Recent Publications by Tulane Public Health Researchers


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The Department of Tropical Medicine
Selected Recent Publications

Researchers	Title	Publication	Abstract
Coleman CA, Muller-Trutwin MC, Apetrei C, Pandrea I.	T regulatory cells: aid or hindrance in the clearance of disease.	J Cell Mol Med 2007;11(6):1291-1325.	CD4+ CD25+ T regulatory cells (Tregs) are classified as a subset of T cells whose role is the suppression and regulation of immune responses to self and non-self. Since their discovery in the early 1970s, the role of CD4+ CD25+ Tregs in both autoimmune and infectious disease has continued to expand. This review exam-ines the recent advances on the role CD4+ CD25+ Tregs may be playing in various diseases regarding pro-gression or protection. In addition, advances made in the purification and manipulation of CD4+ CD25+ Tregs using new cell markers, techniques and antibodies are discussed. Ultimately, an overall understanding of the exact mechanism which CD4+ CD25+ Tregs implement during disease progression will enhance our ability to manipulate CD4+ CD25+ Tregs in a clinically beneficial manner.
Mzayek F, Hassig S, Sherwin R, Hughes J, Chen W, Srinivasan S, Berenson G.	The association of birth weight with developmental trends in blood pressure from childhood through mid-adulthood: the Bogalusa Heart Study.	Am J Epididemiol 2007;166(4):413-20.	Low birth weight has been found to be associated with cardiovascular mortality and morbidity and with an adverse profile of several cardiovascular risk factors. The inverse association between birth weight and blood pressure was consistently reported from many populations. Using longitudinal data from the Bogalusa Heart Study (Louisiana), the authors investigated the association between birth weight and progression of blood pressure through early adulthood, comparing that relation between African Americans and Whites. Birth data of 2,275 participants, screened two or more times in the Bogalusa Heart Study between 1973 and 2001, were retrospectively obtained from birth certificates and were linked to their clinical, laboratory, and socioeconomic and lifestyle data in the Bogalusa Heart Study data sets. Birth weight was inversely associated with systolic blood pressure, diastolic blood pressure, and pulse pressure (p<or=0.01 for all). For every 1-kg increase in birth weight, systolic blood pressure dropped by 1.9 mmHg (95% confidence interval: -2.6, -1.3), diastolic blood pressure by 0.7 mmHg (95% confidence interval: -1.2, -0.2), and pulse pressure by 1.2 mmHg (95% confidence interval: -1.7, -0.7). The interaction of birth weight with ethnicity was not significant for any outcome. Birth weight was inversely associated with later blood pressure. The strength of that association did not differ between African Americans and Whites.
Fair J, Jentes E, Inapogui A, Kourouma K, Goba A, Bah A, Tounkara M, Coulibaly M, Garry RF, Bausch DG.	Lassa virus-infected rodents in refugee camps in Guinea: a looming threat to public health in a politically unstable region.	Vector Borne Zoonotic Dis 2007;7(2):167-71.	Rodent-borne and other communicable diseases are of particular concern to vulnerable populations in complex humanitarian emergencies. We assessed the risk of Lassa fever to refugees and humanitarian aid workers in the Forest Region of Guinea by trapping rodents and testing them for the presence of Lassa virus infection. Our study provides a point prevalence of Lassa virus-infected rodents in various refugee camps in Guinea, suggesting that the risk of disease may be highest in camps further south toward the border with Liberia. The methodology used represents a potential model for rapid public health assessments in the setting of complex humanitarian emergencies.
Gautam R, Carter AC, Katz N, Butler IF, Barnes M, Hasegawa A, Ratterree M, Silvestri G, Marx PA, Hirsch VM, Pandrea I, Apetrei C	In vitro characterization of primary SIVsmm isolates belonging to different lineages.	Virology. 2007 Jun 5. 362(2):257-70	We report in vitro characterization of 11 SIVsmm strains of six lineages co-circulating in naturally infected sooty mangabeys (SMs) from US Primate Centers and showed no major differences in the in vitro replication pattern between different SIVsmm lineages. Primary SIVsmm isolates utilized CCR5 and Bonzo co-receptors in vitro. SIVsmm growth in human T cell lines was isolate-, not lineage-specific, with poor replication on Molt4-Clone8, CEMss and PM1 cells and better replication on MT2, SupT1 and CEMx174 cells. All primary SIVsmm isolates replicated on SM and human PBMCs. In vitro replication in macaques varied widely, with moderate to high replication in pig-tailed macaque PBMCs, enhanced by CD8+ T cell depletion, and highly variable replication on rhesus macaque (Rh) PBMCs. Primary SIVsmm isolates replicated in Rh monocyte-derived dendritic cells (MDDCs) and monocyte-derived macrophages (MDMs). Invivo, SIVsmm isolates replicated at high levels in all SIVsmm-infected Rh. The poor in vitro replication of primary SIVsmm isolates in Rh cells did not correlate with in vivo replication, emphasizing the value of in vivo studies.
Brindley PJ, Pearce EJ	Genetic manipulation of schistosomes	Int J Parasitology	In contrast to the situations with model organisms and parasitic protozoa, progress with gene manipulation with schistosomes has been delayed by impediments that include our inability to maintain the life cycle in vitro, absence of immortalized cell lines, large genome sizes, unavailability of drug resistance markers, and other difficulties. However, in the past few years, tangible progress has been reported towards development of tools for gene manipulation and transgenesis of schistosomes, and there is reason to believe that the filed is on the verge of transformation into an era where genetic manipulation is routine. Recent reports dealing with approaches and tools to manipulate the genome and gene expression in schistosomes are reviewed here.
Pandrea I, Apetrei C, Gordon S, Barbercheck J, Dufour J, Bohm R, Sumpter B, Roques P, Marx PA, Hirsch VM, Kaur A, Lackner AA, Veazey RS, Silvestri G	Paucity of CD4+CCR5+ T cells is a typical feature of natural SIV hosts	Blood. 2007 Feb 1. 109(3):1069-76	In contrast to lentiviral infections of humans and macaques, simian immunodeficiency virus (SIV) infection of natural hosts is nonpathogenic despite high levels of viral replication. However, the mechanisms underlying this absence of disease are unknown. Here we report that natural hosts for SIV infection express remarkably low levels of CCR5 on CD4+ T cells isolated from blood, lymph nodes, and mucosal tissues. Given that this immunologic feature is found in 5 different species of natural SIV hosts (sooty mangabeys, African green monkeys, mandrills, suntailed monkeys, and chimpanzees) but is absent in 5 nonnatural/recent hosts (humans, rhesus, pigtail cynomolgus macaques, and baboons), it may represent a key feature of the coevolution between the virus and its natural hosts that led to a nonpathogenic infection. Beneficial effects of low CCR5 expression on CD4+ T cells may include the reduction of target cells for viral replication and a decreased homing of activated CD4+ T cell to inflamed tissue.
Bausch DG, Nichol ST, Muyembe-Tamfum JJ, Borchert M, Rollin PE, Sleurs H, Campbell P, Tshioko FK, Roth C, Colebunders R, Pirard P, Mardel S, Olinda LA, Zeller H, Tshomba A, Kulidri A, Libande ML, Mulangu S, Formenty P, Grein T, Leirs H, Braack L, Ksiazek T, Zaki S, Bowen MD, Smit SB, Leman PA, Burt FJ, Kemp A, Swanepoel R, the International Scientific and Technical Committee for Marburg Hemorrhagic Fever Control in the Democratic Republic of the Congo	Marburg Hemorrhagic Fever Associated with Multiple Genetic Lineages of Virus	N Engl J Med 2006; 355:909-919, Aug 31, 2006	Background An outbreak of Marburg hemorrhagic fever was first observed in a gold-mining village in northeastern Democratic Republic of the Congo in October 1998. Methods We investigated the outbreak of Marburg hemorrhagic fever most intensively in May and October 1999. Sporadic cases and short chains of human-to-human transmission continued to occur until September 2000. Suspected cases were identified on the basis of a case definition; cases were confirmed by the detection of virus antigen and nucleic acid in blood, cell culture, antibody responses, and immunohistochemical analysis. Results A total of 154 cases (48 laboratory-confirmed and 106 suspected) were identified (case fatality rate, 83 percent); 52 percent of cases were in young male miners. Only 27 percent of these men reported having had contact with other affected persons, whereas 67 percent of patients who were not miners reported such contact (P<0.001). Most of the affected miners (94 percent) worked in an underground mine. Cessation of the outbreak coincided with flooding of the mine. Epidemiologic evidence of multiple introductions of infection into the population was substantiated by the detection of at least nine genetically distinct lineages of virus in circulation during the outbreak. Conclusions Marburg hemorrhagic fever can have a very high case fatality rate. Since multiple genetic variants of virus were identified, ongoing introduction of virus into the population helped perpetuate this outbreak. The findings imply that reservoir hosts of Marburg virus inhabit caves, mines, or similar habitats.
Oberhelman RA, Soto-Castellares G, Caviedes L, Castillo ME, Kissinger P, Moore DA, Evans C, Gilman RH	Improved recovery of Mycobacterium tuberculosis from children using the microscopic observation drug susceptibility method	Pediatrics. 118(1):e100-6, 2006 Jul	Objectives The diagnosis of pulmonary tuberculosis presents challenges in children, because symptoms are nonspecific, sputa are not accessible, and Mycobacterium tuberculosis cultures and smears often are negative. The Microscopic Observation Drug Susceptibility technique is a simple, inexpensive method for Mycobacterium tuberculosis isolation with superior speed and sensitivity over Lowenstein-Jensen culture in studies of adults with pulmonary tuberculosis. The objective of this study was to determine whether Microscopic Observation Drug Susceptibility culture can improve the sensitivity and speed of Mycobacterium tuberculosis recovery among Peruvian children with symptoms suggestive of pulmonary tuberculosis. Methods Two specimens of each type (gastric aspirate, nasopharyngeal aspirate, and stool specimens) were collected from each patient, examined by auramine stain, and cultured by Microscopic Observation Drug Susceptibility and Lowenstein-Jensen techniques. Patients (n=165) were enrolled between April 2002 and February 2004 at the Instituto de Salud del Nino, the major pediatric hospital in Lima, Peru. Inclusion criteria were age < or = 12 years, Stegen-Toledo clinical score > or = 5 points, and absence of antituberculous therapy. The main outcome measurements were (1) proportion of specimens that were culture positive by Microscopic Observation Drug Susceptibility versus Lowenstein-Jensen and (2) days required for positive culture result, stratified by specimen type and auramine stain result. Results Fifteen (9%) patients had at least 1 positive Mycobacterium tuberculosis culture (from stool in 3 cases, nasopharyngeal aspirate in 8 cases, and gastric aspirate in 15 cases). Thirty-eight culture-positive specimens were obtained (22 gastric aspirate, 12 nasopharyngeal aspirates, and 4 stools). Microscopic Observation Drug Susceptibility provided significantly more positive cultures than Lowenstein-Jensen (33 of 38 specimens culture positive by Microscopic Observation Drug Susceptibility vs 21 of 38 by Lowenstein-Jensen). This was attributed to enhanced recovery of Mycobacterium tuberculosis from auramine-negative specimens (19 of 23 by Microscopic Observation Drug Susceptibility vs 9 of 23 by Lowenstein-Jensen), in contrast to similar detection rates for the 2 tests with auramine-positive samples. Similar results were found for analyses that were limited to gastric aspirates. Isolation was faster by Microscopic Observation Drug Susceptibility than Lowenstein-Jensen. Conclusions Isolation of Mycobacterium tuberculosis from children with suspected pulmonary tuberculosis by Microscopic Observation Drug Susceptibility demonstrated greater yield and faster recovery than by Lowenstein-Jensen method, significantly improving local capabilities to detect pediatric tuberculosis in resource-poor settings.
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