PLoS neglected tropical diseases · 2025
Engineered Nanobodies for early and accurate diagnosis of dengue virus infection.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Pavan María Florencia, Malnero Cristian Miguel, Mora Alvarado María Emilia, Carzoglio María Camila, Rojas Yesica Paredes, Bruno Agostina, Vidakovics Laura Perez, Hanke Leo, Castello Alejandro, McInerney Gerald, García Cybele Carina, Parreño Viviana, Ibañez Lorena Itatí
Аннотация
BACKGROUND: Dengue virus (DENV), a mosquito-borne flavivirus responsible for dengue disease, has emerged as an escalating global health concern, with cases increasing sharply in recent decades. In Argentina, dengue has transitioned from a sporadic disease to a recurrent epidemic, now affecting 18 of 23 provinces and exposing gaps in diagnostic capacity.
METHODOLOGY AND PRINCIPAL FINDINGS: The DENV genome encodes the non-structural protein 1 (NS1), a key biomarker for early infection detection. Given the limited access to commercially available diagnostic kits within the public health system, we developed a combined ELISA system incorporating Nanobodies designed to target NS1 across all four DENV serotypes as detection antibodies. This system demonstrates excellent discriminative performance (AUC > 0.9), with a diagnostic sensitivity of 93.6% (95% CI: 86.6-97.6%) and a specificity of 81.1% (95% CI: 70.3-89.3%). The analytical sensitivity showed strong correlation between sera pool dilutions and detected signals, with a limit of detection aligning with reported NS1 concentrations in human samples. While the system exhibits limitations in detecting NS1 from DENV-4, it successfully identified cases in patients five days post-symptom onset who were initially considered epidemiologically negative for dengue infection.
SIGNIFICANCE: Our results underscore the urgent need for accessible, high-precision diagnostic tools in regions facing a surge in dengue outbreaks. Additionally, they highlight the necessity of revising current diagnostic algorithms to enhance the detection of late-presenting cases.
METHODOLOGY AND PRINCIPAL FINDINGS: The DENV genome encodes the non-structural protein 1 (NS1), a key biomarker for early infection detection. Given the limited access to commercially available diagnostic kits within the public health system, we developed a combined ELISA system incorporating Nanobodies designed to target NS1 across all four DENV serotypes as detection antibodies. This system demonstrates excellent discriminative performance (AUC > 0.9), with a diagnostic sensitivity of 93.6% (95% CI: 86.6-97.6%) and a specificity of 81.1% (95% CI: 70.3-89.3%). The analytical sensitivity showed strong correlation between sera pool dilutions and detected signals, with a limit of detection aligning with reported NS1 concentrations in human samples. While the system exhibits limitations in detecting NS1 from DENV-4, it successfully identified cases in patients five days post-symptom onset who were initially considered epidemiologically negative for dengue infection.
SIGNIFICANCE: Our results underscore the urgent need for accessible, high-precision diagnostic tools in regions facing a surge in dengue outbreaks. Additionally, they highlight the necessity of revising current diagnostic algorithms to enhance the detection of late-presenting cases.