Impact of screening and doxycycline prevention on the syphilis epidemic among men who have sex with men in British Columbia: a mathematical modelling study.

Background: Men who have sex with men (MSM) in British Columbia (BC) are disproportionately affected by infectious syphilis and HIV. In this study, we developed a co-interaction model and evaluated the impact and effectiveness of possible interventions among different MSM subgroups on the syphilis epidemic. Methods: We designed a deterministic compartmental model, which stratified MSM by HIV status and HIV pre-exposure prophylaxis (HIV-PrEP) usage into (1) HIV-negative/unaware MSM (HIV-PrEP not recommended, not on HIV-PrEP), (2) HIV-negative/unaware MSM with HIV-PrEP recommended (not on HIV-PrEP), (3) HIV-negative/unaware MSM actively on HIV-PrEP, and (4) MSM diagnosed with HIV. We estimated the effect of scaling up syphilis testing frequency from Status Quo to six-, four-, and three-months, increasing the percentage of MSM using doxycycline prevention (Doxy-P) to 25%, 50%, and 100% of the target level, and a combination of both among subgroups (2)-(4). We also assessed the impact of these interventions on the syphilis incidence rates from 2020 to 2034 in comparison to the Status Quo scenario where no intervention was introduced. Findings: Under the Status Quo scenario, with the expansion of the HIV-PrEP program to improve syphilis testing, the syphilis incidence rate was estimated to peak at 16.1 [Credible Interval (CI):14.2-17.9] per 1,000 person-years (PYs) in 2023 and decrease to 6.7 (CI:3.8-10.9) per 1,000 PYs by 2034. The syphilis incidence rate in 2034 was estimated at 0.7 (0.3-1.3) per 1,000 PYs if MSM diagnosed with HIV could be tested every four months, and at 1.5 (0.7-3.0) per 1,000 PYs if HIV-negative/unaware MSM actively on HIV-PrEP could be tested every three months. By achieving 100% of the target coverage of Doxy-P, the syphilis incidence rate was estimated at 1.4 (0.5-3.4) if focusing on MSM diagnosed with HIV, and 2.6 (1.2-5.1) per 1,000 PYs if focusing on HIV-negative/unaware MSM actively on HIV-PrEP. Under the combined interventions, the syphilis incidence rate could be as low as 0.0 (0.0-0.1) and 0.8 (0.3-1.8) per 1,000 PYs, respectively. Interpretation: The HIV-PrEP program in BC plays a crucial role in increasing syphilis testing frequency among high-risk MSM and reducing syphilis transmission among this group. In addition, introducing Doxy-P can be an effective complementary strategy to minimize syphilis incidence, especially among MSM diagnosed with HIV. Funding: This work was funded by the Canadian Institutes of Health Research.

Effect of Human Mobility on the Spatial Spread of Airborne Diseases: An Epidemic Model with Indirect Transmission.

We extended a class of coupled PDE-ODE models for studying the spatial spread of airborne diseases by incorporating human mobility. Human populations are modeled with patches, and a Lagrangian perspective is used to keep track of individuals' places of residence. The movement of pathogens in the air is modeled with linear diffusion and coupled to the SIR dynamics of each human population through an integral of the density of pathogens around the population patches. In the limit of fast diffusion pathogens, the method of matched asymptotic analysis is used to reduce the coupled PDE-ODE model to a nonlinear system of ODEs for the average density of pathogens in the air. The reduced system of ODEs is used to derive the basic reproduction number and the final size relation for the model. Numerical simulations of the full PDE-ODE model and the reduced system of ODEs are used to assess the impact of human mobility, together with the diffusion of pathogens on the dynamics of the disease. Results from the two models are consistent and show that human mobility significantly affects disease dynamics. In addition, we show that an increase in the diffusion rate of pathogen leads to a lower epidemic.

Non-pharmaceutical intervention levels to reduce the COVID-19 attack ratio among children.

The attack ratio in a subpopulation is defined as the total number of infections over the total number of individuals in this subpopulation. Using a methodology based on an age-stratified transmission dynamics model, we estimated the attack ratio of COVID-19 among children (individuals 0-11 years) when a large proportion of individuals eligible for vaccination (age 12 and above) are vaccinated to contain the epidemic among this subpopulation, or the effective herd immunity (with additional physical distancing measures). We describe the relationship between the attack ratio among children, the time to remove infected individuals from the transmission chain and the children-to-children daily contact rate while considering the increased transmissibility of virus variants (using the Delta variant as an example). We illustrate the generality and applicability of the methodology established by performing an analysis of the attack ratio of COVID-19 among children in the population of Canada and in its province of Ontario. The clinical attack ratio, defined as the number of symptomatic infections over the total population, can be informed from the attack ratio and both can be reduced substantially via a combination of reduced social mixing and rapid testing and isolation of the children.

The basic reproduction number of COVID-19 across Africa.

The pandemic of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) took the world by surprise. Following the first outbreak of COVID-19 in December 2019, several models have been developed to study and understand its transmission dynamics. Although the spread of COVID-19 is being slowed down by vaccination and other interventions, there is still a need to have a clear understanding of the evolution of the pandemic across countries, states and communities. To this end, there is a need to have a clearer picture of the initial spread of the disease in different regions. In this project, we used a simple SEIR model and a Bayesian inference framework to estimate the basic reproduction number of COVID-19 across Africa. Our estimates vary between 1.98 (Sudan) and 9.66 (Mauritius), with a median of 3.67 (90% CrI: 3.31-4.12). The estimates provided in this paper will help to inform COVID-19 modeling in the respective countries/regions.

Mitigating co-circulation of seasonal influenza and COVID-19 pandemic in the presence of vaccination: A mathematical modeling approach.

The co-circulation of two respiratory infections with similar symptoms in a population can significantly overburden a healthcare system by slowing the testing and treatment. The persistent emergence of contagious variants of SARS-CoV-2, along with imperfect vaccines and their waning protections, have increased the likelihood of new COVID-19 outbreaks taking place during a typical flu season. Here, we developed a mathematical model for the co-circulation dynamics of COVID-19 and influenza, under different scenarios of influenza vaccine coverage, COVID-19 vaccine booster coverage and efficacy, and testing capacity. We investigated the required minimal and optimal coverage of COVID-19 booster (third) and fourth doses, in conjunction with the influenza vaccine, to avoid the coincidence of infection peaks for both diseases in a single season. We show that the testing delay brought on by the high number of influenza cases impacts the dynamics of influenza and COVID-19 transmission. The earlier the peak of the flu season and the greater the number of infections with flu-like symptoms, the greater the risk of flu transmission, which slows down COVID-19 testing, resulting in the delay of complete isolation of patients with COVID-19 who have not been isolated before the clinical presentation of symptoms and have been continuing their normal daily activities. Furthermore, our simulations stress the importance of vaccine uptake for preventing infection, severe illness, and hospitalization at the individual level and for disease outbreak control at the population level to avoid putting strain on already weak and overwhelmed healthcare systems. As such, ensuring optimal vaccine coverage for COVID-19 and influenza to reduce the burden of these infections is paramount. We showed that by keeping the influenza vaccine coverage about 35% and increasing the coverage of booster or fourth dose of COVID-19 not only reduces the infections with COVID-19 but also can delay its peak time. If the influenza vaccine coverage is increased to 55%, unexpectedly, it increases the peak size of influenza infections slightly, while it reduces the peak size of COVID-19 as well as significantly delays the peaks of both of these diseases. Mask-wearing coupled with a moderate increase in the vaccine uptake may mitigate COVID-19 and prevent an influenza outbreak.

Assessing the impact of adherence to Non-pharmaceutical interventions and indirect transmission on the dynamics of COVID-19: a mathematical modelling study.

Adherence to public health policies such as the non-pharmaceutical interventions implemented against COVID-19 plays a major role in reducing infections and controlling the spread of the diseases. In addition, understanding the transmission dynamics of the disease is also important in order to make and implement efficient public health policies. In this paper, we developed an SEIR-type compartmental model to assess the impact of adherence to COVID-19 non-pharmaceutical interventions and indirect transmission on the dynamics of the disease. Our model considers both direct and indirect transmission routes and stratifies the population into two groups: those that adhere to COVID-19 non-pharmaceutical interventions (NPIs) and those that do not adhere to the NPIs. We compute the control reproduction number and the final epidemic size relation for our model and study the effect of different parameters of the model on these quantities. Our results show that there is a significant benefit in adhering to the COVID-19 NPIs.

SARS-CoV-2 and self-medication in Cameroon: a mathematical model.

Self-medication is an important initial response to illness in Africa. This mode of medication is often done with the help of African traditional medicines. Because of the misconception that African traditional medicines can cure/prevent all diseases, some Africans may opt for COVID-19 prevention and management by self-medicating. Thus to efficiently predict the dynamics of COVID-19 in Africa, the role of the self-medicated population needs to be taken into account. In this paper, we formulate and analyse a mathematical model for the dynamics of COVID-19 in Cameroon. The model is represented by a system of compartmental age-structured ODEs that takes into account the self-medicated population and subdivides the human population into two age classes relative to their current immune system strength. We use our model to propose policy measures that could be implemented in the course of an epidemic in order to better handle cases of self-medication.

A co-interaction model of HIV and syphilis infection among gay, bisexual and other men who have sex with men.

We developed a mathematical model to study the co-interaction of HIV and syphilis infection among gay, bisexual and other men who have sex with men (gbMSM). We qualitatively analysed the model and established necessary conditions under which disease-free and endemic equilibria are asymptotically stable. We gave analytical expressions for the reproduction number, and showed that whenever the reproduction numbers of sub-models and co-interaction model are less than unity, the epidemics die out, while epidemics persist when they are greater than unity. We presented numerical simulations of the full model and showed qualitative changes of the dynamics of the full model to changes in the transmission rates. Our numerical simulations using a set of reasonable parameter values showed that: (a) both diseases die out or co-exist whenever their reproduction number is less than or exceed unity. (b) HIV infection impacts syphilis prevalence negatively and vice versa. (c) one possibility of lowering the co-infection of HIV and syphilis among gbMSM is to increase both testing and treatment rates for syphilis and HIV infection, and decrease the rate at which HIV infected individuals go off treatment.

A novel approach to modelling the spatial spread of airborne diseases: an epidemic model with indirect transmission.

We formulated and analyzed a class of coupled partial and ordinary differential equation (PDE-ODE) model to study the spread of airborne diseases. Our model describes human populations with patches and the movement of pathogens in the air with linear diffusion. The diffusing pathogens are coupled to the SIR dynamics of each population patch using an integro-differential equation. Susceptible individuals become infected at some rate whenever they are in contact with pathogens (indirect transmission), and the spread of infection in each patch depends on the density of pathogens around the patch. In the limit where the pathogens are diffusing fast, a matched asymptotic analysis is used to reduce the coupled PDE-ODE model into a nonlinear system of ODEs, which is then used to compute the basic reproduction number and final size relation for different scenarios. Numerical simulations of the reduced system of ODEs and the full PDE-ODE model are consistent, and they predict a decrease in the spread of infection as the diffusion rate of pathogens increases. Furthermore, we studied the effect of patch location on the spread of infections for the case of two population patches. Our model predicts higher infections when the patches are closer to each other.

The potential impact of initiating antiretroviral therapy with integrase inhibitors on HIV transmission risk in British Columbia, Canada.

BACKGROUND: Available agents within the integrase strand-transfer inhibitor (INSTI) class have been shown to lead to a faster decay in viral load than other regimens. Therefore, we estimated the potential reduction in HIV transmission risk among antiretroviral-naïve individuals initiating on INSTI-based antiretroviral therapy (ART), focusing on the gay, bisexual and other men who have sex with men (gbMSM) population and various degrees of sexual activity. METHODS: Using two mathematical models that estimate the HIV transmission risk corresponding to different viral loads, we estimated the average probability of HIV transmission per risky contact for gbMSM during the six months post-ART initiation, stratified by stage of HIV infection, viral load at ART initiation and type of first-line ART (i.e., INSTI or non-INSTI-based ART). This study focused individuals who initiated ART between 2011 and 2016 with at least one year of follow-up in British Columbia, Canada. FINDINGS: Time to first virologic suppression for INSTI-based regimens was 21.4 days (95% credible interval (CI) 19.9-23.2), compared to 58.6 days (95% CI 54.1-62.2) for non-INSTI regimens. We showed that INSTI-based regimens could reduce the HIV transmission risk by at least 25% among those with viral load ≥ 5 log10 copies/mL at ART initiation. INTERPRETATION: Initiating ART on INSTI-based regimens has the potential to reduce HIV transmission risk among individuals with high baseline viral load levels, especially among those with high levels of sexual activity. FUNDING: The British Columbia Ministry of Health, the Canadian Institutes of Health Research, and the Michael Smith Foundation for Health Research.

Epidemic models with heterogeneous mixing and indirect transmission.

We develop an age of infection model with heterogeneous mixing in which indirect pathogen transmission is considered as a good way to describe contact that is usually considered as direct and we also incorporate virus shedding as a function of age of infection. The simplest form of SIRP epidemic model is introduced and it serves as a basis for the age of infection model and a 2-patch SIRP model where the risk of infection is solely dependent on the residence times and other environmental factors. The computation of the basic reproduction number [Formula: see text], the initial exponential growth rate and the final size relation is done and by mathematical analysis, we study the impact of patches connection and use the final size relation to analyse the ability of disease to invade over a short period of time.