Assessing the burden of dengue among household members in Alaminos, Laguna, the Philippines: a prospective cohort study

Abstract

Background: The incidence of dengue is increasing rapidly and is a challenging health issue in the Philippines. Epidemiological data are largely based on a passive-surveillance reporting system, which leads to substantial under-reporting of cases.

Objectives: To estimate dengue infection and disease incidence prospectively at the community level in an endemic area of the Philippines using an active surveillance strategy.

Methods: We implemented active surveillance in the highly endemic community of Alaminos, Laguna. The study consisted of a 1-year follow-up with 2 visits scheduled at the start and end of the study, as well as regular active surveillance in between and unscheduled visits for suspected cases. Blood samples were collected and analyzed to detect dengue during the first scheduled visit and all unscheduled visits, and clinical examination was performed at all visits (registered at clinicaltrials.gov NCT02766088).

Results: We enrolled 500 participants, aged from 6 months to 50 years; 76.2% were found positive for immunoglobulin G (95% confidence interval [CI], 71.9-80.0), with 92.0% among those aged 9-17 years. Active (weekly) surveillance identified 4 virologically confirmed cases of dengue (incidence proportion 0.8; 95% CI 0.3-2.1); all in participants aged ≤14 years.

Conclusions: Routine surveillance programs such as sentinel sites are needed to characterize the entire clinical spectrum of symptomatic dengue, disease incidence, and transmission in the community.

Keywords: Philippines; dengue; epidemiology; reverse transcriptase-polymerase chain reaction; sentinel surveillance.

© 2021 GlaxoSmithKline Biologicals SA, published by Sciendo.

Figures

Figure 1

Schematic representation of the study design. *Blood samples were collected at Visit 2, but not analyzed due to early study termination. **Body temperature ≥ 38.0 °C within the past 8 days lasting from 36–48 h to 7 days, potentially accompanied by other signs of dengue that by the study investigator’s opinion could only be related to dengue; †SDCs confirmed by RT-qPCR or NS1. 1. Detailed clinical examination assessing the participant’s general condition, cardiac and respiratory rates, blood pressure, dengue-associated clinical signs, and symptoms. 2a. Used for ELISA to detect anti-DENV indirect IgG. 2b. Used for i. DENV RT-qPCR, ii. DENV isolation for sequencing purposes, iii. DENV sequence, iv. DENV NS1 rapid test (ICT) or ELISA, v. IgM/IgG rapid test (ICT) or SD Bioline Dengue Duo (dengue NS1 antigen and IgG/IgM). 3. Participants were advised to contact study investigators to report any sign or symptom they perceived as an SAE. All SAEs related to study procedures (blood collection) were recorded and evaluated by the study investigator along with related signs, symptoms, and relevant clinical information. 4. A. Warning signs. At least one of the following should be present: abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, liver enlargement, increase in hematocrit concurrent with a rapid decrease in platelet count, lethargy, restlessness. B. Criteria for severe dengue. Dengue with at least one of the following: severe plasma leakage leading to shock, fluid accumulation with respiratory distress, severe bleeding, severe organ involvement, failure of heart and other organs. DENV, dengue virus; ELISA, enzyme-linked immunosorbent assay; ICT, immunochromatographic assay; IgG, immunoglobulin G; IgM, immunoglobulin M; NS1, nonstructural protein 1; RT-qPCR, reverse-transcriptase quantitative polymerase chain reaction; SAE, serious adverse event; SDC, suspected dengue case.

Figure 2

SDCs. *SDCs confirmed by RT-qPCR or NS1. To be classified with a SDC a study participant should have a body temperature of ≥38.0 °C within the past 8 days lasting from 36–48 h to 7 days, potentially accompanied by other signs of dengue that by the study investigator’s opinion could only be related to dengue; †SDCs not classified as confirmed virologically or probable. Warning signs. At least one of the following should be present: abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, liver enlargement, increase in hematocrit concurrent with a rapid decrease in platelet count, lethargy, restlessness. Criteria for severe dengue. Dengue with at least one of the following: severe plasma leakage leading to shock, fluid accumulation with respiratory distress, severe bleeding, severe organ involvement, failure of heart and other organs. DENV, dengue virus; ELISA, enzyme-linked immunosorbent assay; ICT, immunochromatographic assay; IgG, immunoglobulin G; IgM, immunoglobulin M; na, not available; NS1, nonstructural protein 1; RT-qPCR, reverse-transcriptase quantitative polymerase chain reaction; SDC, suspected dengue case.

Figure 3

Plain language summary.