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Biomedical subjects

Simon Brooker

Publications and source records attributed to Simon Brooker.

At least 19 recordsLinked to original sources

Repeatability of paired counts.

The Bland and Altman technique is widely used to assess the variation between replicates of a method of clinical measurement. It yields the repeatability, i.e. the value within which 95 per cent of repeat measurements lie. The valid use of the technique requires that the variance is constant over the data range. This is not usually the case for counts of items such as CD4 cells or parasites, nor is the log transformation applicable to zero counts. We investigate the properties of generalized differences based on Box-Cox transformations. For an example, in a data set of hookworm eggs counted by the Kato-Katz method, the square root transformation is found to stabilize the variance. We show how to back-transform the repeatability on the square root scale to the repeatability of the counts themselves, as an increasing function of the square mean root egg count, i.e. the square of the average of square roots. As well as being more easily interpretable, the back-transformed results highlight the dependence of the repeatability on the sample volume used.

Algorithms↗

The co-distribution of Plasmodium falciparum and hookworm among African schoolchildren.

BACKGROUND: Surprisingly little is known about the geographical overlap between malaria and other tropical diseases, including helminth infections. This is despite the potential public health importance of co-infection and synergistic opportunities for control. METHODS: Statistical models are presented that predict the large-scale distribution of hookworm in sub-Saharan Africa (SSA), based on the relationship between prevalence of infection among schoolchildren and remotely sensed environmental variables. Using a climate-based spatial model of the transmission potential for Plasmodium falciparum malaria, adjusted for urbanization, the spatial congruence of populations at coincident risk of infection is determined. RESULTS: The model of hookworm indicates that the infection is widespread throughout Africa and that, of the 179.3 million school-aged children who live on the continent, 50.0 (95% CI: 48.9-51.1) million (27.9% of total population) are infected with hookworm and 45.1 (95% CI: 43.9-46) million are estimated to be at risk of coincident infection. CONCLUSION: Malaria and hookworm infection are widespread throughout SSA and over a quarter of school-aged children in sub-Saharan Africa appear to be at risk of coincident infection and thus at enhanced risk of clinical disease. The results suggest that the control of parasitic helminths and of malaria in school children could be viewed as essential co-contributors to promoting the health of schoolchildren.

Africa South of the Sahara↗

Spatial epidemiology of human schistosomiasis in Africa: risk models, transmission dynamics and control.

This paper reviews recent studies on the spatial epidemiology of human schistosomiasis in Africa. The integrated use of geographical information systems, remote sensing and geostatistics has provided new insights into the ecology and epidemiology of schistosomiasis at a variety of spatial scales. Because large-scale patterns of transmission are influenced by climatic conditions, an increasing number of studies have used remotely sensed environmental data to predict spatial distributions, most recently using Bayesian methods of inference. Such data-driven approaches allow for a more rational implementation of intervention strategies across the continent. It is suggested that improved incorporation of transmission dynamics into spatial models and assessment of uncertainties inherent in data and modelling approaches represent important future research directions.

Africa↗

Age-related changes in hookworm infection, anaemia and iron deficiency in an area of high Necator americanus hookworm transmission in south-eastern Brazil.

Surprisingly few detailed age-stratified data exist on the epidemiology of hookworm and iron status, especially in Latin America. We present data from a cross-sectional survey examining 1332 individuals aged 0-86 years from a community in south-east Brazil for hookworm, anaemia and iron deficiency. Sixty-eight percent of individuals were infected with the human hookworm Necator americanus. The force of infection (lambda=0.354) was similar to estimates from other areas of high hookworm transmission. Individuals from poorer households had significantly higher prevalence and intensity of infection than individuals from better-off households. The prevalence of anaemia, iron deficiency and iron-deficiency anaemia was 11.8%, 12.7% and 4.3%, respectively. Anaemia was most prevalent among young children and the elderly. Univariate analysis showed that haemoglobin and serum ferritin were both significantly negatively associated with hookworm intensity among both school-aged children and adults. Multivariate analysis showed that, after controlling for socio-economic status, iron indicators were significantly associated with heavy hookworm infection. Our results indicate that, even in areas where there is a low overall prevalence of anaemia, hookworm can still have an important impact on host iron status, especially in school-aged children and the elderly.

Adolescent↗

Contrasting patterns in the small-scale heterogeneity of human helminth infections in urban and rural environments in Brazil.

Marked heterogeneity exists in the patterns of parasitic infection between individuals, households and communities. Analysis of parasite distributions within populations is complicated by the fact that parasite distributions are highly aggregated and few studies have explicitly incorporated this distribution when investigating small-scale spatial heterogeneities. This study aimed to quantify the small-scale (within- and between-household) heterogeneity of helminth infection in an area of Minas Gerais State, Brazil, with rural and urban sectors. Parasitological data from a cross-sectional survey of 1,249 individuals aged 0-86 years from 242 households were analysed. Within-household clustering of infection was assessed using random effect logistic regression models and between-household spatial heterogeneity was assessed using a Bayesian negative binomial spatial model. The overall prevalence of hookworm (Necator americanus) was 66.9%, the prevalence of Schistosoma mansoni was 44.9% and the prevalence of Ascaris lumbricoides was 48.8%. Statistical analysis indicated significant (within) household and (between household) spatial clustering of hookworm in both rural and urban areas and of S. mansoni in rural areas. There was no evidence of either household or spatial clustering of S. mansoni in urban areas. The spatial correlation of S. mansoni was estimated to reduce by half over a distance of 700 m in the rural area. Rural hookworm had a much smaller half-distance (28 m) and urban hookworm showed an even smaller half-distance (12 m). We suggest that such species-specific differences in patterns of infection by environment are primarily due to variation in exposure and parasite life cycle, although host genetic factors cannot be ruled out.

Adolescent↗

New technologies for the control of human hookworm infection.

Since the 1990s, the major approach to hookworm control has been morbidity reduction in school-aged children by periodic deworming with benzimidazoles. Now, efforts are underway to determine the feasibility of integrating deworming with control programs that target other neglected tropical diseases. However, the sustainability of benzimidazole deworming for hookworm is of concern because of the variable efficacy of mebendazole, high rates of post-treatment reinfection and possible development of drug resistance. This requires parallel efforts to develop new and complementary hookworm control tools, such as new anthelmintic drugs (e.g. tribendimidine) and a recombinant hookworm vaccine. It is hoped that, ultimately, anthelmintic vaccination will be linked to deworming as part of an expanded control package.

Ancylostomatoidea↗

Soil-transmitted helminth infections: ascariasis, trichuriasis, and hookworm.

The three main soil-transmitted helminth infections, ascariasis, trichuriasis, and hookworm, are common clinical disorders in man. The gastrointestinal tract of a child living in poverty in a less developed country is likely to be parasitised with at least one, and in many cases all three soil-transmitted helminths, with resultant impairments in physical, intellectual, and cognitive development. The benzimidazole anthelmintics, mebendazole and albendazole, are commonly used to remove these infections. The use of these drugs is not limited to treatment of symptomatic soil-transmitted helminth infections, but also for large-scale prevention of morbidity in children living in endemic areas. As a result of data showing improvements in child health and education after deworming, and the burden of disease attributed to soil-transmitted helminths, the worldwide community is awakening to the importance of these infections. Concerns about the sustainability of periodic deworming with benzimidazole anthelmintics and the emergence of resistance have prompted efforts to develop and test new control tools.

Animals↗

Mapping the global distribution of trachoma.

OBJECTIVE: We aimed to summarize and map the existing global population-based data on active trachoma and trichiasis. Detailed distribution maps of various infectious diseases have proved a valuable tool in their control. Such maps play an important role in assessing the magnitude of the problem, defining priority areas for control, monitoring changes, and advocacy. Until now, information on trachoma prevalence at within country levels has not been systematically collated, analysed and reported. METHODS: We gathered the last 18 years' worth of reported data on active trachoma in children aged less than 10 years, and the last 25 years of reported trichiasis in adults aged 15 years and over from 139 population-based surveys in 33 countries. We collated these data into one database using the "district" (second administrative level) as the standard unit of reporting. We used Geographical Information Systems as a database and cartographic tool to generate a global map of the prevalence of trachoma and trichiasis. FINDINGS: We obtained data on active trachoma and trichiasis from 18 countries in the WHO African Region, 6 in the Eastern Mediterranean Region, 3 in the South-East Asia Region, 3 in the Western Pacific Region and 2 in the Region of the Americas. In 23 countries suspected of having endemic trachoma no reliable district-level population-based data were available. In China and India, data were limited to a few districts. The data highlighted important regional differences and marked national variations in prevalence of active trachoma and trichiasis. CONCLUSION: This is the first attempt to summarize and map the existing population-based data on active trachoma and trichiasis. The lack of data in many countries remains an important obstacle to trachoma control efforts.

Adolescent↗

Hookworm vaccines: past, present, and future.

Hookworms are gastrointestinal nematodes that infect almost 1 billion people in developing countries. The main clinical symptom of human hookworm infections is iron-deficiency anaemia, a direct consequence of the intestinal blood loss resulting from the parasite's feeding behaviour. Although treatment is available and currently used for the periodic removal of adult hookworms from patients, this approach has not effectively controlled hookworm in areas of rural poverty. Furthermore, treated individuals remain susceptible to reinfection following exposure to third-stage infective hookworm larvae in the soil as early as 4-12 months after drug treatment. Therefore, a prophylactic vaccine against hookworm infection would provide an attractive additional tool for the public-health control of this disease. The feasibility of developing a vaccine is based on the previous success of an attenuated larval vaccine against canine hookworm. Several laboratory and field studies have explored the development of a human anti-hookworm vaccine, describing potential protective mechanisms and identifying candidate antigens, one of which is now in clinical trials. The current roadmap that investigators have conceived has been influenced by vaccine development for blood-feeding nematodes of livestock and companion animals; however, recombinant vaccines have yet to be developed for nematodes that parasitise animals or human beings. The roadmap also addresses the obstacles facing development of a vaccine for developing countries, where there is no commercial market.

Global Health↗

Synergistic associations between hookworm and other helminth species in a rural community in Brazil.

OBJECTIVE: To identify possible synergistic associations of hookworm and other helminths. METHOD: Cross-sectional survey of all households within 10 km2 of Americaninhas, a rural community in Minas Gerais, Brazil. We determined the prevalence and intensity of single and multiple helminth species infection in an age-stratified sample of 1332 individuals from 335 households. RESULTS: Hookworm was the most prevalent helminth infection (68.2%), followed by Ascaris lumbricoides (48.8%) and Schistosoma mansoni (45.3%). Overall, 60.6% of individuals harboured mixed helminth infections. Multivariate analysis indicated significant positive associations for co-infection with hookworm and S. mansoni and for co-infection with hookworm and A. lumbricoides. Co-infections with hookworm and A. lumbricoides resulted in higher egg counts for both, suggesting a synergistic relationship between these species, although, we found important age differences in this relationship. However, the intensity of S. mansoni or A. lumbricoides co-infection did not differ from that of mono-infection. CONCLUSION: These results have implications for the epidemiology, immunology and control of multiple helminth infections. More research is needed to examine the rates of re-infection and immune responses after chemotherapy, and to what extent the effects of polyparasitism are altered by chemotherapy.

Adolescent↗

Bayesian spatial analysis and disease mapping: tools to enhance planning and implementation of a schistosomiasis control programme in Tanzania.

OBJECTIVE: To predict the spatial distributions of Schistosoma haematobium and S. mansoni infections to assist planning the implementation of mass distribution of praziquantel as part of an on-going national control programme in Tanzania. METHODS: Bayesian geostatistical models were developed using parasitological data from 143 schools. RESULTS: In the S. haematobium models, although land surface temperature and rainfall were significant predictors of prevalence, they became non-significant when spatial correlation was taken into account. In the S. mansoni models, distance to water bodies and annual minimum temperature were significant predictors, even when adjusting for spatial correlation. Spatial correlation occurred over greater distances for S. haematobium than for S. mansoni. Uncertainties in predictions were examined to identify areas requiring further data collection before programme implementation. CONCLUSION: Bayesian geostatistical analysis is a powerful and statistically robust tool for identifying high prevalence areas in a heterogeneous and imperfectly known environment.

Adolescent↗

Spatial epidemiology of Plasmodium vivax, Afghanistan.

Plasmodium vivax is endemic to many areas of Afghanistan. Geographic analysis helped highlight areas of malaria risk and clarified ecologic risk factors for transmission. Remote sensing enabled development of a risk map, thereby providing a valuable tool to help guide malaria control strategies.

Adolescent↗

Progress towards countrywide control of schistosomiasis and soil-transmitted helminthiasis in Uganda.

Schistosomiasis caused by infection with Schistosoma mansoni is a serious public health burden in 38 of the 56 districts of Uganda. This article reviews the initial experience of the national control programme. Launched in 2003, this started with a pilot phase with the main aim of utilizing the experience to formulate feasible and appropriate methods of drug delivery. Overall, 432,746 people were treated and coverage was 91.4% in schools and 64.7% in communities. The issues raised by independent evaluators included that most communities did not participate in the selection of community drug distributors (CDD) and that teachers and CDDs needed refresher training mainly on health education and the management of side effects. As a way forward, it is suggested that the Ministry of Health should integrate deworming into the existing health infrastructure so that every time a child is reached for any health service, the child is also de-wormed.

Adolescent↗

Schistosoma mansoni in pregnancy and associations with anaemia in northwest Tanzania.

Schistosomiasis among pregnant women has been inadequately investigated. In order to determine the importance of Schistosoma mansoni in this subgroup, we conducted a cross-sectional survey of 972 women in Tanzania and investigated the prevalence of Schistosoma mansoni, hookworm and malaria and their associations with anaemia. Overall, 63.5% of women were infected with S. mansoni, with prevalence highest among younger women and decreasing with increasing age. The prevalence of hookworm was 56.3%, and 16.4% of women had malaria parasitaemia. Overall, 66.4% of women were anaemic. Increased risk of anaemia was associated with heavy infection with S. mansoni but not hookworm or Plasmodium falciparum parasitaemia.

Adolescent↗

Antibodies against a secreted protein from hookworm larvae reduce the intensity of hookworm infection in humans and vaccinated laboratory animals.

The development of a vaccine would provide an important new tool for the control of human hookworm infection. On the basis of successful vaccination of laboratory animals with living irradiated, third-stage hookworm larvae (L3), we examined the antibody responses of individuals from hookworm endemic areas of Brazil and China against the most abundant L3 secreted antigens, the ancylostoma secreted proteins, ASP-1 and ASP-2. Logistic regression was used to investigate the effects of antibody isotype responses to ASPs on the risk of an individual harboring heavy hookworm infection. A significant protective association was observed between increasing anti-ASP-2 IgE levels and the risk of heavy hookworm infection. To confirm that ASP-2 is a protective antigen, laboratory dogs were immunized with recombinant ASP-2 formulated with the GlaxoSmithKline Adjuvant, AS03. Sera obtained from the immunized dogs exhibited high geometric mean antibody titers, immunoprecipitated native ASP-2 from L3 extracts and localized the site of ASP-2 expression to the glandular esophagus and body channels exiting to the cuticle. The sera also exhibited an increased ability to inhibit migration of L3 through tissue in vitro relative to sera from AS03-injected controls. Upon L3 challenge, the ASP-2 vaccinated dogs exhibited significant reductions in fecal egg counts and intestinal hookworm burden. These findings provide strong support for the development of an effective recombinant vaccine against hookworm infection in humans.

Adolescent↗

Epidemiology of helminth infections and their relationship to clinical malaria in southwest Uganda.

It has recently been suggested that helminth infections may adversely influence susceptibility to other infections, including malaria. To investigate this hypothesis in a sub-Saharan African setting, surveys of helminth infections were conducted in 2003 among individuals who had been under weekly active case detection for clinical malaria during the preceding 18 months in four villages in Kabale District, southwest Uganda. Overall, 47.3% of individuals had at least one intestinal nematode species infection: hookworm, Ascaris lumbricoides and Trichuris trichiura were detected in 32.1, 17.4 and 8.1% of individuals, respectively. We found evidence of significant household clustering of A. lumbricoides, T. trichiura and hookworm, and clustering of heavy infection of each species. The association between helminth infection and clinical malaria was investigated in two villages and no evidence for an association was observed between the presence of infection or heavy infection and risk of malaria.

Animals↗