Co-infection Model Research Articles

Quantifying the impact of vaccination on transmission and diversity of influenza A variants in pigs

ABSTRACT Global evolutionary dynamics of influenza A virus (IAV) are fundamentally driven by the extent of virus diversity generated, transmitted, and shaped in individual hosts. How vaccination affects the degree of IAV genetic diversity that can be transmitted and expanded in pigs is unknown. To evaluate the effect of vaccination on the transmission of genetically distinct IAV variants and their diversity after transmission in pigs, we examined the whole genome of IAV recovered from the nasal cavities of pigs vaccinated with different influenza immunization regimens after being infected simultaneously by H1N1 and H3N2 IAVs using a seeder pig model. We found that the seeder pigs harbored more diversified virus populations than the contact pigs. Among contact pigs, H3N2 and H1N1 viruses recovered from pigs vaccinated with a single dose of an unmatched modified live vaccine generally accumulated more extensive genetic mutations than non-vaccinated pigs. Furthermore, the non-sterilizing immunity elicited by the single-dose-modified live vaccine may have exerted positive selection on H1 antigenic regions as we detected significantly higher nonsynonymous but lower synonymous evolutionary rates in H1 antigenic regions than non-antigenic regions. In addition, we observed that the vaccinated pigs shared significantly less proportion of H3N2 variants with seeder pigs than unvaccinated pigs. These results indicated that vaccination might reduce the impact of transmitted influenza variants on the overall diversity of IAV populations harbored in recipient pigs and that within-host genetic selection of IAV is more likely to occur in pigs vaccinated with improperly matched vaccines. IMPORTANCE Understanding how vaccination shapes the diversity of influenza variants that transmit and propagate among pigs is essential for designing effective IAV surveillance and control programs. Current knowledge about the transmission of IAV variants has primarily been explored in humans during natural infection. However, how immunity elicited by improperly matched vaccines affects the degree of IAV genetic diversity that can be transmitted and expanded in pigs at the whole-genome level is unknown. We analyzed IAV sequences from samples collected daily from experimentally infected pigs vaccinated with various protocols in a field-represented IAV co-infection model. We found that vaccine-induced non-sterilizing immunity might promote genetic variation on the IAV genome and drive positive selection at antigenic sites during infection. In addition, a smaller proportion of H3N2 viral variants were shared between seeder pigs and vaccinated pigs, suggesting the influence of vaccination on shaping the virus genomic diversity in recipient pigs during the transmission events.

A fractional-order model of COVID-19 and Malaria co-infection

This paper explores the co-infection dynamics of coronavirus disease 2019 (COVID-19) and Malaria using Caputo-type fractional derivative to further understand the disease interactions and implement effective control strategies. We demonstrate the positivity and boundedness of the solution through Laplace transform techniques and establish the existence and uniqueness of the solution, showcasing model stability using fractional-order stability theory. Simulation experiments across varying fractional orders and disease classes offer insights into the co-infection dynamics. This is a new model and the findings underscore the potential impact of control measures on mitigating co-infection under endemic conditions. We conclude that infection with malaria does not guarantee immunity to COVID-19 and infection with COVID-19 as well does not guarantee immunity to malaria.

A dynamical optimal control theory and cost-effectiveness analyses of the HBV and HIV/AIDS co-infection model

Studies have shown that the co-infection of Human Immunodeficiency Virus (HIV) and Hepatitis B Virus (HBV) poses a major threat to the public health due to their combined negative impacts on health and increased risk of complications. Even though, some scholars formulated and analyzed the HBV and HIV co-infection model they did not consider the compartment that contains protected individuals against both HBV and HIV infections. They incorporated the optimal control theory and cost-effectiveness analysis simultaneously. With this in mind, we are motivated to formulate and analyze the HBV and HIV co-infection model, considering the protected group and incorporating optimal control theory and cost-effectiveness. In this study, we have theoretically computed all of the models disease-free equilibrium points, all the models effective reproduction numbers and unique endemic equilibrium points. The two sub-models disease-free equilibrium points are locally as well as globally asymptotically stable whenever their associated effective reproduction numbers are less than one. We reformulated the optimal control problem by incorporating five time-dependent control measures and conducted its theoretical analysis by utilizing the Pontryagin's maximum principle. Using the fourth order Runge–Kutta numerical method and MATLAB ODE45, we performed the numerical simulations with various combinations of control efforts to verify the theoretical results and investigate the impacts of the suggested protection and treatment control strategies for both the HBV and HIV diseases. Also, we carried out a cost-effectiveness analysis of the proposed control strategies. Eventually, we compared our model results with other researcher similar model results whenever cost-effectiveness analysis is not carried out the findings of this particular study suggest that implementing each of the proposed control strategies simultaneously has a high potential to reduce and control the spread of HBV and HIV co-infections in the community. According to the cost-effectiveness analysis, implementing the HBV treatment and the HIV and HBV co-infection treatment measures has a high potential effect on reducing and controlling the HBV and HIV co-infection transmission problem in the community.

Stability and Hopf bifurcation of TB-COVID-19 coinfection model with impact of time delay

Stability and Hopf bifurcation of TB-COVID-19 coinfection model with impact of time delay

A two-strain COVID-19 co-infection model with strain 1 vaccination

COVID-19 has caused substantial morbidity and mortality worldwide. Previous models of strain 1 vaccination with re-infection when vaccinated, as well as infection with strain 2 did not consider co-infected classes. To fill this gap, a two co-circulating COVID-19 strains model with strain 1 vaccination, and co-infected is formulated and theoretically analyzed. Sufficient conditions for the stability of the disease-free equilibrium and single-strain 1 and -strain 2 endemic equilibria are obtained. Results show as expected that (1) co-infected classes play a role in the transmission dynamics of the disease (2) a high efficacy vaccine could effectively help mitigate the spread of co-infection with both strain 1 and 2 compared to the low-efficacy vaccine. Sensitivity analysis reveals that the main drivers of the effective reproduction number Re are primarily the effective contact rate for strain 2 (β2), the strain 2 recovery rate (τ2), and the vaccine efficacy or infection reduction due to the vaccine (η). Thus, implementing intervention measures to mitigate the spread of COVID-19 should not ignore the co-infected individuals who can potentially spread both strains of the disease.

The underlying mechanism of single and co-infection of DIV1 and WSSV in Litopenaeus vannamei

Viral diseases are one of the important factors restricting the shrimp industry. Decapod iridescent virus 1 (DIV1) and White spot syndrome virus (WSSV) are the two most harmful viruses to shrimp. DIV1 and WSSV were found to be carried and infected simultaneously in several samples of cultured and wild shrimps. In this study, the co-infection model of DIV1 and WSSV in Litopenaeus vannamei was constructed by TaqMan probe quantitative detection (qPCR), intestinal section, and transcriptome analysis. Our study also evaluated the virulence of the virus by calculating LC50 and detected the replication rates of DIV1 and WSSV at 7-time points and 2 tissues in L. vannamei by qPCR. As a result, DIV1 and WSSV could infect L. vannamei singly or co-infect L. vannamei. DIV1 replicated the fastest, at 12–16 h post-injection (hpi). The WSSV virus replicates the fastest 20–24 hpi. In different tissues, the amount of DIV1 carried by blood cells is higher than that in muscle, while WSSV is the opposite. In addition, the intestinal responses of DIV1 and WSSV single and co-infection of L. vannamei were explored using the RNA-Seq platform and bioinformatics analysis, and the differential expressed genes (DEGs) screened by comparison were as follows: there were significant differences in DEGs between the PBS group and the three virus infection groups, and there were differences in DEGs between the PBS group and single virus infection groups (the DIV1 group and the WSSV group), but there was no significant difference in the DEGs between the 2 single virus infection groups, and the Combine-infected group, especially, the DEGs between the WSSV group and the Combine-infected group were only 39. According to the above conclusions, it can be inferred that WSSV plays a major role in co-infection. In addition, pathways related to vitamin metabolism were significantly enriched in the viral infection group compared to the PBS group. Glycolysis/Gluconeogenesis, a hallmark of the Warburg effect, is also significantly enriched after viral infection. In this study, the co-infection phenomenon of DIV1 and WSSV was found for the first time in L. vannamei, which provided a new idea for developing and screening molecular markers for new strains resistant to complex viruses in L. vannamei.

Clinical prediction model for bacterial co-infection in hospitalized COVID-19 patients during four waves of the pandemic.

Estimates of bacterial coinfection in COVID-19 patients are highly variable and depend on many factors. Patients with severe or critical COVID-19 requiring intensive care unit admission have the highest risk of infection-related complications and death. Thus, the study of the incidence and risk factors for bacterial coinfection in this population is of special interest and may help guide empiric antibiotic therapy and avoid unnecessary antimicrobial treatment. The prediction model based on clinical criteria and simple laboratory tests may be a useful tool to predict bacterial co-infection in patients hospitalized with severe COVID-19.

The role of Helicobacter pylori in augmenting the severity of SARS-CoV-2 related gastrointestinal symptoms: An insight from molecular mechanism of co-infection

Coinfection of pathogenic bacteria and viruses is associated with multiple diseases. During the COVID-19 pandemic, the co-infection of other pathogens with SARS-CoV-2 was one of the important determinants of the severity. Although primarily a respiratory virus gastric manifestation of the SARS-CoV-2 infection was widely reported. This study highlights the possible consequences of SARS-CoV-2 -Helicobacter pylori coinfection in the gastrointestinal cells. We utilized the transfection and infection model for SARS-CoV-2 spike Delta (δ) and H. pylori respectively in colon carcinoma cell line HT-29 to develop the coinfection model to study inflammation, mitochondrial function, and cell death. The results demonstrate increased transcript levels of inflammatory markers like TLR2 (p < 0.01), IL10 (p < 0.05), TNFα (p < 0.05) and CXCL1 (p < 0.05) in pre-H. pylori infected cells as compared to the control. The protein levels of the β-Catenin (p < 0.01) and c-Myc (p < 0.01) were also significantly elevated in pre-H. pylori infected group in case of co-infection. Further investigation of apoptotic and necrotic markers (Caspase-3, Caspase-8, and RIP-1) reveals a necroptotic cell death in the coinfected cells. The infection and coinfection also damage the mitochondria in HT-29 cells, further implicating mitochondrial dysfunction in the necrotic cell death process. Our study also highlights the detrimental effect of pre-H. pylori exposure in the coinfection model compared to post-exposure and lone infection of H. pylori and SARS-CoV-2. This knowledge could aid in developing targeted interventions and therapeutic strategies to mitigate the severity of COVID-19 and improve patient outcomes.

Concurrent TB and HIV therapies effectively control clinical reactivation of TB during co-infection but fail to eliminate chronic immune activation.

The majority of Human Immunodeficiency Virus (HIV) negative individuals exposed to Mycobacterium tuberculosis (Mtb) control the bacillary infection as latent TB infection (LTBI). Co-infection with HIV, however, drastically increases the risk to progression to tuberculosis (TB) disease. TB is therefore the leading cause of death in people living with HIV (PLWH) globally. Combinatorial antiretroviral therapy (cART) is the cornerstone of HIV care in humans and reduces the risk of reactivation of LTBI. However, the immune control of Mtb infection is not fully restored by cART as indicated by higher incidence of TB in PLWH despite cART. In the macaque model of co-infection, skewed pulmonary CD4+ TEM responses persist, and new TB lesions form despite cART treatment. We hypothesized that regimens that concurrently administer anti-TB therapy and cART would significantly reduce TB in co-infected macaques than cART alone, resulting in superior bacterial control, mitigation of persistent inflammation and lasting protective immunity. We studied components of TB immunity that remain impaired after cART in the lung compartment, versus those that are restored by concurrent 3 months of once weekly isoniazid and rifapentine (3HP) and cART in the rhesus macaque (RM) model of LTBI and Simian Immunodeficiency Virus (SIV) co-infection. Concurrent administration of cART + 3HP did improve clinical and microbiological attributes of Mtb/SIV co-infection compared to cART-naïve or -untreated RMs. While RMs in the cART + 3HP group exhibited significantly lower granuloma volumes after treatment, they, however, continued to harbor caseous granulomas with increased FDG uptake. cART only partially restores the constitution of CD4 + T cells to the lung compartment in co-infected macaques. Concurrent therapy did not further enhance the frequency of reconstituted CD4+ T cells in BAL and lung of Mtb/SIV co-infected RMs compared to cART, and treated animals continued to display incomplete reconstitution to the lung. Furthermore, the reconstituted CD4+ T cells in BAL and lung of cART + 3HP treated RMs exhibited an increased frequencies of activated, exhausted and inflamed phenotype compared to LTBI RMs. cART + 3HP failed to restore the effector memory CD4+ T cell population that was significantly reduced in pulmonary compartment post SIV co-infection. Concurrent therapy was associated with the induction of Type I IFN transcriptional signatures and led to increased Mtb-specific TH1/TH17 responses correlated with protection, but decreased Mtb-specific TNFa responses, which could have a detrimental impact on long term protection. Our results suggest the mechanisms by which Mtb/HIV co-infected individuals remain at risk for progression due to subsequent infections or reactivation due of persisting defects in pulmonary T cell responses. By identifying lung-specific immune components in this model, it is possible to pinpoint the pathways that can be targeted for host-directed adjunctive therapies for TB/HIV co-infection.

Pathogenicity of duck circovirus and novel goose parvovirus co-infection in SPF ducks

ABSTRACT Duck circovirus (DuCV) is one of the most prevalent infectious viruses in the duck industry in China. Although the clinical signs vary, it often causes immunosuppression in the host and leads to secondary infection with other pathogens. Novel goose parvovirus (NGPV) mainly infects ducks and causes short beak and dwarfism syndrome in ducks. However, the incidence of infection in ducks has increased in recent years, and the phenomenon of mixed infection with DuCV is common, resulting in more severe clinical morbidity. However, there are no systematic studies evaluating the presence of mixed infections. In order to investigate the synergistic pathogenicity of DuCV and NGPV co-infection in SPF ducks, a comparative experiment using DuCV and NGPV co-infection and mono-infection bird models was established. The results showed that the clinical signs of short beak, dwarfism and immunosuppression were more obvious in DuCV and NGPV co-infected ducks; the tissue damage of target organs was more serious, and the viral titre in organs and cloacal swabs were more significant compared with those of SPF ducks infected with only one virus. The results indicated that co-infection with DuCV and NGPV could promote viral replication and cause more severe tissue damage and immunosuppression than single virus infection. The present study reveals that the co-infection of NGPV and DuCV has a synergistic pathogenic effect from the aspect of pathogenicity, and the conclusions drawn not only clarify the direction of the subsequent research on the mechanism of co-infection of NGPV and DuCV, but also provide a scientific basis for the research on the co-infection of immunosuppressive pathogens and other pathogens.

Comparative Cross-Kingdom DDA- and DIA-PASEF Proteomic Profiling Reveals Novel Determinants of Fungal Virulence and a Putative Druggable Target.

Accurate and reliable detection of fungal pathogens presents an important hurdle to manage infections, especially considering that fungal pathogens, including the globally important human pathogen, Cryptococcus neoformans, have adapted diverse mechanisms to survive the hostile host environment and moderate virulence determinant production during coinfections. These pathogen adaptations present an opportunity for improvements (e.g., technological and computational) to better understand the interplay between a host and a pathogen during disease to uncover new strategies to overcome infection. In this study, we performed comparative proteomic profiling of an in vitro coinfection model across a range of fungal and bacterial burden loads in macrophages. Comparing data-dependent acquisition and data-independent acquisition enabled with parallel accumulation serial fragmentation technology, we quantified changes in dual-perspective proteome remodeling. We report enhanced and novel detection of pathogen proteins with data-independent acquisition-parallel accumulation serial fragmentation (DIA-PASEF), especially for fungal proteins during single and dual infection of macrophages. Further characterization of a fungal protein detected only with DIA-PASEF uncovered a novel determinant of fungal virulence, including altered capsule and melanin production, thermotolerance, and macrophage infectivity, supporting proteomics advances for the discovery of a novel putative druggable target to suppress C. neoformans pathogenicity.

Co-infection dynamics of B. afzelii and TBEV in C3H mice: insights and implications for future research.

Ticks are important vectors of disease, particularly in the context of One Health, where tick-borne diseases (TBDs) are increasingly prevalent worldwide. TBDs often involve co-infections, where multiple pathogens co-exist in a single host. Patients with chronic Lyme disease often have co-infections with other bacteria or parasites. This study aimed to create a co-infection model with Borrelia afzelii and tick-borne encephalitis virus (TBEV) in C3H mice and to evaluate symptoms, mortality, and pathogen level compared to single infections. Successful co-infection of C3H mice with B. afzelii and TBEV was achieved. Outcomes varied, depending on the timing of infection. When TBEV infection followed B. afzelii infection by 9 days, TBEV symptoms worsened and virus levels increased. Conversely, mice infected 21 days apart with TBEV showed milder symptoms and lower mortality. Simultaneous infection resulted in mild symptoms and no deaths. However, our model did not effectively infect ticks with TBEV, possibly due to suboptimal dosing, highlighting the challenges of replicating natural conditions. Understanding the consequences of co-infection is crucial, given the increasing prevalence of TBD. Co-infected individuals may experience exacerbated symptoms, highlighting the need for a comprehensive understanding through refined animal models. This study advances knowledge of TBD and highlights the importance of exploring co-infection dynamics in host-pathogen interactions.

Wavelet Collocation Method for HIV-1/HTLV-I Co-Infection Model Using Hermite Polynomial.

In this study, the dynamic behavior of fractional order co-infection model with human immunodeficiency virus type 1 (HIV-1) and human T-lymphotropic virus type I (HTLV-I) is analyzed using operational matrix of Hermite wavelet collocation method. Also, the uniqueness and existence of solutions are calculated based on the fixed point hypothesis. For the fractional order co-infection model, its positivity and boundedness are demonstrated. Furthermore, different types of Ulam-Hyres stability are also discussed. The numerical solution of the model are obtained by using the operational matrix of the Hermite wavelet approach. This scheme is used to solve the system of nonlinear equationsthat are very fruitful and easy to implement. Additionally, the stability analysis of the numerical scheme is explained. The mathematical model taken in this work incorporates the biological characteristics of both HIV-1 and HTLV-I. After that all the equilibrium points of the fractional order co-infection model are found and their existence conditions are explored with the help of the Caputo derivative. The global stability of all equilibrium points of this model are determined with the help of Lyapunov functions and the LaSalle invariance principle. Convergence analysis is also discussed. Hermite wavelet operational matrix methods are more accurate and convergent than other numerical methods. Lastly, variations in model dynamics are found when examining different fractional order values. These findings will be valuable to biologists in the treatment of HIV-1/HTLV-I.

Stability Analysis for Co-Dynamics of COVID-19 and HIV-AIDS with Public Sensitization and Education as Controls

Infectious diseases have denied humanity joy and resources over the centuries. Major diseases such as rabies (1885), whooping cough (1914), flu influenza (1945), and COVID-19 changed the course of life. Hence, a need for alternative methods of combating infections with optimal cost. The coronavirus has shocked the world and it was devastating. The human immunodeficiency virus (HIV) epidemic has caused individuals to rethink their sexual lives, especially in Africa, where the disease has plagued several souls. The authors developed a compartmental model for co-infection of COVID-19 and HIV infection with optimal control. The following controls were incorporated into the model: education/sensitization of susceptible populations, use of anti-retroviral therapy, treatment of co-infected populations, and treatment of the COVID-19-infected population are essential in the fight against HIV and COVID-19 infections. Qualitative and quantitative solutions to the model were determined and analyzed. The HIV-COVID-19-free equilibrium of the co-dynamics model was found to be locally asymptotically stable whenever the reproductive rate was less than one and unstable otherwise. The co-dynamic model was extended to include some controls. This was to establish which strategy is suitable for combating the spread of the COVID-19-infected population. The results of our numerical simulations revealed that in combating COVID-19 and HIV spread, education of susceptible populations and treatment of COVID-19-infected populations are the best options. There has been a reduction in COVID-19 infection, an increase in the COVID-19 recovery population, and a substantial reduction in COVID-19 populations due to this control strategy. The findings of this study are an important step in the fight against HIV and COVID-19. Hence, policymakers should place priority on public education on HIV/COVID-19 infections and treatment of the COVID-infected population when combating these diseases.

A Mathematical Model for the Co-infection Dynamics of Pneumocystis Pneumonia and HIV/AIDS with Treatment

The control of opportunistic infections among HIV infected individuals should be one of the major public health concerns in reducing mortality rate of individuals living with HIV/AIDS. In this study a deterministic co-infection mathematical model is developed to provide a quantification of treatment at each contagious stage against Pneumocystis Pneumonia (PCP) among HIV infected individuals on ART. The goal is to minimize the co-infection burden by putting the curable PCP under control. The disease-free equilibria for the HIV/AIDS sub-model, PCP sub-model and the co-infection model are shown to be locally asymptotically stable when their associated disease threshold parameter is less than a unity. By use of suitable Lyapunov functions, the endemic equilibria corresponding to HIV/AIDS and PCP sub-models are globally asymptotically stable whenever the HIV/AIDS related basic reproduction number &amp;lt;I&amp;gt;R&amp;lt;/I&amp;gt;&amp;lt;sub&amp;gt;0&amp;lt;I&amp;gt;H&amp;lt;/I&amp;gt;&amp;lt;/sub&amp;gt; and the PCP related reproduction number &amp;lt;I&amp;gt;R&amp;lt;/I&amp;gt;&amp;lt;sub&amp;gt;0&amp;lt;I&amp;gt;P&amp;lt;/I&amp;gt;&amp;lt;/sub&amp;gt; are respectively greater than a unity. The sensitivity analysis results implicate that the effective contact rates are the main mechanisms fueling the proliferation of the two diseases and on the other hand treatment efforts play an important role in reducing the incidence. The model numerical results reveal that PCP carriers have a considerable contribution in the transmission dynamics of PCP. Furthermore, treatment of PCP at all contagious phases significantly reduces the burden with HIV/AIDS and PCP co-infection.

Robustness and exploration between the interplay of the nonlinear co-dynamics HIV/AIDS and pneumonia model via fractional differential operators and a probabilistic approach

In this article, we considered a nonlinear compartmental mathematical model that assesses the effect of treatment on the dynamics of HIV/AIDS and pneumonia (H/A-P) co-infection in a human population at different infection stages. Understanding the complexities of co-dynamics is now critically necessary as a consequence. The aim of this research is to construct a co-infection model of H/A-P in the context of fractional calculus operators, white noise and probability density functions, employing a rigorous biological investigation. By exhibiting that the system possesses non-negative and bounded global outcomes, it is shown that the approach is both mathematically and biologically practicable. The required conditions are derived, guaranteeing the eradication of the infection. Furthermore, adequate prerequisites are established, and the configuration is tested for the existence of an ergodic stationary distribution. For discovering the system’s long-term behavior, a deterministic-probabilistic technique for modeling is designed and operated in MATLAB. By employing an extensive review, we hope that the previously mentioned approach improves and leads to mitigating the two diseases and their co-infections by examining a variety of behavioral trends, such as transitions to unpredictable procedures. In addition, the piecewise differential strategies are being outlined as having promising potential for scholars in a range of contexts because they empower them to include particular characteristics across multiple time frame phases. Such formulas can be strengthened via classical techniques, power law, exponential decay, generalized Mittag-Leffler kernels, probability density functions and random procedures. Furthermore, we get an accurate description of the probability density function encircling a quasi-equilibrium point if the effect of H/A-P minimizes the propagation of the co-dynamics. Consequently, scholars can obtain better outcomes when analyzing facts using random perturbations by implementing these strategies for challenging issues. Random perturbations in H/A-P co-infection are crucial in controlling the spread of an epidemic whenever the suggested circulation is steady and the amount of infection eliminated is closely correlated with the random perturbation level.

The Impact of SIV-Induced Immunodeficiency on SARS-CoV-2 Disease, Viral Dynamics, and Antiviral Immune Response in a Nonhuman Primate Model of Coinfection.

The effects of immunodeficiency associated with chronic HIV infection on COVID-19 disease and viral persistence have not been directly addressed in a controlled setting. In this pilot study, we exposed two pigtail macaques (PTMs) chronically infected with SIVmac239, exhibiting from very low to no CD4 T cells across all compartments, to SARS-CoV-2. We monitored the disease progression, viral replication, and evolution, and compared these outcomes with SIV-naïve PTMs infected with SARS-CoV-2. No overt signs of COVID-19 disease were observed in either animal, and the SARS-CoV-2 viral kinetics and evolution in the SIVmac239 PTMs were indistinguishable from those in the SIV-naïve PTMs in all sampled mucosal sites. However, the single-cell RNA sequencing of bronchoalveolar lavage cells revealed an infiltration of functionally inert monocytes after SARS-CoV-2 infection. Critically, neither of the SIV-infected PTMs mounted detectable anti-SARS-CoV-2 T-cell responses nor anti-SARS-CoV-2 binding or neutralizing antibodies. Thus, HIV-induced immunodeficiency alone may not be sufficient to drive the emergence of novel viral variants but may remove the ability of infected individuals to mount adaptive immune responses against SARS-CoV-2.

Dynamical analysis of SARS-CoV-2-Dengue co-infection mathematical model with optimum control and sensitivity analyses

This study develops an epidemic model to analyze the dynamics of SARS-CoV-2 and dengue coinfection in a population. The population is divided into sixteen compartments for humans and three for vectors. The model’s validity is ensured by maintaining bounded and non-negative solutions. The Basic Reproduction Number (BRN) is calculated for each sub-model to assess stability at equilibrium points. Sensitivity analysis identifies key parameters influencing the model. The complete coinfection model is analyzed to identify equilibrium points and evaluate stability conditions. The reciprocal influence of SARS-CoV-2 and dengue diseases is examined. An optimal control problem is formulated, incorporating six strategies: COVID-19 protection, mosquito bite prevention, treatment for COVID-19 and dengue, mosquito control, and coinfection treatment. Numerical simulations validate the effectiveness of these control strategies for the coinfection model and its sub-models.

Indoleamine-2,3-dioxygenase inhibition improves immunity and is safe for concurrent use with cART during Mtb/SIV coinfection.

Chronic immune activation promotes tuberculosis (TB) reactivation in the macaque Mycobacterium tuberculosis (M. tuberculosis)/SIV coinfection model. Initiating combinatorial antiretroviral therapy (cART) early lowers the risk of TB reactivation, but immune activation persists. Studies of host-directed therapeutics (HDTs) that mitigate immune activation are, therefore, required. Indoleamine 2,3, dioxygenase (IDO), a potent immunosuppressor, is one of the most abundantly induced proteins in NHP and human TB granulomas. Inhibition of IDO improves immune responses in the lung, leading to better control of TB, including adjunctive to TB chemotherapy. The IDO inhibitor D-1 methyl tryptophan (D1MT) is, therefore, a bona fide TB HDT candidate. Since HDTs against TB are likely to be deployed in an HIV coinfection setting, we studied the effect of IDO inhibition in M. tuberculosis/SIV coinfection, adjunctive to cART. D1MT is safe in this setting, does not interfere with viral suppression, and improves the quality of CD4+ and CD8+ T cell responses, including reconstitution, activation and M. tuberculosis-specific cytokine production, and access of CD8+ T cells to the lung granulomas; it reduces granuloma size and necrosis, type I IFN expression, and the recruitment of inflammatory IDO+ interstitial macrophages (IMs). Thus, trials evaluating the potential of IDO inhibition as HDT in the setting of cART in M. tuberculosis/HIV coinfected individuals are warranted.

Elevated Inflammation Associated with Markers of Neutrophil Function and Gastrointestinal Disruption in Pilot Study of Plasmodium fragile Co-Infection of ART-Treated SIVmac239+ Rhesus Macaques.

Human immunodeficiency virus (HIV) and malaria, caused by infection with Plasmodium spp., are endemic in similar geographical locations. As a result, there is high potential for HIV/Plasmodium co-infection, which increases the pathology of both diseases. However, the immunological mechanisms underlying the exacerbated disease pathology observed in co-infected individuals are poorly understood. Moreover, there is limited data available on the impact of Plasmodium co-infection on antiretroviral (ART)-treated HIV infection. Here, we used the rhesus macaque (RM) model to conduct a pilot study to establish a model of Plasmodium fragile co-infection during ART-treated simian immunodeficiency virus (SIV) infection, and to begin to characterize the immunopathogenic effect of co-infection in the context of ART. We observed that P. fragile co-infection resulted in parasitemia and anemia, as well as persistently detectable viral loads (VLs) and decreased absolute CD4+ T-cell counts despite daily ART treatment. Notably, P. fragile co-infection was associated with increased levels of inflammatory cytokines, including monocyte chemoattractant protein 1 (MCP-1). P. fragile co-infection was also associated with increased levels of neutrophil elastase, a plasma marker of neutrophil extracellular trap (NET) formation, but significant decreases in markers of neutrophil degranulation, potentially indicating a shift in the neutrophil functionality during co-infection. Finally, we characterized the levels of plasma markers of gastrointestinal (GI) barrier permeability and microbial translocation and observed significant correlations between indicators of GI dysfunction, clinical markers of SIV and Plasmodium infection, and neutrophil frequency and function. Taken together, these pilot data verify the utility of using the RM model to examine ART-treated SIV/P. fragile co-infection, and indicate that neutrophil-driven inflammation and GI dysfunction may underlie heightened SIV/P. fragile co-infection pathogenesis.