Guillermo Gonzalvez

Effect of urbanisation on asthma, allergy and airways inflammation in a developing country setting

Background Asthma is a growing public health problem in developing countries. However, few studies have studied the role of urbanisation in this phenomenon. It was hypothesised that children living in a peri-urban setting in Peru have higher rates of asthma and allergy than rural counterparts. Methods 1441 adolescents aged 13–15 years were enrolled from two settings: a peri-urban shanty town in Lima (n=725) and 23 rural villages in Tumbes (n=716). Participants filled in questionnaires on asthma and allergy symptoms, environmental exposures and sociodemographics, and underwent spirometry, and exhaled nitric oxide (eNO) and allergy skin testing. Indoor particulate matter (PM) concentrations were measured in 170 households. Results Lima adolescents had higher rates of lifetime wheezing (22% vs 10%), current asthma symptoms (12% vs 3%) and physician-diagnosed asthma (13% vs 2%; all p <0.001). Current rhinitis (23% vs 12%), eczema (12% vs 0.4%), atopy (56% vs 38%), personal history of cigarette smoking (7.4% vs 1.3%) and mean indoor PM (31 vs 13 μg/m3) were also higher in Lima (all p <0.001). The peri-urban environment of Lima was associated with a 2.6-fold greater odds (95% CI 1.3 to 5.3) of asthma in multivariable regression. Forced expiratory volumes were higher and FEV1/FVC (forced expiratory volume in 1 s/forced vital capacity) ratios were lower in Lima (all p <0.001). Higher eNO values in Lima (p <0.001) were attributable to higher rates of asthma and atopy. Conclusions Peri-urban adolescents had more asthma, atopy and airways inflammation and were exposed to more indoor pollution. The findings provide evidence of the risks posed to lung health by peri-urban environments in developing countries.

Strategies for the elimination of taeniasis/cysticercosis

Advances in the field of neurocysticercosis continue to shape our understanding of the disease and our efforts to control it. Several attempts have been made to eradicate the disease with active interventions such as changing domestic pig-raising practices, mass chemotherapy of porcine cysticercosis and taeniasis, selective detection and treatment of taeniasis, and community health education. Moreover, ongoing progress in the diagnosis of taeniasis and the development of a porcine vaccine against cysticercosis in Australia, Mexico and Peru has yielded at least one effective vaccine that is currently available. Thus far, however, attempted interventions have only been successful in temporarily disrupting transmission of the disease. Controlled data on the efficacy and acceptability of the different interventions is urgently needed to provide a base-line schematic for intervention which could later be tailored to each particular endemic scenario.

Epilepsy and neurocysticercosis: an incidence study in a Peruvian rural population.

Background: Epilepsy is a serious neurological disorder and neurocysticercosis (NCC), the central nervous system infection by the larvae of Taenia solium, is the main cause of acquired epilepsy in developing countries. NCC is becoming more frequent in industrialized countries due to immigration from endemic areas. Previously reported epilepsy incidences range from 30 to 50/100,000 people in industrialized countries and 90 to 122/100,000 people in developing countries. Objectives: To determine the incidence of epilepsy in a cysticercosis endemic area of Peru.Methods: A screening survey for possible seizure cases was repeated biannually in this cohort for a period of 5 years (1999–2004) using a previously validated questionnaire. All positive respondents throughout the study were examined by a trained neurologist in the field to confirm the seizure. If confirmed, they were offered treatment, serological testing, neuroimaging (CT scans and MRI) and clinical follow-up. Results: The cohort study comprised 817 individuals. The overall epilepsy incidence rate was 162.3/100,000 person-years, and for epileptic seizures, 216.6/100,000 person-years. Out of the 8 individuals who had epileptic seizures, 4 had markers for NCC (neuroimaging and/or serology). Conclusion: The incidence of epilepsy in this area endemic for cysticercosis is one of the highest reported worldwide.

Elimination of Taenia solium Transmission in Northern Peru

BACKGROUND Taeniasis and cysticercosis are major causes of seizures and epilepsy. Infection by the causative parasite Taenia solium requires transmission between humans and pigs. The disease is considered to be eradicable, but data on attempts at regional elimination are lacking. We conducted a three-phase control program in Tumbes, Peru, to determine whether regional elimination would be feasible. METHODS We systematically tested and compared elimination strategies to show the feasibility of interrupting the transmission of T. solium infection in a region of highly endemic disease in Peru. In phase 1, we assessed the effectiveness and feasibility of six intervention strategies that involved screening of humans and pigs, antiparasitic treatment, prevention education, and pig replacement in 42 villages. In phase 2, we compared mass treatment with mass screening (each either with or without vaccination of pigs) in 17 villages. In phase 3, we implemented the final strategy of mass treatment of humans along with the mass treatment and vaccination of pigs in the entire rural region of Tumbes (107 villages comprising 81,170 people and 55,638 pigs). The effect of the intervention was measured after phases 2 and 3 with the use of detailed necropsy to detect pigs with live, nondegenerated cysts capable of causing new infection. The necropsy sampling was weighted in that we preferentially included more samples from seropositive pigs than from seronegative pigs. RESULTS Only two of the strategies implemented in phase 1 resulted in limited control over the transmission of T. solium infection, which highlighted the need to intensify the subsequent strategies. After the strategies in phase 2 were implemented, no cyst that was capable of further transmission of T. solium infection was found among 658 sampled pigs. One year later, without further intervention, 7 of 310 sampled pigs had live, nondegenerated cysts, but no infected pig was found in 11 of 17 villages, including all the villages in which mass antiparasitic treatment plus vaccination was implemented. After the final strategy was implemented in phase 3, a total of 3 of 342 pigs had live, nondegenerated cysts, but no infected pig was found in 105 of 107 villages. CONCLUSIONS We showed that the transmission of T. solium infection was interrupted on a regional scale in a highly endemic region in Peru. (Funded by the Bill and Melinda Gates Foundation and others.).

Neurocysticercosis as a Cause of Epilepsy and Seizures in Two Community-Based Studies in a Cysticercosis-Endemic Region in Peru

Background The prevalence of epilepsy added to inadequate treatment results in chronic morbidity and considerable mortality in poor populations. Neurocysticercosis (NCC), a helminthic disease of the central nervous system, is a leading cause of seizures and epilepsy in most of the world. Methods Taking advantage of a cysticercosis elimination program, we performed two community-based cross-sectional studies between 2006 and 2007 in 58 rural communities (population 20,610) to assess the prevalence and characteristics of epilepsy and epileptic seizures in this endemic region. Serological and computed tomography (CT) data in individuals with epilepsy were compared to previous surveys in general population from the same region. Principal findings In two surveys, 17,450 individuals were evaluated. Lifetime prevalence of epilepsy was 17.25/1000, and prevalence of active epilepsy was 10.8/1000 inhabitants. The prevalence of epilepsy increased after age 25 years and dropped after age 45. Only 24% (45/188) of patients with active epilepsy were taking antiepileptic drugs, all at sub-therapeutic doses. Antibodies to cysticercosis were found in approximately 40% of individuals with epilepsy in both studies. In one survey only individuals presenting strong antibody reactions were significantly associated with having epilepsy (OR 5.74; p<0.001). In the second, the seroprevalence as well as the proportion presenting strong antibody reactions were both significantly higher in individuals with epilepsy (OR 2.2 and 4.33, respectively). Brain CT showed NCC-compatible images in 109/282 individuals with epilepsy (39%). All individuals with viable parasites on CT were seropositive. Conclusion The prevalence of epilepsy in this cysticercosis endemic region is high and NCC is an important contributor to it.

Geographic Correlation between Tapeworm Carriers and Heavily Infected Cysticercotic Pigs

Background Neurocysticercosis is a leading cause of preventable epilepsy in the developing world. Sustainable community-based interventions are urgently needed to control transmission of the causative parasite, Taenia solium. We examined the geospatial relationship between live pigs with visible cysticercotic cysts on their tongues and humans with adult intestinal tapeworm infection (taeniasis) in a rural village in northern Peru. The objective was to determine whether tongue-positive pigs could indicate high-risk geographic foci for taeniasis to guide targeted screening efforts. This approach could offer significant benefit compared to mass intervention. Methods We recorded geographic coordinates of all village houses, collected stool samples from all consenting villagers, and collected blood and examined tongues of all village pigs. Stool samples were processed by enzyme-linked immunosorbent assay (ELISA) for presence of Taenia sp. coproantigens indicative of active taeniasis; serum was processed by enzyme-linked immunoelectrotransfer blot for antibodies against T. solium cysticercosis (EITB LLGP) and T. solium taeniasis (EITB rES33). Findings Of 548 pigs, 256 (46.7%) were positive for antibodies against cysticercosis on EITB LLGP. Of 402 fecal samples, 6 (1.5%) were positive for the presence of Taenia sp. coproantigens. The proportion of coproantigen-positive individuals differed significantly between residents living within 100-meters of a tongue-positive pig (4/79, 5.1%) and residents living >100 meters from a tongue-positive pig (2/323, 0.6%) (p = 0.02). The prevalence of taeniasis was >8 times higher among residents living within 100 meters of a tongue-positive pig compared to residents living outside this range (adjusted PR 8.1, 95% CI 1.4–47.0). Conclusions Tongue-positive pigs in endemic communities can indicate geospatial foci in which the risk for taeniasis is increased. Targeted screening or presumptive treatment for taeniasis within these high-risk foci may be an effective and practical control intervention for rural endemic areas.

Epidemiología y control de la cisticercosis en el Perú

Neurocysticercosis, the infection of the human central nervous system by the larval stage of the cestode Taenia solium, is an important cause of epilepsy and other neurological manifestations in Peru and most developing countries. Since 1987, the Cysticercosis Working Group in Peru has performed a series of epidemiological studies which led to estimate the impact and to better understand the transmission of Taenia solium. This information was later applied to the design and execution of a control program in Tumbes, in the Northern Coast of Peru. This paper reviews the main epidemiological findings, as well as the conceptual framework of the elimination program and the tools used. Advances in the control of taeniasis/cysticercosis in our country open the road towards its elimination and potential eradication.

The Peru Urban versus Rural Asthma (PURA) Study: methods and baseline quality control data from a cross-sectional investigation into the prevalence, severity, genetics, immunology and environmental factors affecting asthma in adolescence in Peru

Objectives According to a large-scale international survey, Peru has one of the highest prevalences of asthma worldwide; however, data from this survey were limited to participants from urban Lima. The authors sought to characterise the epidemiology of asthma in Peru in two regions with disparate degrees of urbanisation. In this manuscript, the authors summarise the study design and implementation. Design A cross-sectional study. Participants Using census data of 13–15-year-old adolescents from two communities in Peru, the authors invited a random sample of participants in Lima (n=725) and all adolescents in Tumbes (n=716) to participate in our study. Primary and secondary outcome measures The authors asked participants to complete a questionnaire on asthma symptoms, environmental exposures and socio-demographics and to undergo spirometry before and after bronchodilator, skin allergy testing and exhaled nitric oxide testing. The authors obtained blood samples for haematocrit, total IgE levels, vitamin D levels and DNA in all participants and measured indoor particulate matter concentrations for 48 h in a random subset of 70–100 households at each site. Results Of 1851 eligible participants, 1441 (78%) were enrolled and 1159 (80% of enrolled) completed all physical tests. 1283 (89%) performed spirometry according to standard guidelines, of which 86% of prebronchodilator tests and 92% of postbronchodilator tests were acceptable and reproducible. 92% of allergy skin tests had an adequate negative control. The authors collected blood from 1146 participants (79%) and saliva samples from 148 participants (9%). Overall amounts of DNA obtained from blood or saliva were 25.8 μg, with a 260/280 ratio of 1.86. Conclusions This study will contribute to the characterisation of a variety of risk factors for asthma, including urbanisation, total IgE levels, vitamin D levels and candidate genes, in a resource-poor setting. The authors present data to support high quality of survey, allergic, spirometric and genetic data collected in our study.

High Prevalence of Asymptomatic Neurocysticercosis in an Endemic Rural Community in Peru.

Background Neurocysticercosis is a common helminthic infection of the central nervous system and an important cause of adult-onset epilepsy in endemic countries. However, few studies have examined associations between neurologic symptoms, serology and radiographic findings on a community-level. Methodology We conducted a population-based study of resident’s ≥2 years old in a highly endemic village in Peru (pop. 454). We applied a 14 -question neurologic screening tool and evaluated serum for antibodies against Taenia solium cysticercosis using enzyme-linked immunoelectrotransfer blot (LLGP-EITB). We invited all residents ≥18 years old to have non-contrast computerized tomography (CT) of the head. Principal findings Of the 385 residents who provided serum samples, 142 (36.9%) were seropositive. Of the 256 residents who underwent CT scan, 48 (18.8%) had brain calcifications consistent with NCC; 8/48 (17.0%) reported a history of headache and/or seizures. Exposure to T. solium is very common in this endemic community where 1 out of 5 residents had brain calcifications. However, the vast majority of people with calcifications were asymptomatic. Conclusion This study reports a high prevalence of NCC infection in an endemic community in Peru and confirms that a large proportion of apparently asymptomatic residents have brain calcifications that could provoke seizures in the future.

El Niño adversely affected childhood stature and lean mass in northern Peru

BackgroundEl Niño is responsible for natural disasters and infectious disease outbreaks worldwide. During the 1997–1998 El Niño, northern Peru endured extreme rainfall and flooding. Since short stature may occur as a result of undernutrition or repeated infections during childhood, both of which are highly prevalent during natural disasters, we sought to determine if the 1997–1998 El Niño had an adverse effect on stature and body composition a decade later. In 2008–2009, we measured height, weight, and bioimpedance in a random sample of 2,095 children born between 1991 and 2001 in Tumbes, Peru.ResultsHeight-for-age increased by 0.09 SD/year of birth between 1991 and 1997 (P < 0.001), indicating overall improvements in health over time in the study area; however, this rate fell to 0.04 SD/year of birth during and shortly after El Niño, less than half the rate prior to El Niño (P = 0.046). Height shortfalls were even greater in children residing in households most likely to be flooded after El Niño. Any improvement over time was completely blunted and became negative in children living in households with flood likelihoods of ≥7% (P = 0.001). In the subset of 912 children with bioimpedance measurements, those born after the onset of El Niño had less lean mass (P < 0.001), whereas fat mass was unaffected (P = 0.48).ConclusionsChildren born during and after 1997–1998 El Niño were on average shorter and had less lean mass for their age and sex than expected had El Niño not occurred. The effects of El Niño on health are long lasting and, given its cyclical nature, may continue to negatively impact future generations.