Complement alternative pathway genetic variation and Dengue infection in the Thai population.

Dengue disease is a mosquito-borne infection caused by Dengue virus. Infection may be asymptomatic or variably manifest as mild Dengue fever (DF) to the most severe form, Dengue haemorrhagic fever (DHF). Mechanisms that influence disease severity are not understood. Complement, an integral component of the immune system, is activated during Dengue infection and the degree of activation increases with disease severity. Activation of the complement alternative pathway is influenced by polymorphisms within activation (factor B rs12614/rs641153, C3 rs2230199) and regulatory [complement factor H (CFH) rs800292] proteins, collectively termed a complotype. Here, we tested the hypothesis that the complotype influences disease severity during secondary Dengue infection. In addition to the complotype, we also assessed two other disease-associated CFH polymorphisms (rs1061170, rs3753394) and a structural polymorphism within the CFH protein family. We did not detect any significant association between the examined polymorphisms and Dengue infection severity in the Thai population. However, the minor allele frequencies of the factor B and C3 polymorphisms were less than 10%, so our study was not sufficiently powered to detect an association at these loci. We were also unable to detect a direct interaction between CFH and Dengue NS1 using both recombinant NS1 and DV2-infected culture supernatants. We conclude that the complotype does not influence secondary Dengue infection severity in the Thai population.

Failure of carbazochrome sodium sulfonate (AC-17) to prevent dengue vascular permeability or shock: a randomized, controlled trial.

OBJECTIVE: We studied the ability of carbazochrome sodium sulfonate (AC-17) to prevent capillary permeability in dengue hemorrhagic fever/dengue shock syndrome. METHOD: A randomized, placebo-controlled trial in 95 children stratified by age and sex was conducted in two hospitals during 1992. AC-17 (n = 45 cases) or B vitamins as placebo (n = 50) were given as a bolus infusion and then as a continuous drip for 24 hours; a total of 300 mg of AC-17 was administered on the first 2 days and 150 mg on the third day. RESULTS: The two groups were comparable in age, sex, duration of illness, and clinical manifestations. No significant difference in shock or pleural effusion was noted between the two groups. Shock developed in 8.9% (4/45) of patients in the AC-17 group and 6% (3/50) in the placebo group (p = 0.44). Pleural effusion was found at 0, 24, 48, and 72 hours after admission in 4.4%, 20%, 31.1%, and 20% in the AC-17 group and 2%, 14%, 28%, and 14% in the placebo group, respectively. CONCLUSION: Administration of AC-17 does not prevent plasma leakage or shock in dengue hemorrhagic fever/dengue shock syndrome.

Failure of high-dose methylprednisolone in established dengue shock syndrome: a placebo-controlled, double-blind study.

OBJECTIVE: Steroids are widely used in Thailand and other dengue-endemic countries to treat severe dengue shock syndrome. This study was designed to determine whether a single high dose of methylprednisolone will reduce mortality in children with dengue shock syndrome who did not respond to simple fluid and plasma replacement therapy. METHODS: A prospective, randomized, double-blind, controlled trial was conducted in two hospitals in Khon Kaen Thailand during June to September in 1987 and 1988. Sixty-three children with severe dengue shock syndrome were randomized into two groups; the first group received a single dose of methylprednisolone (30 mg/kg) and the second group received placebo. RESULTS: There was no significant difference in mortality between the two groups (P = .63). The mortality rate was 12.5% (4/32) in the steroid group and 12.9% (4/31) in the group that received placebo. The sequelae at 2 weeks among treatment and control survivors were not significantly different. These two groups were comparable in age, sex, severity of illness, and duration of shock at the outset of the study. The two treatment groups were similar in subsequent hospital course as determined by maximum and minimum hematocrit level and bleeding severity. The numbers of patients in each group who had liver failure and evidence of disseminated intravascular clotting defect were also comparable. Complications such as occurrence of fever after shock, pneumonia, convulsion, cardiac arrest, pulmonary hemorrhage, and positive hemoculture were not significantly different in the treatment and control groups. CONCLUSIONS: A single high dose of methylprednisolone does not reduce mortality in severe dengue shock syndrome which does not respond to conventional critical care.