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Biomedical subjects

S Vannaphan

Publications and source records attributed to S Vannaphan.

16 recordsLinked to original sources
PubMed2005

Curdlan sulphate in human severe/cerebral Plasmodium falciparum malaria.

Preclinical studies have shown that curdlan sulphate (CRDS), a sulphated 1-->3-beta-D glucan, inhibits Plasmodium falciparum in vitro and down-modulates the immune response. A direct, non-specific effect on cytoadherence and rosetting may be predicted, as has been described with other sulphated polysaccharides, e.g. heparin. The anticoagulant effect of CRDS is 10-fold lower than heparin. Curdlan sulphate has, therefore, emerged as a candidate for adjunct medication in the treatment of severe/cerebral malaria. Two clinical studies were conducted using CRDS as adjunct medication to conventional therapy (artesunate) in patients with severe and severe/cerebral malaria. Both studies were double-blind and placebo-controlled to evaluate the efficacy and safety of the combination. Curdlan sulphate appeared to reduce the severity of the disease process, e.g. fever clearance time was shortened. Due to the small number of patients, there was no difference in mortality. The two treatment arms in both studies showed similar results for all laboratory parameters. The only adverse event recorded during CRDS treatment was an increase in activated partial thromboplastin time. This can be monitored easily. It seems that the patients who may benefit most are severe/cerebral cases with no organ damage on admission.

Adolescent↗
PubMed2002

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

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.

Adult↗
PubMed2001

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.

Adult↗
PubMed2001

Association of splenomegaly with cerebral malaria and decreased concentrations of reactive nitrogen intermediates in Thailand.

The role of the spleen during Plasmodium falciparum malaria in humans is unclear. In Thailand, malaria transmission is low and splenomegaly is rarer than in high transmission areas. We compared the prevalence of splenomegaly between 52 cerebral malaria patients and 191 patients without complications despite a high parasite biomass. We also measured concentrations of reactive nitrogen intermediates (RNIs) in a fraction of these cases recruited in 1998 (24 cerebral malaria and 56 controls). Splenomegaly was significantly associated with cerebral malaria (adjusted odds ratio = 2.07 [95% confidence interval = 1-4.2]; P = 0.048). There was a linear trend for this association (P = 0.0003). After adjusting for potential confounders, concentrations of RNIs were significantly lower in the presence of splenomegaly (P = 0.01). These results suggest that in humans, as in animal models, the spleen may be involved in the pathogenesis of cerebral malaria. The relationship between RNI concentrations and the spleen suggest that nitric oxide may have a regulating role in the complex physiology of the spleen during malaria.

Adult↗
PubMed2001

Association of hepatomegaly and jaundice with acute renal failure but not with cerebral malaria in severe falciparum malaria in Thailand.

We conducted a case record study comparing liver tests abnormalities in 20 malaria-related acute renal failure cases without cerebral malaria, 52 cerebral malaria cases without other organ impairment, 189 cases of nonsevere malaria associated with a high parasite burden, and 131 cases of mild Plasmodiumfalciparum malaria. Jaundice and hepatomegaly were significantly associated with renal failure (adjusted odds ratio [AOR], 3.3, 95% confidence interval [CI], 1.3-8.6, P = 0.01; and AOR, 1.7 95% CI, 1.13-2.4, P = 0.01) but not with cerebral malaria (AOR, 1, 95% CI, 0.5-2, P = 0.8; and AOR, 1.08, 95% CI, 0.8-1.8, P = 0.5). Patients with acute renal failure were significantly older and had increased liver abnormalities compared with other groups. Although an increase in the proportion of mature schizonts over ring forms was significantly associated with cerebral malaria, it did not seem to have affected acute renal failure. These results suggested that cytoadherence was not the main determinant for renal failure and that jaundice itself may have potentiated the effects of hypovolemia.

Acute Kidney Injury↗
PubMed2001

Helminth infections are associated with protection from malaria-related acute renal failure and jaundice in Thailand.

Following studies showing an association between helminth infections and protection from cerebral malaria, we compared 22 patients with malaria-associated acute renal failure with 157 patients with moderately severe malaria. Helminths were associated with protection from renal failure (adjusted odds ratio [AOR], 0.16 [0.03-0.85], P = 0.03). Helminth-infected controls were less likely to have jaundice (AOR, 0.39 [0.16-0.96], P = 0.04) or to have peripheral mature schizonts (AOR, 0.2 [0.07-0.62], P = 0.005) than controls without helminths. This suggested that preexisting helminth infections may have been protective by influencing sequestration and obstructive jaundice, 2 possible determinants of acute tubular necrosis.

Acute Kidney Injury↗
PubMed2000

Prognostic significance of skin and subcutaneous fat sequestration of parasites in severe falciparum malaria.

Intradermal blood smear, histopathologic and immunohistologic studies were performed in severe malaria (n=10) and uncomplicated malaria (n=10) patients during positive parasitemia and within 6 hours after negative parasitemia by finger prick smears. Intradermal blood smears showed asexual forms and intraleukocytic pigments when finger prick blood smears showed negative results; however intradermal blood smear did not indicate disease severity within 6 hours after negative parasitemia by finger prick. Histopathologic findings showed 15 fold higher parasitized red blood cells sequestered in vessels of subcutaneous fatty tissue in severe malaria than in uncomplicated malaria (p<0.001) and may indicate disease severity. A panel of polyclonal antibodies against cytokines applied to skin biopsies clearly detected a higher titer against tumor necrosis factor-alpha (TNFalpha) and interleukin-10 (IL-10) in dermal vessels and stratum granulosum respectively, in severe malaria compared with uncomplicated malaria. Results of the study suggest that histopathology and immunohistology of skin and subcutaneous fatty tissue may indicate prognostic severity of malaria and may be associated with focal accumulation of cytokines.

Adipose Tissue↗
PubMed1999

Treatment of malarial acute renal failure by hemodialysis.

We studied 112 patients with malarial acute renal failure (ARF) during the period 1991-1997 at Bangkok Hospital for Tropical Diseases (Mahidol University, Bangkok, Thailand). Hemodialysis was performed in 101 (90.2%) of these patients. The mean number of times the patients were hemodialyzed was 6.5 (range = 1-27). Ninety-three (83.0%) patients were oliguric and the remainder were nonoliguric. Patients who had oliguric renal failure required more hemodialyses and had more complications than the nonoliguric patients. The oliguric patients had an eight-fold higher risk of requiring six or more hemodialyses (95% confidence interval = 1.2-53.9, P = 0.0008). The overall mortality rate was 10.7% (12 of 112). Eleven of the patients who died were jaundiced and eight of them had cerebral malaria with a Glasgow Coma Score < or = 8. We conclude that hemodialysis is a useful treatment for oliguric and nonoliguric ARF from severe malaria, particularly when initiated early in the course of the illness.

Acute Kidney Injury↗
PubMed1998

Pentoxifylline as an ancillary treatment for severe falciparum malaria in Thailand.

Pentoxifylline, an inhibitor of tumor necrosis factor, has been evaluated as an antimalarial agent in combination with artesunate in 45 patients with severe falciparum malaria. Patients were admitted to the intensive care unit at the Hospital for Tropical Diseases in Bangkok, Thailand, and randomly assigned to treatment for 72 hr with a combination of intravenously administered artesunate and 1) placebo, 2) low-dose pentoxifylline (0.83 mg/kg/hr), or 3) high-dose pentoxifylline (1.67 mg/kg/hr). All 45 patients had one or more manifestations of severe malaria such as cerebral malaria (n = 18), renal failure requiring hemodialysis (n = 9), azotemia (n = 8), jaundice (n = 25), or hyperparasitemia (n = 30). The overall severity was comparable in the three groups. Clinical outcome was assessed with respect to the parasite clearance time and the fever clearance time in all patients. In addition, a number of subsidiary outcome variables were examined in specific subgroups, including the recovery time from coma for patients with cerebral malaria, the duration of intubation in patients with respiratory distress, the number of hemodialysis treatments needed for patients with acute renal failure, and the number of units of blood administered to patients requiring transfusion. Concentrations of tumor necrosis factor were reduced in all three groups at 48 hr after treatment. No significant differences among the three treatment groups were found for any of the outcome variables examined. We conclude that the addition of pentoxifylline to artesunate therapy for severe malaria produced no evident clinical benefit.

Adolescent↗
PubMed1998

Pulmonary edema in cerebral malaria patients in Thailand.

Pulmonary edema is a serious complication of falciparum malaria that usually occurs in association with cerebral malaria, acute renal failure, high parasitemias, or delayed antimalarial treatment. From 1993 to 1996, 120 adult patients admitted to the intensive care unit of the Bangkok Hospital for Tropical Diseases were enrolled in a prospective study to assess the combination of artesunate and mefloquine for the treatment of cerebral malaria. Twenty-five patients (21%) presented with pulmonary edema and a majority developed complications in other organs as well, especially acute renal failure. In most patients (19 of 25), pulmonary edema was noted on the first day of admission and was associated with higher parasitemias and levels of acidemia, than in patients without pulmonary edema. Ten of the 25 patients diagnosed with pulmonary edema developed signs consistent with adult respiratory distress syndrome (ARDS). The mean central venous pressure when pulmonary edema was diagnosed was markedly lower in ARDS than in non-ARDS patients, supporting the argument that fluid imbalance is not essential for malaria-induced lung injury. Seven of 10 patients with ARDS died, 5 within 24 hours of admission, but there were no deaths in the 15 pulmonary edema patients without ARDS. Early diagnosis and prompt treatment remain important principles to reduce the morbidity and mortality associated with complicated falciparum malaria. This report emphasizes that ARDS, when concurrently occurs, is a poor prognostic clinical indicator in cerebral malaria.

APACHE↗
PubMed1997

Complement activation in severe Plasmodium falciparum malaria.

We determined indices of plasma complement activation (C3, C4, Bb, C4d, iC3b, and SC5b-9), levels of tumor necrosis factor (TNF) and interleukin-6, and the APACHE II score in 23 patients with complicated Plasmodium falciparum malaria. On admission, plasma concentrations of Bb, SC5b-9, and C4d were markedly increased compared to healthy control subjects (n = 24) (4.5 +/- 1.9 vs 1.5 +/- 0.6 mg/L; 1125.7 +/- 496.9 vs 183.2 +/- 76.5 microg/L; and 15.7 +/- 5.7 vs 7.2 +/- 1.4 mg/L, P < 0.01 for all). In contrast C3 and iC3b concentrations were decreased (631.4 +/- 247 vs 947.3 +/- 243.2 and 105 +/- 17.9 vs 151.3 +/- 14.5 mg/L; P < 0.01 for both). Plasma C4 concentrations in malaria were not different from normal controls. Plasma Bb, C3, and iC3b levels normalized on day 7 of treatment, whereas SC5b-9 and C4d levels remained elevated. A significant correlation between elevated TNF levels and Bb (r = 0.507) and SC5b-9 (r = 0.448, P < 0.01 for both) and a negative correlation between iC3b and SC5b-9 and TNF levels existed (r = -0.537 and r = -0.466, P < 0.01 for both). In addition, a significant correlation between C3 and iC3b (r = 0.689) and C4 and C4d (r = 0.737) existed. However, no relation between clinical disease severity and complement fragments existed. The results demonstrate that both the classical and the alternative pathways of the complement system are profoundly activated in complicated malaria.

Adult↗
PubMed1997

Increased gastrointestinal permeability in patients with Plasmodium falciparum malaria.

Sequential gastrointestinal permeability in patients with Plasmodium falciparum malaria was determined by measuring the permeation of sucrose, lactulose, and mannitol to assess both gastric and small intestine permeability. Sucrose absorption (gastroduodenal permeability) was increased in patients with severe malaria (defined as either >5% parasitemia or a serum bilirubin level of >50 micromol/L) and became normal by day 2 following treatment. A similar proportion of patients with uncomplicated malaria had increased gastroduodenal permeability initially, which resolved by day 7 of treatment. During acute malarial illness, the lactulose: mannitol (L:M) ratio in urine was increased and was found to be higher in patients with severe malaria than in those with uncomplicated malaria and in controls, but this ratio reverted to normal during convalescence. At the time of admission, the L:M ratios in patients with uncomplicated malaria were increased but became normal by day 2 after treatment. Conversely, the duration of increased L:M ratios in patients with severe malaria was longer. By day 7, the L:M ratios in patients with severe malaria were higher than those in patients with uncomplicated malaria and in controls. We conclude that gastrointestinal permeability is increased during severe and uncomplicated falciparum malaria but reverts to normal during convalescence.

Adolescent↗
PubMed1996

Big endothelin in patients with complicated Plasmodium falciparum malaria.

Plasma concentrations of big endothelin-1 were determined by ELISA in 18 patients with complicated Plasmodium falciparum malaria in Bangkok. Before therapy, elevated levels were recorded (21 +/- 12 vs. 2.9 +/- 1.1 pmol/L in age- and sex-matched healthy subjects; P < .001). Even 7 days after therapy, elevated concentrations were seen (25 +/- 14 pmol/L). Plasma endothelin levels were correlated with levels of tumor necrosis factor-alpha (r = .632, P < .01), and a negative correlation with platelet counts was seen (r = .783, P < .005). No relation between plasma endothelin concentrations and parasitemia, fever, or other indices of severe infection (hypotension, renal, hepatic or pulmonary impairment, cerebral malaria) existed. During and after complicated malaria, increased levels of plasma endothelin could contribute to malarial pathology or reflect endothelial damage or both.

Antimalarials↗
PubMed1995

Magnetic resonance imaging of the brain in patients with cerebral malaria.

In a prospective study of cerebral malaria, 24 adults with this disease underwent magnetic resonance imaging (MRI) of the brain. Four patients died. Two of these patients (nos. 17 and 24) had breathing abnormalities requiring ventilatory support followed by clinical signs of brain death. Four days later MRI of patient 17 showed gross swelling of the brain, and 5 hours later MRI of patient 24 showed foramen magnum herniation. Twenty-two patients had no evidence of cerebral edema, but MRI revealed that brain volume during acute cerebral malaria was slightly greater than that during the convalescent phase of the disease. This difference was attributed to an increase in the volume of intracerebral blood. The cerebral volume was lower during early convalescence than several months later. The volume of the brain in patients with cerebral malaria is increased. This increased volume probably results from sequestration of parasitized erythrocytes and compensatory vasodilatation rather than from edema. Brain stem herniation may occur, but its temporal relation to brain death in cases of cerebral malaria remains uncertain.

Acute Disease↗
PubMedDate not supplied

Clinical trial of sequential treatments of moderately severe and severe malaria with dihydroartemisinin suppository followed by mefloquine in Thailand.

One hundred and fifty patients with severe falciparum malaria were administered sequential combination of dihydroartemisinin suppository followed by an oral mefloquine tablet. Dihydroartemisinin suppositories (80 mg/capsule) were given rectally once daily for 3 days with a total dose of 8-10 mg/kg. Two doses of mefloquine, 15 mg/kg/dose and 10 mg/kg/dose, were given at 72 hr and 84 hr, respectively. The mean [SD] parasite clearance time and fever clearance time were 46.1 [15.7] hr and 82.5 [59.6] hr, respectively. No death or major adverse drug effects occurred. The cure rate at 28 days of inpatient follow-up was 95% (113 of 119 patients). In severe malaria, dihydroartemisinin suppository followed by oral mefloquine is a suitable alternative treatment to parenteral drugs.

Administration, Oral↗