Indu Pillaveetil Sathyadas, Anish Thekkumkara Surendran, Chintha Sujatha, Libu Gnanaseelan Kanakamma, Tony Lawrence, Siju Nalinakshan Sudha, Sreekumar Easwaran, Santhoshkumar Asokan, Aravind Reghukumar, Saradadevi Karunakaran Lalithabai, Sunija Sahadevan, Johnson Jaichand, Anupriya Madhukumar Geethakumari, Mathew Thomas, Reena Kalathil Joseph, Meenakshy Vasu, Namitha Premaletha, Kumar Narendran Pradeep, Kumari Roop, Mohamed Ahmed Jamsheed, Nagpal Bhupender, Sarkar Swarup, Sadanandan Rajeev, Velayudhan Raman
Department of Community Medicine, Govt Medical College, Thiruvananthapuram, Kerala University of Health Sciences, India.
Molecular Virology Laboratory, Rajiv Gandhi Centre for Biotechnology (RGCB), Thiruvananthapuram, Kerala, India.
Lancet Reg Health Southeast Asia. 2023 Dec 11;22:100337. doi: 10.1016/j.lansea.2023.100337. eCollection 2024 Mar.
Dengue shows high geographic heterogeneity within and across endemic countries. In the context of increasing burden and predicted outbreaks due to climate change, understanding the heterogeneity will enable us to develop region specific targeted interventions, including vaccination. World Health Organisation (WHO) suggests standard methodologies to study the burden and heterogeneity at national and subnational levels. Regional studies with robust and standard methodology to capture heterogeneity are scarce. We estimated the seroprevalence of dengue in children aged 9-12 years and the force of infection in Kerala, India, from where Zika cases also have been reported recently.
We conducted a school-based cross-sectional survey in 38 clusters; selected by stratified random sampling, representing rural, urban, high burden and low-burden administrative units. Validation of Indirect IgG ELISA was done by Plaque Reduction Neutralization Test (PRNT) using the local isolates of all four serotypes. Force of infection (FOI) was estimated using the WHO-FOI calculator. We conducted a follow-up survey among a subsample of seronegative children, to estimate the rate of sero-conversion.
Among 5236 children tested, 1521 were positive for anti-dengue IgG antibody. The overall seroprevalence in the state was 29% (95% CI 24.1-33.9). The validity corrected seroprevalence was 30.9% in the overall sample, 46.9% in Thiruvananthapuram, 26.9% in Kozhikkode and 24.9% in Kollam. Age-specific seroprevalence increased with age; 25.7% at 9 years, 29.5% at 10 years, 30.9% at 11 years and 33.9% at 12 years. Seroprevalence varied widely across clusters (16.1%-71.4%). The estimated force of infection was 3.3/100 person-years and the seroconversion rate was 4.8/100 person-years. 90% of children who tested positive were not aware of dengue infection. All the four serotypes were identified in PRNT and 40% of positive samples had antibodies against multiple serotypes.
The study validates the WHO methodology for dengue serosurveys and confirms its feasibility in a community setting. The overall seroprevalence in the 9-12 year age group is low to moderate in Kerala; there are regional variations; high burden and low burden clusters co-exist in the same districts. The actual burden of dengue exceeds the reported numbers. Heterogeneity in prevalence, the high proportion of inapparent dengue and the hyperendemic situation suggest the need for region-specific and targeted interventions, including vaccination.
World Health Organization.
登革热在流行国家内部和国家之间呈现出高度的地理异质性。在负担不断增加以及气候变化导致预测会出现疫情爆发的背景下，了解这种异质性将使我们能够制定针对特定区域的干预措施，包括疫苗接种。世界卫生组织（WHO）建议采用标准方法来研究国家和次国家层面的负担及异质性。采用稳健且标准方法来捕捉异质性的区域研究较为匮乏。我们估计了印度喀拉拉邦9至12岁儿童的登革热血清流行率以及感染率，最近该地区也报告了寨卡病例。
我们在38个群组中开展了一项基于学校的横断面调查；通过分层随机抽样选取，代表农村、城市、高负担和低负担行政单位。使用所有四种血清型的本地分离株，通过空斑减少中和试验（PRNT）对间接IgG ELISA进行验证。使用WHO感染率计算器估计感染率。我们对血清阴性儿童的一个子样本进行了随访调查，以估计血清转化率。
在5236名接受检测的儿童中，1521名抗登革热IgG抗体呈阳性。该邦的总体血清流行率为29%（95%可信区间24.1 - 33.9）。总体样本中经有效性校正的血清流行率为30.9%，在 Thiruvananthapuram为46.9%，在科泽科德为26.9%，在科拉姆为24.9%。特定年龄的血清流行率随年龄增加；9岁时为25.7%，10岁时为29.5%，11岁时为30.9%，12岁时为33.9%。各群组间血清流行率差异很大（16.1% - 71.4%）。估计的感染率为3.3/100人年，血清转化率为4.8/100人年。90%检测呈阳性的儿童不知道自己感染了登革热。在PRNT中鉴定出了所有四种血清型，40%的阳性样本具有针对多种血清型的抗体。
该研究验证了WHO登革热血清学调查方法，并证实了其在社区环境中的可行性。喀拉拉邦9至12岁年龄组的总体血清流行率处于低至中等水平；存在区域差异；高负担和低负担群组在同一地区共存。登革热的实际负担超过了报告数字。流行率的异质性、隐性登革热的高比例以及高度流行的情况表明需要采取针对特定区域和目标的干预措施，包括疫苗接种。
世界卫生组织。
