News Article | May 9, 2017
Researchers have identified a metabolite 'signature' that can accurately distinguish typhoid from other fever-inducing tropical diseases using patient blood samples. The research, published in the journal eLife, builds on previous results from 2014 showing that metabolite markers can distinguish between typhoid infection caused by different organisms. Many tropical diseases, such as typhoid and malaria, present with similar symptoms, making accurate diagnosis challenging and delaying effective treatment. A further problem with diagnosing typhoid is that currently available tests are not sensitive enough, and some patients are later found to have the disease, even though an organism cannot be cultured from their blood. The researchers used an approach called 'metabolomics', which involves measuring many small metabolites in a biological sample, to try and identify patterns that are unique to different diseases. In a previous study, they used this method to identify metabolic 'signatures' that could successfully differentiate between typhoid caused by two closely related organisms -- Salmonella Typhi and Salmonella Paratyphi A. "We wanted to assess if metabolomics could accurately diagnose typhoid in patients from different regions with a wider range of tropical diseases," says senior author Professor Stephen Baker, molecular microbiologist at Oxford University Clinical Research Unit, Vietnam. "We thought that this approach would more closely reflect the real situation where patients with fever-inducing diseases present with non-specific symptoms." Baker and his research collaborators collected blood samples from multiple patients from Bangladesh, who fell into three groups: patients who had Salmonella Typhi in their blood, those who were suspected of having typhoid from their symptoms, and a third group who were suspected of having a different tropical disease characterised by fever (a 'fever-control' group). Using mass spectrometry, the team analysed the metabolites in each patient blood sample to generate a metabolic 'signature' for two patient groups: those whose blood tested positive for typhoid, and fever controls. They then used this as a model to predict the identity of individual samples in a third group: patients suspected of having typhoid from their symptoms. They found that the model had excellent predictive power for distinguishing between culture-positive typhoid patients and patients with other types of tropical disease. "A major challenge in typhoid diagnosis is diagnosing true typhoid patients who have a negative blood culture result," explains first author Elin Näsström, a graduate student at Umeå University, Sweden. "We wanted to see if the detected metabolomics could help further distinguish these groups." As hoped, their predictive model pinpointed five out of nine blood-test-negative samples that were actually typhoid positive. And three out of five patients who were suspected of typhoid from their symptoms were also indicated to be typhoid-positive by their metabolite signature. To validate the signature further, the team studied an additional collection of blood samples from patients in Bangladesh and Senegal. They then compared these profiles against the original data from Nepal patients, published in the 2014 study by Näsström et al. From these combined analyses, they identified 24 metabolites that were consistently different between patients who had typhoid, and those who had other diseases including malaria. "Our results demonstrated a metabolite panel that can distinguish typhoid from other fever-inducing diseases, providing a new approach for typhoid diagnostics," Baker concludes. "The next challenges are to corroborate these metabolites in larger patient numbers and try and incorporate them into simple diagnostic test formats. This approach could be potentially expanded into other tropical diseases, eventually allowing for more accurate diagnosis and more effective treatment, and hopefully reducing the use of unnecessary antimicrobials." The paper, 'Reproducible diagnostic metabolites in plasma from typhoid fever patients in Asia and Africa', can be freely accessed online at http://dx. . It builds upon the previous study, 'Salmonella Typhi and Salmonella Paratyphi A elaborate distinct systemic metabolite signatures during enteric fever', which can be freely accessed at http://dx. . Contents, including text, figures and data, are free to reuse under a CC BY 4.0 license. eLife is a unique collaboration between the funders and practitioners of research to improve the way important research is selected, presented, and shared. eLife publishes outstanding works across the life sciences and biomedicine -- from basic biological research to applied, translational, and clinical studies. All papers are selected by active scientists in the research community. Decisions and responses are agreed by the reviewers and consolidated by the Reviewing Editor into a single, clear set of instructions for authors, removing the need for laborious cycles of revision and allowing authors to publish their findings quickly. eLife is supported by the Howard Hughes Medical Institute, the Max Planck Society, and the Wellcome Trust. Learn more at elifesciences.org. The Oxford University Clinical Research Unit (OUCRU) is a large-scale clinical and public health research unit with campuses in Ho Chi Minh City and Hanoi in Vietnam. OUCRU is hosted by the Hospital of Tropical Diseases (HTD) in Ho Chi Minh City, and the National Hospital for Tropical Diseases (NHTD) in Hanoi. As a Wellcome Trust Major Overseas Programme, OUCRU has received considerable support from the Trust since its establishment in 1991. The work of the unit covers clinical and public health research and includes work in immunology, host and pathogen genetics, molecular biology, virology, mathematical modelling, bioinformatics, biostatistics and epidemiology. Overall, OUCRU aims to have a positive and significant impact on global health and, in particular, the prevention, diagnosis and treatment of infectious diseases. This is being achieved via an integrated long-term research programme, contributions to training, the scientific literature, national and international meetings and membership of national and international committees. Priority is given to health issues important to the hospitals, and to Vietnam as a whole. All work is intended not only to benefit the patients seen daily at our host hospitals, but also to help improve patient care throughout the country. http://www.
Nguyen H.P.,Hospital of Tropical Diseases |
Hanson J.,Cairns Base Hospital |
Nguyen T.H.,Hospital of Tropical Diseases |
Tran T.H.,Hospital of Tropical Diseases |
And 10 more authors.
PLoS ONE | Year: 2011
Background: Optimising the fluid resuscitation of patients with severe malaria is a simple and potentially cost-effective intervention. Current WHO guidelines recommend central venous pressure (CVP) guided, crystalloid based, resuscitation in adults. Methods: Prospectively collected haemodynamic data from intervention trials in Vietnamese adults with severe malaria were analysed retrospectively to assess the responses to fluid resuscitation. Results: 43 patients were studied of whom 24 received a fluid load. The fluid load resulted in an increase in cardiac index (mean increase: 0.75 L/min/m2 (95% Confidence interval (CI): 0.41 to 1.1)), but no significant change in acid-base status post resuscitation (mean increase base deficit 0.6 mmol/L (95% CI: -0.1 to 1.3). The CVP and PAoP (pulmonary artery occlusion pressure) were highly inter-correlated (rs = 0.7, p&0.0001), but neither were correlated with acid-base status (arterial pH, serum bicarbonate, base deficit) or respiratory status (PaO2/FiO2 ratio). There was no correlation between the oxygen delivery (DO2) and base deficit at the 63 time-points where they were assessed simultaneously (rs=-0.09, p=0.46). Conclusions: In adults with severe falciparum malaria there was no observed improvement in patient outcomes or acid-base status with fluid loading. Neither CVP nor PAoP correlated with markers of end-organ perfusion or respiratory status, suggesting these measures are poor predictors of their fluid resuscitation needs. © 2011 Phu et al.
Tho D.Q.,University of Oxford |
Lan N.T.N.,Pham Ngoc Thach Hospital for Tuberculosis and Lung Diseases |
Chau N.V.V.,Hospital of Tropical Diseases |
Farrar J.,University of Oxford |
Caws M.,University of Oxford
International Journal of Tuberculosis and Lung Disease | Year: 2011
SETTING: Pham Ngoc Thach Tuberculosis Reference Hospital, Ho Chi Minh City, Viet Nam. DESIGN: A multiplex allele-specific polymerase chain reaction (MAS-PCR) was developed to detect mutations at the two most common sites responsible for isonia-zid (INH) resistance in Mycobacterium tuberculosis: katG315 and inhA-15. The MAS-PCR is able to detect rare mutations at katG315, in addition to katG S315T. Conventional phenotypic proportion drug susceptibility testing on Löwenstein-Jensen media was used as a gold standard to compare the sensitivity and specificity of the commercial MTBDRplus line-probe assay and the MAS-PCR in 100 INH-resistant and 50 INH-susceptible isolates collected consecutively at Pham Ngoc Thach Hospital reference laboratory. RESULTS: The sensitivity and specificity on culture isolates were 90% (n = 90/100, 95%CI 0.83-0.94) and 100% (n = 50/50, 95%CI 0.93-1.0), respectively, for the MAS-PCR and the MTBDRplus assay. CONCLUSION: The MAS-PCR described here represents an alternative method for rapid screening for INH resistance in M. tuberculosis isolates. © 2011 The Union.
Polycarpou A.,London School of Hygiene and Tropical Medicine |
Walker S.L.,London School of Hygiene and Tropical Medicine |
Lockwood D.N.,London School of Hygiene and Tropical Medicine |
Lockwood D.N.,Hospital of Tropical Diseases
Current Opinion in Infectious Diseases | Year: 2013
Purpose of Review: This review focuses on recent work in leprosy pathogenesis. New research of both innate and adaptive immune responses to Mycobacterium leprae is described. The proposition that Mycobacterium lepromatosis is a new species causing leprosy is discussed. Recent Findings: Modulation of the lipid metabolism and reprogramming of adult Schwann cells have both been suggested as mechanisms used by M. leprae to disseminate the disease. New markers associated with localized, disseminated disease or the occurrences of leprosy reactions include the human interferons, CD163, microRNA-21, NOD2, galectin-3 and toll-like receptor 4. The role of keratinocytes instead of macrophages is underlined in the pathogenesis of leprosy. Adaptive immunity reports focus on the role of T regulatory cells and cytokines secreted by T helper cells in leprosy. Finally, a newly identified species named M. lepromatosis has been detected in patients with leprosy and severe erythema nodosum leprosum. Summary: Novel biological pathways have been identified to be associated with the clinical phenotype of leprosy or the occurrence of leprosy reactions. Future work should include larger numbers of clinical samples from across the leprosy spectrum in order to give new insights in the pathogenesis and management of the disease. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.
de Lemos P.A.P.,Hospital of Tropical Diseases |
Garcia-Zapata M.T.A.,Hospital of Tropical Diseases
International Journal of Tropical Medicine | Year: 2010
The frequency of Trichomonas vaginalis infection in HIV-positive and negative women attending hospitals in Goiania, Brazil was evaluated using the gold standard diagnostic method of culture. A total of 237 vaginal swab specimens were examined: 125 (52.7%) comprising the HIV-positive group and 112 (47.3%) the HIV-negative control group. T. vaginalis was detected in 13.5% of the women, 23 (18.4%) of whom were HIV-positive while 9 (8.0%) were HIV-negative. This difference was statistically significant however, infection by this parasite was not found to be associated with immune status. T. vaginalis was found in 23.1% of the pregnant women and there was a statistically significant difference in the rate of infection by this parasite between the pregnant HIV-positive and the pregnant HIV-negative women (25.8% versus 12.5%). T. vaginalis was more prevalent in HIV-positive compared to HIV-negative women however, no association was found between the infection and the immune status of the patients. © Medwell Journals, 2010.
PubMed | Hospital of Tropical Diseases
Type: Journal Article | Journal: PloS one | Year: 2011
Optimising the fluid resuscitation of patients with severe malaria is a simple and potentially cost-effective intervention. Current WHO guidelines recommend central venous pressure (CVP) guided, crystalloid based, resuscitation in adults.Prospectively collected haemodynamic data from intervention trials in Vietnamese adults with severe malaria were analysed retrospectively to assess the responses to fluid resuscitation.43 patients were studied of whom 24 received a fluid load. The fluid load resulted in an increase in cardiac index (mean increase: 0.75 L/min/m(2) (95% Confidence interval (CI): 0.41 to 1.1)), but no significant change in acid-base status post resuscitation (mean increase base deficit 0.6 mmol/L (95% CI: -0.1 to 1.3). The CVP and PAoP (pulmonary artery occlusion pressure) were highly inter-correlated (r(s)=0.7, p<0.0001), but neither were correlated with acid-base status (arterial pH, serum bicarbonate, base deficit) or respiratory status (PaO(2)/FiO(2) ratio). There was no correlation between the oxygen delivery (DO(2)) and base deficit at the 63 time-points where they were assessed simultaneously (r(s)=-0.09, p=0.46).In adults with severe falciparum malaria there was no observed improvement in patient outcomes or acid-base status with fluid loading. Neither CVP nor PAoP correlated with markers of end-organ perfusion or respiratory status, suggesting these measures are poor predictors of their fluid resuscitation needs.