Presence of anti-chikungunya IgG by age (years) in febrile patients, southern Sri Lanka, 2007.

<p>Presence of anti-chikungunya IgG by age (years) in febrile patients, southern Sri Lanka, 2007.</p

Distribution of febrile patients with and without acute chikungunya infection by month, southern Sri Lanka, 2007.

<p>Distribution of febrile patients with and without acute chikungunya infection by month, southern Sri Lanka, 2007.</p

Alignment of the amino acid sequence surrounding the chikungunya virus E1-226 region.

<p>Amino acid sequence corresponding to the E1 gene was translated from the nucleotide sequences of the three Sri Lankan isolates and compared the amino acid sequences of the isolates described in Schuffennecker et al 2006, PLoS Med and Kumar et al 2008, JGV [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0082259#B10" target="_blank">10</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0082259#B11" target="_blank">11</a>]. Position E1-226 is highlighted (E1-226 corresponds to position 1035 in the polyprotein). </p

Phylogenetic relationship of Sri Lankan chikungunya virus (CHIKV) isolates.

<p>Sequences corresponding to the CHIKV structural genes from the six Sri Lankan isolates were compared to published CHIKV sequences [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0082259#B6" target="_blank">6</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0082259#B8" target="_blank">8</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0082259#B10" target="_blank">10</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0082259#B11" target="_blank">11</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0082259#B16" target="_blank">16</a>]. Region of isolation is indicated by text color: West Africa (Red), Asia (Blue), East/South/Central Africa (Green), Reunion Island (Pink) and India/Sri Lanka (Orange). Isolates from the current study are indicated in bold-italics.</p

Age distribution of patients with and without acute chikungunya infection, southern Sri Lanka, 2007.

<p>Age distribution of patients with and without acute chikungunya infection, southern Sri Lanka, 2007.</p

Emergence of Epidemic Dengue-1 Virus in the Southern Province of Sri Lanka

<div><p>Background</p><p>Dengue is a frequent cause of acute febrile illness with an expanding global distribution. Since the 1960s, dengue in Sri Lanka has been documented primarily along the heavily urbanized western coast with periodic shifting of serotypes. Outbreaks from 2005–2008 were attributed to a new clade of DENV-3 and more recently to a newly introduced genotype of DENV-1. In 2007, we conducted etiologic surveillance of acute febrile illness in the Southern Province and confirmed dengue in only 6.3% of febrile patients, with no cases of DENV-1 identified. To re-evaluate the importance of dengue as an etiology of acute febrile illness in this region, we renewed fever surveillance in the Southern Province to newly identify and characterize dengue.</p><p>Methodology/Principal Findings</p><p>A cross-sectional surveillance study was conducted at the largest tertiary care hospital in the Southern Province from 2012–2013. A total of 976 patients hospitalized with acute undifferentiated fever were enrolled, with 64.3% male and 31.4% children. Convalescent blood samples were collected from 877 (89.6%). Dengue virus isolation, dengue RT-PCR, and paired IgG ELISA were performed. Acute dengue was confirmed as the etiology for 388 (39.8%) of 976 hospitalizations, with most cases (291, 75.0%) confirmed virologically and by multiple methods. Among 351 cases of virologically confirmed dengue, 320 (91.2%) were due to DENV-1. Acute dengue was associated with self-reported rural residence, travel, and months having greatest rainfall. Sequencing of selected dengue viruses revealed that sequences were most closely related to those described from China and Southeast Asia, not nearby India.</p><p>Conclusions/Significance</p><p>We describe the first epidemic of DENV-1 in the Southern Province of Sri Lanka in a population known to be susceptible to this serotype because of prior study. Dengue accounted for 40% of acute febrile illnesses in the current study. The emergence of DENV-1 as the foremost serotype in this densely populated but agrarian population highlights the changing epidemiology of dengue and the need for continued surveillance and prevention.</p></div

Evaluation of the WHO 2009 classification for diagnosis of acute dengue in a large cohort of adults and children in Sri Lanka during a dengue-1 epidemic

<div><p>Background</p><p>Dengue is a leading cause of fever and mimics other acute febrile illnesses (AFI). In 2009, the World Health Organization (WHO) revised criteria for clinical diagnosis of dengue.</p><p>Methodology/Principal findings</p><p>The new WHO 2009 classification of dengue divides suspected cases into three categories: dengue without warning signs, dengue with warning signs and severe dengue. We evaluated the WHO 2009 classification vs physicians’ subjective clinical diagnosis (gestalt clinical impression) in a large cohort of patients presenting to a tertiary care center in southern Sri Lanka hospitalized with acute febrile illness. We confirmed acute dengue in 388 patients (305 adults ≥ 18 years and 83 children), including 103 primary and 245 secondary cases, of 976 patients prospectively enrolled with AFI. At presentation, both adults and children with acute dengue were more likely than those with other AFI to have leukopenia and thrombocytopenia. Additionally, adults were more likely than those with other AFI to have joint pain, higher temperatures, and absence of crackles on examination whereas children with dengue were more likely than others to have sore throat, fatigue, oliguria, and elevated hematocrit and transaminases. Similarly, presence of joint pain, thrombocytopenia, and absence of cough were independently associated with secondary vs primary dengue in adults whereas no variables were different in children. The 2009 WHO dengue classification was more sensitive than physicians’ clinical diagnosis for identification of acute dengue (71.5% vs 67.1%), but was less specific. However, despite the absence of on-site diagnostic confirmation of dengue, clinical diagnosis was more sensitive on discharge (75.2%). The 2009 WHO criteria classified almost 75% as having warning signs, even though only 9 (2.3%) patients had evidence of plasma leakage and 16 (4.1%) had evidence of bleeding</p><p>Conclusions/Significance</p><p>In a large cohort with AFI, we identified features predictive of dengue vs other AFI and secondary vs primary dengue in adults versus children. The 2009 WHO dengue classification criteria had high sensitivity but low specificity compared to physicians’ gestaldt diagnosis. Large cohort studies will be needed to validate the diagnostic yield of clinical impression and specific features for dengue relative to the 2009 WHO classification criteria.</p></div

Proportion with acute dengue among patients hospitalized with acute febrile illness at a tertiary care hospital in southern Sri Lanka, June 2012- May 2013.

<p>Monthly rainfall for the Galle district is depicted by the line graph.</p

Receiver operating characteristic (ROC) curves of the performance of the WHO classification criteria for dengue and the treating physician’s clinical diagnosis at admission and at discharge for the identification of laboratory-confirmed acute dengue in children and adults enrolled with acute febrile illness in southern Sri Lanka, 2012–2013.

<p>Receiver operating characteristic (ROC) curves of the performance of the WHO classification criteria for dengue and the treating physician’s clinical diagnosis at admission and at discharge for the identification of laboratory-confirmed acute dengue in children and adults enrolled with acute febrile illness in southern Sri Lanka, 2012–2013.</p

Comparison of clinical and laboratory features in febrile children and adults with and without acute dengue, southern Sri Lanka, 2012–2013.

<p>Comparison of clinical and laboratory features in febrile children and adults with and without acute dengue, southern Sri Lanka, 2012–2013.</p