Naval Medical Research Center Detachment

Lima, Peru

Naval Medical Research Center Detachment

Lima, Peru
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Hayat A.M.,U.S. Army | Tribble D.R.,Uniformed Services University of the Health Sciences | Sanders J.W.,Naval Medical Research Center Detachment | Faix D.J.,Naval Health Research Center | And 3 more authors.
Journal of Travel Medicine | Year: 2011

Background. Many studies have found acute gastrointestinal infections to be among the most likely reason for clinic visits among forward deployed soldiers and are considered a significant contributor to morbidity in this population. This occurs despite the controlled food and water distribution systems under which military populations operate. Furthermore, recent studies have indicated that providers often fail to appropriately identify and treat the typical causes of these infections. To adequately address this issue, an assessment of gaps in knowledge, practice, and management of acute diarrhea in deployed troops was conducted. Methods. A multiple-choice survey was developed by clinical researchers with expertise in travelers' diarrhea (TD) and provided to a convenience sample of clinical providers with a broad range of training and operational experience. The survey evaluated provider's knowledge of TD along with their ability to identify etiologies of various syndromic categories of acute gastrointestinal infections. Providers were also queried on selection of treatment approaches to a variety of clinical-based scenarios. Results. A total of 117 respondents completed the survey. Most were aware of the standard definition of TD (77%); however, their knowledge about the epidemiology was lower, with less than 24% correctly answering questions on etiology of diarrhea, and 31% believing that a viral pathogen was the primary cause of watery diarrhea during deployment. Evaluation of scenario-based responses showed that 64% of providers chose not to use antibiotics to treat moderate TD. Furthermore, 19% of providers felt that severe inflammatory diarrhea was best treated with hydration only while 25% felt hydration was the therapy of choice for dysentery. Across all provider types, three practitioner characteristics appeared to be related to better scores on responses to the nine management scenarios: having a Doctor of Medicine or Doctor of Osteopathy degree, greater knowledge of TD epidemiology, and favorable attitudes toward antimotility or antibiotic therapy. Conclusion. Results from this survey support the need for improving knowledge and management of TD among deploying providers. The information from this study should be considered to support the establishment and dissemination of military diarrhea-management guidelines to assist in improving the health of military personnel. © 2011 International Society of Travel Medicine.

Garcia H.H.,Instituto Nacional Of Ciencias Neurologicas | Garcia H.H.,Cayetano Heredia Peruvian University | Lescano A.G.,Cayetano Heredia Peruvian University | Lescano A.G.,Naval Medical Research Center Detachment | And 11 more authors.
British Journal of Clinical Pharmacology | Year: 2011

AIMS: Neurocysticercosis is the most common cause of acquired epilepsy in the world. Antiparasitic treatment of viable brain cysts is of clinical benefit, but current antiparasitic regimes provide incomplete parasiticidal efficacy. Combined use of two antiparasitic drugs may improve clearance of brain parasites. Albendazole (ABZ) has been used together with praziquantel (PZQ) before for geohelminths, echinococcosis and cysticercosis, but their combined use is not yet formally recommended and only scarce, discrepant data exist on their pharmacokinetics when given together. We assessed the pharmacokinetics of their combined use for the treatment of neurocysticercosis. METHODS A randomized, double-blind, placebo-controlled phase II evaluation of the pharmacokinetics of ABZ and PZQ in 32 patients with neurocysticercosis was carried out. Patients received their usual concomitant medications including an antiepileptic drug, dexamethasone, and ranitidine. Randomization was stratified by antiepileptic drug (phenytoin or carbamazepine). Subjects had sequential blood samples taken after the first dose of antiparasitic drugs and again after 9days of treatment, and were followed for 3months after dosing. RESULTS Twenty-one men and 11 women, aged 16 to 55 (mean age 28)years were included. Albendazole sulfoxide concentrations were increased in the combination group compared with the ABZ alone group, both in patients taking phenytoin and patients taking carbamazepine. PZQ concentrations were also increased by the end of therapy. There were no significant side effects in this study group. CONCLUSIONS Combined ABZ + PZQ is associated with increased albendazole sulfoxide plasma concentrations. These increased concentrations could independently contribute to increased cysticidal efficacy by themselves or in addition to a possible synergistic effect. © 2011 The Authors. British Journal of Clinical Pharmacology © 2011 The British Pharmacological Society.

Liebman K.A.,University of California at Davis | Stoddard S.T.,University of California at Davis | Stoddard S.T.,U.S. National Institutes of Health | Morrison A.C.,University of California at Davis | And 11 more authors.
PLoS Neglected Tropical Diseases | Year: 2012

Background: Knowledge of spatial patterns of dengue virus (DENV) infection is important for understanding transmission dynamics and guiding effective disease prevention strategies. Because movement of infected humans and mosquito vectors plays a role in the spread and persistence of virus, spatial dimensions of transmission can range from small household foci to large community clusters. Current understanding is limited because past analyses emphasized clinically apparent illness and did not account for the potentially large proportion of inapparent infections. In this study we analyzed both clinically apparent and overall infections to determine the extent of clustering among human DENV infections. Methodology/Principal Findings: We conducted spatial analyses at global and local scales, using acute case and seroconversion data from a prospective longitudinal cohort in Iquitos, Peru, from 1999-2003. Our study began during a period of interepidemic DENV-1 and DENV-2 transmission and transitioned to epidemic DENV-3 transmission. Infection status was determined by seroconversion based on plaque neutralization testing of sequential blood samples taken at approximately six-month intervals, with date of infection assigned as the middate between paired samples. Each year was divided into three distinct seasonal periods of DENV transmission. Spatial heterogeneity was detected in baseline seroprevalence for DENV-1 and DENV-2. Cumulative DENV-3 seroprevalence calculated by trimester from 2001-2003 was spatially similar to preexisting DENV-1 and DENV-2 seroprevalence. Global clustering (case-control Ripley's K statistic) appeared at radii of ~200-800 m. Local analyses (Kuldorf spatial scan statistic) identified eight DENV-1 and 15 DENV-3 clusters from 1999-2003. The number of seroconversions per cluster ranged from 3-34 with radii from zero (a single household) to 750 m; 65% of clusters had radii >100 m. No clustering was detected among clinically apparent infections. Conclusions/Significance: Seroprevalence of previously circulating DENV serotypes can be a predictor of transmission risk for a different invading serotype and, thus, identify targets for strategically placed surveillance and intervention. Seroprevalence of a specific serotype is also important, but does not preclude other contributing factors, such as mosquito density, in determining where transmission of that virus will occur. Regardless of the epidemiological context or virus serotype, human movement appears to be an important factor in defining the spatial dimensions of DENV transmission and, thus, should be considered in the design and evaluation of surveillance and intervention strategies.

Morrison A.C.,University of California at Davis | Morrison A.C.,Naval Medical Research Center Detachment | Minnick S.L.,University of California at Davis | Rocha C.,Naval Medical Research Center Detachment | And 13 more authors.
PLoS Neglected Tropical Diseases | Year: 2010

Background: Comprehensive, longitudinal field studies that monitor both disease and vector populations for dengue viruses are urgently needed as a pre-requisite for developing locally adaptable prevention programs or to appropriately test and license new vaccines. Methodology and Principal Findings: We report the results from such a study spanning 5 years in the Amazonian city of Iquitos, Peru where DENV infection was monitored serologically among ~2,400 members of a neighborhood-based cohort and through school-based absenteeism surveillance for active febrile illness among a subset of this cohort. At baseline, 80% of the study population had DENV antibodies, seroprevalence increased with age, and significant geographic variation was observed, with neighborhood-specific age-adjusted rates ranging from 67.1 to 89.9%. During the first 15 months, when DENV-1 and DENV-2 were co-circulating, population-based incidence rates ranged from 2-3 infections/100 person-years (pyears). The introduction of DENV-3 during the last half of 2001 was characterized by 3 distinct periods: amplification over at least 5-6 months, replacement of previously circulating serotypes, and epidemic transmission when incidence peaked at 89 infections/100 p-years. Conclusions/Significance: Neighborhood-specific baseline seroprevalence rates were not predictive of geographic incidence patterns prior to the DENV-3 introduction, but were closely mirrored during the invasion of this serotype. Transmission varied geographically, with peak incidence occurring at different times among the 8 geographic zones in ~16 km 2 of the city. The lag from novel serotype introduction to epidemic transmission and knowledge of spatially explicit areas of elevated risk should be considered for more effective application of limited resources for dengue prevention.

Yori P.,Biomedical Research Unit | Olortegui M.P.,Biomedical Research Unit | Pan W.,Duke University | Sanders J.W.,Naval Medical Research Center Detachment | And 3 more authors.
International Journal of Epidemiology | Year: 2012

Background: The adverse impact of Plasmodium vivax on child health beyond acute febrile illness is poorly studied. The effect of vivax malaria on child growth was evaluated and compared with diarrhoeal disease and non-specific fever. Methods: Using data from a 43-month longitudinal cohort of children 0-72 months of age (n = 442) in the Peruvian Amazon, ponderal and linear growth velocities over 2-, 4- and 6-month periods were examined using longitudinal models and related to the incidence of disease during the same period. Results: An episode of vivax malaria led to 138.6 g (95% confidence interval (CI) 81.9-195.4), 108.6 g (62.8-153.2) and 61 g (20.9-101.1) less weight gain over 2-, 4- and 6-month intervals, respectively. These deficits were larger than both diarrhoea (21.9, 17.2 and 13.8 g less weight gain, respectively) and fever (39.0, 30.3 and 25.6 g less weight gain, respectively). An incident episode of vivax also led to 0.070 cm (0.004-0.137) and 0.083 cm (0.015-0.151) less linear growth over 4 and 6 months, respectively, which were also larger than deficits from diarrhoea (0.029 and 0.028 cm, respectively) and fever (not associated with linear growth deficits). Despite the larger effect of P. vivax incident episodes on growth of a particular child, diarrhoeal disease had a larger cumulative impact on growth deficits as diarrhoeal incidence rates in this community are >10-fold higher than vivax malaria. Conclusions: Disease control measures for vivax malaria and diarrhoeal disease have the potential to improve the growth of children in endemic areas. Published by Oxford University Press on behalf of the International Epidemiological Association © The Author 2012; all rights reserved.

Ellis A.M.,University of California at Davis | Ellis A.M.,U.S. National Institutes of Health | Garcia A.J.,University of Florida | Focks D.A.,University of Florida | And 4 more authors.
American Journal of Tropical Medicine and Hygiene | Year: 2011

Models can be useful tools for understanding the dynamics and control of mosquito-borne disease. More detailed models may be more realistic and better suited for understanding local disease dynamics; however, evaluating model suitability, accuracy, and performance becomes increasingly difficult with greater model complexity. Sensitivity analysis is a technique that permits exploration of complex models by evaluating the sensitivity of the model to changes in parameters. Here, we present results of sensitivity analyses of two interrelated complex simulation models of mosquito population dynamics and dengue transmission. We found that dengue transmission may be influenced most by survival in each life stage of the mosquito, mosquito biting behavior, and duration of the infectious period in humans. The importance of these biological processes for vector-borne disease models and the overwhelming lack of knowledge about them make acquisition of relevant field data on these biological processes a top research priority. Copyright © 2011 by The American Society of Tropical Medicine and Hygiene.

Maves R.C.,Naval Medical Research Center Detachment | Maves R.C.,Naval Medical Center San Diego | Castillo R.,Naval Medical Research Center Detachment | Guillen A.,Clinica San Borja | And 9 more authors.
Antimicrobial Agents and Chemotherapy | Year: 2011

Brucellosis is an important public health problem in Peru. We evaluated 48 human Brucella melitensis biotype 1 strains from Peru between 2000 and 2006. MICs of isolates to doxycycline, azithromycin, gentamicin, rifampin, ciprofloxacin, and trimethoprim-sulfamethoxazole were determined by the Etest method. All isolates were sensitive to tested drugs during the periods of testing. Relapses did not appear to be related to drug resistance. Copyright © 2011, American Society for Microbiology. All Rights Reserved.

Trivedi K.H.,University of California at Irvine | Schlett C.D.,Uniformed Services University of the Health Sciences | Tribble D.R.,Uniformed Services University of the Health Sciences | Monteville M.R.,US Marine Corps | And 2 more authors.
Digestive Diseases and Sciences | Year: 2011

Background and Aim Mental and physical health-related quality of life (HRQOL) are important health impact measures following military deployment. While conditions such as post-traumatic stress disorder (PTSD) are known to adversely affect QOL, little is known about the effect of post-infectious functional gastrointestinal disorders (PIFGID). Our aim was to evaluate the risk of PI-FGID and its impact on HRQOL among military personnel returning from deployment. Methods A cross-sectional cohort of active-duty military deployed to Egypt or Turkey between 2004 and 2005 was asked to complete a questionnaire (Rome II and SF-36 instruments) on travelers' diarrhea (TD) during deployment and FGID symptoms and HRQOL 6 months after returning from deployment. Results A total of 121 military personnel returning from Egypt (n = 33) and Turkey (n = 88) completed the postdeployment questionnaire. Nearly half (48.3%) met the definition for an FGID at the time of the survey, and 53% of individuals reporting one or more episodes of TD during deployment developed an FGID, compared to 33% of those not reporting TD (odds ratio [OR] 2.2, P = 0.08). Compared to those not meeting the FGID criteria, those with post-deployment FGID had lower mean mental HRQOL scores (-13.4%, P<0.0001) and lower physical HRQOL scores (-7.2%, P = 0.004). Conclusions There was a high prevalence of FGID symptoms in military personnel returning from deployment, and TD was a noted risk factor. FGID and symptoms decreased QOL, with mental HRQOL being affected more than physical HRQOL. These findings require further research in order to assess the long-term impact of these and other post-infectious sequela related to TD during deployments among returning veterans. © Springer Science+Business Media, LLC 2011.

Dharia N.V.,Scripps Research Institute | Plouffe D.,Genomics Institute of the Novartis Research Foundation | Bopp S.E.R.,Scripps Research Institute | Gonzalez-Paez G.E.,Scripps Research Institute | And 8 more authors.
Genome Research | Year: 2010

Here, we fully characterize the genomes of 14 Plasmodium falciparum patient isolates taken recently from the Iquitos region using genome scanning, a microarray-based technique that delineates the majority of single-base changes, indels, and copy number variants distinguishing the coding regions of two clones. We show that the parasite population in the Peruvian Amazon bears a limited number of genotypes and low recombination frequencies. Despite the essentially clonal nature of some isolates, we see high frequencies of mutations in subtelomeric highly variable genes and internal var genes, indicating mutations arising during self-mating or mitotic replication. The data also reveal that one or two meioses separate different isolates, showing that P. falciparum clones isolated from different individuals in defined geographical regions could be useful in linkage analyses or quantitative trait locus studies. Through pairwise comparisons of different isolates we discovered point mutations in the apicoplast genome that are close to known mutations that confer clindamycin resistance in other species, but which were hitherto unknown in malaria parasites. Subsequent drug sensitivity testing revealed over 100-fold increase of clindamycin EC50 in strains harboring one of these mutations. This evidence of clindamycin-resistant parasites in the Amazon suggests that a shift should be made in health policy away from quinine + clindamycin therapy for malaria in pregnant women and infants, and that the development of new lincosamide antibiotics for malaria should be reconsidered.

Maves R.C.,Naval Medical Research Center Detachment | Ore R.M.C.,Naval Medical Research Center Detachment | Porter K.R.,Naval Medical Research Center | Kochel T.J.,Naval Medical Research Center Detachment
Vaccine | Year: 2011

Psoralens are photoreactive compounds that cross-link pyrimidines after exposure to UVA radiation. In this experiment, we tested the protective efficacy of a psoralen-inactivated dengue vaccine candidate in non-human primates. Two groups of 7 Aotus nancymaae monkeys received either 10ng per dose of inactivated DENV1 plus alum adjuvant or alum alone (controls). Doses were injected intradermally on days 0, 14, and 28. Monkeys then received a challenge inoculation of 1.1×10 4PFUs of WestPac 74 DENV-1 on day 132. At 62 days, only 1/7 vaccinated monkeys had detectable IgM, but IgG and neutralizing antibody remained detectable in 7/7. No IgM, IgG, or neutralizing antibody was detectable in control monkeys. DENV-1 viremia was detected after challenge in 3/7 vaccinated monkeys and 5/6 control monkeys (with one removed due to pregnancy) (p=0.27), but days of viremia were reduced from 3.67 days/animal among controls to 0.71 days/animal among vaccinated monkeys (p=0.051). Psoralen-inactivated DENV1 is immunogenic in Aotus nancymaae with a trend towards a reduction in days of viremia following experimental challenge. © 2011.

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