Andrea Gazzinelli

A research agenda for helminth diseases of humans: The problem of helminthiases

A disproportionate burden of helminthiases in human populations occurs in marginalised, low-income, and resource-constrained regions of the world, with over 1 billion people in developing areas of sub-Saharan Africa, Asia, and the Americas infected with one or more helminth species. The morbidity caused by such infections imposes a substantial burden of disease, contributing to a vicious circle of infection, poverty, decreased productivity, and inadequate socioeconomic development. Furthermore, helminth infection accentuates the morbidity of malaria and HIV/AIDS, and impairs vaccine efficacy. Polyparasitism is the norm in these populations, and infections tend to be persistent. Hence, there is a great need to reduce morbidity caused by helminth infections. However, major deficiencies exist in diagnostics and interventions, including vector control, drugs, and vaccines. Overcoming these deficiencies is hampered by major gaps in knowledge of helminth biology and transmission dynamics, platforms from which to help develop such tools. The Disease Reference Group on Helminths Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), was given the mandate to review helminthiases research and identify research priorities and gaps. In this review, we provide an overview of the forces driving the persistence of helminthiases as a public health problem despite the many control initiatives that have been put in place; identify the main obstacles that impede progress towards their control and elimination; and discuss recent advances, opportunities, and challenges for the understanding of the biology, epidemiology, and control of these infections. The helminth infections that will be discussed include: onchocerciasis, lymphatic filariasis, soil-transmitted helminthiases, schistosomiasis, food-borne trematodiases, and taeniasis/cysticercosis.

Cytokine production associated with periportal fibrosis during chronic schistosomiasis mansoni in humans

ABSTRACT Volunteers living in an area where schistosomiasis mansoni is endemic were subjected to ultrasound examination and classified into groups according to the levels of fibrosis diagnosed, namely, absence of indications of fibrosis (group 0), incipient fibrosis (group 1), and moderate/severe fibrosis (group 2). Peripheral blood mononuclear cells (PBMC) collected from the volunteers were stimulated with soluble antigens from adult schistosomes or from schistosome eggs, and the production of the cytokines gamma interferon, tumor necrosis factor alpha, transforming growth factor β (TGF-β), interleukin-4 (IL-4), IL-10, and IL-13 was determined. Potential associations of the level of fibrosis with age, sex, intensity of infection, and cytokine production were investigated between the three groups. Univariate analysis identified associations of age (>50), gender (male), and absence of eggs/g of feces with moderate/severe fibrosis and an association of intensity of infection (>100 eggs) with incipient fibrosis. When cytokine production in PBMC cultures stimulated by soluble egg antigens was categorized as low or high, significant differences in the distribution of IL-13 levels were established between groups 0 and 2. No significant differences were detected between the groups in the cytokines produced by PBMC cultures stimulated with soluble antigens from adult schistosomes. When all variables were tested in multivariate analyses, only IL-13 was strongly associated with fibrosis (odds ratio = 5.8; 95% confidence interval [CI] = 1.1 to 30.5). While high levels of TGF-β appeared to be associated with protection against fibrosis, the strength of the association was low.

Exposure to Schistosoma mansoni infection in a rural area in Brazil. II: household risk factors.

A number of studies have pointed out the potential importance of the household in the transmission of schistosomiasis. The clustering of domestic activities associated with water collection, storage, and usage can result in the sharing of transmission sites and infective water contact behaviours. In this study, we employed a variance component method to estimate effects due to individual risk factors and shared residence on the variance in faecal egg counts during Schistosoma mansoni infection. A suite of covariates, which included demographic, socioeconomic, water supply, and water contact behaviour terms, contributed 15% to the variance in faecal egg counts. Shared residence alone accounted for 28% of the variance in faecal egg excretion. When both the suite of covariates and shared residence were considered in the same model, shared residence still contributed 22% to the variance in infection intensity. These results point to the importance of shared residence as a means of capturing the complex interrelationship between shared demographic, socioeconomic, physical environmental, and behavioural factors that influence transmission of schistosomiasis at the household level.

Transmission of Helicobacter pylori infection in families of preschool-aged children from Minas Gerais, Brazil.

We evaluated the role of the family in the transmission of Helicobacter pylori infection in preschool‐aged children from a rural district in the State of Minas Gerais, Brazil. Sixty‐six families (66 index children, 63 mothers, 60 fathers and 134 siblings), defined as at least one parent living in the same household with at least one offspring up to 8 years old, were studied. Odds ratios (OR) and 95% confidence intervals (CI) were estimated by logistic regression controlling for age, gender, number of children in household and H. pylori status of the father, mother and siblings. The prevalence of the infection was 69.7% (469 of 673) and it increased with age (P < 0.001). Positive mothers were a strong and independent risk factor for infection (OR 22.70; 95% CI 2.31–223.21). Positive siblings were also positively associated with infection (OR 1.81; 95% CI 1.01–3.30).

Prevalence of metabolic syndrome in a rural area of Brazil

CONTEXT AND OBJECTIVE Metabolic syndrome (MS) is recognized worldwide as an important public health concern. However, little information is available for rural populations in Brazil. The aim was to determine the prevalence and risk factors associated with MS in a rural village in Brazil in 2004. DESIGN AND SETTING Cross-sectional population-based study, in Virgem das Graças, a rural community in the Jequitinhonha Valley, State of Minas Gerais. METHODS MS was the dependent variable, defined as any three of these risk factors: arterial hypertension, high glucose or triglyceride concentrations, low high-density lipoprotein cholesterol and abdominal obesity. MS prevalence, according to selected socioeconomic and demographic variables (age, skin color, marital status, schooling and smoking habits), was determined in 251 subjects aged 20-88 years. Multivariate logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals. RESULTS MS prevalence was 21.6% (7.7% for men and 33.6% for women); the age-adjusted prevalence was 19.0%. The highest prevalences were observed for women > 60 years of age (52.9%) and women with body mass index (BMI) >or= 25 kg/m(2) (64%). Age, sex and BMI were associated risk factors for MS, while skin color was only significantly associated with MS for women. The models were adjusted for age, smoking habits, marital status, skin color and schooling. CONCLUSIONS BMI and age were independently associated factors for MS in this rural community. These findings provide important evidence on the prevalence of MS as a public health problem, particularly for women and overweight individuals.

Microgeographical patterns of schistosomiasis and water contact behavior; examples from Africa and Brazil

This paper examines the results of spatial (microgeographical) water contact/schistosomiasis studies in two African (Egyptian and Kenyan) and one Brazilian communities. All three studies used traditional cartographic and statistical methods but one of them employed also GIS (geographical information systems) tools. The advantage of GIS and their potential role in schistosomiasis control are briefly described. The three cases revealed considerable variation in the spatial distribution of water contact, transmission parameters and infection levels at the household and individual levels. All studies showed considerable variation in the prevalence and intensity of infection between households. They also show a variable influence of distance on water contact behavior associated with type of activity, age, sex, socioeconomic level, perception of water quality, season and availability of water in the home. Water contact behavior and schistosomiasis were evaluated in the Brazilian village of Nova União within the context of water sharing between household and age/sex groups. Recommendations are made for further spatial studies on the transmission and control of schistosomiasis.

A research agenda for helminth diseases of humans: Towards control and elimination

Human helminthiases are of considerable public health importance in sub-Saharan Africa, Asia, and Latin America. The acknowledgement of the disease burden due to helminth infections, the availability of donated or affordable drugs that are mostly safe and moderately efficacious, and the implementation of viable mass drug administration (MDA) interventions have prompted the establishment of various large-scale control and elimination programmes. These programmes have benefited from improved epidemiological mapping of the infections, better understanding of the scope and limitations of currently available diagnostics and of the relationship between infection and morbidity, feasibility of community-directed or school-based interventions, and advances in the design of monitoring and evaluation (M&E) protocols. Considerable success has been achieved in reducing morbidity or suppressing transmission in a number of settings, whilst challenges remain in many others. Some of the obstacles include the lack of diagnostic tools appropriate to the changing requirements of ongoing interventions and elimination settings; the reliance on a handful of drugs about which not enough is known regarding modes of action, modes of resistance, and optimal dosage singly or in combination; the difficulties in sustaining adequate coverage and compliance in prolonged and/or integrated programmes; an incomplete understanding of the social, behavioural, and environmental determinants of infection; and last, but not least, very little investment in research and development (R&D). The Disease Reference Group on Helminth Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), was given the mandate to undertake a comprehensive review of recent advances in helminthiases research, identify research gaps, and rank priorities for an R&D agenda for the control and elimination of these infections. This review presents the processes undertaken to identify and rank ten top research priorities; discusses the implications of realising these priorities in terms of their potential for improving global health and achieving the Millennium Development Goals (MDGs); outlines salient research funding needs; and introduces the series of reviews that follow in this PLoS Neglected Tropical Diseases collection, “A Research Agenda for Helminth Diseases of Humans.”

Exposure to Schistosoma mansoni infection in a rural area of Brazil. I: Water contact

The study of water contact patterns in rural Brazil presents unique challenges due to widely dispersed settlement patterns, the ubiquity of water contact sites, and the privatization of water resources. This study addresses these challenges by comparing the two most widely used methods of assessing water contact behaviour: direct observation and survey. The results of a 7‐day direct observation of water contact were compared with water contact surveys administered 1 week after and then 1 year after the direct observation study. The direct observation study recorded a water contact rate higher than reported by other investigators (3.2 contacts per person per day); however, 75% of these contacts were for females and consisted mainly of domestic activities occurring around the household. A comparison of the frequency of water contact activities between the direct observation and the two surveys revealed several important points. First, no significant differences were found between methods for routine water contact activities (e.g. bathing), indicating that participants were able to accurately self‐report some types of water contact activities. Second, significant differences were found in the recording of water contact activities that took place outside the observation area, indicating that direct observation may under‐report water contact activities in areas where contact sites are dispersed widely. Third, significant differences between the direct observation and the survey method were more common for males than for females, indicating that the combination of widespread water contact sites and gender‐specific division of labour may result in under‐reporting of male contacts by direct observation methods. In short, despite the limitations in the recording of duration and body exposure, the survey method may more accurately record the frequency of water contact activities than direct observation methods in areas of widely dispersed water contact sites. Hence, surveys may be more suitable for the unique challenges of water contact in rural areas of Brazil.

A Multihousehold Study Reveals a Positive Correlation between Age, Severity of Ocular Toxoplasmosis, and Levels of Glycoinositolphospholipid-Specific Immunoglobulin A

A cross-sectional household study involving 499 individuals was undertaken in an area of Minas Gerais state, Brazil, where infection with Toxoplasma gondii is endemic. Nearly 50% (n=247) of the sample had T. gondii-specific antibodies, even individuals in the 5-9-year-old age group. Approximately 12.5% (n=28) of a random subsample of participants who were positive for T. gondii antibodies had ocular lesions associated with T. gondii infection. The frequency of ocular toxoplasmosis increased significantly with age, with approximately 50% of individuals >60 years of age having lesions. The size of the ocular lesion correlated positively (r=0.85; P=.01) with the serum level of immunoglobulin A specific for tachyzoite-derived glycoinositolphospholipids. We found that sharing the same residence accounted for 30% of the variation in infectivity among residents in the sample, whereas age was the main risk factor for development of ocular toxoplasmosis in patients who were positive for T. gondii antibodies.

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.