Laura C. Rodrigues

Study of infectious intestinal disease in England: rates in the community, presenting to general practice, and reported to national surveillance

Abstract Objective: To establish the incidence and aetiology of infectious intestinal disease in the community and presenting to general practitioners. Comparison with incidence and aetiology of cases reaching national laboratory based surveillance. Design: Population based community cohort incidence study, general practice based incidence studies, and case linkage to national laboratory surveillance. Setting: 70 general practices throughout England. Participants: 459 975 patients served by the practices. Community surveillance of 9776 randomly selected patients. Main outcome measures: Incidence of infectious intestinal disease in community and reported to general practice. Results: 781 cases were identified in the community cohort, giving an incidence of 19.4/100 person years (95% confidence interval 18.1 to 20.8). 8770 cases presented to general practice (3.3/100 person years (2.94 to 3.75)). One case was reported to national surveillance for every 1.4 laboratory identifications, 6.2 stools sent for laboratory investigation, 23 cases presenting to general practice, and 136 community cases. The ratio of cases in the community to cases reaching national surveillance was lower for bacterial pathogens (salmonella 3.2:1, campylobacter 7.6:1) than for viruses (rotavirus 35:1, small round structured viruses 1562:1). There were many cases for which no organism was identified. Conclusions: Infectious intestinal disease occurs in 1 in 5 people each year, of whom 1 in 6 presents to a general practitioner. The proportion of cases not recorded by national laboratory surveillance is large and varies widely by microorganism.Ways of supplementing the national laboratory surveillance system for infectious intestinal diseases should be considered.

Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interleukin-10.

BACKGROUND Most of the effort directed at understanding the role infections have in preventing allergy has focused on bacteria and viruses and their ability to divert the immune system towards T-helper-1 responses and away from proallergic T-helper-2 responses. However, helminth infections, highly prevalent in large parts of the developing world, where allergy is uncommon, stimulate strong T-helper-2 responses. We investigated the influence of chronic helminth infections on the prevalence of atopy and aimed to understand the relation at a detailed immunological level. METHODS 520 Gabonese schoolchildren were tested for skin reaction to house-dust mite and other allergens, for Schistosoma haematobium eggs in urine, and for microfilariae in blood samples. Total and mite-specific IgE antibodies were measured. A subsample selected on the basis of their skin test to house-dust mite received detailed immunological investigations. FINDINGS Children with urinary schistosomiasis had a lower prevalence of a positive skin reaction to house-dust mite than those free of this infection (odds ratio 0.32 [95% CI 0.16-0.63]). The degree of sensitisation to house-dust mite could not explain this difference in skin-prick positivity. Schistosome-antigen-specific concentrations of interleukin-10 were significantly higher in infected children, and higher specific concentrations of this anti-inflammatory cytokine were negatively associated with the outcome of skin-test reactivity to mite (0.53 [0.30-0.96]). No association between polyclonal IgE antibodies and skin-test results was found. INTERPRETATION The anti-inflammatory cytokine, interleukin-10, induced in chronic schistosomiasis, appears central to suppressing atopy in African children.

Long-Term Treatment of Intestinal Helminths Increases Mite Skin-Test Reactivity in Gabonese Schoolchildren

BACKGROUND Several studies have shown an inverse association between helminth infections and atopy, but none have clearly established that the pathogens themselves, rather than other associated factors, cause the suppression of atopy. To show a direct link, prospective intervention studies are required. METHODS A randomized, controlled trial was performed to study whether repeated anthelminthic treatment results in increased allergic sensitivity to house dust mites (HDMs) in chronically infected children. The trial population consisted of 317 Gabonese schoolchildren with a high prevalence of intestinal helminths. Intervention consisted of treatment every 3 months with praziquantel and mebendazole and with placebo in the control group. Follow-up lasted 30 months: at 6-month intervals, skin-test sensitivity to mites, helminth infection status, and levels of total IgE were determined. RESULTS Treatment resulted in a significant increase in the rate of developing skin sensitivity to HDMs (hazard ratio, 2.51; 95% confidence interval, 1.85-3.41), which was mediated, in part, by reductions in Ascaris and/or Trichuris infections. Levels of total IgE were reduced, but this did not mediate the effect of treatment on skin-test reactivity. CONCLUSIONS Anthelminthic treatment of chronically infected children results in increased atopic reactivity, which indicates that helminths directly suppress allergic reactions.

Longitudinal study of infectious intestinal disease in the UK (IID2 study): incidence in the community and presenting to general practice

Objectives To estimate, overall and by organism, the incidence of infectious intestinal disease (IID) in the community, presenting to general practice (GP) and reported to national surveillance. Design Prospective, community cohort study and prospective study of GP presentation conducted between April 2008 and August 2009. Setting Eighty-eight GPs across the UK recruited from the Medical Research Council General Practice Research Framework and the Primary Care Research Networks. Participants 6836 participants registered with the 88 participating practices in the community study; 991 patients with UK-acquired IID presenting to one of 37 practices taking part in the GP presentation study. Main outcome measures IID rates in the community, presenting to GP and reported to national surveillance, overall and by organism; annual IID cases and GP consultations by organism. Results The overall rate of IID in the community was 274 cases per 1000 person-years (95% CI 254 to 296); the rate of GP consultations was 17.7 per 1000 person-years (95% CI 14.4 to 21.8). There were 147 community cases and 10 GP consultations for every case reported to national surveillance. Norovirus was the most common organism, with incidence rates of 47 community cases per 1000 person-years and 2.1 GP consultations per 1000 person-years. Campylobacter was the most common bacterial pathogen, with a rate of 9.3 cases per 1000 person-years in the community, and 1.3 GP consultations per 1000 person-years. We estimate that there are up to 17 million sporadic, community cases of IID and 1 million GP consultations annually in the UK. Of these, norovirus accounts for 3 million cases and 130 000 GP consultations, and Campylobacter is responsible for 500 000 cases and 80 000 GP consultations. Conclusions IID poses a substantial community and healthcare burden in the UK. Control efforts must focus particularly on reducing the burden due to Campylobacter and enteric viruses.

Prevalence of major comorbidities in subjects with COPD and incidence of myocardial infarction and stroke: a comprehensive analysis using data from primary care

Background Comorbidities associated with systemic inflammation including cardiovascular disease (CVD), stroke and diabetes mellitus (DM) are common among individuals with chronic obstructive pulmonary disease (COPD). A study was undertaken to quantify the burden of comorbidity and to determine the risk of first acute arteriovascular events among individuals with COPD. Methods The computerised primary care records of 1 204 100 members of the general population aged ≥35 years on 25 February 2005 were searched for recordings of each disease. Data were analysed using multivariate logistic regression. Cox regression was used to determine whether individuals with COPD were at increased risk of acute myocardial infarction (MI) and stroke. Results Cross-sectional analyses showed that physician-diagnosed COPD was associated with increased risks of CVD (OR 4.98, 95% CI 4.85 to 5.81; p<0.001), stroke (OR 3.34, 95% CI 3.21 to 3.48; p<0.001) and DM (OR 2.04, 95% CI 1.97 to 2.12; p<0.001). In the follow-up analyses, after adjusting for confounding by sex and smoking status and stratifying for age, the greatest increase in the rate of acute arteriovascular events was found in the youngest age groups; the HR for acute MI was 10.34 (95% CI 3.28 to 32.60; p<0.001) and for stroke the HR was 3.44 (95% CI 0.85 to 13.84; p<0.001) compared with the oldest age group. Conclusion Individuals with COPD are substantially more likely to have pre-existing CVD, DM or a previous stroke and are at high risk of acute arteriovascular events. National COPD guidelines and models of care need to adapt to provide an integrated approach to addressing these comorbidities.

Protection by BCG Vaccine Against Tuberculosis: A Systematic Review of Randomized Controlled Trials

BACKGROUND Randomized trials assessing BCG vaccine protection against tuberculosis have widely varying results, for reasons that are not well understood. METHODS We examined associations of trial setting and design with BCG efficacy against pulmonary and miliary or meningeal tuberculosis by conducting a systematic review, meta-analyses, and meta-regression. RESULTS We identified 18 trials reporting pulmonary tuberculosis and 6 reporting miliary or meningeal tuberculosis. Univariable meta-regression indicated efficacy against pulmonary tuberculosis varied according to 3 characteristics. Protection appeared greatest in children stringently tuberculin tested, to try to exclude prior infection with Mycobacterium tuberculosis or sensitization to environmental mycobacteria (rate ratio [RR], 0.26; 95% confidence interval [CI], .18-.37), or infants (RR, 0.41; 95% CI, .29-.58). Protection was weaker in children not stringently tested (RR, 0.59; 95% CI, .35-1.01) and older individuals stringently or not stringently tested (RR, 0.88; 95% CI, .59-1.31 and RR, 0.81; 95% CI, .55-1.22, respectively). Protection was higher in trials further from the equator where environmental mycobacteria are less and with lower risk of diagnostic detection bias. These associations were attenuated in a multivariable model, but each had an independent effect. There was no evidence that efficacy was associated with BCG strain. Protection against meningeal and miliary tuberculosis was also high in infants (RR, 0.1; 95% CI, .01-.77) and children stringently tuberculin tested (RR, 0.08; 95% CI, .03-.25). CONCLUSIONS Absence of prior M. tuberculosis infection or sensitization with environmental mycobacteria is associated with higher efficacy of BCG against pulmonary tuberculosis and possibly against miliary and meningeal tuberculosis. Evaluations of new tuberculosis vaccines should account for the possibility that prior infection may mask or block their effects.

Leprosy now: epidemiology, progress, challenges, and research gaps

Leprosy continues to be a challenge to health worldwide, with about 250,000 new cases being detected every year. Despite widespread implementation of effective multidrug therapy, leprosy has not been eliminated. A third of newly diagnosed patients have nerve damage and might develop disabilities, although the proportion varies according to several factors, including level of self-care. Women who develop leprosy continue to be especially disadvantaged, with rates of late diagnosis and disability remaining high in this subgroup. Leprosy was not a specified disease in the Millennium Development Goals, but improvements in the other areas they cover, such as education and levels of poverty, will help leprosy patients and services. We review data and make recommendations for research on diagnosis, treatment, and prevention, such as further use of molecular analysis of the Mycobacterium leprae genome, implementation of BCG vaccination, and administration of chemoprophylaxis to household contacts. We also suggest development of tools for early diagnosis and detection of infection and nerve damage, and formulation of strategies to manage the chronic complications of leprosy, such as immune-mediated reactions and neuropathy.

MMR vaccination and pervasive developmental disorders: a case-control study

BACKGROUND Concern that measles-mumps-rubella (MMR) vaccination might cause autism has led to a fall in vaccine coverage. We investigated whether MMR vaccination is associated with an increased risk of autism or other pervasive developmental disorders. METHODS We did a matched case-control study using the UK General Practice Research Database. Cases were people born in 1973 or later who had first recorded diagnosis of pervasive developmental disorder while registered with a contributing general practice between 1987 and 2001. Controls were matched on age, sex, and general practice. FINDINGS 1294 cases and 4469 controls were included. 1010 cases (78.1%) had MMR vaccination recorded before diagnosis, compared with 3671 controls (82.1%) before the age at which their matched case was diagnosed. After adjustment for age at joining the database, the odds ratio for association between MMR and pervasive developmental disorder was 0.86 (95% CI 0.68-1.09). Findings were similar when restricted to children with a diagnosis of autism, to those vaccinated with MMR before the third birthday, or to the period before media coverage of the hypothesis linking MMR with autism. INTERPRETATION Our findings suggest that MMR vaccination is not associated with an increased risk of pervasive developmental disorders.

Successes and failures in the control of infectious diseases in Brazil: social and environmental context, policies, interventions, and research needs

Despite pronounced reductions in the number of deaths due to infectious diseases over the past six decades, infectious diseases are still a public health problem in Brazil. In this report, we discuss the major successes and failures in the control of infectious diseases in Brazil, and identify research needs and policies to further improve control or interrupt transmission. Control of diseases such as cholera, Chagas disease, and those preventable by vaccination has been successful through efficient public policies and concerted efforts from different levels of government and civil society. For these diseases, policies dealt with key determinants (eg, the quality of water and basic sanitation, vector control), provided access to preventive resources (such as vaccines), and successfully integrated health policies with broader social policies. Diseases for which control has failed (such as dengue fever and visceral leishmaniasis) are vector-borne diseases with changing epidemiological profiles and major difficulties in treatment (in the case of dengue fever, no treatment is available). Diseases for which control has been partly successful have complex transmission patterns related to adverse environmental, social, economic, or unknown determinants; are sometimes transmitted by insect vectors that are difficult to control; and are mostly chronic diseases with long infectious periods that require lengthy periods of treatment.

Effect of BCG revaccination on incidence of tuberculosis in school-aged children in Brazil: the BCG-REVAC cluster-randomised trial.

BACKGROUND Many countries offer a second BCG vaccination to prevent tuberculosis, although there is little evidence of whether this confers additional protection. BCG vaccination is routine in Brazil but BCG revaccination procedures vary by state. We studied revaccination efficacy in two Brazilian cities with tuberculosis prevalence representative of Brazil. METHODS We did a cluster-randomised trial of the protection against tuberculosis from BCG revaccination in school-aged children who had had one BCG vaccination as infants. 767 schools in the cities of Salvador and Manaus, Brazil, participated; schools were the unit of randomisation. The study was open label with no placebo. Cases of tuberculosis were identified through record linkage to the Tuberculosis Control Programme. Revaccination status was masked during linkage and validation of cases. The incidence of tuberculosis was the primary outcome. Analysis was by intention to treat. FINDINGS 386 schools (176,846 children) were assigned BCG revaccination and 365 (171,293 children) no revaccination. 42,053 children in the vaccine group and 47,006 in the control group were absent from school on the day of the visit and were excluded. 31,163 and 27,146, respectively were also excluded because they had no BCG scar, two or more scars, or a doubtful scar on assessment. The crude incidence of tuberculosis in the intervention group was 29.3 per 100,000 person years and in the control group 30.2 per 100,000 person-years (crude-rate ratio 0.97; 95% CI 0.76-1.28). The efficacy of BCG revaccination was 9% (-16 to 29%). INTERPRETATION Revaccination given to children aged 7-14 years in this setting does not provide substantial additional protection and should not be recommended. Follow-up is ongoing and needed to assess the effect of other factors on revaccination efficacy: time since vaccination, age at vaccination, and high or low prevalence of environmental mycobacteria.