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Lim P.-L.,Institute of Infectious Disease and Epidemiology | Han P.,Centers for Disease Control and Prevention | Chen L.H.,Mount Auburn Hospital | Chen L.H.,Harvard University | And 8 more authors.
BMC Infectious Diseases | Year: 2012

Background: Expatriates are a distinct population at unique risk for health problems related to their travel exposure.Methods: We analyzed GeoSentinel data comparing ill returned expatriates with other travelers for demographics, travel characteristics, and proportionate morbidity (PM) for travel-related illness.Results: Our study included 2,883 expatriates and 11,910 non-expatriates who visited GeoSentinel clinics ill after travel. Expatriates were more likely to be male, do volunteer work, be long-stay travelers (>6 months), and have sought pre-travel advice. Compared to non-expatriates, expatriates returning from Africa had higher proportionate morbidity (PM) for malaria, filariasis, schistosomiasis, and hepatitis E; expatriates from the Asia-Pacific region had higher PM for strongyloidiasis, depression, and anxiety; expatriates returning from Latin America had higher PM for mononucleosis and ingestion-related infections (giardiasis, brucellosis). Expatriates returning from all three regions had higher PM for latent TB, amebiasis, and gastrointestinal infections (other than acute diarrhea) compared to non-expatriates. When the data were stratified by travel reason, business expatriates had higher PM for febrile systemic illness (malaria and dengue) and vaccine-preventable infections (hepatitis A), and volunteer expatriates had higher PM for parasitic infections. Expatriates overall had higher adjusted odds ratios for latent TB and lower odds ratios for acute diarrhea and dermatologic illness.Conclusions: Ill returned expatriates differ from other travelers in travel characteristics and proportionate morbidity for specific diseases, based on the region of exposure and travel reason. They are more likely to present with more serious illness. © 2012 Lim et al.; licensee BioMed Central Ltd. Source


Yeo T.W.,Charles Darwin University | Yeo T.W.,Nanyang Technological University | Yeo T.W.,Institute of Infectious Disease and Epidemiology | Lampah D.A.,Menzies Research Institute | And 8 more authors.
PLoS Pathogens | Year: 2015

Tetrahydrobiopterin (BH4) is a co-factor required for catalytic activity of nitric oxide synthase (NOS) and amino acid-monooxygenases, including phenylalanine hydroxylase. BH4 is unstable: during oxidative stress it is non-enzymatically oxidized to dihydrobiopterin (BH2), which inhibits NOS. Depending on BH4 availability, NOS oscillates between NO synthase and NADPH oxidase: as the BH4/BH2 ratio decreases, NO production falls and is replaced by superoxide. In African children and Asian adults with severe malaria, NO bioavailability decreases and plasma phenylalanine increases, together suggesting possible BH4 deficiency. The primary three biopterin metabolites (BH4, BH2 and B0 [biopterin]) and their association with disease severity have not been assessed in falciparum malaria. We measured pterin metabolites in urine of adults with severe falciparum malaria (SM; n=12), moderately-severe malaria (MSM, n=17), severe sepsis (SS; n=5) and healthy subjects (HC; n=20) as controls. In SM, urinary BH4 was decreased (median 0.16 ¼mol/mmol creatinine) compared to MSM (median 0.27), SS (median 0.54), and HC (median 0.34)]; p<0.001. Conversely, BH2 was increased in SM (median 0.91 ¼mol/mmol creatinine), compared to MSM (median 0.67), SS (median 0.39), and HC (median 0.52); p<0.001, suggesting increased oxidative stress and insufficient recycling of BH2 back to BH4 in severe malaria. Overall, the median BH4/BH2 ratio was lowest in SM [0.18 (IQR: 0.04-0.32)] compared to MSM (0.45, IQR 0.27-61), SS (1.03; IQR 0.54-2.38) and controls (0.66; IQR 0.43-1.07); p<0.001. In malaria, a lower BH4/BH2 ratio correlated with decreased microvascular reactivity (r=0.41; p=0.03) and increased ICAM-1 (r=-0.52; p=0.005). Decreased BH4 and increased BH2 in severe malaria (but not in severe sepsis) uncouples NOS, leading to impaired NO bioavailability and potentially increased oxidative stress. Adjunctive therapy to regenerate BH4 may have a role in improving NO bioavailability and microvascular perfusion in severe falciparum malaria. Source


Barber B.E.,Charles Darwin University | William T.,Queen Elizabeth Hospital | Grigg M.J.,Charles Darwin University | Parameswaran U.,Queen Elizabeth Hospital | And 7 more authors.
PLoS Pathogens | Year: 2015

Plasmodium vivax can cause severe malaria, however its pathogenesis is poorly understood. In contrast to P. falciparum, circulating vivax parasitemia is low, with minimal apparent sequestration in endothelium-lined microvasculature, and pathogenesis thought unrelated to parasite biomass. However, the relationships between vivax disease-severity and total parasite biomass, endothelial autocrine activation and microvascular dysfunction are unknown. We measured circulating parasitemia and markers of total parasite biomass (plasma parasite lactate dehydrogenase [pLDH] and PvLDH) in adults with severe (n = 9) and non-severe (n = 53) vivax malaria, and examined relationships with disease-severity, endothelial activation, and microvascular function. Healthy controls and adults with non-severe and severe falciparum malaria were enrolled for comparison. Median peripheral parasitemia, PvLDH and pLDH were 2.4-fold, 3.7-fold and 6.9-fold higher in severe compared to non-severe vivax malaria (p = 0.02, p = 0.02 and p = 0.015, respectively), suggesting that, as in falciparum malaria, peripheral P. vivax parasitemia underestimates total parasite biomass, particularly in severe disease. P. vivax schizonts were under-represented in peripheral blood. Severe vivax malaria was associated with increased angiopoietin-2 and impaired microvascular reactivity. Peripheral vivax parasitemia correlated with endothelial activation (angiopoietin-2, von-Willebrand-Factor [VWF], E-selectin), whereas markers of total vivax biomass correlated only with systemic inflammation (IL-6, IL-10). Activity of the VWF-cleaving-protease, ADAMTS13, was deficient in proportion to endothelial activation, IL-6, thrombocytopenia and vivax disease-severity, and associated with impaired microvascular reactivity in severe disease. Impaired microvascular reactivity correlated with lactate in severe vivax malaria. Findings suggest that tissue accumulation of P. vivax may occur, with the hidden biomass greatest in severe disease and capable of mediating systemic inflammatory pathology. The lack of association between total parasite biomass and endothelial activation is consistent with accumulation in parts of the circulation devoid of endothelium. Endothelial activation, associated with circulating parasites, and systemic inflammation may contribute to pathology in vivax malaria, with microvascular dysfunction likely contributing to impaired tissue perfusion. © 2015 Barber et al. Source


Keel S.,La Trobe University | Malesic L.,Royal Melbourne Hospital | Chan S.-P.,University of Vic | Chan S.-P.,Institute of Infectious Disease and Epidemiology
Indian Journal of Ophthalmology | Year: 2014

Aim: The aim was to ascertain if any differences exist in diurnal central corneal thickness (CCT) and intra-ocular pressure (IOP) between eyes with pseudoexfoliation (PXF) syndrome without glaucoma and eyes with no ocular pathology. A secondary aim was to determine whether there was a significant relationship between CCT and IOP. Settings and Design: This study was a prospective design conducted within a hospital setting. Materials and Methods: The experimental group consisted of seven participants with bilateral PXF (14 eyes) and the control group comprised of 15 participants (30 eyes). Testing included CCT and IOP measured at four different times on one given day (8.00 a.m.; 11 a.m.; 2 p.m. and 5 p.m.). Statistical Analysis: The data were analyzed with the generalized linear latent mixed model. Results: PXF eyes displayed a significantly thinner overall mean CCT (520 μm) compared to controls (530 μm). Furthermore, a significant reduction in CCT and IOP occurred in the PXF group from 8 a.m. to 5 p.m. The mean overall IOP in PXF eyes was significantly lower than the control group. A significant association between IOP and CCT was also found in PXF eyes. Conclusions: Displaying a significantly thinner mean CCT highlights the importance of measuring CCT in an ophthalmic clinical setting as to avoid falsely underestimated IOP measurements in such a high-risk glaucoma population. Furthermore, a statistically significant correlation between IOP and CCT in PXF eyes suggests that the reduction in CCT that occurred in PXF eyes between 8 a.m. and 5 p.m. may be partly responsible for the reduction in IOP measurements. Source


Chronic bacterial, viral and parasitic infections contribute to the morbidity and mortality associated with human immunodeficiency virus (HIV) infection. This study investigated risk factors and time-trends of the seroprevalence of cytomegalovirus (CMV), toxoplasmosis and hepatitis A total antibody; and co-infection with syphilis, hepatitis B and hepatitis C among newly diagnosed HIV individuals in Singapore. This was a cross-sectional study. A random sample of 50% of HIV infected patients who visited the Communicable Disease Centre (CDC), Singapore for first-time care from January 2006 to December 2011 were analysed. Among the 793 study subjects, 93.4% were male; 77.9% of them were of Chinese ethnicity; mean age at HIV diagnosis was 41.4 years; and the mean baseline CD4+ T-cell count was 222 cells/mm3. The prevalence of sero-reactivity for CMV was 96.8%; hepatitis A: 40.9%; and toxoplasmosis: 23.7%. Co-infection with syphilis was identified in 12.3%; hepatitis B: 8.1%; and hepatitis C: 2%. Among those co-infected with hepatitis C, 73.3% of them were intravenous drug user (IVDU). Syphilis co-infection was significantly more common among men who have sex with men (MSM) (multivariate OR: 2.53, 95% CI, 1.31 to 4.90, P = 0.006). This study described the baseline rates of HIV co-infection with syphilis, hepatitis B and C in Singapore, and sero-reactivity to CMV, toxoplasmosis and hepatitis A. The increased rates compared to the general population may have important consequences for disease progression, response to antiretroviral treatment and long-term general health. Source

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