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- Tissera, H, et al.
(author)
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Assessment of severity among adult dengue patients in Colombo district, Sri Lanka
- 2015
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In: Tropical medicine & international health. - : Wiley-Blackwell. - 1360-2276 .- 1365-3156. ; 20:Suppl. 1, s. 416-416
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Journal article (other academic/artistic)abstract
- Introduction: Dengue is a major acute febrile illness in Sri Lanka and reported in epidemic proportions. From 2009 to 2013 an average of 35 000 cases were reported annually with over 60% above 15 years of age. Clinical case classification of dengue was originally based on paediatric patients. Here we assess severity of dengue illness among adults according to both WHO classical and TDR classifications.Methods: A study was conducted in 100 adult patients presenting to ID Hospital, Colombo with fever <7 days, in 2013. All were tested for dengue ELISA NS1/IgM and RT-PCR. Of them 88 were confirmed as having dengue, and were classified into two WHO classifications. Type of care received was categorized into three levels as:Category 1 – general ward,Category 2 – special dengue unit,Category 3 – intensive care unit.Results: According to classical classification, 47 (53.4%) were Dengue Fever (DF) patients. Of them 31and 16 received Category 1 and 2 care respectively. None received Category 3 care. 41 (46.6%) Dengue Haemorrhagic Fever (DHF) patients. Of them 14 received category 1 care while 25 and two received Category 2 and Category 3 care respectively. Classical classification and level of care sensitivity was 62.8% (CI 48–78) while specificity was 68.9% (CI 55–82). According to TDR classification 29 (32.9%) were Dengue patients without warning signs. Of them 22 and 07 received Category 1 and 2 level of care respectively and none went into category 3. 48 (55%) were Dengue with warning signs and 11 (13%) severe dengue patients. Of them 18 received Category 1 care while 39 and two received category 2 and category 3 care respectively. TDR classification and level of care sensitivity was 85.4% (CI 75–95) Specificity 55% (CI 39–70).Conclusions: WHO TDR classification captures more patients who need closer observation in Category 2 and three levels of care than classical classification. This may warrant additional hospital resources in developing country settings.Disclosure: This research was funded by the European Union 7th Framework Programme through 'DengueTools'.
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- Thalagala, N, et al.
(author)
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Costs of dengue hospitalization and public prevention and control activities in urban Sri Lanka
- 2015
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In: Tropical medicine & international health. - : Wiley-Blackwell. - 1360-2276 .- 1365-3156. ; 20:Suppl. 1, s. 379-379
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Journal article (other academic/artistic)abstract
- Introduction: Dengue has become a major public health problem in Sri Lanka; however, the economic impact of the disease has not been studied in this setting. This study assessed the costs of dengue prevention and control activities and the direct medical costs of dengue hospitalizations in the Colombo District, the most affected district with the highest dengue caseloads in the country.Methods: The study was conducted in the epidemic year of 2012. Using information from the official databases of governmental agencies in charge of the dengue prevention and control activities in each administrative unit, we calculated the total financial costs of these activities and the average cost per capita. The direct medical costs of hospitalized dengue cases in the public health sector were derived using operational budgets and a sample of bed head tickets of adult and pediatric patients available from six secondary-level hospitals.Results: In 2012, the total financial cost of dengue prevention and control activities in the Colombo District was about $998 000, or $0.43 per capita. The mean direct medical costs to the public health care system per case of hospitalized dengue fever (DF) and dengue haemoraggic fever (DHF) were $221 and $316 for paediatric partients, respectively, and $203 and $272 for adult patients, respectively.Conclusion: These preliminary results highlight the high economic burden of dengue to the public health sector in the Colombo district in Sri Lanka during an epidemic year and contribute to the sparse literature on the economic burden of dengue in affected countries.Acknowledgements: This research was funded by ‘DengueTools’ of the 7th Framework Programme of the European Community.Disclosure: Nothing to disclose.
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| 4. |
- Tissera, H, et al.
(author)
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Enhanced dengue sentinel surveillance in Sri Lanka
- 2015
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In: Tropical medicine & international health. - [Tissera, H.; Palihawadana, P.; Amarasinghe, A.; Muthukuda, C.; Botheju, C.] Minist Hlth, Epidemiol it, Colombo, Sri Lanka. [Tissera, H.] Natl Dengue Control Unit, Colombo, Sri Lanka. [Gunasena, S.] Med Res Inst, Colombo, Sri Lanka. [da Silva, D.] Genentech Res Inst, Colombo, Sri Lanka. [Sessions, O.] Nanyang Technol Univ, Duke NUS Grad Med Sch, Singapore 639798, Singapore. [Leong, W. -Y.; Wilder-Smith, A.] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore 639798, ngapore. [Lohr, W.; Byass, P.; Wilder-Smith, A.] Umea Univ, Umea, Sweden. [Gubler, D.] Duke NUS Grad Med Sch, Colombo, Sri Lanka.. - 1360-2276 .- 1365-3156. ; 20:Suppl. 1, s. 133-133
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Journal article (other academic/artistic)abstract
- Introduction: Dengue poses a significant socioeconomic and disease burden in Sri Lanka, where the geographic spread, incidence and severity of disease has been increasing since the first dengue hemorrhagic fever (DHF) epidemic occurred in 1989. Periodic epidemics have become progressively larger, peaking in 2012 with 44 456 cases. Passive surveillance was established nationwide more than a decade ago but dengue notifications have been based on clinical diagnosis, with infrequent laboratory confirmation. To obtain more accurate data on the disease burden, a laboratory-based enhanced sentinel surveillance system was established in Colombo Municipality, the area with the highest dengue incidence. Here we describe the study design and the results of the first 2 years (2012–2014).Methods: Three government hospitals and two outpatient clinics in Colombo District were selected for the sentinel surveillance. All patients presenting with undifferentiated fever were enrolled, if consent given, capped at a maximum of 60 patients per week. Acute blood samples were taken from all enrolled subjects and tested by dengue-specific PCR, and NS1, and IgM – ELISA at the time of first presentation. A sub-set of 536 samples was sent to Duke-NUS Singapore for quality assurance, virus isolation and serotyping.Results: Between 1 April, 2012 and 31 March, 2014, 3127 patients were enrolled, 964 (30.9%) as outpatients and 2160 (69.1%) as inpatients. The mean age was 22.3 years (SD = 17.5) and the time of first presentation was at day 4 of illness. For inpatients, 1687 (78.1%) of all febrile cases had laboratory-confirmed dengue. For outpatients, the proportion of confirmed dengue was 237 (24.6%). The mean duration of hospitalization was 4.1 days (SD = 1.85). The proportion of DHF in lab-confirmed hospitalized dengue cases was 22.1% and 4 patients (0.21%) died. Serotypes 1 and 4 were the only viruses detected in this sample (serotype 1: 85%; serotype 4: 15%). The clinicians’ diagnosis for dengue at time of first presentation had a sensitivity of 92% and specificity of 23%.Conclusions: Dengue infection was responsible for a high proportion of febrile illnesses during 2012–2014, with serotypes 1 and 4 circulating. A significant proportion (22%) of hospitalized dengue cases developed DHF, but the case fatality rate was low. Clinicians’ judgment was associated with good sensitivity, but to enhance specificity it is important to add laboratory confirmation of dengue.Disclosure: This research was funded by the European Commission under the 7th Framework and conducted by DengueTools partners (www.denguetools.net).
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| 5. |
- Uehara, A, et al.
(author)
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A hybridization-based enrichment strategy to increase the accuracy of next generation sequencing in phylogenetic analysis of dengue viruses in Sri Lanka
- 2015
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In: Tropical medicine & international health. - : Wiley-Blackwell. - 1360-2276 .- 1365-3156. ; 20:Suppl. 1, s. 120-120
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Journal article (other academic/artistic)abstract
- Introduction: Sri Lanka has experienced confirmed dengue outbreaks since the 1960s although severe dengue disease (DHF/DSS) didn’t appear until 1989. Since then, cyclical outbreaks associated with severe disease have occurred throughout the island. The most recent epidemic began in 2009 with the apparent introduction of a new genotype of DENV-1. To better understand the mechanisms underlying the persistence of this ongoing epidemic, a longitudinal study was conducted in hospitals in the Colombo district from April 2012 to March 2014. In order to glean as much information as possible about the viral genetics from this large cohort, we developed a novel Next Generation Sequencing (NGS) platform that can function without any a priori knowledge of the target dengue genome.Methods: The principle problem encountered when employing NGS directly on patient samples is the high ratio of host to viral RNA. To compensate for this, we developed a hybridization-based enrichment strategy consisting of DENV-specific 120nt, biotinylated oligodeoxynucleotides to capture DENV genomic material from an NGS library prepared directly from patient sera.Results: The strategy developed here allowed us to enrich DENV genomic material over 5000 fold relative to unenriched material. Full genome data and phylogenetic analysis indicate that the DENV-1 are predominantly genotype 1 although a smaller number of genotype 5 isolates was also identified.Conclusion: The platform developed for this study has the inherent ability to capture all four serotypes of DENV and can significantly increase the virus to host RNA ratio. The principle driver of the current dengue epidemic in Sri Lanka is the same DENV-1 genotype that has been in circulation since 2009.This research was funded by the Singapore Infectious Disease Initiative (SIDI/2013/012) and the European Union 7th Framework Programme through ‘DengueTools’. (www.dengue-tools.net).Disclosure: Nothing to disclose.
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| 6. |
- Wojdacz, TK, et al.
(author)
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Clinical significance of DNA methylation in chronic lymphocytic leukemia patients: results from 3 UK clinical trials
- 2019
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In: Blood advances. - : American Society of Hematology. - 2473-9537 .- 2473-9529. ; 3:16, s. 2474-2481
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Journal article (peer-reviewed)abstract
- Chronic lymphocytic leukemia patients with mutated immunoglobulin heavy-chain genes (IGHV-M), particularly those lacking poor-risk genomic lesions, often respond well to chemoimmunotherapy (CIT). DNA methylation profiling can subdivide early-stage patients into naive B-cell–like CLL (n-CLL), memory B-cell–like CLL (m-CLL), and intermediate CLL (i-CLL), with differing times to first treatment and overall survival. However, whether DNA methylation can identify patients destined to respond favorably to CIT has not been ascertained. We classified treatment-naive patients (n = 605) from 3 UK chemo and CIT clinical trials into the 3 epigenetic subgroups, using pyrosequencing and microarray analysis, and performed expansive survival analysis. The n-CLL, i-CLL, and m-CLL signatures were found in 80% (n = 245/305), 17% (53/305), and 2% (7/305) of IGHV-unmutated (IGHV-U) cases, respectively, and in 9%, (19/216), 50% (108/216), and 41% (89/216) of IGHV-M cases, respectively. Multivariate Cox proportional analysis identified m-CLL as an independent prognostic factor for overall survival (hazard ratio [HR], 0.46; 95% confidence interval [CI], 0.24-0.87; P = .018) in CLL4, and for progression-free survival (HR, 0.25; 95% CI, 0.10-0.57; P = .002) in ARCTIC and ADMIRE patients. The analysis of epigenetic subgroups in patients entered into 3 first-line UK CLL trials identifies m-CLL as an independent marker of prolonged survival and may aid in the identification of patients destined to demonstrate prolonged survival after CIT.
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