hookworm infections were associated with lower Hb in school-aged children, while all levels of infection intensity were associated with lower Hb in adults. Among RCTs using albendazole, impact of treatment corresponded to a 1.89 g/l increase (95%CI: 0.13–3.63) in mean Hb while mebendazole had no impact. There was a positive impact of 2.37 g/l (95%CI: 1.33–3.50) on mean Hb when albendazole was co-administered with praziquantel, but no apparent additional benefit of treatment with benzimidazoles combined with iron supplementation. The mean impact of treatment with benzimidazoles alone on moderate anaemia was small (relative risk (RR) 0.87) with a larger effect when combined with praziquantel (RR 0.61).

CONCLUSIONS

Anaemia is most strongly associated with moderate and heavy hookworm infection. The impact of anthelmintic treatment is greatest when albendazole is co-administered with praziquantel.

Objectives

To summarise age- and intensity-stratified associations between human hookworm infection and anaemia and to quantify the impact of treatment with the benzimidazoles, albendazole and mebendazole, on haemoglobin and anaemia in non-pregnant populations.

Methods

Electronic databases (MEDLINE, EMBASE, PubMed) were searched for relevant studies published between 1980 and 2009, regardless of language, and researchers contacted about potential data. Haemoglobin concentration (Hb) was compared between uninfected individuals and individuals harbouring hookworm infections of different intensities, expressed as standardised mean differences (SMD) and 95% confidence intervals (CI). Meta-analysis of randomised control trials (RCTs) investigated the impact of treatment on Hb and anaemia.

Results

Twenty-three cross-sectional studies, six pre- and post-intervention studies and 14 trials were included. Among cross-sectional studies, moderate- and heavy-intensity hookworm infections were associated with lower Hb in school-aged children, while all levels of infection intensity were associated with lower Hb in adults. Among RCTs using albendazole, impact of treatment corresponded to a 1.89 g/l increase (95%CI: 0.13–3.63) in mean Hb while mebendazole had no impact. There was a positive impact of 2.37 g/l (95%CI: 1.33–3.50) on mean Hb when albendazole was co-administered with praziquantel, but no apparent additional benefit of treatment with benzimidazoles combined with iron supplementation. The mean impact of treatment with benzimidazoles alone on moderate anaemia was small (relative risk (RR) 0.87) with a larger effect when combined with praziquantel (RR 0.61).

Conclusions

Anaemia is most strongly associated with moderate and heavy hookworm infection. The impact of anthelmintic treatment is greatest when albendazole is co-administered with praziquantel.

Background

Reliable and updated maps of helminth (worm) infection distributions are essential to target control strategies to those populations in greatest need. Although many surveys have been conducted in endemic countries, the data are rarely available in a form that is accessible to policy makers and the managers of public health programmes. This is especially true in sub-Saharan Africa, where empirical data are seldom in the public domain. In an attempt to address the paucity of geographical information on helminth risk, this article describes the development of an updated global atlas of human helminth infection, showing the example of East Africa.

Methods

Empirical, cross-sectional estimates of infection prevalence conducted since 1980 were identified using electronic and manual search strategies of published and unpublished sources. A number of inclusion criteria were imposed for identified information, which was extracted into a standardized database. Details of survey population, diagnostic methods, sample size and numbers infected with schistosomes and soil-transmitted helminths were recorded. A unique identifier linked each record to an electronic copy of the source document, in portable document format. An attempt was made to identify the geographical location of each record using standardized geolocation procedures and the assembled data were incorporated into a geographical information system.

Results

At the time of writing, over 2,748 prevalence surveys were identified through multiple search strategies. Of these, 2,612 were able to be geolocated and mapped. More than half (58%) of included surveys were from grey literature or unpublished sources, underlining the importance of reviewing in-country sources. 66% of all surveys were conducted since 2000. Comprehensive, countrywide data are available for Burundi, Rwanda and Uganda. In contrast, information for Kenya and Tanzania is typically clustered in specific regions of the country, with few records from areas with very low population density and/or environmental conditions which are unfavourable for helminth transmission. Information is presented on the prevalence and geographical distribution for the major helminth species.

Conclusion

For all five countries, the information assembled in the current atlas provides the most reliable, up-to-date and comprehensive source of data on the distribution of common helminth infections to guide the rational implementation of control efforts.

Our previous studies demonstrate alterations of zinc (Zn) transporter proteins ZnT-1, ZnT-4, and ZnT-6 in vulnerable brain regions of subjects with mild cognitive impairment (MCI), early and late stage Alzheimer's disease (AD) and suggest that disruptions of Zn homeostasis may play a role in the pathogenesis of AD. ZnT-1 exports Zn from the cytosol to extracellular compartments, ZnT-4 transports Zn from the cytosol to lysosomes and endosomes, and ZnT-6 sequesters Zn in the trans-Golgi network. A preclinical stage of AD (PCAD) has been described in which subjects show no overt clinical manifestations of AD but demonstrate significant AD pathology at autopsy. To determine if alterations of ZnT proteins occur in PCAD we measured ZnT-1, ZnT-4, and ZnT-6 in the hippocampus/parahippocampal gyrus (HPG) and cerebellum (CER) of 7 PCAD subjects and 7 age matched normal control (NC) subjects using Western blot analysis and immunohistochemistry. Our results show a significant decrease (P < 0.05) of ZnT-1 in HPG of PCAD subjects, along with an increase of ZnT-4 in PCAD CER and ZnT-6 in PCAD HPG, but a significant decrease in PCAD CER compared to NC subjects. Confocal microscopy of representative sections of HPG shows altered ZnTs are associated with neurons immunopositive for MC-1, a monoclonal antibody that identifies neurons early in formation of neurofibrillary tangles. Overall, our results suggest that alterations in Zn transport proteins may contribute to the pathology observed in PCAD subjects before onset of clinical symptoms.

Background

Implementation of control of parasitic diseases requires accurate, contemporary maps that provide intervention recommendations at policy-relevant spatial scales. To guide control of soil transmitted helminths (STHs), maps are required of the combined prevalence of infection, indicating where this prevalence exceeds an intervention threshold of 20%. Here we present a new approach for mapping the observed prevalence of STHs, using the example of Kenya in 2009.

Methods and Findings

Observed prevalence data for hookworm, Ascaris lumbricoides and Trichuris trichiura were assembled for 106,370 individuals from 945 cross-sectional surveys undertaken between 1974 and 2009. Ecological and climatic covariates were extracted from high-resolution satellite data and matched to survey locations. Bayesian space-time geostatistical models were developed for each species, and were used to interpolate the probability that infection prevalence exceeded the 20% threshold across the country for both 1989 and 2009. Maps for each species were integrated to estimate combined STH prevalence using the law of total probability and incorporating a correction factor to adjust for associations between species. Population census data were combined with risk models and projected to estimate the population at risk and requiring treatment in 2009. In most areas for 2009, there was high certainty that endemicity was below the 20% threshold, with areas of endemicity ≥20% located around the shores of Lake Victoria and on the coast. Comparison of the predicted distributions for 1989 and 2009 show how observed STH prevalence has gradually decreased over time. The model estimated that a total of 2.8 million school-age children live in districts which warrant mass treatment.

Conclusions

Bayesian space-time geostatistical models can be used to reliably estimate the combined observed prevalence of STH and suggest that a quarter of Kenya's school-aged children live in areas of high prevalence and warrant mass treatment. As control is successful in reducing infection levels, updated models can be used to refine decision making in helminth control.

Author Summary

Effective targeting of mass drug administration for the treatment of soil-transmitted helminths (STH) requires reliable, up-to-date maps that indicate where prevalence exceeds the 20% intervention threshold recommended by the World Health Organization. We present a new approach for mapping the prevalence of STH in Kenya, incorporating observed prevalence data from 945 cross-sectional surveys undertaken between 1974 and 2009. The distribution of each species was modelled using model-based geostatistics; models included information on environmental factors, the spatial distribution of existing surveys and when these surveys were conducted. Resulting risk maps were combined and linked with population data enabling estimation of the population at risk of any STH infection and requiring treatment in 2009. In most areas, there was high certainty that combined STH prevalence was below the 20% intervention threshold, with areas of high prevalence located around the shores of Lake Victoria and on the coast. Results also suggest that observed prevalence decreased over time and emphasise the importance of continued surveillance in areas where observed prevalence was historically high. We show how spatial modelling can be used to develop up-to-date maps of STH risk to help improve the precision of decision making in disease control.

Substance Abusers have a large number of medical and psychiatric problems, and 70–90% are smokers. The aim of this analysis was to examine the prevalence and correlates of medical and psychiatric problems in this sample of drug dependent patients who were participants in a multi-site study of smoking cessation interventions while engaged in substance abuse treatment. Descriptive analyses showed at baseline, 72.8% of participants had at least one medical problem and 64.1% had at least one psychiatric diagnosis. Medical problems correlated strongly with age, smoking severity, and pack-years; Psychiatric problems correlated with gender and ethnicity. Smoking cessation treatment was associated with a moderate reduction in the ASI Medical composite score. More research is needed on the possible effects of combined treatment of substance abuse and concurrent medical and psychiatric problems. Offering smoking cessation in conjunction with primary care may be a way to address the health needs of this population.

As part of a training set for automated image analysis, ∼150 000 images of crystallization experiments from 96 diverse macromolecules have been visually classified within seven categories. Outcomes and trends are analyzed.

Structural crystallography aims to provide a three-dimensional representation of macromolecules. Many parts of the multistep process to produce the three-dimensional structural model have been automated, especially through various structural genomics projects. A key step is the production of crystals for diffraction. The target macromolecule is combined with a large and chemically diverse set of cocktails with some leading ideally, but infrequently, to crystallization. A variety of outcomes will be observed during these screening experiments that typically require human interpretation for classification. Human interpretation is neither scalable nor objective, highlighting the need to develop an automatic computer-based image classification. As a first step towards automated image classification, 147 456 images representing crystallization experiments from 96 different macromolecular samples were manually classified. Each image was classified by three experts into seven predefined categories or their combinations. The resulting data where all three observers are in agreement provides one component of a truth set for the development and rigorous testing of automated image-classification systems and provides information about the chemical cocktails used for crystallization. In this paper, the details of this study are presented.

Background

The cellular localization of the α1D-adrenergic receptor (α1D-AR) is controversial. Studies in heterologous cell systems have shown that this receptor is expressed in intracellular compartments. Other studies show that dimerization with other ARs promotes the cell surface expression of the α1D-AR. To assess the cellular localization in vascular smooth muscle cells, we developed an adenoviral vector for the efficient expression of a GFP labeled α1D-AR. We also measured cellular localization with immunocytochemistry. Intracellular calcium levels, measurement of reactive oxygen species and contraction of the rat aorta were used as measures of functional activity.

Results

The adenovirally expressed α1D-AR was expressed in intracellular compartments in human aortic smooth muscle cells. The intracellular localization of the α1D-AR was also demonstrated with immunocytochemistry using an α1D-AR specific antibody. RT-PCR analysis detected mRNA transcripts corresponding to the α1A-α1B- and α1D-ARs in these aortic smooth muscle cells. Therefore, the presence of the other α1-ARs, and the potential for dimerization with these receptors, does not alter the intracellular expression of the α1D-AR. Despite the predominant intracellular localization in vascular smooth muscle cells, the α1D-AR remained signaling competent and mediated the phenylephrine-induced increases in intracellular calcium. The α1D-AR also was coupled to the generation of reactive oxygen species in smooth muscle cells. There is evidence from heterologous systems that the α1D-AR heterodimerizes with the β2-AR and that desensitization of the β2-AR results in α1D-AR desensitization. In the rat aorta, desensitization of the β2-AR had no effect on contractile responses mediated by the α1D-AR.

Conclusion

Our results suggest that the dimerization of the α1D-AR with other ARs does not alter the cellular expression or functional response characteristics of the α1D-AR.

Background

As in all western countries, Australia's older population experiences high levels of hearing impairment coupled with relatively low levels of hearing device usage. Poor hearing diminishes the quality of life of affected individuals and their families. This paper discusses how to improve Australian hearing health policies in order to better combat this impairment amongst older Australians.

Method

We searched the databases Medline, Meditext and Web of Science to find articles that discussed strategies and innovations to assist the hearing health of older people, and related this material to observations made during the Blue Mountains Hearing Study in NSW between 1997 and 2003.

Results and Discussion

The literature search identified five areas for inclusion in a comprehensive hearing health policy in Australia. These are: early intervention; addressing of hearing aid expense; the use of assisted listening devices; hearing rehabilitation, and; screening and education. Further research in Australia is critical if we are to develop a strong approach to the increasing prevalence of age-related hearing loss.

Conclusion

Australia needs to act now to address hearing impairment as it is a major cause of disability in those aged 55 and over. Federal and State governments should collaborate to construct a comprehensive hearing health policy that tackles poor levels of hearing health through early intervention, addressing hearing aid expense, encouraging the use of assisted listening devices, rehabilitation, screening and education. A good start would be to declare age related hearing impairment as a National Health Priority Area.

Radiotherapeutic doses for malignant gliomas are generally palliative because greater, supposedly curative doses would impart clinically unacceptable damage to nearby vital CNS tissues. To improve radiation treatment for human gliomas, we evaluated microbeam radiation therapy, which utilizes an array of parallel, microscopically thin (<100 microm) planar beams (microbeams) of synchrotron-generated X rays. Rats with i.c. 9L gliosarcoma tumors were exposed laterally to a single microbeam, 27 pm wide and 3.8 mm high, stepwise, to produce irradiation arrays with 50, 75, or 100 microm of on-center beam spacings and 150, 250, 300, or 500 Gy of in-slice, skin-entrance, single-exposure doses. The resulting array size was 9 mm wide and 10.4 mm high (using three 3.8-mm vertical tiers); the beam's median energy was -70 keV. When all data were collated, the median survival was 70 days; no depletion of nerve cells was observed. However, when data from the highest skin-entrance dose and/or the smallest microbeam spacings were excluded, the median survival time of the subset of rats was 170 days, and no white matter necrosis was observed. Others have reported unilateral single-exposure broad-beam irradiation of i.c. 9L gliosarcomas at 22.5 Gy with a median survival of only -34 days and with severe depletion of neurons. These results suggest that the therapeutic index of unidirectional microbeams is larger than that of the broad beams and that an application for microbeam radiation therapy in treating certain malignant brain tumors may be found in the future.