Modelling the impact of antibody-dependent enhancement on disease severity of Zika virus and dengue virus sequential and co-infection

Abstract

Human infections with viruses of the genus Flavivirus , including dengue virus (DENV) and Zika virus (ZIKV), are of increasing global importance. Owing to antibody-dependent enhancement (ADE), secondary infection with one Flavivirus following primary infection with another Flavivirus can result in a significantly larger peak viral load with a much higher risk of severe disease. Although several mathematical models have been developed to quantify the virus dynamics in the primary and secondary infections of DENV, little progress has been made regarding secondary infection of DENV after a primary infection of ZIKV, or DENV-ZIKV co-infection. Here, we address this critical gap by developing compartmental models of virus dynamics. We first fitted the models to published data on dengue viral loads of the primary and secondary infections with the observation that the primary infection reaches its peak much more gradually than the secondary infection. We then quantitatively show that ADE is the key factor determining a sharp increase/decrease of viral load near the peak time in the secondary infection. In comparison, our simulations of DENV and ZIKV co-infection (simultaneous rather than sequential) show that ADE has very limited influence on the peak DENV viral load. This indicates pre-existing immunity to ZIKV is the determinant of a high level of ADE effect. Our numerical simulations show that (i) in the absence of ADE effect, a subsequent co-infection is beneficial to the second virus; and (ii) if ADE is feasible, then a subsequent co-infection can induce greater damage to the host with a higher peak viral load and a much earlier peak time for the second virus, and for the second peak for the first virus.

Developing Risk Assessment Criteria and Predicting High- and Low-Dengue Risk Villages for Strengthening Dengue Prevention Activities: Community Participatory Action Research, Thailand

“…People who are infected subsequently with a different dengue virus type may experience “antibody-dependent enhancement,” a condition that occurs when the immune response worsens dengue clinical symptoms, increasing the risk of severe dengue. 10 Antibody-dependent enhancement of dengue infection assumes a level of immunity in the community showing that the higher the outbreaks in the area, the higher is the herd immunity, compared to low level outbreak areas. Therefore, areas with high dengue risk in the past 5 years should have low outbreak in the following year.…”

“…Among them, 1.8 billion live in South-East Asia and Western Pacific regions, and 500 000 dengue cases require hospitalization yearly, with a death rate of 2.5%. 1 - 3 The main risk factors of dengue include rainfall, temperature, 4 , 5 mosquito density, 6 density of people, 7 , 8 dengue types, 5 non-specific treatment, 1 , 2 no effective dengue vaccine, 5 , 9 ineffective drugs, 5 human immunity, 10 people’s movement across areas, 11 , 12 population density, 13 attitude toward dengue prevention, 14 , 15 and occupation. 12 Interventions to address dengue problems combine community mobilization, entomological methods, and chemical and biological controls.…”

COVID-19 adaptive humoral immunity models: weakly neutralizing versus antibody-disease enhancement scenarios

“…As to date there is no clear evidence that ADE occurs in COVID-19 severe patients, we assume that ADE only happens upon challenge. We started from a classic viral-host dynamics ( [28], [37]) that we modified by adding parameter β 1 to account for a possible ADE mechanism. In order to keep the model at its lowest complexity, we do not distinguish between ADE triggering antibodies and neutralizing antibodies.…”

“…We set ω to 2.0 × 10 3 virions per infected cells per day. Clearance rate was restricted between 1 and 10 day −1 , [37], [41], and set to 3 in our simulation. The median duration of the disease for mild cases was considered to be 10 days.…”

COVID-19: Progress in diagnostics, therapy and vaccination

“…Although antibodies are generally beneficial and protective, in rare cases, pathogen-specific antibodies could promote pathology, resulting in a phenomenon known as antibody-dependent enhancement (ADE) 140 , 141 . The ADE phenomenon is documented for dengue virus and other viruses 142 , 143 .…”