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

2020 ◽  
Vol 7 (4) ◽  
pp. 191749 ◽  
Author(s):  
Biao Tang ◽  
Yanni Xiao ◽  
Beate Sander ◽  
Manisha A. Kulkarni ◽  
RADAM-LAC Research Team ◽  
...  
Keyword(s):  
Viral Load ◽  
Dengue Virus ◽  
Zika Virus ◽  
Primary Infection ◽  
Secondary Infection ◽  
Peak Time ◽  
Virus Dynamics ◽  
Antibody Dependent Enhancement ◽  
Secondary Infections ◽  
Peak Viral Load

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.

scholarly journals Estimation of Dengue Virus IgM Persistence Using Regression Analysis

2011 ◽  
Vol 18 (12) ◽  
pp. 2183-2185 ◽  
Author(s):  
Harry E. Prince ◽  
Jose L. Matud
Keyword(s):  
Regression Analysis ◽  
Dengue Virus ◽  
Primary Infection ◽  
Secondary Infection ◽  
Disease Onset ◽  
Decay Rates ◽  
Point Index ◽  
Infection Group ◽  
Secondary Infections

ABSTRACTDengue virus IgM persistence was estimated using follow-up sera from 98 patients (60 with primary infections and 38 with secondary infections) whose first-specimen IgM index was strongly positive, suggesting recent disease onset. Regression analysis of the follow-up IgM index versus days between samples yielded a trend line that reached the cut-point index (1.10) at 179 days for the primary infection group and 139 days for the secondary infection group. This difference reflected significantly higher first-sample IgM indices in primary infections than in secondary infections rather than differences in IgM decay rates.

scholarly journals Primary infection with dengue or Zika virus does not affect the severity of heterologous secondary infection in macaques

2019 ◽  
Author(s):  
Meghan E. Breitbach ◽  
Christina M. Newman ◽  
Dawn M. Dudley ◽  
Laurel M. Stewart ◽  
Matthew T. Aliota ◽  
...  
Keyword(s):  
Zika Virus ◽  
Primary Infection ◽  
Rhesus Macaques ◽  
Secondary Infection ◽  
Denv Infection ◽  
The Other ◽  
Sample Type ◽  
Zikv Infection ◽  
Secondary Infections ◽  
Cynomolgus Macaques

AbstractZika virus (ZIKV) and dengue virus (DENV) are genetically and antigenically related flaviviruses that now co-circulate in much of the tropical and subtropical world. The rapid emergence of ZIKV in the Americas in 2015 and 2016, and its recent associations with Guillain-Barré syndrome, birth defects, and fetal loss have led to the hypothesis that DENV infection induces cross-reactive antibodies that influence the severity of secondary ZIKV infections. It has also been proposed that pre-existing ZIKV immunity could affect DENV pathogenesis. We examined outcomes of secondary ZIKV infections in three rhesus and fifteen cynomolgus macaques, as well as secondary DENV-2 infections in three additional rhesus macaques up to a year post-primary ZIKV infection. Although cross-binding antibodies were detected prior to secondary infection for all animals and cross-neutralizing antibodies were detected for some animals, previous DENV or ZIKV infection had no apparent effect on the clinical course of heterotypic secondary infections in these animals. All animals had asymptomatic infections and, when compared to controls, did not have significantly perturbed hematological parameters. Rhesus macaques infected with DENV-2 approximately one year after primary ZIKV infection had higher vRNA loads in plasma when compared with serum vRNA loads from ZIKV-naive animals infected with DENV-2, but a differential effect of sample type could not be ruled out. In cynomolgus macaques, the serotype of primary DENV infection did not affect the outcome of secondary ZIKV infection.Author summaryPre-existing immunity to one of the four DENV serotypes is known to increase the risk of severe disease upon secondary infection with a different serotype. Due to the antigenic similarities between ZIKV and DENV, it has been proposed that these viruses could interact in a similar fashion. Data from in vitro experiments and murine models suggests that pre-existing immunity to one virus could either enhance or protect against infection with the other. These somewhat contradictory findings highlight the need for immune competent animal models for understanding the role of cross-reactive antibodies in flavivirus pathogenesis. We examined secondary ZIKV or DENV infections in rhesus and cynomolgus macaques that had previously been infected with the other virus. We assessed the outcomes of secondary ZIKV or DENV infections by quantifying vRNA loads, clinical and laboratory parameters, body temperature, and weight for each cohort of animals and compared them with control animals. These comparisons demonstrated that within a year of primary infection, secondary infections with either ZIKV or DENV were similar to primary infections and were not associated with enhancement or reduction in severity of disease based on the outcomes that we assessed.

Demonstration of marmosets (Callithrix jacchus) as a non-human primate model for secondary dengue virus infection: high levels of viraemia and serotype cross-reactive antibody responses consistent with secondary infection of humans

2014 ◽  
Vol 95 (3) ◽  
pp. 591-600 ◽  
Author(s):  
Meng Ling Moi ◽  
Tomohiko Takasaki ◽  
Tsutomu Omatsu ◽  
Shinichiro Nakamura ◽  
Yuko Katakai ◽  
...  
Keyword(s):  
Dengue Virus ◽  
Primary Infection ◽  
Secondary Infection ◽  
Denv Infection ◽  
Callithrix Jacchus ◽  
Antibody Responses ◽  
Infection Model ◽  
Primate Model ◽  
Bhk Cells ◽  
Denv Serotypes

There are four dengue virus (DENV) serotypes. Primary infection with one does not confer protective immunity against the others. We have reported previously that the marmoset (Callithrix jacchus) is a useful primary DENV infection model. It has been reported that secondary DENV infection with a heterotypic serotype induces viraemia kinetics and antibody responses that differ from those in primary infection. Thus, it is important to determine the utility of the marmoset as a model for secondary DENV infection. Marmosets were infected with heterologous DENV by secondary inoculation, and viraemia kinetics and antibody responses were analysed. The marmosets consistently developed high levels of viraemia after the secondary inoculation with heterologous DENV serotypes. IgM responses were lower compared with primary inoculation responses, whilst IgG responses were rapid and high. Neutralizing activities, which possessed serotype cross-reactive activities, were detected as early as 4 days after inoculation. In addition, infectious viraemia titres were higher when assayed with Fcγ receptor-expressing baby hamster kidney (BHK) cells than when assayed with conventional BHK cells, suggesting the presence of infectious virus–antibody immune complexes. After secondary infection with heterotypic DENV, the marmosets demonstrated viraemia kinetics, IgM and IgG responses, and high levels of serotype cross-reactive neutralizing antibody responses, all of which were consistent with secondary DENV infection in humans. The results indicate the marmoset as a useful animal for studying secondary, as well as primary, DENV infection.

Strongyloides ratti: 1. Parasitological observations on primary and secondary infections in the small intestine of rats

1977 ◽  
Vol 51 (4) ◽  
pp. 301-308 ◽  
Author(s):  
R. Moqbel ◽  
D. A. Denham
Keyword(s):  
Small Intestine ◽  
Primary Infection ◽  
Secondary Infection ◽  
Secondary Infections

ABSTRACTAdult Strongyloides ratti were expelled from the small intestine of rats starting 14—18 days after a primary infection. In a secondary infection very few adult worms developed and most of these were expelled before day 14. At the time of expulsion the worms migrated posteriorly in the intestine and their size decreased.

scholarly journals Protein Disulfide Isomerase Inhibitor Suppresses Viral Replication and Production during Antibody-Dependent Enhancement of Dengue Virus Infection in Human Monocytic Cells

Viruses ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 155 ◽  
Author(s):  
Nantapon Rawarak ◽  
Aroonroong Suttitheptumrong ◽  
Onrapak Reamtong ◽  
Kobporn Boonnak ◽  
Sa-nga Pattanakitsakul
Keyword(s):  
Dengue Virus ◽  
Protein Disulfide Isomerase ◽  
Early Stage ◽  
Secondary Infection ◽  
Protein Translation ◽  
Virus Infectivity ◽  
Disulfide Isomerase ◽  
Antibody Dependent Enhancement ◽  
Altered Proteins ◽  
Protein Disulfide

One of several mechanisms that leads to the development of dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) is called antibody-dependent enhancement (ADE). Monocytes can be infected by the ADE phenomenon, which occurs in dengue secondary infection. This study aimed to investigate the proteins involved in ADE of DENV infection in the human monocytic cell line U937. The phosphoproteins were used to perform and analyze for protein expression using mass spectrometry (GeLC-MS/MS). The differential phosphoproteins revealed 1131 altered proteins compared between isotype- and DENV-specific antibody-treated monocytes. The altered proteins revealed 558 upregulated proteins and 573 downregulated proteins. Protein disulfide isomerase (PDI), which is an enzyme that had a high-ranking fold change and that catalyzes the formation, breakage, and rearrangement of disulfide bonds within a protein molecule, was selected for further study. PDI was found to be important for dengue virus infectivity during the ADE model. The effect of PDI inhibition was also shown to be involved in the early stage of life cycle by time-of-drug-addition assay. These results suggest that PDI is important for protein translation and virion assembly of dengue virus during infection in human monocytes, and it may play a significant role as a chaperone to stabilize dengue protein synthesis.

scholarly journals Primary and Probable Secondary Dengue Virus (DV) Infection Rates in Relation to Age among DV IgM-Positive Patients Residing in the United States Mainland Versus the Caribbean Islands

2011 ◽  
Vol 19 (1) ◽  
pp. 105-108 ◽  
Author(s):  
Harry E. Prince ◽  
Cindy Yeh ◽  
Mary Lapé-Nixon
Keyword(s):  
United States ◽  
Dengue Virus ◽  
Infection Rate ◽  
Primary Infection ◽  
Secondary Infection ◽  
The United States ◽  
Infection Rates ◽  
Caribbean Island ◽  
Caribbean Islands ◽  
The Caribbean

ABSTRACTDengue virus (DV) primary infection and probable secondary infection rates in relation to patient age (years) were determined for DV IgM-positive U.S. mainland residents (presumed travelers to areas of DV endemicity) and Caribbean island (area of DV endemicity) residents by evaluating IgG status and IgG avidity. Regardless of place of residence, most patients ≤20 years old exhibited primary infection and most patients >60 years old exhibited probable secondary infection. Among patients 21 to 60 years old, the primary infection rate was markedly higher in U.S. residents.

Hymenolepis microstoma: a change in susceptibility to resistance with increasing age of the parasite

Parasitology ◽  
1977 ◽  
Vol 75 (2) ◽  
pp. 241-249 ◽  
Author(s):  
R. J. Howard
Keyword(s):  
Bile Duct ◽  
Primary Infection ◽  
Secondary Infection ◽  
Similar Rate ◽  
Rate Of Growth ◽  
Secondary Infections ◽  
Hymenolepis Microstoma

Hymenolepis microstoma from secondary infections in mice were found to grow initially more slowly than H. microstoma from primary infections. Eventually a similar rate of growth was attained by both kinds of worm. After transplantation, young worms (≤4 days old) grew more slowly in previously infected than in naive mice. In contrast, 10-day-old worms grew equally well in naive or resistant mice. The administration of cortisone to mice during a secondary infection of H. microstoma inhibited the stunting of growth in young worms which were able to grow as well as those in a primary infection. The effects of the cortisone persisted for less than 4 days. Worms in a secondary infection given 4days after cortisone treatment were stunted in growth. These experiments suggest that the susceptibility of the worms to the resistance of the mouse applies to the first 4 days within the host. The loss or reduction of this susceptibility might be associated with the worms' entry into the bile duct which occurs 3–4 days after infection.

scholarly journals Wrong person, place and time: viral load and contact network structure predict SARS-CoV-2 transmission and super-spreading events

2020 ◽  
Author(s):  
Ashish Goyal ◽  
Daniel B Reeves ◽  
E. Fabian Cardozo-Ojeda ◽  
Joshua T Schiffer ◽  
Bryan T. Mayer
Keyword(s):  
Viral Load ◽  
High Viral Load ◽  
Physical Contact ◽  
Therapeutic Interventions ◽  
Contact Network ◽  
Infected Person ◽  
Infected People ◽  
Viral Shedding ◽  
Secondary Infections ◽  
Peak Viral Load

SARS-CoV-2 is difficult to contain because many transmissions occur during the pre-symptomatic phase of infection. Moreover, in contrast to influenza, while most SARS-CoV-2 infected people do not transmit the virus to anybody, a small percentage secondarily infect large numbers of people. We designed mathematical models of SARS-CoV-2 and influenza which link observed viral shedding patterns with key epidemiologic features of each virus, including distributions of the number of secondary cases attributed to each infected person (individual R0) and the duration between symptom onset in the transmitter and secondarily infected person (serial interval). We identify that people with SARS-CoV-2 or influenza infections are usually contagious for fewer than one day congruent with peak viral load several days after infection, and that transmission is unlikely below a certain viral load. SARS-CoV-2 super-spreader events with over 10 secondary infections occur when an infected person is briefly shedding at a very high viral load and has a high concurrent number of exposed contacts. The higher predisposition of SARS-CoV-2 towards super-spreading events is not due to its 1-2 additional weeks of viral shedding relative to influenza. Rather, a person infected with SARS-CoV-2 exposes more people within equivalent physical contact networks than a person infected with influenza, likely due to aerosolization of virus. Our results support policies that limit crowd size in indoor spaces and provide viral load benchmarks for infection control and therapeutic interventions intended to prevent secondary transmission.

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