Efficacy of rupatadine in reducing the incidence of dengue haemorrhagic fever in patients with acute dengue: A randomised, double blind, placebo-controlled trial.

BACKGROUND: Rupatadine was previously shown to reduce endothelial dysfunction in vitro, reduced vascular leak in dengue mouse models and to reduce the extent of pleural effusions and thrombocytopenia in patients with acute dengue. Therefore, we sought to determine the efficacy of rupatadine in reducing the incidence of dengue haemorrhagic fever (DHF) in patients with acute dengue. METHODS AND FINDINGS: A phase 2, randomised, double blind, placebo controlled clinical trial was carried out in patients with acute dengue in Sri Lanka in an outpatient setting. Patients with ≤3 days since the onset of illness were either recruited to the treatment arm of oral rupatadine 40mg for 5 days (n = 123) or the placebo arm (n = 126). Clinical and laboratory features were measured daily to assess development of DHF and other complications. 12 (9.7%) patients developed DHF in the treatment arm compared to 22 (17.5%) who were on the placebo although this was not significant (p = 0.09, relative risk 0.68, 95% CI 0.41 to 1.08). Rupatadine also significantly reduced (p = 0.01) the proportion of patients with platelet counts <50,000 cells/mm3 and significantly reduced (p = 0.04) persisting vomiting, headache and hepatic tenderness (p<0.0001) in patients. There was a significant difference in the duration of illness (p = 0.0002) although the proportion of individuals who required hospital admission in both treatment arms. Only 2 patients on rupatadine and 3 patients on the placebo developed shock, while bleeding manifestations were seen in 6 patients on rupatadine and 7 patients on the placebo. CONCLUSIONS: Rupatadine appeared to be safe and well tolerated and showed a trend towards a reducing proportion of patients with acute dengue who developed DHF. Its usefulness when used in combination with other treatment modalities should be explored. TRIAL REGISTRATION: International Clinical Trials Registration Platform: SLCTR/2017/024.

Sri Lanka's early success in the containment of COVID-19 through its rapid response: Clinical & epidemiological evidence from the initial case series.

BACKGROUND: Despite the rising global burden, Sri Lanka reported a relatively low caseload and mortality (13 deaths as of 20 October 2020) for COVID-19. This warrants exploration of the clinical and epidemiological characteristics of the case series during the initial passive case detection phase in Sri Lanka, in order to understand the success in containment of the disease for more than nine months in the country through its initial early and rapid pandemic response. METHODS: A retrospective study was conducted using secondary data (hospital records and investigation reports) extracted from all laboratory-confirmed patients admitted to the three main state-sector hospitals in Sri Lanka from 11 March to 7 April 2020. Clinical outcomes were categorized as mild, severe and critical, as per the international classification. Kruskal-Wallis H, Mann Whitney U and Fisher's exact tests compared differences between the variables. RESULTS: The case series comprised 146 live discharges and six deaths. Majority were males (63.2%); mean age of 40.9 (SD = 17.9); and symptomatic (72.4%). Sixty-one (40.1%) had co-morbidities, the commonest being diabetes (20.4%) and hypertension (17.8%). Mild (93.4%), severe (2.6%) and critical (4.0%) disease outcomes were noted. Disease severity was significantly higher with older age (p = 0.037), co-morbidities (p = 0.026); and higher white-cell (p = 0.045) and lymphocyte (p = 0.043) counts; but not with being symptomatic (p = 0.683). The commonest symptoms were fever (62.5%), dry cough (48.0%) and sore throat (26.9%). The median duration (IQR) was 3.0 (1.0-5.0) and 18.0 (15.0-29.5) days, respectively before and during hospitalization. CONCLUSIONS: In contrast to high-risk countries, the younger age, milder disease and low mortality observed in local patients during the initial phase of the pandemic, reflect the early success in containment of the pandemic in Sri Lanka. However, once the disease becomes severe, the factors determining disease fatality remain the same as in other countries. This highlights the value of establishing strong public health systems and disease surveillance in a country, which could provide long-term effects on disease control.