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Biomedical subjects

Laura C Rodrigues

Publications and source records attributed to Laura C Rodrigues.

35 records · Page 2Linked to original sources

Validation of the diagnosis of autism in general practitioner records.

BACKGROUND: We report on the validity of the computerized diagnoses of autism in a large case-control study investigating the possible association between autism and the measles, mumps and rubella vaccine in the UK using the General Practitioner Research Database (GPRD). We examined anonymized copies of all relevant available clinical reports, including general practitioners' (GP) notes, consultant, speech therapy and educational psychologists reports, on 318 subjects born between 1973 and 1997 with a diagnosis of autism or a related disorder recorded in their electronic general practice record. METHODS: Data were abstracted to a case validation form allowing for the identification of developmental symptoms relevant to the diagnosis of pervasive developmental disorders (PDDs). Information on other background clinical and familial features was also abstracted. A subset of 50 notes was coded independently by 2 raters to derive reliability estimates for key clinical characteristics. RESULTS: For 294 subjects (92.5%) the diagnosis of PDD was confirmed after review of the records. Of these, 180 subjects (61.2%) fulfilled criteria for autistic disorder. The mean age at first recording of a PDD diagnosis in the GPRD database was 6.3 years (SD = 4.6). Consistent with previous estimates, the proportion of subjects experiencing regression in the course of their development was 19%. Inter-rater reliability for the presence of a PDD diagnosis was good (kappa =.73), and agreement on clinical features such as regression, age of parental recognition of first symptoms, language delay and presence of epilepsy was also good (kappas ranging from.56 to 1.0). CONCLUSIONS: This study provides evidence that the positive predictive value of a diagnosis of autism recorded in the GPRD is high.

Age of Onset↗

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.

Adolescent↗

Congenital syphilis: identification of two distinct profiles of maternal characteristics associated with risk.

BACKGROUND: Behavioral and socioeconomic factors create considerable obstacles to the elimination of congenital syphilis. A clear understanding of maternal risk factors is important to define interventions in every community. GOAL: The goal of this study was to investigate maternal risk factors for congenital syphilis. STUDY DESIGN: We conducted a case-control and descriptive analysis of 3 groups of live born infants and their mothers consisting of: group I (cases of congenital syphilis), group II (neonates without congenital syphilis whose mothers had been adequately treated for syphilis), and group III (random sample of newborn infants whose mothers have not had syphilis). Data were prospectively collected from personal interview and antenatal records. RESULTS: In the case-control study, including groups I and III, the maternal characteristics independently associated with congenital syphilis in the logistic regression were monthly per capita income under 30 US dollars (odds ratio [OR], 2.8; 95% confidence interval [CI], 1.1-7.4), single status (OR, 2.8; 95% CI, 1.1-7.8), and less than 6 prenatal visits (OR, 3.2; 95% CI, 1.3-8.1). Comparison between groups I and II (only mothers who have had syphilis) showed a strong protective association of prenatal care with congenital syphilis (OR, 0.05; 95% CI, 0.00-0.39). Additional analysis identified 2 separate profiles of maternal characteristics, one consisting of low socioeconomic status and the other of risk behaviors. Some women who had syphilis before or during pregnancy received adequate prenatal care and delivered infants without congenital syphilis. Most of these women had high-risk behaviors but they were, in general, less poor, older, and more educated than mothers of infants with congenital syphilis. CONCLUSIONS: Risk behaviors and low socioeconomic characteristics constituted 2 separate maternal profiles associated with congenital syphilis. Socioeconomic risk factors interfered more with prenatal care. To become more effective, the strategies for prevention of congenital syphilis should be targeted to each maternal profile.

Adult↗

Design of the leprosy component of the Brazilian BCG revaccination trial for assessing BCG effectiveness against leprosy in school children.

BACKGROUND: BCG vaccination confers protection against leprosy, and vaccination among household contacts has been recommended in Brazil. Nevertheless, vaccination of the entire community against leprosy is not advocated as leprosy has low incidence in most populations. Despite that, in Brazil, BCG vaccination is recommended among school children to prevent tuberculosis and this large scale vaccination may also affect the occurrence of leprosy, which led to investigations of its impact on leprosy in endemic areas of Brazil. OBJECTIVES: To estimate the effectiveness against leprosy of a dose of BCG vaccine given to school children in a population with a high coverage of neonatal BCG. Long term objectives are to compare the impact of vaccination among schoolchildren with the existing recommendation to vaccinate household contacts of leprosy. STUDY DESIGN: Cluster randomized controlled field trial with no placebo. STUDY POPULATION: Children aged 7 to 14 years attending state schools with high coverage of neonatal BCG. METHODS: 286 state schools in the city of Manaus, Brazil, were randomized to receive BCG or not. Identifying information was collected for 152,438 school children, of whom 72,980 are in intervention schools. BCG vaccination was given intradermically to children in schools allocated to vaccination. Follow-up relies on ascertainement of cases diagnosed at the health services and notified to the reference center for leprosy.

Adolescent↗

Neonatal BCG protection against leprosy: a study in Manaus, Brazilian Amazon.

There is clear evidence that BCG protects against leprosy, but cross-immunity with environmental mycobacteria can interfere with vaccination protection. Some have cast doubts whether BCG vaccination can offer a significant impact against leprosy in the Brazilian Amazon, which is an endemic area for leprosy and with a high prevalence of environmental mycobacteria. This study was designed to estimate the vaccine effectiveness of neonatal BCG against leprosy in Amazon region, in Brazil. This is a cohort study nested in a randomized community trial. The study had two main results. First, neonatal BCG vaccination in Brazilian Amazon elicited protection of 74% (95% CI 57-86) against all forms of leprosy cases. Second, the highest protection was observed for multibacillary cases, 93% (95% CI 71-98). It is concluded that the study provides evidence that neonatal BCG may have an important and overlooked impact on the occurrence and transmission of leprosy, maybe even more in the future when the cohort which received a high coverage of BCG reaches the age of high incidence of leprosy.

Adolescent↗

Guillain-Barré syndrome associated with Campylobacter jejuni infection in England, 2000-2001.

Guillain-Barré syndrome (GBS) is a rare but serious complication of infectious intestinal disease due to Campylobacter jejuni. To date, estimates of the burden of C. jejuni-associated GBS have been based on limited data regarding the proportion of GBS attributable to this pathogen. In this paper, we combine data obtained from Sweden and a large study of infectious intestinal disease with routine and surveillance data from England to estimate the number and proportion of GBS cases attributable to C. jejuni. We estimate that, between 1 April 2000 and 31 March 2001, symptomatic C. jejuni infection was responsible for 157 cases of GBS, constituting approximately 15% of all GBS cases in England.

Campylobacter Infections↗

BCG (Bacille of Calmette-Guérin) revaccination leads to improved in vitro IFN-gamma response to mycobacterial antigen independent of tuberculin sensitization in Brazilian school-age children.

Tuberculin skin test (TST) response and cytokine production in finger stab-derived whole blood cultures from 136 BCG scar-positive school-age children were evaluated before and after BCG revaccination. Fifty-four percent of the children increased in vitro production of IFN-gamma after revaccination, and this increase was highly significant for previously unresponsive children (P<0.0001). No correlation was found between TST response and cytokine production. Our data suggest that the in vitro IFN-gamma response to mycobacterial antigens can be boosted by BCG revaccination and may contribute to the search of correlates of protection to be used for the evaluation of new mycobacterial vaccines.

Antigens, Bacterial↗

Reduced risk of atopy among school-age children infected with geohelminth parasites in a rural area of the tropics.

BACKGROUND: Childhood infections might protect against the expression of atopy. Geohelminths are among the most prevalent infections of childhood and might contribute to the low prevalence of allergic disease reported from rural areas of the tropics. OBJECTIVE: We sought to establish whether geohelminth infections protect against atopy and to explore whether this protection is dependent on infection chronicity. METHODS: The risk of atopy (measured by means of allergen skin test reactivity) associated with active geohelminth infections (measured by means of the presence of eggs in stool samples) or with chronic geohelminth infections (measured by means of high levels [>/=3564 IU/mL] of total serum IgE or the presence of detectable anti-Ascaris lumbricoides IgG4 antibodies) was investigated in an analytic cross-sectional study conducted among school-age children attending rural schools in Pichincha Province in Ecuador. RESULTS: A total of 2865 children aged 5 to 19 years from 55 schools was examined. Active infection with any geohelminth and infections with A lumbricoides or Ancylostoma duodenale were associated with significant protective effects against allergen skin test reactivity. Children with the highest levels of total IgE or with anti-A lumbricoides IgG4 antibodies were protected against skin test reactivity also, and the protective effects of high IgE or anti-A lumbricoides IgG4 and or active geohelminth infections were statistically independent. CONCLUSION: Active infections with geohelminth parasites and the presence of serologic markers of chronic infections (high levels of total serum IgE or anti-A lumbricoides IgG4) are independent protective factors against allergen skin test reactivity among school-age children living in an endemic region of the rural tropics.

Adolescent↗

The study of infectious intestinal disease in England: what risk factors for presentation to general practice tell us about potential for selection bias in case-control studies of reported cases of diarrhoea.

BACKGROUND: Cases reported to national surveillance systems commonly form the sampling frame for population-based case-control studies of infectious intestinal diseases (IID). However, reported cases represent a minority of all cases in the population, differ systematically from unreported cases, and their use in case-control studies could introduce biases. Case reporting is a selective process involving multiple stages, the first of which requires presentation by a symptomatic person to the health services. Factors affecting a person's likelihood of presentation will thus affect the characteristics of reported cases. METHODS: Data from a large study of IID in England were used to investigate factors influencing presentation to a general practitioner (GP) following an episode of IID. Multivariable logistic regression was performed, comparing GP presenters with non-presenters. Explanatory variables used were illness severity, recent foreign travel and socioeconomic indicators. RESULTS: Severe illness (OR = 12.54, 95% CI: 7.58-20.74), recent foreign travel (OR = 2.4, 95% CI: 1.39-4.14), leaving full-time education at an earlier age (OR = 2.06, 95% CI: 1.22-3.50) and housing categories representing lower socioeconomic status (SES) were all independently associated with GP presentation. CONCLUSIONS: Case reporting to national surveillance is shaped by complex biological and social factors, of which illness severity appears to be the most important. Results from case-control studies comparing cases of IID identified by surveillance with population controls are likely to generalize mainly to cases severe enough to be reported. Controlling for educational and SES (mostly housing) is required.

Acute Disease↗

Tuberculin reactivity in a population of schoolchildren with high BCG vaccination coverage.

OBJECTIVE: To investigate the influence of BCG vaccination or revaccination on tuberculin skin test reactivity, in order to guide the correct interpretation of this test in a setting of high neonatal BCG vaccination coverage and an increasing BCG revaccination coverage at school age. METHODS: We conducted tuberculin skin testing and BCG scar reading in 1 148 children aged 7-14 years old in the city of Salvador, Bahia, Brazil. We measured the positive effect of the presence of one or two BCG scars on the proportion of tuberculin skin test results above different cut-off levels (induration sizes of > or = 5 mm, > or = 10 mm, and > or = 15 mm) and also using several ranges of induration size (0, 1-4, 5-9, 10-14, and > or = 15 mm). We also measured the effects that age, gender, and the school where the child was enrolled had on these proportions. RESULTS: The proportion of tuberculin results > or = 10 mm was 14.2% (95% confidence interval (CI) = 8.0%-20.3%) for children with no BCG scar, 21.3% (95% CI = 18.5%-24.1%) for children with one BCG scar, and 45.0% (95% CI = 32.0%-58.0%) for children with two BCG scars. There was evidence for an increasing positive effect of the presence of one and two BCG scars on the proportion of results > or = 5 mm and > or = 10 mm. Similarly, there was evidence for an increasing positive effect of the presence of one and two scars on the proportion of tuberculin skin test results in the ranges of 5-9 mm and of 10-14 mm. The BCG scar effect on the proportion of results > or = 5 mm and > or = 10 mm did not vary with age. There was no evidence for BCG effect on the results > or = 15 mm. CONCLUSIONS: In Brazilian schoolchildren, BCG-induced tuberculin reactivity is indistinguishable, for results under 15 mm, from reactivity induced by Mycobacterium tuberculosis infection. BCG revaccination at school age increases the degree of BCG-induced tuberculin reactivity found among schoolchildren. This information should be taken into account in tuberculin skin test surveys intended to estimate M. tuberculosis prevalence or to assess transmission patterns as well as in tuberculin skin testing of individuals used as an auxiliary tool in diagnosing tuberculosis. Taking this information into consideration is especially important when there is increasing BCG revaccination coverage.

Adolescent↗

Indoor and peridomestic transmission of American cutaneous leishmaniasis in northwestern Argentina: a retrospective case-control study.

A case-control study was carried out during 1990-1994 to identify risk factors associated with American cutaneous leishmaniasis (ACL) in Santiago del Estero, Argentina. The study subjects consisted of 171 cases and 308 controls matched by age, sex, and place of residence. The analysis was performed by conditional logistic regression. Risk factors found to be significantly associated with ACL were related to indoor transmission (few rooms in the house, dirt floor, and a permanent opening in lieu of a window); peridomestic transmission (presence of a pond or woodland within 150 m of the house and an agricultural area within 200 m of the house); and human behavior (sleeping in the backyard, collecting water, bathing, and performing agricultural activities). Most transmission appears to have occurred indoors and in the peridomicile. These environments should be included in further research and control policies.

Adolescent↗

Evaluation of adverse effects of vaccines: the case-control approach.

When the hypothesis of a link between vaccination and a possible adverse outcome arises, further investigation is required to confirm or refute the suspicion. Given the rarity of most serious adverse effects, a case-control approach will often be chosen. This paper discusses aspects of the design, analysis and interpretation of case-control studies to evaluate vaccine adverse effects. Potential biases (and how to minimise such biases) in the selection of cases and assessment of vaccine exposure and the potential for confounding are discussed. Finally the increasing use of electronic databases in the evaluation of vaccine adverse effects is considered.

Case-Control Studies↗

Outbreak of aseptic meningitis and mumps after mass vaccination with MMR vaccine using the Leningrad-Zagreb mumps strain.

Data from routine surveillance during two mass immunisation campaigns (MIC) with Measles-mumps-rubella (MMR)vaccine using Leningrad-Zagreb mumps strain in two states in Brazil were analysed to estimate the risk of vaccine-related meningitis and mumps. Increase in the incidence of the two diseases was observed in both states, 3 weeks after the vaccination campaigns. The estimated number of doses applied per one case of vaccine-related meningitis ranged from 6199 (95% CI: 4854-8058) to 19,247 (95% CI: 12,648-29,513) depending on the diagnostic criteria used and state. It was 300 doses (95% CI: 286-317) for each case of mumps. The implications for vaccination policy are discussed.

Child↗

Morbidity and nutritional impairment in relation to CD4 count in a Zambian population with high HIV prevalence.

The HIV epidemic has greatly increased morbidity in many African cities and severe undernutrition is a prominent feature of the clinical presentation. However, there is little information about the relationship of morbidity or nutritional status to immune damage at a population level. We report a cross-sectional study of morbidity and nutritional status in relation to CD4 count in an impoverished urban community in Lusaka, Zambia, at enrollment into a longitudinal study. Over a 2 month period in 1999, 261 (52%) of 506 adults resident in one area were interviewed and examined. Of 186 adults who consented to testing, 33 (51%) of 65 who were HIV seropositive reported symptoms of disease compared to 39 (32%) of 121 who were HIV seronegative (OR 2.2, 95%CI 1.1-4.2; P=0.02). Peripheral blood CD4 counts in HIV seronegative individuals were broadly similar to norms in developed countries, but 8 (7%) had CD4 counts below 500 cells/microl. Morbidity in HIV seropositive adults was dominated by tuberculosis (n=11), other respiratory infections (5) or persistent diarrhoea (4), and affected individuals had a wide range of CD4 counts. Nutritional impairment was evident in HIV seropositive adults with clinical evidence of opportunistic infection (OI), not those with asymptomatic HIV infection. Unexpectedly, we also noted that systolic blood pressure was reduced progressively in HIV infection and in those with OI. In conclusion, HIV-related morbidity was dominated by a small number of treatable infectious diseases occurring over a wide range of CD4 count. Nutritional impairment was associated with OI.

Adult↗

Design of the Brazilian BCG-REVAC trial against tuberculosis: a large, simple randomized community trial to evaluate the impact on tuberculosis of BCG revaccination at school age.

This paper describes the design and baseline results of a large and simple randomized controlled trial of the protection against tuberculosis of a dose of Bacillus Calmette Guerin (BCG) vaccination given to school children in a population with a high coverage of neonatal BCG (The Brazilian BCG-REVAC trial). The study started in 1996 and is a pair-matched and stratified-cluster randomized controlled trial with no placebo. The study population consists of children aged 7-14 years enrolled in 763 state schools from the cities of Salvador and Manaus, Brazil. Schools were the unit of randomization. Identifying information was collected for 354,708 school children. The final study population, after exclusions on the basis of age, BCG scar readings and absence from school on the day of the study visit, consists of 242,401 children, of whom 125,403 are in intervention schools. Follow-up relies on ascertainment of cases diagnosed at the health services and notified to the tuberculosis control program surveillance system. Blindness is guaranteed during linkage and validation of cases. Analysis is planned for the next 12 months, where efficacy will be estimated by calculating incidence of tuberculosis in the vaccine and control groups, taking into consideration the cluster design. The intervention studied, a second BCG vaccination, is widely used, although the World Health Organization does not recommend it on the basis of absence of evidence of protection or lack of protection. The results of the trial will make it possible for BCG revaccination practice to be informed by evidence. This is an example of a large simple and relatively inexpensive effectiveness trial, resulting from good collaboration between academia and health and education services enabling developing countries to define policies that are relevant for their reality.

Adolescent↗

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.

Asperger Syndrome↗