Use of Household Cluster Investigations to Identify Factors Associated with Chikungunya Virus Infection and Frequency of Case Reporting in Puerto Rico

<div><p>Background</p><p>Chikungunya virus (CHIKV) is transmitted by <i>Aedes</i> species mosquitoes and is the cause of an acute febrile illness characterized by potentially debilitating arthralgia. After emerging in the Caribbean in late 2013, the first locally-acquired case reported to public health authorities in Puerto Rico occurred in May 2014. During June–August 2014, household-based cluster investigations were conducted to identify factors associated with infection, development of disease, and case reporting.</p><p>Methodology/Principal Findings</p><p>Residents of households within a 50-meter radius of the residence of laboratory-positive chikungunya cases that had been reported to Puerto Rico Department of Health (PRDH) were offered participation in the investigation. Participants provided a serum specimen and answered a questionnaire that collected information on demographic factors, household characteristics, recent illnesses, healthcare seeking behaviors, and clinical diagnoses. Current CHIKV infection was identified by rRT-PCR, and recent CHIKV infection was defined by detection of either anti-CHIKV IgM or IgG antibody. Among 250 participants, 74 (30%) had evidence of CHIKV infection, including 12 (5%) with current and 62 (25%) with recent CHIKV infection. All specimens from patients with CHIKV infection that were collected within four days, two weeks, and three weeks of illness onset were positive by RT-PCR, IgM ELISA, and IgG ELISA, respectively. Reporting an acute illness in the prior three months was strongly associated with CHIKV infection (adjusted odds ratio [aOR] = 21.6, 95% confidence interval [CI]: 9.24–50.3). Use of air conditioning (aOR = 0.50, 95% CI = 0.3–0.9) and citronella candles (aOR = 0.4, 95% CI = 0.1–0.9) were associated with protection from CHIKV infection. Multivariable analysis indicated that arthralgia (aOR = 51.8, 95% CI = 3.8–700.8) and skin rash (aOR = 14.2, 95% CI = 2.4–84.7) were strongly associated with CHIKV infection. Hierarchical cluster analysis of signs and symptoms reported by CHIKV-infected participants demonstrated that fever, arthralgia, myalgia, headache, and chills tended to occur simultaneously. Rate of symptomatic CHIKV infection (defined by arthralgia with fever or skin rash) was 62.5%. Excluding index case-patients, 22 (63%) participants with symptomatic CHIKV infection sought medical care, of which 5 (23%) were diagnosed with chikungunya and 2 (9%) were reported to PRDH.</p><p>Conclusions/Significance</p><p>This investigation revealed high rates of CHIKV infection among household members and neighbors of chikungunya patients, and that behavioral interventions such as use of air conditioning were associated with prevention of CHIKV infection. Nearly two-thirds of patients with symptomatic CHIKV infection sought medical care, of which less than one-quarter were reportedly diagnosed with chikungunya and one-in-ten were reported to public health authorities. These findings emphasize the need for point-of-care rapid diagnostic tests to optimize identification and reporting of chikungunya patients.</p></div

Laboratory Results for the Fatal Laboratory Positive Dengue Cases, 2007, Puerto Rico.

<p>DPO = day post onset of fever; DENV = dengue virus; RT-PCR = reverse transcriptase polymerase chain reaction; MAC-ELISA = IgM antibody capture enzyme linked immunosorbent assay; ELISA = enzyme linked immunosorbent assay; WNV = West Nile virus; PRNT = plaque reduction neutralization test; IgM Lepto = IgM ELISA ImmunoDOT assay for <i>Leptospira;</i> IHC = immunohistochemical microscopy; NEG = negative test result; POS = positive test result; N/A = not applicable for patient; QNS = quantity not sufficient to perform test indicated.</p>†<p>These samples where whole blood collected at time of death.</p

Clinical Features of the Fatal Laboratory-positive Dengue Cases at Time of Death or End of Hospital Stay, 2007, Puerto Rico.

<p>This table describes the clinical features of laboratory positive dengue case-patients at time of death or end of hospital stay.</p>†<p>DHF = dengue hemorrhagic fever; PLT = platelet; HCT = hematocrit; GI = gastrointestinal; ICH = intracranial hemorrhage; LOS = length of stay.</p>‡<p>DHF criteria as defined by World Health Organization in Dengue Hemorrhagic Fever: Diagnosis, Treatment, Prevention and Control. Second edition. Geneva: World Health Organization.</p

Demographics, pre-existing medical conditions, household characteristics, and mosquito avoidance behaviors associated with chikungunya virus infection among household-based cluster investigations participants in Puerto Rico, 2014 (N = 250).

<p>Demographics, pre-existing medical conditions, household characteristics, and mosquito avoidance behaviors associated with chikungunya virus infection among household-based cluster investigations participants in Puerto Rico, 2014 (N = 250).</p

Dendrogram of hierarchical cluster analysis of symptoms among household-based cluster investigation participants that reported an acute illness in the previous three months, Puerto Rico, 2014

<p>Dendrogram of hierarchical cluster analysis of symptoms among household-based cluster investigation participants that reported an acute illness in the previous three months, Puerto Rico, 2014</p

Illness and health care seeking behaviors of household-based cluster investigation participants that reported an acute illness in the previous three months, Puerto Rico, 2014.

<p>Illness and health care seeking behaviors of household-based cluster investigation participants that reported an acute illness in the previous three months, Puerto Rico, 2014.</p

Duration of detection of diagnostic markers of chikungunya virus infection by test and time of specimen collection post-illness-onset.

<p>Duration of detection of diagnostic markers of chikungunya virus infection by test and time of specimen collection post-illness-onset.</p

Virus-Specific Differences in Rates of Disease during the 2010 Dengue Epidemic in Puerto Rico

<div><p>Background</p><p>Dengue is a potentially fatal acute febrile illness (AFI) caused by four mosquito-transmitted dengue viruses (DENV-1–4) that are endemic in Puerto Rico. In January 2010, the number of suspected dengue cases reported to the passive dengue surveillance system exceeded the epidemic threshold and an epidemic was declared soon after.</p> <p>Methodology/Principal Findings</p><p>To characterize the epidemic, surveillance and laboratory diagnostic data were compiled. A suspected case was a dengue-like AFI in a person reported by a health care provider with or without a specimen submitted for diagnostic testing. Laboratory-positive cases had: (i) DENV nucleic acid detected by reverse transcriptase-polymerase chain reaction (RT-PCR) in an acute serum specimen; (ii) anti-DENV IgM antibody detected by ELISA in any serum specimen; or (iii) DENV antigen or nucleic acid detected in an autopsy-tissue specimen. In 2010, a total of 26,766 suspected dengue cases (7.2 per 1,000 residents) were identified, of which 46.6% were laboratory-positive. Of 7,426 RT-PCR-positive specimens, DENV-1 (69.0%) and DENV-4 (23.6%) were detected more frequently than DENV-2 (7.3%) and DENV-3 (<0.1%). Nearly half (47.1%) of all laboratory-positive cases were adults, 49.7% had dengue with warning signs, 11.1% had severe dengue, and 40 died. Approximately 21% of cases were primary DENV infections, and 1–4 year olds were the only age group for which primary infection was more common than secondary. Individuals infected with DENV-1 were 4.2 (95% confidence interval [CI]: 1.7–9.8) and 4.0 (95% CI: 2.4–6.5) times more likely to have primary infection than those infected with DENV-2 or -4, respectively.</p> <p>Conclusions/Significance</p><p>This epidemic was long in duration and yielded the highest incidence of reported dengue cases and deaths since surveillance began in Puerto Rico in the late 1960's. This epidemic re-emphasizes the need for more effective primary prevention interventions to reduce the morbidity and mortality of dengue.</p> </div

Rates of laboratory-positive cases by municipality, Puerto Rico, 2010.

<p>Rates were calculated by dividing case numbers by municipality-specific populations and grouping by quintile of rate of all laboratory-positive cases. Rates shown are: (<b>A</b>) All laboratory-positive cases; or laboratory-positive cases with DENV-1 (<b>B</b>), DENV-2 (<b>C</b>), or DENV-4 (<b>D</b>) detected by RT-PCR.</p

Demographic and clinical characteristics of suspected dengue cases by diagnostic test result, Puerto Rico, 2010.

<p>DHF = dengue hemorrhagic fever.</p