Sombat Treeprasertsuk

Ascaris lumbricoides infection is associated with protection from cerebral malaria

Following reports of increased IgE in severe malaria and hypothesizing that helminth coinfections could modify its outcome, we conducted a retrospective case–control study to establish whether helminths affect the evolution of Plasmodium falciparum malaria. Some 182 severe cases, 315 mild controls and 40 controls with circulating schizonts were examined for intestinal helminths. Comparing cerebral malaria with mild controls, Ascaris lumbricoides was associated with a protective adjusted odds ratio (OR) of 0.58 (0.32–1.03) P = 0.06, for coinfection with Ascaris and Necator americanus, OR = 0.39 (0.17–0.88) P = 0.02. Protection followed a dose–effect trend (P = 0.008). When comparing cerebral malaria cases and controls with circulating schizonts the OR was 0.25 (0.009–0.67) P = 0.006. We hypothesized that Ascaris infected patients may have had decreased cyto‐adherence, possibly through endothelial cell receptor downregulation and/or decreased splenic clearance leading to the absence of selection of virulent P. falciparum strains. IgE‐anti‐IgE immune complexes resulting from helminth preinfection may have an important role in influencing clinical presentation of severe malaria, and in establishing malaria tolerance, through the CD23/NO pathway.

The Framingham risk score and heart disease in nonalcoholic fatty liver disease

The accuracy of the Framingham risk score (FRS) in identifying patients with nonalcoholic fatty liver disease (NAFLD) at higher 10‐year coronary heart disease (CHD) risk remains unknown. We aimed at evaluating both the baseline probability of CHD as predicted by the FRS and the actual long‐term occurrence of CHD in NAFLD patients. This was a longitudinal study of a community‐based cohort. A total of 309 NAFLD patients were followed up for 11.5 ± 4.1 years (total 3554 person‐years). The overall calculated 10‐year CHD risk was significantly higher in the NAFLD cohort than the absolute CHD risk predicted by the FRS for persons of the same age and gender (10.9 ± 9.3% vs. 9.9 ± 5.9%, respectively, P < 0.0001), and higher in men than women (12.6 ± 10.3% vs. 9.6 ± 8.1%, respectively, P = 0.006). New onset CHD occurred in 34 patients (11% vs. 10.9% predicted at baseline, P = NS), whereas 279 (89%) patients did not develop CHD. Using multivariable analysis, the FRS was the only variable significantly associated with new onset CHD (OR = 1.13, 95% CI = 1.05–1.21; P = 0.001). A FRS cut‐point of 11 in women, and 6 in men had a sensitivity of 80% and 74%, respectively, and a negative predictive value of 97% and 93% respectively. NAFLD patients have a higher 10‐year CHD risk than the general population of the same age and gender. The FRS accurately predicts the higher 10‐year CHD risk in NAFLD patients, and helps identify those patients expected to derive the most benefit from early intervention to prevent CHD events.

Decreased hemoglobin concentrations, hyperparasitemia, and severe malaria are associated with increased Plasmodium falciparum gametocyte carriage.

To determine factors influencing gametocyte carriage, a cross-sectional study was conducted among 512 patients admitted for Plasmodium falciparum malaria. After adjustments for potential confounders, hemoglobin concentrations were lower in gametocyte carriers 10.5 (±2.5) than in patients without gametocytes 12.5 (±2.3) (P < 0.0001). Hemoglobin concentrations were negatively correlated with peak gametocyte counts (Spearmans ρ = −0.37, P < 0.0001) and gametocyte carriage durations (Spearmans ρ = −0.30, P < 0.0001). Adjustments for the duration of the malaria episode and other potential confounders did not alter the association (P < 0.0001). After adjustment for potential confounders, the median asexual parasitemia was higher in patients with gametocytes than in patients without gametocytes (P = 0.003). Severe malaria cases were more likely to have gametocytes (65%) than malaria with hyperparasitemia (38%) or mild malaria (31%) (P = 0.0001). These findings suggest that events surrounding anemia and tissue hypoxia stimulate Plasmodium falciparum gametocytogenesis.

Chloroquine sensitivity of Plasmodium vivax in Thailand.

Chloroquine has been the standard treatment for Plasmodium vivax malaria for more than 40 years in most regions of the world. Recently, however, chloroquine-resistant P. vivax has been reported from Oceania, several parts of Asia, and South America. In order to assess the situation in Thailand, 886 patients with vivax malaria who were admitted to the Bangkok Hospital for Tropical Diseases from 1992 to 1997 were followed prospectively. Most of the patients had been infected on the western border of Thailand and were experiencing their first malarial infection when admitted. All received oral chloroquine (approximately 25 mg base/kg body weight, administered over 3 days) and then were randomized to receive primaquine (15 mg daily for 14 days) or no further treatment. All the patients were initially responsive to chloroquine, clearing their parasitaemias within 7 days, and there were no significant differences in the clinical or parasitological responses between those treated with primaquine and those given no further treatment. Plasmodium vivax parasitaemias re-appeared within 28 days of chloroquine treatment in just four patients. In each of these four cases, re-treatment with the same regimen of chloroquine resulted in eradication of the parasitaemia, with no further appearance of parasitaemia during the next, 28-day, follow-up period. These data indicate that virtually all acute (i.e. blood-stage) P. vivax infections acquired in Thailand can still be successfully treated with chloroquine.

NAFLD fibrosis score: A prognostic predictor for mortality and liver complications among NAFLD patients

AIM To study whether the severity of liver fibrosis estimated by the nonalcoholic fatty liver disease (NAFLD) fibrosis score can predict all-cause mortality, cardiac complications, and/or liver complications of patients with NAFLD over long-term follow-up. METHODS A cohort of well-characterized patients with NAFLD diagnosed during the period of 1980-2000 was identified through the Rochester Epidemiology Project. The NAFLD fibrosis score (NFS) was used to separate NAFLD patients with and without advanced liver fibrosis. We used the NFS score to classify the probability of fibrosis as < -1.5 for low probability, > -1.5 to < 0.67 for intermediate probability, and > 0.67 for high probability. Primary endpoints included all-cause death and cardiovascular- and/or liver-related mortality. From the 479 patients with NAFLD assessed, 302 patients (63%) greater than 18 years old were included. All patients were followed, and medical charts were reviewed until August 31, 2009 or the date when the first primary endpoint occurred. By using a standardized case record form, we recorded a detailed history and physical examination and the use of statins and metformin during the follow-up period. RESULTS A total of 302/479 (63%) NAFLD patients (mean age: 47 ± 13 year) were included with a follow-up period of 12.0 ± 3.9 year. A low probability of advanced fibrosis (NFS < -1.5 at baseline) was found in 181 patients (60%), while an intermediate or high probability of advanced fibrosis (NSF > -1.5) was found in 121 patients (40%). At the end of the follow-up period, 55 patients (18%) developed primary endpoints. A total of 39 patients (13%) died during the follow-up. The leading causes of death were non-hepatic malignancy (n = 13/39; 33.3%), coronary heart disease (CHD) (n = 8/39; 20.5%), and liver-related mortality (n = 5/39; 12.8%). Thirty patients had new-onset CHD, whereas 8 of 30 patients (27%) died from CHD-related causes during the follow-up. In a multivariate analysis, a higher NFS at baseline and the presence of new-onset CHD were significantly predictive of death (OR = 2.6 and 9.2, respectively; P < 0.0001). Our study showed a significant, graded relationship between the NFS, as classified into 3 subgroups (low, intermediate and high probability of liver fibrosis), and the occurrence of primary endpoints. The use of metformin or simvastatin for at least 3 mo during the follow-up was associated with fewer deaths in patients with NAFLD (OR = 0.2 and 0.03, respectively; P < 0.05). Additionally, the rate of annual NFS change in patients with an intermediate or high probability of advanced liver fibrosis was significantly lower than those patients with a low probability of advanced liver fibrosis (0.06 vs 0.09, P = 0.004). The annual NFS change in patients who died was significantly higher than those in patients who survived (0.14 vs 0.07, P = 0.03). At the end of the follow-up, we classified the patients into 3 subgroups according to the progression pattern of liver fibrosis by comparing the NFS at baseline to the NFS at the end of the follow-up period. Most patients were in the stable-fibrosis (60%) and progressive-fibrosis (37%) groups, whereas only 3% were in the regressive fibrosis. CONCLUSION A higher NAFLD fibrosis score at baseline and a new onset of CHD were significantly predictive of death in patients with NAFLD.

Intestinal helminths and malnutrition are independently associated with protection from cerebral malaria in thailand

Abstract Although human infection with Ascaris appears to be associated with protection from cerebral malaria, there are many potential socio-economic and nutritional confounders related to helminth infection that need to be considered. In a hospital-based study, 37 cases of cerebral malaria and 61 cases of non-severe malaria with high parasite biomass (i.e. hyperparasitaemia and/or circulating schizonts) answered a structured questionnaire and were screened for intestinal helminths. Logistic regression was then used to adjust for the potential confounders. The adjusted odds ratios (OR) and their 95% confidence intervals (CI) still showed a significant protective association for helminths (OR=0.24; CI=0.07-0.78; P=0.02) and malnutrition (OR=0.11; CI=0.02-0.58; P=0.01), with no evidence of interaction between the two. There was also a significant dose-effect trend for the helminth infections (P=0.048). These results, despite coming from a hospital-based study, indicate that the apparent association between helminths and protection from cerebral malaria is not the result of socio-economic or nutritional confounders.

The Future Outlook of Antimalarial Drugs and Recent Work on the Treatment of Malaria

With the emergence of multidrug-resistant falciparum malaria, new drugs and drugs in combination are urgently needed. New antimalarial drugs investigated at the Hospital for Tropical Diseases of the Faculty of Tropical Medicine at Mahidol University in Bangkok, Thailand in recent years for treatment of uncomplicated and severe falciparum malaria are as follows: atovaquone, and artemisinin derivatives (artesunate, artemether, arteether, and dihydroartemisinin) combined with other antimalarials.Malarone, artemisinin derivatives combined with lumefantrine or doxycycline, and mefloquine combined with tetracycline or doxycycline have been evaluated with improvement of the cure rate in uncomplicated malaria. Artemisinin derivatives intravenously or intrarectally combined with mefloquine may be alternatives to intravenous quinine for treatment of severe malaria. In Thailand, drug treatment for uncomplicated malaria consists of the combinations or artesunate plus mefloquine or artemether plus lumefantrine or quinine plus tetracycline. In treatment of severe malaria, antimalarial drugs of choice are intravenous quinine or artemisinin derivatives.

Socio-economic and environmental protective/risk factors for severe malaria in Thailand

We conducted a cross-sectional study to identify the socio-economic and environmental protective/risk factors for severe malaria in Thailand. Forty-six cases of severe malaria, 72 cases of non-severe malaria with high parasite biomass and 40 mild malaria cases were included. When comparing severe malaria and non-severe malaria with high parasite biomass, specific logistic regression models showed a significant protective effect for helminths, adjusted odds ratio 0.24 (0.07-0.78) for low body mass index (BMI), adjusted odds ratio 0.11 (0.02-0.58). When comparing severe and mild malaria, a longer residence duration, adjusted odds ratio 0.36 (0.09-0.83) and the use of antimalarial self-medication, adjusted odds ratio 0.08 (0.009-0.84) were associated with protection from severe malaria. Using stepwise logistic regression with all the variables inserted in the model yielded similar results. These findings suggest specific immunity and self-medication control parasite multiplication whereas helminths and malnutrition more specifically affect the pathogenesis of severe malaria.

Flexible spectral imaging color enhancement plus probe-based confocal laser endomicroscopy for gastric intestinal metaplasia detection

Probe‐based confocal laser endomicroscope (pCLE) has been applied for the early detection and confirmation of many gastrointestinal neoplasms; however, its use in gastric intestinal metaplasia (GIM) detection has not yet been validated. The objective of this study was to assess the diagnostic yield of magnifying flexible spectral imaging color enhancement (ME‐FICE) plus pCLE for GIM detection.

Combination of EUS-FNA and elastography (strain ratio) to exclude malignant solid pancreatic lesions: A prospective single-blinded study.

Negative results of EUS‐FNA for solid pancreatic lesions (SPL) can be false ones. Combination with strain ratio (SR) may ensure a correct benign diagnosis of SPL.