Enrollment of dengue patients in a prospective cohort study in Umphang District, Thailand, during the COVID‐19 pandemic: Implications for research and policy

Abstract Background and Aims Dengue is endemic in Thailand and imposes a high burden on the health system and society. We conducted a prospective cohort study in Umphang District, Tak Province, Thailand, to investigate the share of dengue cases with long symptoms and their duration. Here we present the results of the enrollment process during the COVID‐19 pandemic with implications and challenges for research and policy. Methods In a prospective cohort study conducted in Umphang District, Thailand, we examined the prevalence of persistent symptoms in dengue cases. Clinically diagnosed cases were offered free laboratory testing, We enrolled ambulatory dengue patients regardless of age who were confirmed through a highly sensitive laboratory strategy (positive NS1 and/or IgM), agreed to follow‐up visits, and gave informed consent. We used multivariate logistic regressions to assess the probability of clinical dengue being laboratory confirmed. To determine the factors associated with study enrollment, we analyzed the relationship of patient characteristics and month of screening to the likelihood of participation. To identify underrepresented groups, we compared the enrolled cohort to external data sources. Results The 150 clinical cases ranged from 1 to 85 years old. Most clinical cases (78%) were confirmed by a positive laboratory test, but only 19% of those confirmed enrolled in the cohort study. Women, who were half as likely to enroll as men, were underrepresented in the cohort. Conclusions The Thai physicians' clinical diagnoses at this rural district hospital had good agreement with laboratory diagnoses. By identifying underrepresented groups and disparities, future studies can ensure the creation of statistically representative cohorts to maximize their scientific value. This involves recruiting and retaining underrepresented groups in health research, such as women in this study. Promising strategies for meaningful inclusion include multi‐site enrollment, offering in‐home or virtual services, and providing in‐kind benefits like childcare for underrepresented groups.


Section S1. Dengue epidemiology in Thailand
The first dengue cases in Thailand were reported in 1949, and all serotypes have circulated since the early 1960s [1][2][3].Dengue is now considered a major public health threat in Thailand and is a notifiable disease [1,2].Dengue surveillance is passive and records cases, severity, and demographic characteristics of suspected dengue cases.Limited access to healthcare, poverty, misdiagnosis, and limitations in surveillance result in an underestimation of the disease burden of dengue in Thailand [2,4,5].
As in other countries, epidemics follow a cyclic pattern and are affected by climate variables, such as rainfall and temperature, with transmission peaks during the wet season (mid-May to mid-October) [2,6,7].The annual incidence of reported dengue ranged from 36 to 137 per 100,000 population for dengue fever and 27 to 101 per 100,000 population for dengue hemorrhagic fever in 2011-2018 [2].
There has been a slow shift in the age group with the highest incidence of dengue from younger individuals aged 5-14 in 2000-2011 moving towards higher prevalence among older individuals aged 15 to 24 years in 2011-2018 [1,2].Dengue hemorrhagic fever and dengue shock syndrome were more common among individuals aged 5-14; the more severe cases suggest these children may have a second DENV infection [4].The overall hospitalization rate was 63% (62-66%) in 2011-2018. 3Dengue epidemiology varies substantially within the country [1,2].
There was a total of 81 reported dengue cases in Umphang District from January through December 2020, of which 51 (63%) were classified as dengue fever, and 30 (37%) were classified as dengue hemorrhagic fever.These represent about 11% of the dengue cases reported in Tak Province in 2020 [3].

Section S2. Patient inclusion and exclusion criteria
Eligibility into the study required satisfying all five of these inclusion criteria: 1.The patient has confirmed dengue according to the treating clinician using Thai criteria of clinical diagnosis and routine laboratory testing as well as the additional NS-1 or IgG/IgM.
2. The patient expects to remain in the study area for at least 30 days to be available for in-person follow-up visits.
3. The patient intends to be available to provide follow-up information over the next six months, if needed, either in person or by phone.

The patient (if an adult) or caretaker (if a child) gives appropriate informed written consent and
assent for children aged 15-17 years.
The exclusion criteria are failing to satisfy one or more of the above inclusion conditions.Dengue positive was defined as a recent laboratory-confirmed DENV infection with NS1 and/or IgM positive.80% of men, 75% of women, and 78% overall had laboratory confirmation.

Figure S4 .
Figure S4.Number of patients screened and lab confirmed by days elapsed since the onset of illness.....

Figure S4 .
Figure S4.Number of patients screened and lab confirmed by days elapsed since the onset of illness.The onset of illness is self-reported.The total number of symptomatic patients screened was 147 because 3 patients did not report any symptoms before screening and were therefore excluded from this figure.The breakdown of the 147 patients by testing status is 75 NS1 positive, 68 IgM positive, 29 both NS1 and IgM positive, 114 NS1 and/or IgM positive, and 33 neither NS1 nor IgM positive.

Figure S5 .
Figure S5.Number of men and women screened regardless of symptoms (n=150) and laboratory-confirmed dengue (n=117) patients.Dengue positive was defined as a recent laboratory-confirmed DENV infection with NS1 and/or IgM positive.80% of men, 75% of women, and 78% overall had laboratory confirmation.

Table S1 .
Cross tabulation of laboratory positivity of dengue cases by NS-1, IgM, and IgG (N=150)+ Frequency of patients screened and lab-confirmed recent dengue infection (bi-monthly, December 2020 to November 2021) with % laboratory-confirmed dengue.Dengue positive was defined as a recent laboratory confirmed DENV infection with NS1 and/or IgM positive.
Figure S3.Percent of patients clinically diagnosed with dengue who were laboratory confirmed (NS-1, IgM, either test, both tests)