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Biomedical subjects

Simon Brooker

Publications and source records attributed to Simon Brooker.

At least 19 recordsLinked to original sources

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↗

Rapid assessment of Schistosoma mansoni: the validity, applicability and cost-effectiveness of the Lot Quality Assurance Sampling method in Uganda.

Rapid and accurate identification of communities at highest risk of morbidity from schistosomiasis is key for sustainable control. Although school questionnaires can effectively and inexpensively identify communities with a high prevalence of Schistosoma haematobium, parasitological screening remains the preferred option for S. mansoni. To help reduce screening costs, we investigated the validity of Lot Quality Assurance Sampling (LQAS) in classifying schools according to categories of S. mansoni prevalence in Uganda, and explored its applicability and cost-effectiveness. First, we evaluated several sampling plans using computer simulation and then field tested one sampling plan in 34 schools in Uganda. Finally, cost-effectiveness of different screening and control strategies (including mass treatment without prior screening) was determined, and sensitivity analysis undertaken to assess the effect of infection levels and treatment costs. In identifying schools with prevalences > or =50%, computer simulations showed that LQAS had high levels of sensitivity and specificity (>90%) at sample sizes <20. The method also provides an ability to classify communities into three prevalence categories. Field testing showed that LQAS where 15 children were sampled had excellent diagnostic performance (sensitivity: 100%, specificity: 96.4%, positive predictive value: 85.7% and negative predictive value: 92.3%). Screening using LQAS was more cost-effective than mass treating all schools (US$218 vs. US$482/high prevalence school treated). Threshold analysis indicated that parasitological screening and mass treatment would become equivalent for settings where prevalence > or =50% in 75% of schools and for treatment costs of US$0.19 per schoolchild. We conclude that, in Uganda, LQAS provides a rapid, valid and cost-effective method for guiding decision makers in allocating finite resources for the control of schistosomiasis.

Adolescent↗

Evaluating the epidemiological impact of national control programmes for helminths.

During the past decade, there has been renewed commitment to programmes for helminth control, and several international initiatives have been launched. Scientific evaluation of large-scale interventions to reduce the incidence of infection and associated morbidity and mortality is vital, not only to demonstrate health benefits, but also to assess cost-effectiveness to show that monies from donor agencies have been used wisely. Using the example of schistosomiasis, this article outlines a framework for the evaluation of the impact of national control programmes, highlighting the important epidemiological and practical issues that must be addressed.

Animals↗

Epidemiology of anthroponotic cutaneous leishmaniasis in Afghan refugee camps in northwest Pakistan.

During November and December 1998, 16 Afghan refugee camps were surveyed for anthroponotic cutaneous leishmaniasis (ACL). Prevalence of active lesions and scars amongst the population was 2.7% and 2.4%, respectively. Between camps the prevalence of active lesions varied from 0.3 to 8.8% and that of scars from 0.3 to 5.8%. Random-effects logistic regression indicated that risk of active ACL was associated with age but not gender. This model also indicated a significant clustering at the household level. The average annual force of ACL infection was estimated to be 0.046 per year (4.6 cases/1000 persons/year) over the past 10 years. Based on the evidence from this study an intervention strategy was formulated for all camps with reported ACL cases. This includes targeting of active cases with insecticide-treated nets, sold at a highly subsidised price.

Adolescent↗

Human hookworm infection in the 21st century.

The scientific study of human hookworm infection began at the dawn of the twentieth century. In recent years, there have been dramatic improvements in our understanding of many aspects of this globally widespread parasite. This chapter reviews recent advances in our understanding in the biology, immunology, epidemiology, public health significance and control of hookworm, and to look forward to the study of this important parasite in the 21st century. Advances in molecular biology has lead to the identification of a variety of new molecules from hookworms, which have importance either in the molecular pathogenesis of hookworm infection or in the host-parasite relationship; some are also promising vaccine targets. At present, relatively little is known about the immune responses to hookworm infection, although it has recently been speculated that hookworm and other helminths may modulate specific immune responses to other pathogens and vaccines. Our epidemiological understanding of hookworm has improved through the development of mathematical models of transmission dynamics, which coupled with decades of field research across multiple epidemiological settings, have shown that certain population characteristics can now be recognised as common to the epidemiology, population biology and control of hookworm and other helminth species. Recent recognition of the subtle, but significant, impact of hookworm on health and education, together with the simplicity, safety, low cost and efficacy of chemotherapy has spurred international efforts to control the morbidity due to infection. Large-scale treatment programmes are currently underway, ideally supported by health education and integrated with the provision of improved water and sanitation. There are also on-going efforts to develop novel anthelmintic drugs and anti-hookworm vaccines.

Ancylostomatoidea↗

Epidemiology and geography of Schistosoma mansoni in Uganda: implications for planning control.

Intestinal schistosomiasis caused by infection with Schistosoma mansoni is a widespread public health problem in Uganda. Although long known to be endemic, its current distribution within the country requires updating of parasitological data to help guide planned control. We report such data collected between 1998 and 2002 from 201 schools and 68 communities across Uganda. In accordance with epidemiological expectation, prevalence and intensity increased with age, peaking at 10-20 years and thereafter declined moderately with age, whereas intensity declined more rapidly with age, and the prevalence of infection in a school was non-linearly related to the mean intensity of infection. We used geographical information systems to map the distribution of infection and to overlay parasitological data with interpolated environmental surfaces. The derived maps indicate both a widespread occurrence of infection and a marked variability in infection prevalence, with prevalence typically highest near the lakeshore and along large rivers. No transmission occurred at altitudes >1400 m or where total annual rainfall was <900 mm; limits which can help estimate the population at risk of schistosomiasis. The results are discussed in reference to the ecology of infection and provide an epidemiological framework for the design and implementation of control efforts underway in Uganda.

Adolescent↗

Exposure to Schistosoma mansoni infection in a rural area in Brazil. Part III: household aggregation of water-contact behaviour.

Much research points to the importance of the household in the study of water-borne diseases such as schistosomiasis. An important aspect of the household is the clustering of domestic activities associated with water collection, storage and usage. Such activities can result in the sharing of water-contact sites and water-contact behaviour, which expose household members to similar risks of infection. In previous studies, we determined that shared residence accounted for 28% of the variance in Schistosoma faecal egg excretion rates. We now quantify the effect of shared residence on the variation in water-related health behaviours. We found that shared residence accounted for 30% of the variation in total water contacts per week. It also accounted for a large proportion of the variation in individual water-contact behaviour: e.g. agricultural contacts (63%), washing limbs (56%) or bathing (41%). These results implicate the household as an important composite measure of the complex relationships between socioeconomic, environmental and behavioural factors that influence water-contact behaviour and, therefore, the transmission of schistosomiasis. Our results also support a focus on the household in the implementation of schistosomiasis prevention and control efforts.

Activities of Daily Living↗

Spatial clustering of malaria and associated risk factors during an epidemic in a highland area of western Kenya.

The epidemiology of malaria over small areas remains poorly understood, and this is particularly true for malaria during epidemics in highland areas of Africa, where transmission intensity is low and characterized by acute within and between year variations. We report an analysis of the spatial distribution of clinical malaria during an epidemic and investigate putative risk factors. Active case surveillance was undertaken in three schools in Nandi District, Western Kenya for 10 weeks during a malaria outbreak in May-July 2002. Household surveys of cases and age-matched controls were conducted to collect information on household construction, exposure factors and socio-economic status. Household geographical location and altitude were determined using a hand-held geographical positioning system and landcover types were determined using high spatial resolution satellite sensor data. Among 129 cases identified during the surveillance, which were matched to 155 controls, we identified significant spatial clusters of malaria cases as determined using the spatial scan statistic. Conditional multiple logistic regression analysis showed that the risk of malaria was higher in children who were underweight, who lived at lower altitudes, and who lived in households where drugs were not kept at home.

Adolescent↗

Leishmaniasis in refugee and local Pakistani populations.

The epidemiology of anthroponotic cutaneous leishmaniasis was investigated in northwest Pakistan. Results suggested similar patterns of endemicity in both Afghan refugee and Pakistani populations and highlighted risk factors and household clustering of disease.

Adult↗

Malaria morbidity among school children living in two areas of contrasting transmission in western Kenya.

Research in malaria-endemic areas is usually focused on malaria during early childhood. Less is known about malaria among older school age children. The incidence of clinical attacks of malaria was monitored, using active case detection in primary schools, in two areas of western Kenya that differ in the intensity of transmission. Clinical malaria was more common in schools in the Nandi highlands, with a six-fold higher incidence of malaria attacks during the malaria epidemic in 2002, compared with school children living in a holoendemic area with intense perennial transmission during the same period. The high incidence coupled with the high parasite densities among cases is compatible with a low level of protective immunity in the highlands. The malaria incidence among school children exposed to intense year-round transmission (26 per 100 school children per year) was consistent with reports from other holoendemic areas. Taken together with other published studies, the data suggest that malaria morbidity among school age children increases as transmission intensity decreases. The implications for malaria control are discussed.

Adolescent↗

Quantification of clinical morbidity associated with schistosome infection in sub-Saharan Africa.

Health policy making in developing countries requires estimates of the (global) burden of disease. At present, most of the available data on schistosomiasis is limited to numbers of individuals harbouring the infection. We explored the relationship between the presence of schistosome infection and clinical morbidity, in order to estimate numbers of individuals with disease-specific morbidity for Schistosoma haematobium and Schistosoma mansoni infection in sub-Saharan Africa. We searched the literature for cross-sectional data from field studies reporting both schistosome infection and morbidity. This was used to derive a functional relationship between morbidity and infection. After standardisation for diagnostic method, the number of individuals with specific types of clinical morbidity or pathology was predicted. As only aggregated prevalences of infection were available for countries or areas, we adjusted for heterogeneity in infection levels within communities in those countries. In total, 70 million individuals out of 682 million (2000 estimate) in sub-Saharan Africa were estimated to experience haematuria in the last 2 weeks associated with S. haematobium infection, and 32 million dysuria. Ultrasound detected serious consequences of S. haematobium, major bladder wall pathology and major hydronephrosis, were predicted at 18 and 10 million, respectively. Infection with S. mansoni was estimated to cause diarrhoea in 0.78 million individuals, blood in stool in 4.4 million and hepatomegaly in 8.5 million. As the associations between prevalence of S. mansoni infection and prevalence of diarrhoea and blood in stool were not very clear, the resulting estimates may be underestimations. Using the very limited data available, we estimated the mortality rates due to non-functioning kidney (from S. haematobium) and haematemesis (from S. mansoni) at 150000 and 130000 per year. Given the overall high number of cases with schistosomiasis-related disease and associated death, we conclude that schistosomiasis remains an important public health problem in sub-Saharan Africa.

Africa South of the Sahara↗