Paredes-Olortegui M.,Asociacion Benefica PRISMA |
Connolly E.,Infant Bacterial Therapeutics AB N A
American Journal of Tropical Medicine and Hygiene | Year: 2014
Clinical research on probiotics presents challenging issues for researchers, regulators, and funding agencies, and these issues become more complex when United States federally funded research is conducted outside the United States. Here, we describe the design and results of a Phase I safety study of Lactobacillus reuteri DSM 17938 conducted as a community-based trial under the Food and Drug Administration Investigative New Drug (FDA IND) program in a small town in the Peruvian Amazon. Forty-five healthy adults 18 to 65 years of age were randomized in a 2:1 ratio to receive either Lactobacillus reuteri 108 organisms once daily for 5 days or an identical appearing placebo. Results showed no evidence of invasive infection resulting from probiotic administration and no differences between groups. Although we encountered several challenges in conducting an FDA-approved safety trial in this setting, the rigorously collected contextually relevant data will be very valuable to support later Phase II/III studies of L. reuteri for use in similar settings. Copyright © 2014 by The American Society of Tropical Medicine and Hygiene.
Levy M.Z.,University of Pennsylvania |
Small D.S.,University of Pennsylvania |
Vilhena D.A.,University of Pennsylvania |
Bowman N.M.,Johns Hopkins Hospital |
And 6 more authors.
PLoS Computational Biology | Year: 2011
Vector-borne transmission of Chagas disease has become an urban problem in the city of Arequipa, Peru, yet the debilitating symptoms that can occur in the chronic stage of the disease are rarely seen in hospitals in the city. The lack of obvious clinical disease in Arequipa has led to speculation that the local strain of the etiologic agent, Trypanosoma cruzi, has low chronic pathogenicity. The long asymptomatic period of Chagas disease leads us to an alternative hypothesis for the absence of clinical cases in Arequipa: transmission in the city may be so recent that most infected individuals have yet to progress to late stage disease. Here we describe a new method, epicenter regression, that allows us to infer the spatial and temporal history of disease transmission from a snapshot of a population's infection status. We show that in a community of Arequipa, transmission of T. cruzi by the insect vector Triatoma infestans occurred as a series of focal micro-epidemics, the oldest of which began only around 20 years ago. These micro-epidemics infected nearly 5% of the community before transmission of the parasite was disrupted through insecticide application in 2004. Most extant human infections in our study community arose over a brief period of time immediately prior to vector control. According to our findings, the symptoms of chronic Chagas disease are expected to be absent, even if the strain is pathogenic in the chronic phase of disease, given the long asymptomatic period of the disease and short history of intense transmission. Traducción al español disponible en Alternative Language Text S1/A Spanish translation of this article is available in Alternative Language Text S1.
Paredes Olortegui M.,Asociacion Benefica Prisma |
Escobedo K.,Us Naval Medical Research Center Unit 6 |
Florin D.,Us Naval Medical Research Center Unit 6 |
Rengifo Pinedo S.,Asociacion Benefica Prisma |
And 6 more authors.
Malaria Journal | Year: 2013
Background: Plasmodium vivax and Plasmodium falciparum cause a significant illness burden in Peru. Anopheline indices for populated communities in the peri-Iquitos region of Loreto have been reported to be remarkably low, with entomological inoculation rates (EIR) estimated at one to 30 infective bites per year based on a few studies in close proximity to the urban centre of Iquitos and surrounding deforested areas. Local reports suggest that a large number of the reported cases are contracted outside of populated communities in undeveloped riverine areas frequented by loggers and fishermen. Methods. To better understand vectorial capacity in suspected high malaria transmission zones in a rural district near Iquitos, Peru, mosquito collections were conducted at different points in the seasonality of malaria transmission in 21 sites frequented by occupational labourers. Prevalence of Plasmodium spp in vectors was determined by circumsporozoite protein ELISA on individual mosquitoes. Slide surveillance was performed for humans encountered in the zone. Results: In total, of 8,365 adult female mosquitoes examined, 98.5% were identified as Anopheles darlingi and 117 (1.4%) tested positive for sporozoites (P. falciparum, P. vivax VK210 or P. vivax VK247). Measured human biting rates at these sites ranged from 0.102 to 41.13 bites per person per hour, with EIR values as high as 5.3 infective bites per person per night. Six percent of the 284 blood films were positive for P. vivax or P. falciparum; however, 88% of the individuals found to be positive were asymptomatic at the time of sampling. Conclusions: The results of this study provide key missing indices of prominent spatial and temporal heterogeneity of vectorial capacity in the Amazon Basin of Peru. The identification of a target human subpopulation as a principal reservoir and dispersion source of Plasmodium species has important implications for vaccine development and the delivery of effective targeted malaria control strategies. © 2013 Parker et al.; licensee BioMed Central Ltd.
Olortegui M.P.,Asociacion Benefica PRISMA
Current Opinion in Infectious Diseases | Year: 2010
Purpose of review: Shigella is the principal cause of clinical dysentery and an important cause of morbidity and mortality among children in impoverished regions. The purpose of this review is to present key findings in the areas of epidemiology, disease control, and treatment of shigellosis. Recent findings: Recent research activity has advanced the understanding of the epidemiology and host-pathogen interactions. Increased investment and activity in the area of vaccine development have lead to a diversification of candidates and ongoing technical advances yet continue to yield disappointing results in clinical trials in endemic populations and among the most relevant age groups (children under 2 years of age). The description of the rapid spread of quinolone resistance requires monitoring to ensure appropriate case management, particularly in south-east Asia. The evaluation of adjunctive nutritional therapy in endemic areas has supported the use of green bananas in shortening the duration of Shigella dysentery and persistent diarrhea due to Shigella, as well as improving weight gain in early convalescence. Summary: Despite a great level of activity in basic sciences, there continues to be a large gap in the ability to translate these findings into disease control measures or therapeutic options for individuals living in areas in which shigellosis is endemic. © 2010 Lippincott Williams & Wilkins.
Olortegui M.P.,Asociacion Benefica PRISMA |
Asayag C.R.,Hospital Regional Of Iquitos
American Journal of Tropical Medicine and Hygiene | Year: 2013
Long-lasting insecticidal net (LLIN) use is a proven malaria prevention method. Mass distribution has greatly expanded LLIN access in sub-Saharan Africa, but a gap remains between LLIN ownership and use. Furthermore, LLINs wear out more quickly than anticipated. This paper suggests a participatory research strategy - trials of improved practices (TIPs) - that could identify locally appropriate approaches to prolonging net life and increasing effective use. We used TIPs to overcome barriers to optimal net use in the Peruvian Amazon. Working with 15 families in three villages, we tested home treatment of cotton nets, use of an alternative netting fabric, and alternative washing and care instructions. TIPs helped confirm feasibility of these interventions. Although our findings are time- and context-specific, TIPs could help improve consistency and effectiveness of current LLIN use and prolong net lifespan in sub-Saharan Africa and elsewhere. This would help maximize the value of shrinking donor resources for malaria. Copyright © 2013 by The American Society of Tropical Medicine and Hygiene.
Walter L.,New York Hospital Queens |
Cabrerra L.,Asociacion Benefica PRISMA |
Gravitt P.E.,Sharpe and Dohme Corporation |
Marks M.A.,Sharpe and Dohme Corporation
Sexually Transmitted Infections | Year: 2016
Purpose The incidence of human papillomavirus (HPV) associated head and neck cancers (HNCs) have been increasing in Peru. However, the burden of oral HPV infection in Peru has not been assessed. The objective of this cross-sectional study was to estimate the prevalence and correlates of oral HPV infection in a populationbased sample from males and females from Lima, Peru. Methods Between January 2010 and June 2011, a population-based sample of 1099 individuals between the ages of 10 and 85 from a low-income neighbourhood in Lima, Peru was identified through random household sampling. Information on demographic, sexual behaviours, reproductive factors and oral hygiene were collected using intervieweradministered questionnaires. Oral rinse specimens were collected from each participant, and these specimens were genotyped using the Roche Linear Array assay. ORs were used to assess differences in the prevalence of any oral HPV and any high-risk oral HPV infection by demographic factors, sexual practices and oral hygiene among individuals 15+ years of age. Results The prevalence of any HPV and any high-risk HPV (HR-HPV) was 6.8% and 2.0%, respectively. The three most common types were HPV 55 (3.4%), HPV 6 (1.5%) and HPV 16 (1.1%). Male sex (aOR, 2.21; 95% CI 1.22 to 4.03) was associated with any HPV infection after adjustment. Conclusions The prevalence of oral HPV in this study was similar to estimates observed in the USA. Higher prevalence of oral infections in males was consistent with a male predominance of HPV-associated HNCs and may signal a sex-specific aetiology in the natural history of infection.
Sterling R.,Asociacion Benefica PRISMA |
Miranda J.J.,Cayetano Heredia Peruvian University |
Gilman R.H.,Asociacion Benefica PRISMA |
Gilman R.H.,University of Arizona |
And 5 more authors.
American Journal of Physical Anthropology | Year: 2012
While childhood malnutrition is associated with increased morbidity and mortality, less well understood is how early childhood growth influences height and body composition later in life. We revisited 152 Peruvian children who participated in a birth cohort study between 1995 and 1998, and obtained anthropometric and bioimpedance measurements 11-14 years later. We used multivariable regression models to study the effects of childhood anthropometric indices on height and body composition in early adolescence. Each standard deviation decrease in length-for-age at birth was associated with a decrease in adolescent height-for-age of 0.7 SD in both boys and girls (all P < 0.001) and 9.7 greater odds of stunting (95% CI 3.3-28.6). Each SD decrease in length-for-age in the first 30 months of life was associated with a decrease in adolescent height-for-age of 0.4 in boys and 0.6 standard deviation in girls (all P < 0.001) and with 5.8 greater odds of stunting (95% CI 2.6-13.5). The effect of weight gain during early childhood on weight in early adolescence was more complex to understand. Weight-for-length at birth and rate of change in weight-for-length in early childhood were positively associated with age- and sex-adjusted body mass index and a greater risk of being overweight in early adolescence. Linear growth retardation in early childhood is a strong determinant of adolescent stature, indicating that, in developing countries, growth failure in height during early childhood persists through early adolescence. Interventions addressing linear growth retardation in childhood are likely to improve adolescent stature and related-health outcomes in adulthood. © 2012 Wiley Periodicals, Inc.
Castro-Sesquen Y.E.,Asociacion Benefica PRISMA |
Gilman R.H.,Johns Hopkins University |
Yauri V.,Asociacion Benefica PRISMA |
Angulo N.,Asociacion Benefica PRISMA |
And 5 more authors.
American Journal of Pathology | Year: 2011
The guinea pig (Cavia porcellus) is a natural reservoir for Trypanosoma cruzi but has seldom been used as an experimental infection model. We developed a guinea pig infection model for acute and chronic Chagas disease. Seventy-two guinea pigs were inoculated intradermally with 104 trypomastigotes of T. cruzi strain Y (experimental group); 18 guinea pigs were used as control group. Eight animals from the experimental group and two from the control group were sacrificed 5, 15, 20, 25, 40, 55, 115, 165, and 365 days after inoculation. During the acute phase (15 to 55 days), we observed parasitemia (with a peak on day 20) and positive IgM and IgG Western blots with anti-shed acute-phase antigen bands. The cardiac tissue showed vasculitis, necrosis (on days 40 to 55), moderate to severe inflammation, and abundant amastigote nests. Smaller numbers of amastigote nests were also present in kidney, brain, and other organs. In the early chronic phase (115 to 165 days), parasitemia disappeared and antiT. cruzi IgG antibodies were still detectable. In cardiac tissue, the number of amastigote nests and the grade of inflammation decreased. In the chronic phase (365 days), the cardiac tissue showed vasculitis and fibrosis; detectable parasite DNA was associated with higher grades of inflammation. The experimental T. cruzi infection model in guinea pigs shows kinetics and pathologic changes similar to those of the human disease. © 2011 American Society for Investigative Pathology.
Zevallos K.,Cayetano Heredia Peruvian University |
Vergara K.C.,Asociacion Benefica PRISMA |
Vergara A.,Asociacion Benefica PRISMA |
Vidal C.,Ministerio de Salud de Loreto |
And 2 more authors.
American Journal of Tropical Medicine and Hygiene | Year: 2010
The tuberculin skin test (TST) quantifies cell-mediated immunity to tuberculosis antigens. Helminths suppress cell-mediated immunity, so we studied the effect of helminth infection and deworming on the TST in a randomized, double-blind, placebo-controlled study in an indigenous Amazon community (N = 195). Stool microscopy diagnosed helminths in 98% and co-infection with multiple species in 24% of study subjects. The TST was positive (≥ 10 mm) for 49%, and responses increased with age (P < 0.001), Bacille Calmette Guerin (BCG) vaccination (P = 0.01), and tuberculosis contact (P = 0.05). TST results had no association with helminth-egg concentrations, species, or co-infections (all P > 0.1). One month after deworming with albendazole (three daily 400-mg doses), helminths were reduced, but 63% remained infected with helminths. Albendazole did not cause a change in TST size (P = 0.8) or positivity (P = 0.9) relative to placebo. Thus, TST reactions were unaffected by albendazole therapy that partially cured intestinal helminth infections, and TST interpretation was unaffected by high-burden helminth infections and co-infection with multiple helminth species. Copyright © 2010 by The American Society of Tropical Medicine and Hygiene.
Bailey S.L.,University of Sussex |
Roper M.H.,Asociacion Benefica Prisma |
Huayta M.,Cayetano Heredia Peruvian University |
Trejos N.,Ministerio de Salud |
And 3 more authors.
International Journal of Tuberculosis and Lung Disease | Year: 2011
BACKGROUND: In high tuberculosis (TB) burden, r esource-poor countries, sputum smear microscopy remains the mainstay of diagnosis. The low sensitivity of this test means that patients with smear-negative but culture-positive TB pass undetected through the health care system. Such clinical episodes are missed opportunities for diagnosis and interruption of transmission, which might be averted through the application of more sensitive diagnostic tests. OBJECTIVES: To estimate the proportion of incident TB cases that might have been detected earlier than the actual date of diagnosis if a test more sensitive than smear microscopy had been used at an earlier presentation episode. METHOD: Retrospective cohort study in urban Peru, investigating health care facility interactions for symptoms suggestive of TB prior to TB diagnosis through patient interviews and a review of clinical records. RESULTS: Of 212 participants enrolled, 58% had one or more clinical interactions prior to their diagnostic episode. Of those with a prior episode, the median number of episodes was three. The median delay to diagnosis from first presentation was 26 days. CONCLUSION: There are clear missed opportunities for earlier TB diagnosis, delaying treatment initiation and continued spread of Mycobacterium tuberculosis to the community. The implementation of sensitive diagnostic tests appropriate to resource-poor settings should be given high priority.