Cytokine levels as biomarkers for leptospirosis patients.

Inflammatory mediators were suggested to be biomarkers for prediction of disease severity. In this study, we investigated the levels of IL-6, IL-8, IL-10 and TNF-α in leptospirosis patients with mild or severe illnesses. Sera samples were divided into two groups. The OI group and NOI groups included sera from patients with and without organ involvement, respectively. Each group consisted of 20 pairs of sera. Twenty-five sera from healthy individuals were included as controls. Cytokine levels were compared. Although IL-6, IL-8 and IL-10 levels in acute sera from the OI group were significantly higher than NOI group, only IL-8 level was significantly higher in the OI group when cytokine levels in convalescent sera were compared. TNF-α, an inflammatory cytokine widely studied in leptospirosis was not significantly different between two groups of patients. Our data suggested that IL-6, IL-8 and IL-10 were involved in disease severity. However, time of specimen collection could affect the significant levels of cytokines especially as biomarkers for monitoring disease severity.

HIV in young people: characteristics and predictors for late diagnosis of HIV.

Late diagnosis of human immunodeficiency virus (HIV) infection remains a challenging issue, especially in young population, which accounts for approximately half of new HIV infections. This study aimed to assess factors associated with late diagnosis of HIV infection in young people. It employed a hospital-based case-control design, conducted during January 2012 through August 2013. A total of 193 patients aged 18-25 years old from 21 hospitals across Thailand were studied. Late diagnosis was defined as presentation when the CD4 cell count was less than 350 cells/µL within 12 months of the first HIV diagnosis, or AIDS-defining event is present within 12 months of the first HIV diagnosis. Factors associated with the late diagnosis of HIV were those who: did not live with their parent (OR 3.87; 95% CI 1.40-10.66), had no children (OR 3.25; 95% CI 1.27-8.31), had their first sexual intercourse at age older than 18 years (OR 4.25; 95% CI 1.27-14.22), had same-age or older partners (OR 3.36; 95% CI 1.39-8.08), were substance users (OR 3.65; 95% CI 1.22-10.88), believed they changed their behaviors after receiving HIV education (OR 2.48; 95% CI 1.02-5.99), and sought care at regional (OR 3.19; 95% 1.31-7.79) or general hospitals (OR 3.34; 95% 1.07-10.35). Strategies for early HIV detection in young people should be reconsidered; particularly the involvement of parents and targeting the right population.

Model for predicting the burden and cost of treatment in cervical cancer and HPV-related diseases in Thailand.

PURPOSE: Cervical cancer is a significant health burden in many countries. Long-term cost of care is still not well understood. We aimed to evaluate the long-term burden of illness and healthcare resource utilization associated with cervical cancer, cervical intraepithelial neoplasia (CIN) and genital warts from the care provider perspective. METHOD: We developed a health state-transition Markov model to portray the algorithm of treatment of stages of cervical cancer, CIN and genital warts by tracking a hypothetical lifetime cohort of 12-year-old girls. Costs in this study were unit cost; capital costs and labor costs were included in the unit cost for inpatients and out-patients. RESULTS: The highest incidence of CIN and genital warts was observed in women aged 20-30 years old. For cervical cancer, the highest incidence was 45-55 years. Death rate was estimated at 2%, 8%, 84% and 94% in cervical cancer Stage IA1, IA2-IIA, IIB-IVA and IVB, respectively. The estimated mean direct cost per patient with cervical cancer Stage IA1, IA2-IIA, IIB-IVA, IVB, CIN1, CIN2/3 and genital warts were 41,117 Thai Baht ($1,277 US), 97,250 Thai Baht ($3,020 US), 402,683 Thai Baht ($12,506 US), 322,619 Thai Baht ($10,019 US), 5,381 Thai Baht ($167 US), 49,933 Thai Baht ($1.551 US) and 3,585 Thai Baht ($111 US), respectively. Cost for survival or death case was indifferent. The overall lifetime costs from the provider perspective were evaluated at 859.1 million Baht ($26.7 million US) per a cohort of 100,000 women which corresponds to approximately 4,244 million Baht ($131.8 million US) for the current number of Thai 12-year-old girls. CONCLUSIONS: HPV-related diseases impose health and cost burdens in Thailand. The national immunization programme to reduce this burden as well as further research to evaluate the impact is keenly expected.

Increased alanine aminotransferase level and future risk of type 2 diabetes and impaired fasting glucose among the employees in a university hospital in Thailand.

AIM: The purpose of this study was to determine the association between baseline alanine aminotransferase (ALT) levels, and future risk of impaired fasting glucose and type 2 diabetes among the employees of a university hospital in Bangkok, Thailand. METHODS: Totally, 2370 and 1619 workers without diabetes and impaired fasting glucose (IFG) at baseline, respectively, who were 35 years or older were followed during 2001-2005. Diagnosis of IFG and type 2 diabetes was based on the fasting plasma glucose levels of 100-125 and greater or equal to 126 mg/dl, respectively. RESULTS: Higher baseline ALT levels were associated with future diabetes risk in an obvious dose-response manner (the OR [95% CI] for the groups with baseline ALT of 17-22, 23-38, and greater than 38 mg/dl comparing to the group with baseline ALT of 1-16 mg/dl were 4.75 [1.25-18.10], 6.14 [1.54-24.45], and 7.19 [1.32-39.16], respectively). Magnitude of association were even higher among those with existing IFG at baseline. The association patterns were consistent for both genders. Concerning the IFG risk, while those who developed IFG had significantly higher baseline ALT levels than those who remained normal at the end of follow-up period, further analyses did not show that baseline ALT was significantly associated with future IFG risk. CONCLUSION: Present study provided supporting evidence from a cohort of Asian subjects about the ALT and future type 2 diabetes risk.

Seroepidemiologic studies of humoral immune response to the Plasmodium falciparum antigens in Thailand.

We have investigated seroreactivity against Plasmodium falciparum crude parasite antigens, the P. falciparum ring-infected erythrocyte surface antigen (Pf155/RESA), as well as against two synthetic peptides (EENV)6 and (EENVEHDA)3 that represent important epitopes of Pf155/RESA. The study population consisted of 421 children and adult Thais living in an area with moderate malaria transmission. We related these serologic findings to some important epidemiologic baseline data collected in the study area. The parasite rate in study subjects was 18.76%. Sixty-two percent were seropositive to crude P. falciparum antigens, 30.3% to the Pf155/RESA antigen, 23.05% to (EENV)6, and 20.17% to (EENVEHDA)3. Antibody responses to crude P. falciparum antigens and to Pf155/RESA were age dependent and increased with exposure. There was evidence that Pf155/RESA antibodies might play a role in protective immunity in this population. Since Pf155/RESA is a potential vaccine candidate antigen, the information obtained from these field studies will provide some seroepidemiologic baseline data for subsequent vaccine trials.

Economic impact of tuberculosis at the household level.

OBJECTIVE: Previous economic analyses of tuberculosis control interventions have focused on the provider perspective. To assess the overall economic impact of the disease and the adequacy of current control strategies from a societal viewpoint, the determination of direct and indirect patient costs is required. SETTING AND DESIGN: In a cross-sectional survey, all adult tuberculosis patients who completed treatment between August 1996 and February 1997 at 16 randomly selected government health care facilities in Thailand (n = 673) were interviewed using a structured questionnaire. Information were obtained on direct and indirect patient costs before and after diagnosis, and on financing methods and changes in household consumption patterns. All results were stratified for three levels of patient household income: above national average, below national average but above the poverty line, and below the poverty line. RESULTS: Illness-related costs particularly affected patients with incomes below the poverty line (n = 153). In this group, average out-of-pocket expenditures for the disease amounted to more than 15% of annual household income, while incomes were reduced by 5 % due to illness-related effects. Expenditures were most frequently financed from household savings or transfer payments from community members and relatives. However, 11.8% of patient households took out bank loans, and 15.9% sold part of their property. CONCLUSION: The current low case detection and treatment completion rates for tuberculosis patients in Thailand may partly be due to the inability of poor patients to cope with the economic consequences of diagnosis and treatment. Suggested improvements include the strict enforcement of an existing government policy of free care, the further decentralization of services to reduce travel costs and work absences, and social security payments for patients undergoing treatment.

Randomized controlled trial of directly observed treatment (DOT) for patients with pulmonary tuberculosis in Thailand.

While directly observed treatment (DOT) has been recommended as the standard approach to tuberculosis control, empirical data on its feasibility and efficiency are still scarce. We conducted a controlled trial of DOT at 15 health care facilities at various levels of the government health care system in Thailand. A total of 836 patients diagnosed between August 1996 and October 1997 were randomly assigned to be treated either under DOT or self-supervised using monthly drug supplies (SS). Options for treatment supervisors were health staff, community members or members of the patients' families. Treatment outcomes were compared on the basis of cure, treatment-completion, default and death rates. In both study arms, treatment outcomes were improved compared to pre-study conditions. Cure and treatment-completion rates were significantly higher in the DOT cohort (76% and 84%) than in the SS group (67% and 76%). The benefits of DOT were more pronounced at district and provincial hospitals (DOT cure rate 81% vs. 69% in the SS group), while differences for patients treated at referral centres were non-significant (DOT cure rate 72% vs. 66% in the SS group). No significant differences in outcomes could be observed between patient groups receiving DOT under the various options for treatment supervisors. DOT appears especially suited for treatment at decentralized facilities. While a general focus on programme performance can improve outcomes, DOT provides significant additional benefits. If basic conditions are met, a DOT strategy can be tailored to country-specific conditions by exploring multiple observation options, without decreasing its effectiveness.

Modeling factors influencing malaria incidence in Myanmar.

This is a documentary study to determine factors influencing malaria incidence in Myanmar. The period of study covered was from 1989 to 1998 using time series data. Multiple regression analysis was performed on the dependent variable, yearly incidence of malaria in Myanmar, with hypothesized independent variables including variables related to epidemiology, demography, service and socioeconomic status. Malaria incidence was inversely associated with the government budget for malaria control at the 5% level and with the case fatality rate of malaria at the 10% level. Other variables: yearly gross domestic product, yearly proportion of Plasmodium falciparum cases and yearly DDT use of spraying displayed expected signs but were not statistically significant.

Ex post and ex ante willingness to pay (WTP) for the ICT Malaria Pf/Pv test kit in Myanmar.

Willingness to pay (WTP) for the ICT Malaria Pf/Pv test kit was assessed by the contingent valuation method using a bidding game approach in two villages in Myanmar. Kankone (KK) village has a rural health center (RHC) and Yae-Aye-Sann (YAS) is serviced by community health worker (CHW). The objectives were to assess WTP for the ICT Malaria Pf/Pv test kit and to determine factors affecting the WTP. In both villages WTP was assessed in two different conditions, ex post and ex ante. The ex post WTP was assessed at an RHC in the KK village and at the residence of a CHW in the YAS village on patients immediately following diagnosis of malaria. The ex ante WTP was assessed by household interviews in both villages on people with a prior history of malaria. Ordinary least squares (OLS) multiple regression analysis was used to analyze factors affecting WTP. The WTP was higher in ex post conditions than ex ante in both villages. WTP was significantly positively associated with the average monthly income of the respondents and severity of illness in both ex post and ex ante conditions (p < 0.001). Distance between the residence of the respondents and the health center was significantly positively associated (p < 0.05) in the ex ante condition in a household survey of YAS village. Traveling time to RHC had a negative relationship with WTP (p < 0.05) in the ex post condition in the RHC survey in KK village.

Epidemiological studies of malaria at Pong Nam Ron, eastern Thailand.

Malaria is still a serious health problem in Thailand. Present attempts at controlling the disease by drug treatment and other means remain unsatisfactory. Thus, development of vaccination against malaria is a major research goal of malaria immunology. The objective of this study was to acquire epidemiological base line data for subsequent vaccine trials. A cross-sectional descriptive survey was conducted among 451 local inhabitants during the beginning of the transmission season in June 1989 at Pong Nam Ron District, Chanthaburi Province, Eastern Thailand where malaria transmission was likely to be high. Following the cross-sectional survey weekly morbidity surveillance was started to detect new cases of malaria by using active and passive case detection at the district hospital, local health centers and at neighboring malaria clinics. Entomological observations were made monthly to determine inoculation rates. Forty-six percent of the population were male and 54% female; one third were under the age of 15 and 14% under the age of 5 years. Eighty percent of the adults were married. Sixty percent of the subjects interviewed gave a history of malarial illness in the past. Malaria, malnutrition, abnormal hemoglobin diseases and parasitic infestation were the main health problems in the study area. The annual parasite incidence of malaria was 149.6/1,000 population and two-thirds of them were asymptomatic indicating a semi-immune condition among these subjects. It was difficult to interpret the results of entomological studies due to low density of the malaria vector.

Malaria in a rural area of eastern Thailand: baseline epidemiological studies at Bo Thong.

Malaria is still a serious health problem in Thailand. Present attempts at controlling the disease by drug treatment and other means remain unsatisfactory. Thus, development of vaccination against malaria is a major research goal of malaria immunology. The objective of this study was to acquire epidemiological base line data for subsequent vaccine trials. A cross-sectional descriptive survey was conducted among 253 local inhabitants during the beginning of the transmission season in July 1989 at Bo Thong District, Chonburi Province, Eastern Thailand where malaria transmission was likely to be moderately high. Following the cross-sectional survey weekly morbidity surveillance was started to detect new cases of malaria by using active and passive case detection at the district hospital, local health centers and at neighboring malaria clinics. Fifty-four percent of the population were male and forty-six percent female: nearly a half (48.3%) were under the age of 15 and 17% under the age of 5 years. Eighty percent of the adults were married. Seventy percent of the subjects interviewed gave a history of malarial illness in the past. Malaria, malnutrition, anemia abnormal hemoglobin diseases and parasitic infestations were the main health problems in the study area. The annual parasite incidence of malaria was 169.4/1,000 population and 77% of parasitemic individuals were asymptomatic, indicating the existence of a semi-immune condition among these subjects. Antibody level to crude parasite antigen increased with age. It is hoped that the information obtained from these field studies may be useful in malaria vaccine trials in the near future.

A longitudinal study of seroreactivities to a major blood stage antigen (Pf155/RESA) of the malaria parasite Plasmodium falciparum in an endemic area of Thailand.

We have performed a longitudinal study of the formation of antibodies to Plasmodium falciparum in an area of Thailand where malaria transmission is moderate and seasonal. The study population comprised 118 subjects living in two villages 230 km southeast of Bangkok. All subjects included in this study were seropositive for antibodies to the blood stages of P. falciparum but only approximately 80% had antibodies to the blood stage antigen Pf155/RESA when assayed by erythrocyte membrane immunofluorescence (EMIF) or peptide ELISA during the period of maximal transmission. The reduced capacity to form these antibodies in a significant fraction of subjects living under comparable environmental and socio-economic conditions may reflect a genetic but antigen specific non-responsiveness. Both seropositivity and mean antibody titers to Pf155/RESA and its B-cell epitopes tended to be slightly higher during the rainy than during the dry season but the seasonal variations were slight and statistically not significant. Parasite rates were significantly higher in the rainy than in the dry season in both the EMIF positive and the EMIF negative groups. However, during the rainy season, the parasite rates in subjects with no or low titered antibodies to Pf155/RESA were significantly higher than those in subjects having such antibodies. The results suggest that antibodies to Pf155/RESA and some of its defined epitopes may be of importance for controlling parasitemias.

Alpha-L-fucosidase as a serum marker of hepatocellular carcinoma in Thailand.

To evaluate the role of serum alpha-L-fucosidase (AFU) in the diagnosis of hepatocellular carcinoma (HCC), we simultaneously studied both AFU activity and alpha-fetoprotein (AFP) level in 60 patients with HCC, 60 patients with cirrhosis and chronic hepatitis each, 30 patients with other liver tumors and 60 healthy subjects. Serum AFU activity in patients with HCC (1,418.62 +/- 575.76 nmol/ml/hr) was significantly higher than that found in cirrhosis (831.25 +/- 261.13 nmol/ml/hr), chronic hepatitis (717.71 +/- 205.86 nmol/ ml/hr) or other tumors (706.68 +/- 197.67 nmol/ml/hr) and in controls (504.18 +/- 121.88 nmol/ml/hr, p < 0.05). With 870 nmol/ml/hr (mean value of controls plus 3 standard deviations) considered as the cut-off point, AFU was more sensitive (81.7 vs 39.1%) but less specific (70.7 vs 99.3%) than AFP at a level of > 400 ng/ml as a tumor marker of HCC. With both markers combined, the sensitivity was improved to as much as 82.6%. AFU activity in HCC patients was correlated to tumor size (r = 0.3529, p = 0.006) but not associated with tumor staging classified by Okuda's criteria (p = 0.1). The AFU activity in the viral hepatitis group (hepatitis B or C) was also significantly higher than in the non-viral group (p = 0.0005). We conclude AFU to be a useful marker, in conjunction with AFP and ultrasonography, for detecting HCC, particularly in patients with underlying viral hepatitis and cirrhosis.

Fast liver alkaline phosphatase isoenzyme in diagnosis of malignant biliary obstruction.

Fast liver alkaline phosphatase isoenzyme was measured by cellulose acetate electrophoresis in the sera obtained from 84 patients with specific hepatobiliary diseases and 10 control subjects. The mean value of this isoenzyme in patients with malignant extrahepatic obstruction was 130.58 +/- 107.08 U/L, significantly higher than that of patients with benign extrahepatic obstruction (65.63 +/- 34.14 U/L), as well as patients with intrahepatic cholestasis and infiltrative liver cancers (65.31 +/- 38.11 U/L and 48.47 +/- 36.85 U/L, respectively). Furthermore, we could not detect this isoenzyme in normal individuals. When 100 U/L was used as a cut-off value to discriminate between patients with malignant extrahepatic obstruction and the remaining hepatobiliary disorders, the sensitivity, specificity and accuracy of the test were 63 per cent, 84 per cent and 80 per cent, respectively. It is concluded that the fast liver isoenzyme could be a useful marker in diagnosis of malignant extrahepatic obstruction.

Clinical characteristics and prognosis of hepatocellular carcinoma: analysis based on serum alpha-fetoprotein levels.

The purpose of this study was to determine whether a relation does exist between clinicopathologic features and the prognosis of hepatocellular carcinoma (HCC) with respect to serum alpha-fetoprotein (AFP) levels at diagnosis. We reviewed the clinical data of 309 pathologically proven HCC cases divided into three groups: group 1 with normal AFP (<20 IU/mL), group 2 with moderately elevated AFP (20-399 IU/mL) and group 3 with markedly elevated AFP (> or =400 IU/mL). Of these, there were 76 (24.6%), 78 (25.2%), and 155 patients (50.2%) in groups 1, 2, and 3, respectively. We found that HCC patients with high AFP tended to have greater tumor size, bilobar involvement, massive or diffuse types, and portal vein thrombosis. Nonetheless, we could not establish a correlation between increased AFP and Okuda's stages, degree of tumor differentiation, or extrahepatic metastasis. The median survival rates in groups 1 (6 months) and 2 (7 months) were significantly longer than that of group 3 (3 months). On multivariate logistic regression analysis, positive hepatitis B surface antigen (HBsAg) status and bilobar tumor involvement represented the independent factors for predicting high AFP values. We concluded that AFP is useful not only for diagnosis, but also as a prognostic indicator in patients with HCC . However, it cannot be considered a sensitive tumor marker, particularly during the early stages in HBsAg-negative patients.

Nalbuphine versus propofol for treatment of intrathecal morphine-induced pruritus after cesarean delivery.

UNLABELLED: In this prospective, randomized, double-blinded study, we compared the efficacy of nalbuphine and propofol for treating intrathecal morphine-induced pruritus after cesarean delivery. One-hundred-eighty-one parturients who developed moderate to severe pruritus after the administration of intrathecal morphine were randomly allocated into two groups. One group received 3 mg IV nalbuphine (n = 91), and the other received 20 mg IV propofol (n = 90). The improvement of pruritus and other adverse effects was determined at 10 min after study drug administration. The treatment success rate was higher in the Nalbuphine group than in the Propofol group (83% vs 61%; P < 0.001). Among the successfully treated patients, recurrence rates of moderate to severe pruritus within 4 h were not significantly different (nalbuphine 9% versus propofol 7%; P = 0.76). Other side effects, such as decreased analgesia, increased nausea, vomiting, increased sedation, pain on injection, and dizziness, were not significantly different between groups. Sedation and pain on injection, which were the two most common side effects, were minor and clinically inconsequential. IMPLICATIONS: Nalbuphine was superior to propofol for the treatment of intrathecal morphine-induced pruritus after cesarean delivery.