Us Naval Medical Research Unit No 2

Jakarta, Indonesia

Us Naval Medical Research Unit No 2

Jakarta, Indonesia
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Blair P.J.,Us Naval Medical Research Unit No 2 | Wierzba T.F.,Us Naval Medical Research Unit No 2 | Touch S.,Kingdom of Cambodia Ministry of Health | Vonthanak S.,National Institute of Public Health | And 6 more authors.
Epidemiology and Infection | Year: 2010

The epidemiology, symptomology, and viral aetiology of endemic influenza remain largely uncharacterized in Cambodia. In December 2006, we established passive hospital-based surveillance to identify the causes of acute undifferentiated fever in patients seeking healthcare. Fever was defined as tympanic membrane temperature >38C. From December 2006 to December 2008, 4233 patients were screened for influenza virus by real-time reverse-transcriptase polymerase chain reaction (rRT-PCR). Of these patients, 1151 (272%) were positive for influenza. Cough (688% vs. 505%, P<00001) and sore throat (550% vs. 419%, P<00001) were more often associated with laboratory-confirmed influenza-infected patients compared to influenza-negative enrollees. A clear influenza season was evident between July and December with a peak during the rainy season. Influenza A and B viruses were identified in 768 (663%) and 388 (337%) of the influenza-positive population (n=1153), respectively. In December 2008, passive surveillance identified infection of the avian influenza virus H5N1 in a 19-year-old farmer from Kandal province who subsequently recovered. From a subset of diagnostic samples submitted in 2007, 15 A(H1N1), seven A(H3N2) and seven B viruses were isolated. The predominant subtype tested was influenza A(H1N1), with the majority antigenically related to the A/Solomon Island/03/2006 vaccine strain. The influenza A(H3N2) isolates and influenza B viruses analysed were closely related to A/Brisbane/10/2007 or B/Ohio/01/2005 (B/Victoria/2/87-lineage) vaccine strains, respectively. Phylogenetic analysis of the HA1 region of the HA gene of influenza A(H1N1) viruses demonstrated that the Cambodian isolates belonged to clade 2C along with representative H1N1 viruses circulating in SE Asia at the time. These viruses remained sensitive to oseltamivir. In total, our data suggest that viral influenza infections contribute to nearly one-fifth of acute febrile illnesses and demonstrate the importance of influenza surveillance in Cambodia. © 2009 Cambridge University Press.

Vinayak S.,Atlanta Research and Education Foundation | Vinayak S.,National Center for Zoonotic Vector Borne and Enteric Diseases | Alam T.,National Center for Zoonotic Vector Borne and Enteric Diseases | Mixson-Hayden T.,National Center for Zoonotic Vector Borne and Enteric Diseases | And 12 more authors.
PLoS Pathogens | Year: 2010

The Thailand-Cambodia border is the epicenter for drug-resistant falciparum malaria. Previous studies have shown that chloroquine (CQ) and pyrimethamine resistance originated in this region and eventually spread to other Asian countries and Africa. However, there is a dearth in understanding the origin and evolution of dhps alleles associated with sulfadoxine resistance. The present study was designed to reveal the origin(s) of sulfadoxine resistance in Cambodia and its evolutionary relationship to African and South American dhps alleles. We sequenced 234 Cambodian Plasmodium falciparum isolates for the dhps codons S436A/F, A437G, K540E, A581G and A613S/T implicated in sulfadoxine resistance. We also genotyped 10 microsatellite loci around dhps to determine the genetic backgrounds of various alleles and compared them with the backgrounds of alleles prevalent in Africa and South America. In addition to previously known highly-resistant triple mutant dhps alleles SGEGA and AGEAA (codons 436, 437, 540, 581, 613 are sequentially indicated), a large proportion of the isolates (19.3%) contained a 540N mutation in association with 437G/581G yielding a previously unreported triple mutant allele, SGNGA. Microsatellite data strongly suggest the strength of selection was greater on triple mutant dhps alleles followed by the double and single mutants. We provide evidence for at least three independent origins for the double mutants, one each for the SGKGA, AGKAA and SGEAA alleles. Our data suggest that the triple mutant allele SGEGA and the novel allele SGNGA have common origin on the SGKGA background, whereas the AGEAA triple mutant was derived from AGKAA on multiple, albeit limited, genetic backgrounds. The SGEAA did not share haplotypes with any of the triple mutants. Comparative analysis of the microsatellite haplotypes flanking dhps alleles from Cambodia, Kenya, Cameroon and Venezuela revealed an independent origin of sulfadoxine resistant alleles in each of these regions.

Kasper M.R.,Us Naval Medical Research Unit No 2 | Sokhal B.,National Institute of Public Health | Blair P.J.,Us Naval Medical Research Unit No 2 | Wierzba T.F.,Us Naval Medical Research Unit No 2 | Putnam S.D.,Us Naval Medical Research Unit No 2
Diagnostic Microbiology and Infectious Disease | Year: 2010

From December 2006 to April 2009, we conducted an etiology study among Cambodian patients presenting with acute fever of unknown origin. Salmonella enterica serovar Typhi was detected in 0.9% (41/4985) blood cultures. Antimicrobial susceptibility testing showed decreased susceptibility to ampicillin (56% resistant; MIC90, >256 μg/mL), chloramphenicol (56% resistant; MIC90, >256 μg/mL), trimethoprim/sulfamethoxazole (56% resistant; MIC90, >256 μg/mL), nalidixic acid (81% resistant; MIC90, not defined), ciprofloxacin (0% resistant; MIC90, 0.5 μg/mL), and ceftriaxone (0% resistant; MIC90, 0.094 μg/mL). Multidrug resistance, defined as antimicrobial resistance to ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole, was found in 56% of the isolates, and 80% had reduced susceptibility to ciprofloxacin (defined as MIC ≥0.12 μg/mL).

PubMed | Pasteur Institute of Cote dIvoire, Centers for Disease Control and Prevention, Global Disease Detection, University of Pennsylvania and 14 more.
Type: | Journal: Influenza and other respiratory viruses | Year: 2015

Literature on influenza focuses on influenza A, despite influenza B having a large public health impact. The Global Influenza B Study aims to collect information on global epidemiology and burden of disease of influenza B since 2000.Twenty-six countries in the Southern (n = 5) and Northern (n = 7) hemispheres and intertropical belt (n = 14) provided virological and epidemiological data. We calculated the proportion of influenza cases due to type B and Victoria and Yamagata lineages in each country and season; tested the correlation between proportion of influenza B and maximum weekly influenza-like illness (ILI) rate during the same season; determined the frequency of vaccine mismatches; and described the age distribution of cases by virus type.The database included 935 673 influenza cases (2000-2013). Overall median proportion of influenza B was 226%, with no statistically significant differences across seasons. During seasons where influenza B was dominant or co-circulated (>20% of total detections), Victoria and Yamagata lineages predominated during 64% and 36% of seasons, respectively, and a vaccine mismatch was observed in 25% of seasons. Proportion of influenza B was inversely correlated with maximum ILI rate in the same season in the Northern and (with borderline significance) Southern hemispheres. Patients infected with influenza B were usually younger (5-17 years) than patients infected with influenza A.Influenza B is a common disease with some epidemiological differences from influenza A. This should be considered when optimizing control/prevention strategies in different regions and reducing the global burden of disease due to influenza.

Punjabi N.H.,Us Naval Medical Research Unit No 2 | Taylor W.R.J.,Us Naval Medical Research Unit No 2 | Taylor W.R.J.,Tulane University | Murphy G.S.,Us Naval Medical Research Unit No 2 | And 12 more authors.
American Journal of Tropical Medicine and Hygiene | Year: 2012

We conducted a prospective, inpatient fever study in malaria-endemic Papua, Indonesia to determine non-malaria fever etiologies. Investigations included malaria blood films, blood culture, paired serologic samples analysis for dengue, Japanese encephalitis, leptospirosis, scrub typhus, murine typhus, and spotted fever group rickettsia. During 1997-2000, 226 patients (127 males and 99 females) 1-80 years of age (median age = 25 years) were enrolled. Positive blood cultures (n = 34, 15%) were obtained for Salmonella Typhi (n = 13), Escherichia coli (n = 8), Streptococcus pneumoniae (n = 6), Staphylococcus aureus (n = 5), Streptococcus pyogenes (n = 1), and Klebsiella pneumoniae (n = 1). Twenty (8.8%) patients were positive for leptospirosis by polymerase chain reaction. Eighty (35.4%) of 226 patients had &γε; 1 positive serology, diagnostic for 15 rickettsial and 9 dengue cases. Acid-fast bacilli-positive sputum was obtained from three patients. Most common confirmed (81 of 226, 35.8%)/suspected diagnoses were typhoid fever (n = 41), pneumonia (n = 29), leptospirosis (n = 28), urinary tract infections (n = 20), rickettsioses (n = 19), dengue (n = 17), and meningitis/encephalitis (n = 15). There were 17 deaths, 7 (46.7%) were caused by meningitis/encephalitis. Multiple positive serologic results and few confirmed diagnoses indicate the need for improved diagnostics. Copyright © 2012 by The American Society of Tropical Medicine and Hygiene.

Yasuda C.,Us Naval Medical Research Unit No 2 | Sovann L.,Ministry of Health | Kasper M.,Us Naval Medical Research Unit No 2 | Williams M.,Us Naval Medical Research Unit No 2 | Wierzba T.F.,Us Naval Medical Research Unit No 2
Southeast Asian Journal of Tropical Medicine and Public Health | Year: 2012

We conducted clinic-based surveillance for influenza virus among cases with acute febrile illness at 9 medical clinics in south-central Cambodia during 2006-2009. Patients greater than or equal to 24 months old presenting with acute fever (>38°C) were enrolled. In late July 2009, the study identified its first case of pandemic H1N1 (pH1N1) influenza virus infection. The prevalence of pH1N1 infections increased rapidly during August and September and by October, pH1N1 infections had peaked replacing H3N2 as the dominant subtype. The incidence of pH1N1 subsequently decreased, with only one case identified in late December. From late July through December 2009, 42.4% of all influenza cases were caused by pH1N1. Except for headache, less frequently reported among pH1N1-infected patients, patients infected with the pH1N1 reported symptoms (eg, cough, diarrhea, vomiting and nausea) similar to seasonal H3N2 and B virus infections. Among children 6 to 12 years old, there was a higher number of hospitalizations campared to other age groups. Identification of influenza virus types A and B using the QuickVue© rapid diagnostic test was found to be equally sensitive for pH1N1 (50.4%), H3N2 (51.7%) and influenza B (53.9%) viruses, although the sensitivity was low among all subtypes. The pH1N1 virus rapidly became the dominant virus subtype in 2009 in Cambodia, but no symptoms consistently distinguished the pandemic strain from other influenza virus subtypes. The QuickVue© test was as sensitive for detecting pH1N1 viral as well as other circulating seasonal influenza viruses.

Kasper M.R.,Us Naval Medical Research Unit 2 | Wierzba T.F.,Us Naval Medical Research Unit No 2 | Sovann L.,Kingdom of Cambodia Ministry of Health | Blair P.J.,Us Naval Medical Research Unit 2 | Putnam S.D.,Us Naval Medical Research Unit 2
BMC Infectious Diseases | Year: 2010

Background: Influenza-like illness (ILI) is often defined as fever (>38.0°C) with cough or sore throat. In this study, we tested the sensitivity, specificity, and positive and negative predictive values of this case definition in a Cambodia patient population.Methods: Passive clinic-based surveillance was established at nine healthcare centers to identify the causes of acute undifferentiated fever in patients aged two years and older seeking treatment. Fever was defined as tympanic membrane temperature >38°C lasting more than 24 hours and less than 10 days. Influenza virus infections were identified by polymerase chain reaction.Results: From July 2008 to December 2008, 2,639 patients were enrolled. From 884 (33%) patients positive for influenza, 652 presented with ILI and 232 acute fever patients presented without ILI. Analysis by age group identified no significant differences between influenza positive patients from the two groups. Positive predictive values (PPVs) varied during the course of the influenza season and among age groups.Conclusion: The ILI case definition can be used to identify a significant percentage of patients with influenza infection during the influenza season in Cambodia, assisting healthcare providers in its diagnosis and treatment. However, testing samples based on the criteria of fever alone increased our case detection by 34%. © 2010 Kasper et al; licensee BioMed Central Ltd.

Vinayak S.,Centers for Disease Control and Prevention | Alam M.T.,Centers for Disease Control and Prevention | Sem R.,National Malaria Center | Sem R.,Us Naval Medical Research Unit No 2 | And 13 more authors.
Journal of Infectious Diseases | Year: 2010

Background. The emergence of artesunate-mefloquine (AS+MQ)-resistant Plasmodium falciparum in the Thailand-Cambodia region is a major concern for malaria control. Studies indicate that copy number increase and key alleles in the pfmdr1 gene are associated with AS+MQ resistance. In the present study, we investigated evidence for a selective sweep around pfmdr1 because of the spread of adaptive mutation and/or multiple copies of this gene in the P falciparum population in Cambodia. Methods. We characterized 13 microsatellite loci flanking (±99 kb) pfmdr1 in 93 single-clone P falciparum infections, of which 31 had multiple copies and 62 had a single copy of the pfmdr1 gene. Results. Genetic analysis revealed no difference in the mean ( ± standard deviation) expected heterozygosity (He) at loci around single (0.75 ± 0.03) and multiple (0.76 ± 0.04) copies of pfmdr1. Evidence of genetic hitchhiking with the selective sweep of certain haplotypes was seen around mutant (184F) pfmdr1 allele, irrespective of the copy number. There was an overall reduction of 28% in mean He (±SD) around mutant allele (0.56 ± 0.05), compared with wild-type allele (0.84 ± 0.02). Significant linkage disequilibrium was also observed between the loci flanking mutant pfmdr1 allele. Conclusion. The 184F mutant allele is under selection, whereas amplification of pfmdr1 gene in this population occurs on multiple genetic backgrounds. © 2010 by the Infectious Diseases Society of America. All rights reserved.

PubMed | U.S. Army, Communicable Disease Center, Us Naval Medical Research Unit No 2, Naval Medical Research Center and University of Texas Medical Branch
Type: Journal Article | Journal: Genome announcements | Year: 2016

Zika virus is an emerging human pathogen of great concern due to putative links to microcephaly and Guillain-Barre syndrome. Here, we report the complete genomes, including the 5 and 3 untranslated regions, of five Zika virus isolates, one from the Asian lineage and four from the African lineage.

PubMed | Indonesia Research Partnership on Infectious Diseases INA RESPOND, Padjadjaran University and Us Naval Medical Research Unit No 2
Type: | Journal: BioMed research international | Year: 2016

Secondary dengue infection by heterotypic serotypes is associated with severe manifestations of disease, that is, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The World Health Organization (WHO) has recommended criteria based on the hemagglutination inhibition (HI) test to distinguish between primary and secondary dengue infections. Since the HI test has practical limitations and disadvantages, we evaluated the accuracy of WHO HI criteria and compared it with criteria based on an IgG enzyme-linked immunosorbent assay (ELISA) using a plaque reduction neutralization test (PRNT) as the gold standard. Both WHO HI criteria and IgG ELISA criteria performed strongly (16/16) in determining primary infection. However, to determine secondary infection, the IgG ELISA criteria performed better (72/73) compared to the WHO HI criteria (23/73).

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