ORCID Profile
0000-0003-1582-3379
Current Organisation
Pfizer Research Technology Center
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Biological Mathematics | Dynamical Systems in Applications | Applied Mathematics | Stochastic Analysis and Modelling |
Expanding Knowledge in the Biological Sciences | Expanding Knowledge in the Mathematical Sciences | Expanding Knowledge in the Medical and Health Sciences
Publisher: Elsevier BV
Date: 06-2022
Publisher: The Royal Society
Date: 04-2022
Abstract: The emergence of new SARS-CoV-2 variants of concern (VOC) has h ered international efforts to contain the COVID-19 pandemic. VOCs have been characterized to varying degrees by higher transmissibility, worse infection outcomes and evasion of vaccine and infection-induced immunologic memory. VOCs are hypothesized to have originated from animal reservoirs, communities in regions with low surveillance and/or single in iduals with poor immunologic control of the virus. Yet, the factors dictating which variants ultimately predominate remain incompletely characterized. Here we present a multi-scale model of SARS-CoV-2 dynamics that describes population spread through in iduals whose viral loads and numbers of contacts (drawn from an over-dispersed distribution) are both time-varying. This framework allows us to explore how super-spreader events (SSE) (defined as greater than five secondary infections per day) contribute to variant emergence. We find stochasticity remains a powerful determinant of predominance. Variants that predominate are more likely to be associated with higher infectiousness, an SSE early after variant emergence and ongoing decline of the current dominant variant. Additionally, our simulations reveal that most new highly infectious variants that infect one or a few in iduals do not achieve permanence in the population. Consequently, interventions that reduce super-spreading may delay or mitigate emergence of VOCs.
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.MBS.2013.04.014
Abstract: In this paper, a non-linear mathematical model for removing an inorganic pollutant such as chromium from a water body using fungi is proposed and analyzed. It is assumed that the inorganic pollutant is discharged in a water body with a constant rate, which is depleted due to natural factors as well as by fungal absorption using dissolved oxygen in the process. The model is analyzed by using stability theory of differential equations and simulation. The analysis shows that the inorganic pollutant can be removed from the water body by fungal absorption, the rate of removal depends upon the concentration of inorganic pollutant, the density of fungal population and various interaction processes. The simulation analysis of the model confirms the analytical results. It is noted here this theoretical result is qualitatively in line with the experimental observations of one of the authors (Sanghi).
Publisher: Elsevier BV
Date: 06-2016
DOI: 10.1016/J.JTBI.2016.03.018
Abstract: Hepatitis-D virus (HDV) is a satellite virus of hepatitis-B virus (HBV) whose intracellular products are required for the completion of the HDV life cycle. HDV can replicate in a cell without the presence of HBV but needs hepatitis B surface antigen (HBsAg) to complete virus assembly and packaging. In order to better understand HDV dynamics, we developed a mathematical model and successfully simulated HBV and HDV data under a range of scenarios. Compared to HBV mono-infection, dual HDV infection resulted in lower chronic HBV DNA levels, with more marked suppression for coinfection (1 logs HBV DNA copies/ml lower) compared to superinfection (0.6 logs HBV DNA copies/ml). Although they have no effect on HBV, prenylation inhibitors may provide the best therapy for reducing HDV viremia irrespective of the stage in which they are commenced. We found that highly effective long term pegylated interferon (IFN) therapy (99.99%) eliminates HBV and HDV viremia while less effective long term IFN therapy (99%) will only produce approximately 2.03 logs and no decrease in HBV and HDV viremia respectively in both coinfection and superinfection settings. Our study also suggests that there is a substantial difference in the outcome of therapies depending upon the time of commencement. Mathematical modeling of HDV infection can describe the complex interplay between this virus and HBV. Simulations suggest that HDV impacts on the feedback mechanisms that maintain cccDNA levels and that targeting these mechanisms may result in new therapeutic agents for both viruses.
Publisher: Elsevier BV
Date: 2022
Publisher: Elsevier BV
Date: 09-2021
Publisher: MDPI AG
Date: 18-11-2017
DOI: 10.3390/V9110350
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 25-10-2021
Publisher: Public Library of Science (PLoS)
Date: 25-08-2016
Publisher: World Scientific Pub Co Pte Lt
Date: 2014
DOI: 10.1142/S1793524514500089
Abstract: In this paper, a nonlinear mathematical model is proposed and analyzed to study the role of dissolved oxygen (DO)-dependent bacteria on biodegradation of one or two organic pollutant(s) in a water body. In the case of two organic pollutant(s), it is assumed that the one is fast degrading and the other is slow degrading and both are discharged into the water body from outside with constant rates. The density of bacteria is assumed to follow logistic model and its growth increases due to biodegradation of one or two organic pollutant(s) as well as with the increase in the concentration of DO. The model is analyzed using the stability theory of differential equations and by simulation. The model analysis shows that the concentration(s) of one or both organic pollutant(s) decrease(s) as the density of bacteria increases. It is noted that for very large density of bacteria, the organic pollutant(s) may be removed almost completely from the water body. It is found that simulation analysis confirms the analytical results. The results obtained in this paper are in line with the experimental observations published in literature.
Publisher: Cold Spring Harbor Laboratory
Date: 14-09-2020
DOI: 10.1101/2020.09.13.20193508
Abstract: Masks are a vital tool for limiting SARS-CoV-2 spread in the population. Here we utilize a mathematical model to assess the impact of masking on transmission within in idual transmission pairs and at the population level. Our model quantitatively links mask efficacy to reductions in viral load and subsequent transmission risk. Our results reinforce that the use of masks by both a potential transmitter and exposed person substantially reduces the probability of successful transmission, even if masks only lower exposure viral load by ~50%. Slight increases in masking relative to current levels would reduce the reproductive number substantially below 1, particularly if implemented comprehensively in potential super-spreader environments. Our model predicts that moderately efficacious masks that reduce transmission risk by 50% will lower exposure viral load 10-fold among people who do get infected, potentially limiting infection severity. Because peak viral load tends to occur pre-symptomatically, we also identify that antiviral therapy targeting symptomatic in iduals is unlikely to impact transmission risk. Instead, antiviral therapy is only effective for this indication as post-exposure prophylaxis, specifically if given to ~50% of newly infected people within 3 days of an exposure. These results highlight the primacy of masking relative to other biomedical interventions under consideration for limiting the extent of the COVID-19 pandemic prior to widespread implementation of a vaccine.
Publisher: Elsevier BV
Date: 10-2021
Publisher: No publisher found
Date: 2021
Publisher: Springer Science and Business Media LLC
Date: 03-06-2021
DOI: 10.1038/S41562-021-01108-6
Abstract: Exclusive breastfeeding (EBF)—giving infants only breast-milk for the first 6 months of life—is a component of optimal breastfeeding practices effective in preventing child morbidity and mortality. EBF practices are known to vary by population and comparable subnational estimates of prevalence and progress across low- and middle-income countries (LMICs) are required for planning policy and interventions. Here we present a geospatial analysis of EBF prevalence estimates from 2000 to 2018 across 94 LMICs mapped to policy-relevant administrative units (for ex le, districts), quantify subnational inequalities and their changes over time, and estimate probabilities of meeting the World Health Organization’s Global Nutrition Target (WHO GNT) of ≥70% EBF prevalence by 2030. While six LMICs are projected to meet the WHO GNT of ≥70% EBF prevalence at a national scale, only three are predicted to meet the target in all their district-level units by 2030.
Publisher: Elsevier BV
Date: 2022
Publisher: Wiley
Date: 08-12-2014
DOI: 10.1002/MMA.3368
Publisher: Elsevier BV
Date: 12-2019
Publisher: Elsevier BV
Date: 10-2018
DOI: 10.1016/J.JTBI.2018.06.020
Abstract: Out of several phases of HBV infection, the least understood phase is occult hepatitis B virus infection. The paucity of data due to non-availability of biological tissues and the prerequisite of ultra-sensitive assays for the detection of occult hepatitis B virus infection prompted us to utilize mathematical modeling in determining mechanisms that lead to occult hepatitis B virus infection and characteristics of HBV infection during occult hepatitis B virus infection. We proposed two mathematical models (M1 and M2), considering two different phenomenon for episomal maintenance and accumulation of covalently closed circular DNA (cccDNA) in infected hepatocytes: (i) M1 - recirculation of the relaxed circular DNA/double-stranded linear DNA from cytoplasm to the nucleus, and (ii) M2 - reinfection of infected hepatocytes with virions. We further incorporated the dynamics of integrated Hepatitis B virus DNA (iHBV) to investigate its role in the development of occult hepatitis B virus infection. The analysis showed that the main mechanism for the spread of infection during occult hepatitis B virus infection is cell-to-cell transmission and not cell-free virus transmission. A significant viral suppression (of at least 99% from its peak production values) was essential but not sufficient in the development of occult hepatitis B virus infection under M1 however under M2, the viral suppression was neither sufficient nor essential as the inhibition of the production of HBsAg without viral suppression can also explain the development of occult hepatitis B virus infection. Our analysis also revealed that occult hepatitis B virus infection seropositive cases are more likely to progress into liver cirrhosis compared to occult hepatitis B virus infection seronegative cases. The iHBV was found to be mostly silent (by either being absent or non-productive for HBsAg) during occult hepatitis B virus infection. The viral suppression is neither essential nor sufficient to explain the development of occult hepatitis B virus infection on its own. Not only the viral suppression but the inhibition -of the production and the export of HBsAg from cccDNA and iHBV also plays an important role in the development of occult hepatitis B virus infection. This is the first study, which incorporates the dynamics of iHBV and shows that HBV primarily spreads via cell-cell transmission during occult hepatitis B virus infection.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Cold Spring Harbor Laboratory
Date: 24-03-2021
DOI: 10.1101/2021.03.23.21254185
Abstract: The emergence of multiple new SARS-CoV-2 variants, characterized to varying degrees by increased infectivity, higher virulence and evasion of vaccine and infection-induced immunologic memory, has h ered international efforts to contain the virus. While it is generally believed that these variants first develop in single in iduals with poor immunologic control of the virus, the factors governing variant predominance in the population remain poorly characterized. Here we present a mathematical framework for variant emergence accounting for the highly variable number of people secondarily infected by in iduals with SARS-CoV-2 infection. Our simulations suggest that threatening new variants probably develop within infected people fairly commonly, but that most die out and do not achieve permanence in the population. Variants that predominate are more likely to be associated with higher infectiousness, but also the occurrence of a super-spreader event soon after introduction into the population.
Publisher: MDPI AG
Date: 20-03-2021
DOI: 10.3390/V13030516
Abstract: While SARS-CoV-2 specific neutralizing antibodies have been developed for therapeutic purposes, the specific viral triggers that drive the generation of SARS-CoV-2 specific IgG and IgM antibodies remain only partially characterized. Moreover, it is unknown whether endogenously derived antibodies drive viral clearance that might result in mitigation of clinical severity during natural infection. We developed a series of non-linear mathematical models to investigate whether SARS-CoV-2 viral and antibody kinetics are coupled or governed by separate processes. Patients with severe disease had a higher production rate of IgG but not IgM antibodies. Maximal levels of both isotypes were governed by their production rate rather than different saturation levels between people. Our results suggest that an exponential surge in IgG levels occurs approximately 5–10 days after symptom onset with no requirement for continual antigenic stimulation. SARS-CoV-2 specific IgG antibodies appear to have limited to no effect on viral dynamics but may enhance viral clearance late during primary infection resulting from the binding effect of antibody to virus, rather than neutralization. In conclusion, SARS-CoV-2 specific IgG antibodies may play only a limited role in clearing infection from the nasal passages despite providing long-term immunity against infection following vaccination or prior infection.
Publisher: Elsevier BV
Date: 08-2017
Publisher: Elsevier BV
Date: 02-2015
DOI: 10.1016/J.JTBI.2014.11.020
Abstract: The progression of acute hepatitis B virus (HBV) to chronic infection or clearance is highly dependent on the host immune response composed of cytolytic (CTL) and non-cytolytic (non-CTL) effects. Cytolytic processes induce hepatocyte killing while non-CTL processes inhibit intracellular replication. Both effects are widely recognized and accepted. However, there are uncertainties about the assistance provided by either the loss of covalently circular closed DNA (cccDNA) during cell proliferation or the emergence of refractory cells to immune mediated clearance. We developed an agent-based mathematical model and tested the relative roles of different mechanisms of the immune system in the clearance of acute HBV infection. HBV viremia clearance time and hepatocyte turnover (HT) were used as the two major criteria in determining reasonable outcomes. Modelling results in 90% of cells containing between 1 and 17 cccDNA copies and normally distributed at the peak of infection. Variations in p36 levels, responsible for determining export of virions or recirculation to lify cccDNA numbers, have a much greater impact on mean cccDNA level/cell at peak viremia than virus infectivity and cccDNA half-life. A strong CTL effect alone failed to clear infection with HT ≈ 10. Acute infection clearance was possible with combined CTL and non-CTL effects along with complete loss of intracellular viral components during cell proliferation resulting in the desired range of HT (0.7-1). The emergence of cells refractory to infection can reduce HT by up to 90%. However their impact was less effective than complete loss of intracellular viral components during cell proliferation. the existence of refractory cells is not necessary when there is complete loss of intracellular quantities during cell proliferation but is essential with only partial clearance.
Publisher: Oxford University Press (OUP)
Date: 22-03-2022
DOI: 10.1093/OFID/OFAC157
Abstract: Shortening duration of direct-acting antiviral therapy for chronic hepatitis C could provide cost savings, reduce medication exposure, and foster adherence and treatment completion in special populations. The current analysis indicates that measuring hepatitis C virus at baseline and on days 7 and 14 of therapy can identify patients for shortening therapy duration.
Publisher: Elsevier BV
Date: 08-2011
Publisher: American Society for Clinical Investigation
Date: 10-09-2018
DOI: 10.1172/JCI121678
Publisher: American Society of Clinical Oncology (ASCO)
Date: 20-10-2020
DOI: 10.1200/JCO.19.03107
Abstract: To investigate quality-adjusted progression-free survival (QA-PFS) and quality-adjusted time without symptoms or toxicity (Q-TWiST) in a post hoc exploratory analysis of the phase III ARIEL3 study of rucaparib maintenance treatment versus placebo. Patients with platinum-sensitive, recurrent ovarian carcinoma were randomly assigned to rucaparib (600 mg twice per day) or placebo. QA-PFS was calculated as progression-free survival function × the 3-level version of the EQ-5D questionnaire (EQ-5D-3L) index score function. Q-TWiST analyses were performed defining TOX as the mean duration in which a patient experienced grade ≥ 3 treatment-emergent adverse events (TEAEs) or the mean duration in which a patient experienced grade ≥ 2 TEAEs of nausea, vomiting, fatigue, and asthenia. Q-TWiST was calculated as μTOX × TOX + TWiST, with μTOX calculated using EQ-5D-3L data. The visit cutoff was Apr 15, 2017. Mean QA-PFS was significantly longer with rucaparib versus placebo in the intent-to-treat (ITT) population (375 randomly assigned to rucaparib v 189 randomly assigned to placebo difference, 6.28 months [95% CI, 4.85 to 7.47 months]) BRCA-mutant cohort (130 rucaparib v 66 placebo 9.37 months [95% CI, 6.65 to 11.85 months]) homologous recombination deficient (HRD) cohort (236 rucaparib v 118 placebo 7.93 months [95% CI, 5.93 to 9.53 months]) and BRCA wild-type/loss of heterozygosity (LOH) low patient subgroup (107 rucaparib v 54 placebo 2.71 months [95% CI, 0.31 to 4.44 months]). With TOX defined using grade ≥ 3 TEAEs, the difference in mean Q-TWiST (rucaparib v placebo) was 6.88 months (95% CI, 5.71 to 8.23 months), 9.73 months (95% CI, 7.10 to 11.94 months), 8.11 months (95% CI, 6.36 to 9.49 months), and 3.35 months (95% CI, 1.66 to 5.40 months) in the ITT population, BRCA-mutant cohort, HRD cohort, and BRCA wild-type/LOH low patient subgroup, respectively. Q-TWiST with TOX defined using select grade ≥ 2 TEAEs also consistently favored rucaparib. The significant differences in QA-PFS and Q-TWiST confirm the benefit of rucaparib versus placebo in all predefined cohorts.
Publisher: Cambridge University Press (CUP)
Date: 22-02-2013
DOI: 10.1017/S0956792513000065
Abstract: In this paper, a non-linear mathematical model is proposed and analysed to study the role of technology in combating social crimes in a dynamic population by considering immigration and emigration rates of susceptible population and criminals. The problem is modelled by considering five interacting variables, namely the density of susceptible population, the density of criminals, the density of removed (isolated) criminals, the density of crime burden and the level of technology used to control crime. The proposed model is analysed by using the stability theory of differential equation and simulation. The model analysis shows that the crime burden decreases considerably as the level of technology increases. It is noted that the crime in a society can be controlled almost completely if criminals from the general population are removed by intensive use of technology.
Publisher: Elsevier BV
Date: 10-2020
Publisher: Wiley
Date: 24-11-2020
DOI: 10.1111/JVH.13429
Publisher: Springer Science and Business Media LLC
Date: 11-05-2016
DOI: 10.1007/S40261-016-0409-8
Abstract: The cost-effectiveness of highly effective, but costly, peg-interferon (peg-IFN) treatment for chronic hepatitis B (CHB) infections in China is unknown. Endemic hepatitis D virus (HDV) may also modify the effectiveness of any HBV treatment option. The objective of this study is to determine the best antiviral treatment from a societal perspective in the Chinese population, which contains a mix of HBV and HDV infections. A Markov model is developed to simulate the clinical course of CHB and chronic hepatitis D (CHD) in iduals. For a hypothetical Chinese cohort of 10,000 in iduals aged 30-60 years, cost-utility analysis is performed for therapies with: lamivudine, adefovir, telbivudine, entecavir, IFN and Peg-IFN. Costs and quality-adjusted life-years (QALYs) are discounted at 3 % annually. A one-way sensitivity analysis is also conducted. Lamivudine, adefovir, telbivudine, and entecavir are all cost-effective treatments compared to palliative care at an incremental cost-effectiveness ratio (ICER) of -$418, -$197, -$443 and -$317 per QALY, respectively (2015 US dollars). Peg-IFN yields a maximum 156,000 QALYs with an ICER of $1149 per QALY while IFN results in the highest cumulative mortality of 48 % along with the lowest QALY gained. Probabilistic sensitivity analyses confirm that only Peg-IFN and ETV are the only two cost-effective options at the current willingness-to-pay (WTP) of $12,000 in China. However, entecavir has a higher probability of being cost-effective than Peg-IFN at current WTP for all age groups. Peg-IFN generates maximum QALYs compared to lamivudine, adefovir, telbivudine and interferon, and presents itself as a cost-effective option at current WTP. Alternatively entecavir can be used in China, generating 10 % lower QALYs than Peg-IFN but costing less than palliative care.
Publisher: Cold Spring Harbor Laboratory
Date: 07-08-2020
DOI: 10.1101/2020.08.07.20169920
Abstract: 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 (in idual R 0 ) 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. We developed a coupled within-host and between-host mathematical model to identify viral shedding levels required for transmission of SARS-CoV-2 and influenza, and to explain why super-spreading events occur more commonly during SARS-CoV-2 infection.
Publisher: Inderscience Publishers
Date: 2018
Publisher: Cold Spring Harbor Laboratory
Date: 14-12-2020
DOI: 10.1101/2020.12.13.20248120
Abstract: Ongoing SARS-CoV-2 vaccine trials assess vaccine efficacy against disease (VE DIS ), the ability of a vaccine to block symptomatic COVID-19. They will only partially discriminate whether VE DIS is mediated by preventing infection as defined by the detection of virus in the airways (vaccine efficacy against infection defined as VE SUSC ), or by preventing symptoms despite breakthrough infection (vaccine efficacy against symptoms or VE SYMP ). Vaccine efficacy against infectiousness (VE INF ), defined as the decrease in secondary transmissions from infected vaccine recipients versus from infected placebo recipients, is also not being measured. Using mathematical modeling of data from King County Washington, we demonstrate that if the Moderna and Pfizer vaccines, which have observed VE DIS %, mediate VE DIS predominately by complete protection against infection, then prevention of a fourth epidemic wave in the spring of 2021, and associated reduction of subsequent cases and deaths by 60%, is likely to occur assuming rapid enough vaccine roll out. If high VE DIS is explained primarily by reduction in symptoms, then VE INF % will be necessary to prevent or limit the extent of this fourth epidemic wave. The potential added benefits of high VE INF would be evident regardless of vaccine allocation strategy and would be enhanced if vaccine roll out rate is low or if available vaccines demonstrate waning immunity. Finally, we demonstrate that a 1.0 log vaccine-mediated reduction in average peak viral load might be sufficient to achieve VE INF =60% and that human challenge studies with 104 infected participants, or clinical trials in a university student population could estimate VE SUSC , VE SYMP and VE INF using viral load metrics.
Publisher: Elsevier BV
Date: 10-2014
Publisher: MDPI AG
Date: 24-09-2014
DOI: 10.3390/V13101921
Abstract: SARS-CoV-2 vaccine clinical trials assess efficacy against disease (VEDIS), the ability to block symptomatic COVID-19. They only partially discriminate whether VEDIS is mediated by preventing infection completely, which is defined as detection of virus in the airways (VESUSC), or by preventing symptoms despite infection (VESYMP). Vaccine efficacy against transmissibility given infection (VEINF), the decrease in secondary transmissions from infected vaccine recipients, is also not measured. Using mathematical modeling of data from King County Washington, we demonstrate that if the Moderna (mRNA-1273QS) and Pfizer-BioNTech (BNT162b2) vaccines, which demonstrated VEDIS 90% in clinical trials, mediate VEDIS by VESUSC, then a limited fourth epidemic wave of infections with the highly infectious B.1.1.7 variant would have been predicted in spring 2021 assuming rapid vaccine roll out. If high VEDIS is explained by VESYMP, then high VEINF would have also been necessary to limit the extent of this fourth wave. Vaccines which completely protect against infection or secondary transmission also substantially lower the number of people who must be vaccinated before the herd immunity threshold is reached. The limited extent of the fourth wave suggests that the vaccines have either high VESUSC or both high VESYMP and high VEINF against B.1.1.7. Finally, using a separate intra-host mathematical model of viral kinetics, we demonstrate that a 0.6 log vaccine-mediated reduction in average peak viral load might be sufficient to achieve 50% VEINF, which suggests that human challenge studies with a relatively low number of infected participants could be employed to estimate all three vaccine efficacy metrics.
Publisher: Elsevier BV
Date: 10-2021
Publisher: American Association for the Advancement of Science (AAAS)
Date: 20-11-2020
Abstract: We developed a mathematical model to predict the outcomes of different possible COVID-19 treatments.
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.JTBI.2017.04.007
Abstract: Hepatitis B virus (HBV) is endemic in China. Almost 10% of HBV infected in iduals are also infected with hepatitis D virus (HDV) which has a 5-10 times higher mortality rate than HBV mono-infection. The aim of this manuscript is to devise strategies that can not only control HBV infections but also HDV infections in China under the current health care budget in an optimal manner. Using a mathematical model, an annual budget of $10billion was optimally allocated among five interventions namely, testing and HBV adult vaccination, treatment for mono-infected and dually-infected in iduals, second line treatment for HBV mono-infections, and awareness programs. We determine that the optimal strategy is to test and treat both infections as early as possible while applying awareness programs at full intensity. Under this strategy, an additional 19.8million HBV, 1.9million HDV infections and 0.25million lives will be saved over the next 10years at a cost-savings of $79billion than performing no intervention. Introduction of second line treatment does not add a significant economic burden yet prevents 1.4million new HBV infections and 15,000 new HDV infections. Test and treatment programs are highly efficient in reducing HBV and HDV prevalence in the population. Under the current health budget in China, not only test and treat programs but awareness programs and second line treatment can also be implemented that minimizes prevalence and mortality, and maximizes economic benefits.
Publisher: Wiley
Date: 18-02-2014
DOI: 10.1111/NRM.12033
Publisher: Elsevier BV
Date: 06-2020
Publisher: Public Library of Science (PLoS)
Date: 14-10-2014
Publisher: Elsevier BV
Date: 10-2021
Publisher: Elsevier BV
Date: 11-2014
Publisher: eLife Sciences Publications, Ltd
Date: 23-02-2021
DOI: 10.7554/ELIFE.63537
Abstract: SARS-CoV-2 is difficult to contain because many transmissions occur during pre-symptomatic infection. Unlike influenza, most SARS-CoV-2-infected people do not transmit while a small percentage infect large numbers of people. We designed mathematical models which link observed viral loads with epidemiologic features of each virus, including distribution of transmissions attributed to each infected person and duration between symptom onset in the transmitter and secondarily infected person. We identify that people infected with SARS-CoV-2 or influenza can be highly contagious for less than 1 day, congruent with peak viral load. SARS-CoV-2 super-spreader events occur when an infected person is shedding at a very high viral load and has a high number of exposed contacts. The higher predisposition of SARS-CoV-2 toward super-spreading events cannot be attributed to additional weeks of shedding relative to influenza. Rather, a person infected with SARS-CoV-2 exposes more people within equivalent physical contact networks, likely due to aerosolization.
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.TPB.2016.08.004
Abstract: Hepatitis delta virus (HDV) in conjunction with hepatitis B virus (HBV) increases adult morbidity and mortality. A number of studies have performed cost-benefit analyses for HBV interventions, but they have ignored the impact of HDV on these outcomes. Using a mathematical model of HBV-HDV epidemiology, we compare health benefits and cost outcomes of four interventions: testing with HBV adult vaccination (diagnosis), diagnosis with antiviral treatment for HBV infections (mono-infections), diagnosis with antiviral treatment for HBV-HDV infections (dual-infections), and awareness programs. The relationship between optimal levels and outcomes of each of these interventions and HDV prevalence in HBV infected in iduals ranging from 0 to 50% is determined. Over a 50 year period under no intervention, HBV prevalence, per capita total cost and death toll increase by 2.25%, -$11 and 2.6-fold respectively in moderate HDV endemic regions compared to mono-infected regions the corresponding values for high HDV endemic regions are 4.2%, -$21 and 3.9-fold. Optimal interventions can be strategized similarly in mono and dually endemic regions. Only implementation of all four interventions achieves a very low HBV prevalence of around 1.5% in a moderate HDV endemic region such as China, with 2.8 million fewer deaths compared to no intervention. Although the policy of implementation of all four interventions costs additional $382 billion compared to no intervention, it still remains cost-effective with an incremental cost-effectiveness ratio of $1400/QALY. Very high efficacy awareness programs achieve less prevalence with fewer deaths at a lower cost compared to treatment and/or vaccination programs. HDV substantially affects the performance of any HBV-related intervention. Its exclusion results in over-estimation of the effectiveness of HBV interventions.
Publisher: Cold Spring Harbor Laboratory
Date: 22-06-2020
DOI: 10.1101/2020.06.21.163550
Abstract: Remdesivir was recently demonstrated to decrease recovery time in hospitalized patients with SARS-CoV-2 infection. In rhesus macaques, early initiation of remdesivir therapy prevented pneumonia and lowered viral loads in the lung, but viral loads increased in the nasal passages five days after therapy. We developed mathematical models to explain these results. We identified that 1) drug potency is slightly higher in nasal passages than in lungs, 2) viral load decrease in lungs relative to nasal passages during therapy because of infection-dependent generation of refractory cells in the lung, 3) incomplete drug potency in the lung that decreases viral loads even slightly may allow substantially less lung damage, and 4) increases in nasal viral load may occur due to a slight blunting of peak viral load and subsequent decrease of the intensity of the innate immune response, as well as a lack of refractory cells. We also hypothesize that direct inoculation of the trachea in rhesus macaques may not recapitulate natural infection as lung damage occurs more abruptly in this model than in human infection. We demonstrate with sensitivity analysis that a drug with higher potency could completely suppress viral replication and lower viral loads abruptly in the nasal passages as well as the lung. We developed a mathematical model to explain why remdesivir has a greater antiviral effect on SARS CoV-2 in lung versus nasal passages in rhesus macaques.
Publisher: Public Library of Science (PLoS)
Date: 07-09-2018
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 18-04-2015
DOI: 10.1002/HEP.27595
Publisher: American Association for the Advancement of Science (AAAS)
Date: 14-01-2022
Abstract: eCD4Ig has an in vivo IC 50 of 25 μg/ml, and it may induce ART-free virus control if produced continually at 10 5 μg/day or more.
Publisher: Springer Science and Business Media LLC
Date: 2013
Publisher: Springer Science and Business Media LLC
Date: 02-07-2020
DOI: 10.1038/S41591-020-0972-7
Abstract: An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Publisher: World Scientific Pub Co Pte Lt
Date: 18-01-2017
DOI: 10.1142/S1793524517500218
Abstract: Water scarcity is not a new issue, neither is water pollution. While 70% of the earth’s surface is covered with water, only 3% of it is available as fresh water. Moreover the pollution of water resources has dramatically increased the problem of water scarcity over the last century. Bioremediation presents a cheap and effective solution of this problem. In particular, halophiles have been found to be effective in hypersaline wastewater treatment. Therefore, in this paper, we propose a nonlinear mathematical model to study the removal of a pollutant using halophiles in the hypersaline environment. The analysis of the model is being carried out using stability theory of differential equations. The results indicate that halophiles not only help in removing the organic pollutant, but also help in conversion of saline water into fresh water. The numerical simulations along with sensitivity analysis are performed to support the analytical results.
Location: United States of America
Location: United States of America
Start Date: 10-2023
End Date: 10-2023
Amount: $444,000.00
Funder: Australian Research Council
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