Prevalence and clinical manifestations of dengue in older patients in Bangkok Hospital for Tropical Diseases, Thailand.

BACKGROUND: The global incidence of dengue has increased with the ageing population. We examined the prevalence, clinical manifestations and risk factors associated with dengue severity among older patients. METHODS: A retrospective cohort study was conducted at a hospital in Thailand from 2013 to 2018. Data were collected from patient records. Older patients were those aged ≥60 y, whereas adult patients were aged at least 18 y but younger than 60 y. RESULTS: In total, 1822 patients were included in the study. The prevalence of older dengue was 7.96%. Older dengue patients were at a higher risk of developing dengue haemorrhagic fever (DHF) than adult dengue patients (40.69% vs 30.71%). Haematuria was significantly more frequent in older patients (24.82% vs 3.58%), whereas other clinical manifestations had similar frequencies between the groups. Multivariate logistic regression indicated that hypertension (adjusted OR [aOR]=3.549, 95% CI 1.498 to 8.407) and abdominal pain (aOR=10.904, 95% CI 1.037 to 114.710) were significantly associated with DHF among older patients. CONCLUSIONS: Dengue is common in older adults, who also have a higher incidence of developing DHF. Older patients with dengue and comorbid hypertension and abdominal pain should be monitored for their increasing risk of DHF.

Association between Hepatitis B Surface Antigen Levels and the Risk of Hepatocellular Carcinoma in Patients with Chronic Hepatitis B Infection: Systematic Review and Meta-Analysis.

Background: The role of hepatitis B surface antigen (HBsAg) levels in predicting the risk of developing hepatocellular carcinoma (HCC) has remained unclear. The aim of this study was to obtain the most up-to-date estimated measure of the association between HBsAg levels and the development of HCC in patients. Methods: We performed a systematic review by searching for relevant studies on PubMed, Scopus, ProQuest and the Cochrane Central Register of Controlled Trials from January 2002 to November 2017. We presented the effects of HBsAg levels at each cut-off value as the odds ratios (ORs) at 95% confidence interval (CI). We also investigated HCC and its potential risk factors including HBeAg, and HBV DNA. We registered our protocol with the International Prospective Register of Systematic Reviews (PROSPERO) with the registration number CRD42018081138. Results: We selected 10 studies representing 12 541 cases. At the 100 IU/ml cut-off, the OR for HCC at the high HBsAg level versus the low level was 4.99 (95% CI, 3.01­8.29) with high inconsistency (I2=79%). At the 1,000 IU/ml threshold, the pooled OR for HCC at the high HBsAg versus the low level was 2.46 (95% CI, 2.15­2.83) with low variance. We also found correlations between the risk of HCC and male gender (OR=2.12), hepatitis B e-antigen positivity (OR=2.99), or hepatitis B (HBV) viral load ≥ 2,000 IU/ml (OR=4.37). Conclusion: Our study revealed that HBsAg levels ≥ 100 IU/ml, and notably >1,000 IU/ ml, are associated with an increased risk of HCC development.

Awareness, knowledge, and practice for hepatitis B infection in Southeast Asia: a cross-sectional study.

INTRODUCTION: The prevalence of hepatitis B virus (HBV) infection in Southeast Asia is high. Awareness and early detection are essential for timely prevention and treatment. METHODOLOGY: We examined the awareness of, knowledge about, practices and views on treatment for HBV infection in Southeast Asia. A cross-sectional survey was conducted from December 2016 to February 2017 among individuals from six nations in Southeast Asia-Myanmar, Thailand, Vietnam, Cambodia, the Philippines, and Singapore. The study population comprised healthcare and non-healthcare personnel. RESULTS: In total, 799 healthcare personnel and 1079 non-healthcare personnel completed an online survey. The prevalence of the awareness of their own HBV infection status and risk of this regionally endemic infection was 85.6% (684/799) among healthcare personnel and 54.0% (583/1079) among non-healthcare personnel. Similarly, 85.9% of healthcare personnel and 45.5% of non-healthcare personnel had good knowledge about disease transmission, complications, and the need for treatment, and 76.6% of healthcare personnel and 39.8% of non-healthcare personnel followed good HBV infection-prevention practices. Overall, 90.6% found the idea of treatment acceptable. Awareness had a significant impact on both knowledge and practice scores among both healthcare personnel and non-healthcare personnel (p < 0.01) but without statistically significant differences in treatment acceptance between the two groups (p = 0.61). CONCLUSIONS: Awareness of HBV infection was relatively low among non-healthcare personnel in Southeast Asian populations. The provision of additional hepatitis B awareness campaigns is crucial to eliminating viral hepatitis in the region.

Incidence and Clinical Outcome of Acute Liver Failure Caused by Dengue in a Hospital for Tropical Diseases, Thailand.

Acute liver failure is an atypical manifestation of dengue with a high mortality. We performed a retrospective cohort study at the Hospital for Tropical Diseases, Bangkok, Thailand. In total, 1,926 patients with serologically confirmed dengue were enrolled in the study from 2011 to 2015. Of these, six patients presented with acute liver failure, four died, and two survived. The incidence of dengue-associated acute liver failure was 0.31%. Dengue-associated acute liver failure was most common among young adults (median age, 29 years). The median duration from onset of fever to development of acute liver failure was 7.5 days. Patients with the severe stage of dengue had a higher risk of developing acute liver failure (P < 0.001). The baseline risk factors associated with the development of acute liver failure were an age of ≤ 40 years (odds ratio [OR] = 1.5, 95% confidence interval [CI] = 1.1-2.0, P < 0.05), a > 10% ratio of atypical lymphocytes (OR = 2.3, 95% CI = 1.8-3.0, P < 0.001), and a platelet count of < 50,000 mm3 (OR = 2.8, 95% CI = 2.2-3.6, P < 0.001). The incidence of acute liver failure in patients with dengue was quite low, but its impact on morbidity, mortality, and poor clinical outcomes was significant. In summary, this study indicates that various baseline risk factors are associated with acute liver failure in patients with dengue.

Nephrotoxicity caused by oral antiviral agents in patients with chronic hepatitis B treated in a hospital for tropical diseases in Thailand.

BACKGROUND: There is increasing concern about the potential for nephrotoxicity in patients with chronic hepatitis B (CHB) treated long-term with nucleotide analogs. METHODS: We examined renal dysfunction and its associated risk factors in patients with CHB treated with antiviral regimens containing either nucleosides or nucleotide analogs. We undertook a retrospective cohort study from 2006 to 2014 at the Hospital for Tropical Diseases, Bangkok, Thailand, and analyzed the data of 102 patients with a median follow-up time of 44.5 months (range 4-101 months). RESULTS: Seventy-three patients were treated with an antiviral regime containing a nucleoside analog, and 29 with a regime containing a nucleotide analog. Abnormally elevated serum creatinine concentration was observed in 12 patients (11.8 %) after 8 years of treatment. Thirty one percent of patients treated with nucleotide analogs had elevated serum creatinine levels and three of these patients (10.3 %) developed nephrotoxicity. In contrast, serum creatinine concentrations were elevated in three of the 73 patients treated with a nucleoside analog (4.1 %), and none developed nephrotoxicity. The incidence of renal dysfunction by the nucleotide analog regimen was cumulative, with 11.1, 21.0, 26.5 and 47.6 % of patients affected after 2, 4, 6 and 8 years, respectively. Univariate and multivariate analysis indicated that a nucleotide analog-based regimen significantly predicted renal dysfunction (odds ratio 10.5, 95 % confidence intervals 2.6-42.4, P <0.001). CONCLUSION: The long-term use of nucleotide analogs increased the risk of nephrotoxicity in patients with CHB. Thus, the regular assessment of renal function is recommended for all patients with CHB, particularly those treated with a nucleotide analog.

Electron microscopic features of brain edema in rodent cerebral malaria in relation to glial fibrillary acidic protein expression.

The mechanisms leading to cerebral malaria (CM) are not completely understood. Brain edema has been suggested as having an important role in experimental CM. In this study, CBA/CaH mice were infected with Plasmodium berghei ANKA blood-stage and when typical symptoms of CM developed on day 7, brain tissues were processed for electron-microscopic and immunohistochemical studies. The study demonstrated ultrastructural hallmarks of cerebral edema by perivascular edema and astroglial dilatation confirming existing evidence of vasogenic and cytogenic edema. This correlates closely with the clinical features of CM. An adaptive response of astrocytic activity, represented by increasing glial fibrillary acidic protein (GFAP) expression in the perivascular area and increasing numbers of large astrocyte clusters were predominately found in the CM mice. The presence of multivesicular and lamellar bodies indicates the severity of cerebral damage in experimental CM. Congestion of the microvessels with occluded white blood cells (WBCs), parasitized red blood cells (PRBCs) and platelets is also a crucial covariate role for CM pathogenesis.

Distribution of C14-labelled arteether in kidneys and livers of experimental mice after intramuscular injection.

To study the distribution and localization of oil-soluble arteether in experimental mice, we injected C14-labelled arteether (20 microCi/kg body weight) intramuscularly and measured radioactivity in the blood, kidney, and liver. The labelled arteether distributed and localized more to the kidney (819,180.4 +/- 34,134 dpm/cm3) than the liver (288,628.9 +/- 54,954 dpm/cm3) 4 hours post-injection. The main localization of labelled arteether was in the kidney cortex rather than the medulla (p < 0.05). However, the distribution of radioactivity was homogeneous in the liver. The terminal half-life of labelled arteether in the blood was 1.8 hours. The blood:kidney:liver ratio was 1:5:2. These findings show that labelled arteether was distributed quickly and localized in the cytoplasmic cortex of the kidney and homogeneously in the liver.

Genetic diversity of Plasmodium vivax in Kolkata, India.

BACKGROUND: Plasmodium vivax malaria accounts for approximately 60% of malaria cases in Kolkata, India. There has been limited information on the genotypic polymorphism of P. vivax in this malaria endemic area. Three highly polymorphic and single copy genes were selected for a study of genetic diversity in Kolkata strains. METHODS: Blood from 151 patients with P. vivax infection diagnosed in Kolkata between April 2003 and September 2004 was genotyped at three polymorphic loci: the P. vivax circumsporozoite protein (pvcs), the merozoite surface protein 1 (pvmsp1) and the merozoite surface protein 3-alpha (pvmsp3-alpha). RESULTS: Analysis of these three genetic markers revealed that P. vivax populations in Kolkata are highly diverse. A large number of distinguishable alleles were found from three genetic markers: 11 for pvcs, 35 for pvmsp1 and 37 for pvmsp3-alpha. These were, in general, randomly distributed amongst the isolates. Among the 151 isolates, 142 unique genotypes were detected the commonest genotype at a frequency of less than 2% (3/151). The overall rate of mixed genotype infections was 10.6%. CONCLUSION: These results indicate that the P. vivax parasite population is highly diverse in Kolkata, despite the low level of transmission. The genotyping protocols used in this study may be useful for differentiating re-infection from relapse and recrudescence in studies assessing of malarial drug efficacy in vivax malaria.

Study on serum transcobalamin II in patients with murine typhus.

We measured the serum transcobalamin II in murine typhus- infected patients (n = 16) admitted to the Hospital for Tropical Diseases in 1996-1997, compared with healthy controls (n = 60). The results showed that the transcobalamin II (TCII) and total serum unsaturated vitaminB12 binding capacity (UBBC) in patients with murine typhus (2,126.5 pg/ml, range 1,262-4,568 and 3,771.5 pg/ml, range 1,576-6,763 pg/ml) were statistically significantly higher than normal subjects (987.5 pg/ml, range 678-2,000 pg/ml and 1,402 pg/ml, range 932-2,470 ml) (p<0.001). Serum TCII levels in patients (63%) were elevated during the febrile period and returned to normal post-treatment. These findings suggest that patients with murine typhus had stimulation of reticulo-endothelial system, spleen, mesenteric lymph nodes, liver and skin and then released TCII into the blood circulation. The elevation in TCII may be used for confirming a diagnosis of murine typhus.

Elevation of serum transcobalamin II in patients with scrub typhus.

Serum transcobalamin II levels were measured in scrub typhus patients. Eighteen out of fifty-two patients admitted to Maharat Nakhon Ratchasima Hospital were diagnosed with scrub typhus infection. The serum unsaturated vitamin B12 binding protein (UBBC) and total vitamin B12 binding protein (TBBC) levels in these patients were significantly higher than in normal subjects (p < 0.001). The mean serum transcobalamin II level in the typhus patients was also significantly higher than in the normal subjects (p=0.004). There was a significant correlation between serum TCII levels and typhus IgM or IgG titers (p < 0.05), but not to total IgM levels. These findings indicate that patients with scrub typhus had stimulation of the recticuloendothelial system as a result of a considerable increase in transcobalamin II levels.

The hematological status, plasma vitamin B12 and folic acid levels, and intestinal pathology in rats infected with Giardia lamblia.

The purpose of our study was to investigate the hematological status, vitamin B12 and folic acid absorption and intestinal pathology after Giardia lamblia infection in a rat model. Adult Wistar rats were assigned randomly to receive human giardia cysts orally in the amount of 5 x 10(5) or 1.0 x 10(6) cysts, or none in the controls. The results showed that all the rats injected with giardia cysts became infected. The cyst output in the infected rats varied considerably. In rats infected with 5.0 x 10(5) giardia cysts, the incubation period until cyst output was 10 days compared with 4 days in rats infected with the higher amount of 1.0 x 106 giardia cysts. The highest peaks for cysts output in these 2 groups were on days 4-33, which decreased gradually to days 40-58. The hematocrit and hemoglobin levels in the infected rats were statistically significantly lower than in the controls on days 16, 22, 33, and 37 post-infection (p < 0.05). A reverse relationship between giardia cyst output and hemoglobin concentration was found in the infected rats (p = 0.05). There were no significant differences in plasma vitamin B12 and folic acid levels between the infected rats and the control rats. No pathological changes were found in the small intestine of infected rats. These findings suggest that giardiasis did not affect the absorption of plasma vitamin B12 and folic acid but caused anemia in a rat model.

Neuropathologic toxicity of artemisinin derivatives in a mouse model.

Intramuscular administration of high doses of artemether and arteether to experimental mammals produces selective damage to brain stem centers involved predominantly in auditory processing and vestibular reflexes. The relationship between clinical signs of neurotoxicity and neuropathologic toxicity was studied in the mouse. Intramuscular artemether (50-100 mg/kg/day for 28 days) caused dose-dependent neuropathologic damage to the brain stem. There was no pathologic evidence of neuronal death in mice receiving either oral artemether, or oral or intramuscular artesunate, in doses up to 300 mg/kg/day. The neurons in the lower brain stem trapezoid nucleus, the gigantocellular reticular nucleus, and the inferior cerebellar peduncle were the most sensitive to the toxic effects of artemether. All mice with neuropathologic changes also showed behavioral changes, whereas in some mice with gait disturbance, no corresponding histopathologic damage could be detected. Thus clinical assessment was a sensitive measure of neurotoxicity. There may be a reversible component to artemether neurotoxicity.

Assessment of the neurotoxicity of oral dihydroartemisinin in mice.

High doses of the oil-soluble antimalarial artemisinin derivatives artemether and arteether, given by intramuscular injection to experimental mammals, produce an unusual pattern of selective damage to brainstem centres predominantly involved in auditory processing and vestibular reflexes. We have shown recently, in adult Swiss albino mice, that constant exposure either from depot intramuscular injection of oil-based artemisinin derivatives, or constant oral intake carries relatively greater neurotoxic potential than other methods of drug administration. Using the same model, oral dihydroartemisinin suspended in water was administered once or twice daily at different doses ranging from 50 to 300 mg/kg/day for 28 days. The neurotoxic potential of the oral dihydroartemisinin was assessed and compared to that of oral artemether and artesunate. Oral artemether, artesunate, and dihydroartemisinin had similar neurotoxic effects with no significant clinical or neuropathological evidence of toxicity at doses below 200 mg/kg/day. These data indicate that once and twice daily oral administration of artemether, artesunate and dihydroartemisinin is relatively safe when compared to intramuscular administration of the oil-based compounds.