Andres G. Lescano

Effects of stunting, diarrhoeal disease, and parasitic infection during infancy on cognition in late childhood: a follow-up study

BACKGROUND Chronic malnutrition during infancy, marked by stunting, has been associated with poor cognitive function. We assessed the effect of stunting, diarrhoeal disease, and parasitic infections during infancy on cognitive function in late childhood. METHODS We followed up from birth to 2 years, a cohort of 239 Peruvian children for anthropometrics, stool samples, and diarrhoeal status. At 9 years of age, we assessed cognitive function in 143 (69%) with the full-scale intelligence quotient of the Wechsler intelligence scale for children-revised (WISC-R). Findings All findings were adjusted for socioeconomic status and schooling; in addition, findings related to diarrhoea prevalence, Giardia lamblia, and Cryptosporidium parvum were adjusted for severe stunting. During the first 2 years of life, 46 (32%) of 143 children were stunted. Children with severe stunting in the second year of life scored 10 points lower on the WISC-R test (95% CI 2.4--17.5) than children without severe stunting. Children with more than one episode of G lamblia per year scored 4.1 points (0.2--8.0) lower than children with one episode or fewer per year. Neither diarrhoea prevalence nor Cparvum infection was associated with WISC-R scores. INTERPRETATION Malnutrition in early childhood, indexed by stunting, and potentially G lamblia, are associated with poor cognitive function at age 9 years. If the observed associations are causal, then intervention programmes designed to prevent malnutrition and G lamblia early in life could lead to significant improvement in cognitive function of children in similar lower-income communities throughout the less-developed world.

Risk factors for burns in children: crowding, poverty, and poor maternal education

Objective: To characterize the presentation of burns in children and risk factors associated with their occurrence in a developing country as a basis for future prevention programs. Design: Case-control study. Setting: Burn unit of the National Institute of Child Health (Instituto Nacional de Salud del Niño) in Lima, Peru. Methods: A questionnaire was administered to all consenting guardians of children admitted to the burns (cases) and general medicine (controls) units during a period of 14 months. Guardians of patients were questioned regarding etiology of the injury, demographic and socioeconomic data. Results: 740 cases and controls were enrolled. Altogether 77.5% of the cases burns occurred in the patients home, with 67.8% in the kitchen; 74% were due to scalding. Most involved children younger than 5 years. Lack of water supply (odds ratio (OR) 5.2, 95% confidence interval (CI) 2.1 to 12.3), low income (OR 2.8, 95% CI 2.0 to 3.9), and crowding (OR 2.5, 95%CI 1.7 to 3.6) were associated with an increased risk. The presence of a living room (OR 0.6, 95% CI 0.4 to 0.8) and better maternal education (OR 0.6, 95% CI 0.5 to 0.9) were protective factors. Conclusions: To prevent burns interventions should be directed to low socioeconomic status groups; these interventions should be designed accordingly to local risk factors.

Perilesional brain oedema and seizure activity in patients with calcified neurocysticercosis: a prospective cohort and nested case–control study

BACKGROUND Cysticercosis due to Taenia solium is a cause of adult-acquired seizures and epilepsy even in patients with only calcified larval cysts. Transient perilesional brain oedema is seen around the calcified foci but its importance, association with seizures, incidence, and pathophysiology are unknown. METHODS 110 patients with only calcified lesions and a history of seizures or severe headaches were followed prospectively in a cohort design to assess the incidence of seizure relapse. In a nested case-control substudy, perilesional oedema was assessed by MRI at the time of seizure in symptomatic patients and in matched asymptomatic controls taken from the study population. FINDINGS Between November, 1999, and December, 2006, 29 patients had an incident seizure during a median follow up of 32.33 (SD 19.99) months, with an estimated 5-year seizure incidence of 36% (95% CI 25% to 49%). 24 of 29 (83%) patients with seizure relapse had an MRI evaluation within 5 days of the event; perilesional oedema was seen in 12 patients (50%) compared with two (9%) of 23 asymptomatic matched controls. INTERPRETATION Perilesional oedema is common and associated with episodic seizure activity in patients with calcified neurocysticercosis. Our findings are probably representative of symptomatic patients in regions where T solium neurocysticercosis is endemic and suggest a unique and possibly preventable cause of seizures in this population.

Epidemiologic differences between cyclosporiasis and cryptosporidiosis in Peruvian children.

We compared the epidemiologic characteristics of cyclosporiasis and cryptosporidiosis in data from a cohort study of diarrhea in a periurban community near Lima, Peru. Children had an average of 0.20 episodes of cyclosporiasis/year and 0.22 episodes of cryptosporidiosis/year of follow-up. The incidence of cryptosporidiosis peaked at 0.42 for 1-year-old children and declined to 0.06 episodes/child-year for 5- to 9-year-old children. In contrast, the incidence of cyclosporiasis was fairly constant among 1- to 9-year-old children (0.21 to 0.28 episodes/child-year). Likelihood of diarrhea decreased significantly with each episode of cyclosporiasis; for cryptosporidiosis, this trend was not statistically significant. Both infections were more frequent during the warm season (December to May) than the cooler season (June to November). Cryptosporidiosis was more frequent in children from houses without a latrine or toilet. Cyclosporiasis was associated with ownership of domestic animals, especially birds, guinea pigs, and rabbits.

Detection of Taenia solium Antigens and Anti–T. solium Antibodies in Paired Serum and Cerebrospinal Fluid Samples from Patients with Intraparenchymal or Extraparenchymal Neurocysticercosis

BACKGROUND Neurocysticercosis (NCC) is a frequent cause of epilepsy worldwide. Compared with the more common parenchymal brain cysts, extraparenchymal infections are difficult to manage and have a poor prognosis. Serological assays are used to detect circulating Taenia solium antigens or anti-T. solium antibodies in serum or cerebrospinal fluid (CSF) samples. There are no guidelines on whether to use serum or CSF specimens for a particular assay. METHODS We obtained paired serum and CSF samples from 91 patients with NCC (48 had intraparenchymal NCC, and 43 had extraparenchymal NCC) for detection of antibodies, using an enzyme-linked immunotransfer blot (EITB) assay, and antigens, using a monoclonal antibody-based enzyme-linked immunosorbent assay (ELISA). RESULTS For the intraparenchymal NCC group, the EITB assay yielded more true-positive results for serum samples, and the ELISA yielded slightly more true-positive results for CSF samples than for serum samples, but none of these differences were statistically significant. Most patients with calcified NCC were antibody positive but antigen negative. For extraparenchymal disease, all samples were antibody positive, and all but 2 were antigen positive, with most samples containing high antigen levels. CONCLUSIONS The sensitivity of antibody-detecting EITB assays is not increased through the use of CSF samples rather than serum samples. The antigen-detecting ELISA performed better for CSF samples than for serum samples, but for both specimen types it was less sensitive than the EITB assay. Active and inactive NCC are better differentiated from each other by the antigen-detecting ELISA, for both serum and CSF samples. High antigen levels suggest the presence of subarachnoid NCC.

A PfRH5-based vaccine is efficacious against heterologous strain blood-stage Plasmodium falciparum infection in aotus monkeys.

Summary Antigenic diversity has posed a critical barrier to vaccine development against the pathogenic blood-stage infection of the human malaria parasite Plasmodium falciparum. To date, only strain-specific protection has been reported by trials of such vaccines in nonhuman primates. We recently showed that P. falciparum reticulocyte binding protein homolog 5 (PfRH5), a merozoite adhesin required for erythrocyte invasion, is highly susceptible to vaccine-inducible strain-transcending parasite-neutralizing antibody. In vivo efficacy of PfRH5-based vaccines has not previously been evaluated. Here, we demonstrate that PfRH5-based vaccines can protect Aotus monkeys against a virulent vaccine-heterologous P. falciparum challenge and show that such protection can be achieved by a human-compatible vaccine formulation. Protection was associated with anti-PfRH5 antibody concentration and in vitro parasite-neutralizing activity, supporting the use of this in vitro assay to predict the in vivo efficacy of future vaccine candidates. These data suggest that PfRH5-based vaccines have potential to achieve strain-transcending efficacy in humans.

Syndromic Surveillance: Adapting Innovations to Developing Settings

The tools and strategies of syndromic surveillance, say the authors, hold promise for improving public health security in developing countries.

Taenia solium cysticercosis hotspots surrounding tapeworm carriers: Clustering on human seroprevalence but not on seizures

Background Neurocysticercosis accounts for 30%–50% of all late-onset epilepsy in endemic countries. We assessed the clustering patterns of Taenia solium human cysticercosis seropositivity and seizures around tapeworm carriers in seven rural communities in Peru. Methodology The presence of T. solium–specific antibodies was defined as one or more positive bands in the enzyme-linked immunoelectrotransfer blot (EITB). Neurocysticercosis-related seizures cases were diagnosed clinically and had positive neuroimaging or EITB. Principal Findings Eleven tapeworm carriers were identified by stool microscopy. The seroprevalence of human cysticercosis was 24% (196/803). Seroprevalence was 21% >50 m from a carrier and increased to 32% at 1–50 m (p = 0.047), and from that distance seroprevalence had another significant increase to 64% at the homes of carriers (p = 0.004). Seizure prevalence was 3.0% (25/837) but there were no differences between any pair of distance ranges (p = 0.629, Wald test 2 degrees of freedom). Conclusion/Significance We observed a significant human cysticercosis seroprevalence gradient surrounding current tapeworm carriers, although cysticercosis-related seizures did not cluster around carriers. Due to differences in the timing of the two outcomes, seroprevalence may reflect recent T. solium exposure more accurately than seizure frequency.

Species identification after treatment for human taeniasis

Identification of species of human tapeworms is crucial because the consequences of infection by Taenia solium and T saginata are very different. However, evacuation of species-identifiable tapeworms is uncommon and Taenia spp eggs are indistinguishable under the microscope. Treatment of taeniasis consists of niclosamide followed by a purgative. Recently, we adopted preniclosamide and postniclosamide electrolyte-polyethyleneglycol salt (EPS) purges to improve bowel cleaning. Retrospective comparison of traditional castor oil with EPS purge showed that recovery of the tapeworm scolex was significantly improved (20 of 68 vs none of 46, p=0.0001) in the EPS group. Furthermore, 42 of 68 (62%) individuals receiving EPS excreted identifiable gravid proglottids. EPS treatment helps the visual identification of Taenia spp.

Efficacy of combined antiparasitic therapy with praziquantel and albendazole for neurocysticercosis: A double-blind, randomised controlled trial

BACKGROUND Neurocysticercosis causes a substantial burden of seizure disorders worldwide. Treatment with either praziquantel or albendazole has suboptimum efficacy. We aimed to establish whether combination of these drugs would increase cysticidal efficacy and whether complete cyst resolution results in fewer seizures. We added an increased dose albendazole group to establish a potential effect of increased albendazole concentrations. METHODS In this double-blind, placebo-controlled, phase 3 trial, patients with viable intraparenchymal neurocysticercosis were randomly assigned to receive 10 days of combined albendazole (15 mg/kg per day) plus praziquantel (50 mg/kg per day), standard albendazole (15 mg/kg per day), or increased dose albendazole (22·5 mg/kg per day). Randomisation was done with a computer generated schedule balanced within four strata based on number of cysts and concomitant antiepileptic drug. Patients and investigators were masked to group assignment. The primary outcome was complete cyst resolution on 6-month MRI. Enrolment was stopped after interim analysis because of parasiticidal superiority of one treatment group. Analysis excluded patients lost to follow-up before the 6-month MRI. This trial is registered with ClinicalTrials.gov, number NCT00441285. FINDINGS Between March 3, 2010 and Nov 14, 2011, 124 patients were randomly assigned to study groups (41 to receive combined albendazole plus praziquantel [39 analysed], 43 standard albendazole [41 analysed], and 40 increased albendazole [38 analysed]). 25 (64%) of 39 patients in the combined treatment group had complete resolution of brain cysts compared with 15 (37%) of 41 patients in the standard albendazole group (rate ratio [RR] 1·75, 95% CI 1·10-2·79, p=0·014). 20 (53%) of 38 patients in the increased albendazole group had complete cyst resolution at 6-month MRI compared with 15 (37%) of 41 patients in the standard albendazole group (RR 1·44, 95% CI 0·87-2·38, p=0·151). No significant differences in adverse events were reported between treatment groups (18 in combined treatment group, 11 in standard albendazole group, and 19 in increased albendazole group). INTERPRETATION Combination of albendazole plus praziquantel increases the parasiticidal effect in patients with multiple brain cysticercosis cysts without increased side-effects. A more efficacious parasiticidal regime without increased treatment-associated side-effects should improve the treatment and long term prognosis of patients with neurocysticercosis. FUNDING National Institute of Neurological Disorders and Stroke (NINDS), National Institutes of Health.