Factors involved in immunity to Nematospiroides dubius infections in mice

Thesis (M.Sc.) -- University of Adelaide, Dept. of Microbiology and Immunology, 198

FACTORS ASSOCIATED WITH ACUTE RENAL FAILURE IN ADULTS WITH SEVERE FALCIPARUM MALARIA

Abstract. We conducted a retrospective study of patients with severe falciparum malaria to determine factors associated with malarial acute renal failure (MARF). We reviewed 262 medical records of adults hospitalized with severe falciparum malaria in Thailand from 2004 to 2008. The incidence of MARF in our study population was 44% (115/262); 75% (86/115) of these had MARF on admission and 25% (29/115) developed MARF during hospitalization. The majority of MARF patients presented in a hypercatabolic state (62%, 68/109) and were non-oliguric (48%, 55/115) or oliguric (44%, 51/115). Forty-six percent of MARF patients (53/115) required renal replacement therapy for a median duration of 4.5 days. Patients with MARF had significantly higher complication rates (p<0.001), longer duration of hospitalization (p<0.001) and a higher case fatality rate (p=0.001). Using stepwise multiple logistic regression analysis by backward selection method, factors associated with MARF were advanced age [odds ratios (OR); 95% confidence intervals (CI) 1.037 (1

Accuracy of a Commercial IgM ELISA for the Diagnosis of Human Leptospirosis in Thailand

The Leptospira immunoglobulin M enzyme-linked immunosorbent assay (IgM ELISA) has been recommended for the rapid diagnosis of leptospirosis in endemic areas. We conducted a retrospective case-control study of 218 patients (109 leptospirosis cases confirmed by Leptospira culture and/or microscopic agglutination test and 109 control patients with acute febrile illness) to evaluate the diagnostic accuracy of a commercial IgM ELISA (Panbio) in northeast Thailand. Paired serum samples taken on admission and at least 10 days after the onset of symptoms were tested. Using the cutoff value recommended by the manufacturer (11 Panbio units), sensitivity and specificity of IgM ELISA on paired sera were 90.8% and 55.1%. A receiver operating characteristic curve was used to determine the optimal cutoff value. This was 20 Panbio units, which gave a sensitivity and specificity of 76.1% and 82.6%, respectively, on paired sera. We conclude that using either cutoff value, the accuracy of IgM ELISA is limited in our setting

Estimation of the Total Parasite Biomass in Acute Falciparum Malaria from Plasma PfHRP2

BACKGROUND: In falciparum malaria sequestration of erythrocytes containing mature forms of Plasmodium falciparum in the microvasculature of vital organs is central to pathology, but quantitation of this hidden sequestered parasite load in vivo has not previously been possible. The peripheral blood parasite count measures only the circulating, relatively non-pathogenic parasite numbers. P. falciparum releases a specific histidine-rich protein (PfHRP2) into plasma. Quantitative measurement of plasma PfHRP2 concentrations may reflect the total parasite biomass in falciparum malaria. METHODS AND FINDINGS: We measured plasma concentrations of PfHRP2, using a quantitative antigen-capture enzyme-linked immunosorbent assay, in 337 adult patients with falciparum malaria of varying severity hospitalised on the Thai–Burmese border. Based on in vitro production rates, we constructed a model to link this measure to the total parasite burden in the patient. The estimated geometric mean parasite burden was 7 × 10(11) (95% confidence interval [CI] 5.8 × 10(11) to 8.5 × 10(11)) parasites per body, and was over six times higher in severe malaria (geometric mean 1.7 × 10(12), 95% CI 1.3 × 10(12) to 2.3 × 10(12)) than in patients hospitalised without signs of severity (geometric mean 2.8 × 10(11), 95% CI 2.3 × 10(11) to 3.5 × 10(11); p < 0.001). Parasite burden was highest in patients who died (geometric mean 3.4 × 10(12), 95% CI 1.9 × 10(12) to 6.3 × 10(12); p = 0.03). The calculated number of sequestered parasites increased with disease severity and was higher in patients with late developmental stages of P. falciparum present on peripheral blood smears. Comparing model and laboratory estimates of the time of sequestration suggested that admission to hospital with uncomplicated malaria often follows schizogony—but in severe malaria is unrelated to stage of parasite development. CONCLUSION: Plasma PfHRP2 concentrations may be used to estimate the total body parasite biomass in acute falciparum malaria. Severe malaria results from extensive sequestration of parasitised erythrocytes

Evaluation of Hematocrit in Adults with Dengue by a Laboratory Information System

The implementation of a laboratory information system (LIS) at the Hospital for Tropical Diseases in Thailand provides valuable medical resources, particularly for dengue. Hematocrit (Hct), which is often derived from hemoglobin (Hgb), is important in the diagnosis and management of dengue. This study aimed to evaluate the Hct value obtained from the LIS automated analyzer. We prospectively enrolled 163 hospitalized adults with dengue, for whom 1,141 real-time complete blood count (CBC) results were obtained via a hematology analyzer and updated in the LIS database. The median (interquartile range (IQR)) duration of analytic turnaround times (TATs) was 40.0 (30.0–53.0) minutes. Linear regression analysis indicated a significant relationship between Hgb and Hct with a coefficient of determination (Pearson’s R2) of 0.92 at red blood cell distribution width (RDW) ≤18, but Pearson’s R2 decreased to 0.78 at RDW >18. The Hct calculated from the three-fold conversion method and from the analyzer had a Pearson’s R2 of 0.92. At Hgb <12 g/dl and ≥16 g/dl, a greater difference between the two Hct values was observed, with median (IQR) differences of −0.8% (−1.9%–0.2%) and 0.8% (−0.1%–1.7%), respectively (P value <0.05). In conclusion, the Hgb and Hct of patients with dengue were highly correlated at RDW ≤18. The Hct calculated from the three-fold conversion method and from the analyzer had an excellent relationship, except when the Hgb was <12 g/dl or ≥16 g/dl. Apart from routine CBC evaluation, the LIS could help for accurate data collection in clinical research and development

Risk Factors for Multidrug-Resistant Tuberculosis among Patients with Pulmonary Tuberculosis at the Central Chest Institute of Thailand.

There are limited data available on the risk factors for multidrug-resistant tuberculosis (MDR-TB). Therefore, we here conducted a retrospective matched case-control study among adults with pulmonary TB who received treatment at the Central Chest Institute of Thailand (CCIT) between January 2007 and December 2013, in order to determine the risk factors associated with MDR-TB among patients with pulmonary TB. We identified 145 patients with pulmonary MDR-TB (cases) and 145 patients with drug-sensitive pulmonary TB (controls). Multivariate analysis identified the independent risk factors for MDR-TB as follows: (1) ≥ 2 episodes of prior pulmonary TB (odds ratio [OR] 39.72, 95% confidence interval (95% CI) 7.86-200.66), (2) duration of illness > 60 days (OR 3.08, 95% CI 1.52-6.22), (3) sputum acid fast bacilli smear 3+ (OR 13.09, 95% CI 4.64-36.91), (4) presence of lung cavities (OR 3.82, 95% CI 1.89-7.73), and (5) presence of pleural effusion (OR 2.75, 95% CI 1.06-7.16). Prior pulmonary TB management with a non-category I regimen (P = 0.012) and having treatment failure or default as treatment outcomes (P = 0.036) were observed in a higher proportion among patients with MDR-TB. Particular characteristics of lung cavities, including the maximum diameter ≥ 30 mm (P < 0.001), the number of cavities ≥ 3 (P = 0.001), bilateral involvement (P < 0.001), and ≥ 2 lung zones involved (P = 0.001) were more commonly observed in patients with MDR-TB. In conclusion, these clinical factors and chest radiographic findings associated with MDR-TB among patients with pulmonary TB may help physicians to provide proper management of cases for prevention of the development and spread of MDR-TB in future

Clinical factors for severity of Plasmodium falciparum malaria in hospitalized adults in Thailand.

Plasmodium falciparum is a major cause of severe malaria in Southeast Asia, however, there is limited information regarding clinical factors associated with the severity of falciparum malaria from this region. We performed a retrospective case-control study to compare clinical factors and outcomes between patients with severe and non-severe malaria, and to identify clinical factors associated with the requirement for intensive care unit (ICU) admission of patients with severe falciparum malaria among hospitalized adults in Southeast Asia. A total of 255 patients with falciparum malaria in the Hospital for Tropical Diseases in Bangkok, Thailand between 2006 and 2012 were included. We identified 104 patients with severe malaria (cases) and 151 patients with non-severe malaria (controls). Patients with falciparum malaria with following clinical and laboratory characteristics on admission (1) referrals, (2) no prior history of malaria, (3) body temperature of >38.5°C, (4) white blood cell counts >10×10(9)/µL, (5) presence of schizonts in peripheral blood smears, and (6) albumin concentrations of <3.5 g/dL, were more likely to develop severe malaria (P<0.05). Among patients with severe malaria, patients who met ≥3 of the 2010 WHO criteria had sensitivity of 79.2% and specificity of 81.8% for requiring ICU admission. Multivariate analysis identified the following as independent associated factors for severe malaria requiring ICU admission; (1) ethnicity of Thai [odds ratio (OR) = 3.601, 95% confidence interval (CI) = 1.011-12.822] or Myanmar [OR = 3.610, 95% CI = 1.138-11.445]; (2) referrals [OR = 3.571, 95% CI = 1.306-9.762]; (3) no prior history of malaria [OR = 5.887, 95% CI = 1.354-25.594]; and (4) albumin concentrations of <3.5 g/dL [OR = 7.200, 95% CI = 1.802-28.759]. Our findings are important for the clinical management of patients with malaria because it can help early identification of patients that could develop severe malaria and require ICU admission. Early identification and the timely initiation of appropriate treatments may well improve the outcomes and reduce the mortality of these patients

Flow diagram of the study.

<p>Flow diagram of the study.</p