Mathematical analysis of a Wolbachia invasive model with imperfect maternal transmission and loss of Wolbachia infection

Arboviral infections, especially dengue, continue to cause significant health burden in their endemic regions. One of the strategies to tackle these infections is to replace the main vector agent, Ae. aegypti, with the ones incapable of transmitting the virus. Wolbachia, an intracellular bacterium, has shown promise in achieving this goal. However, key factors such as imperfect maternal transmission, loss of Wolbachia infection, reduced reproductive capacity and shortened life-span affect the dynamics of Wolbachia in different forms in the Ae. aegypti population. In this study, we developed a Wolbachia transmission dynamic model adjusting for imperfect maternal transmission and loss of Wolbachia infection. The invasive reproductive number that determines the likelihood of replacement of the Wolbachia-uninfected (WU) population is derived and with it, we established the local and global stability of the equilibrium points. This analysis clearly shows that cytoplasmic incompatibility (CI) does not guarantee establishment of the Wolbachia-infected (WI) mosquitoes as imperfect maternal transmission and loss of Wolbachia infection could outweigh the gains from CI. Optimal release programs depending on the level of imperfect maternal transmission and loss of Wolbachia infection are shown. Hence, it is left to decision makers to either aim for replacement or co-existence of both populations

A Systematic Review of Mathematical Models of Dengue Transmission and Vector Control: 2010–2020

Vector control methods are considered effective in averting dengue transmission. However, several factors may modify their impact. Of these controls, chemical methods, in the long run, may increase mosquitoes’ resistance to chemicides, thereby decreasing control efficacy. The biological methods, which may be self-sustaining and very effective, could be hampered by seasonality or heatwaves (resulting in, e.g., loss of Wolbachia infection). The environmental methods that could be more effective than the chemical methods are under-investigated. In this study, a systematic review is conducted to explore the present understanding of the effectiveness of vector control approaches via dengue transmission models

Modelling the ecological dynamics of mosquito populations with multiple co-circulating Wolbachia strains

Wolbachia intracellular bacteria successfully reduce the transmissibility of arthropod-borne viruses (arboviruses) when introduced into virus-carrying vectors such as mosquitoes. Despite the progress made by introducing Wolbachia bacteria into the Aedes aegypti wild-type population to control arboviral infections, reports suggest that heat-induced loss-of-Wolbachia-infection as a result of climate change may reverse these gains. Novel, supplemental Wolbachia strains that are more resilient to increased temperatures may circumvent these concerns, and could potentially act synergistically with existing variants. In this article, we model the ecological dynamics among three distinct mosquito (sub)populations: a wild-type population free of any Wolbachia infection; an invading population infected with a particular Wolbachia strain; and a second invading population infected with a distinct Wolbachia strain from that of the first invader. We explore how the range of possible characteristics of each Wolbachia strain impacts mosquito prevalence. Further, we analyse the differential system governing the mosquito populations and the Wolbachia infection dynamics by computing the full set of basic and invasive reproduction numbers and use these to establish stability of identified equilibria. Our results show that releasing mosquitoes with two different strains of Wolbachia did not increase their prevalence, compared with a single-strain Wolbachia-infected mosquito introduction and only delayed Wolbachia dominance

Mathematical analysis of a two-strain tuberculosis model in Bangladesh

Tuberculosis (TB) is an airborne infectious disease that causes millions of deaths worldwide each year (1.2 million people died in 2019). Alarmingly, several strains of the causative agent, Mycobacterium tuberculosis (MTB)—including drug-susceptible (DS) and drug-resistant (DR) variants—already circulate throughout most developing and developed countries, particularly in Bangladesh, with totally drug-resistant strains starting to emerge. In this study we develop a two-strain DS and DR TB transmission model and perform an analysis of the system properties and solutions. Both analytical and numerical results show that the prevalence of drug-resistant infection increases with an increasing drug use through amplification. Both analytic results and numerical simulations suggest that if the basic reproduction numbers of both DS (R0s) and DR (R0r) TB are less than one, i.e. max[R0s, R0r]max[R0s,1], then DS TB dies out but DR TB persists in the population, and if R0s>max[R0r,1] both DS TB and DR TB persist in the population. Further, sensitivity analysis of the model parameters found that the transmission rate of both strains had the greatest influence on DS and DR TB prevalence. We also investigated the effect of treatment rates and amplification on both DS and DR TB prevalence; results indicate that inadequate or inappropriate treatment makes co-existence more likely and increases the relative abundance of DR TB infections

A review: Aedes-borne arboviral infections, controls and Wolbachia-based strategies

Arthropod-borne viruses (Arboviruses) continue to generate significant health and economic burdens for people living in endemic regions. Of these viruses, some of the most important (e.g., dengue, Zika, chikungunya, and yellow fever virus), are transmitted mainly by Aedes mosquitoes. Over the years, viral infection control has targeted vector population reduction and inhibition of arboviral replication and transmission. This control includes the vector control methods which are classified into chemical, environmental, and biological methods. Some of these control methods may be largely experimental (both field and laboratory investigations) or widely practised. Perceptively, one of the biological methods of vector control, in particular, Wolbachia-based control, shows a promising control strategy for eradicating Aedes-borne arboviruses. This can either be through the artificial introduction of Wolbachia, a naturally present bacterium that impedes viral growth in mosquitoes into heterologous Aedes aegypti mosquito vectors (vectors that are not natural hosts of Wolbachia) thereby limiting arboviral transmission or via Aedes albopictus mosquitoes, which naturally harbour Wolbachia infection. These strategies are potentially undermined by the tendency of mosquitoes to lose Wolbachia infection in unfavourable weather conditions (e.g., high temperature) and the inhibitory competitive dynamics among co-circulating Wolbachia strains. The main objective of this review was to critically appraise published articles on vector control strategies and specifically highlight the use of Wolbachia-based control to suppress vector population growth or disrupt viral transmission. We retrieved studies on the control strategies for arboviral transmissions via arthropod vectors and discussed the use of Wolbachia control strategies for eradicating arboviral diseases to identify literature gaps that will be instrumental in developing models to estimate the impact of these control strategies and, in essence, the use of different Wolbachia strains and feature

A resurgence and re-emergence of diphtheria in Nigeria, 2023

[Extract] Diphtheria is a highly contagious vaccine-preventable bacterial infection caused by Corynebacterium diphtheriae that primarily infects the throat (pharynx and tonsils) and nose. The bacterium has an estimated basic reproduction number of 1.7–4.3. Although diphtheria is treatable if detected early, it can lead to severe complications such as respiratory failure, heart problems and even deaths (case-fatality ratio among untreated, never vaccinated cases 28.8–29.2%). It remains a health problem in low-resource countries, particularly where vaccination uptake and coverage are low and where sanitation conditions remain poor

Change in outbreak epicentre and its impact on the importation risks of COVID-19 progression: A modelling study

Background The outbreak of Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) that was first detected in the city of Wuhan, China has now spread to every inhabitable continent, but now the attention has shifted from China to other epicentres. This study explored early assessment of the influence of spatial proximities and travel patterns from Italy on the further spread of SARS-CoV-2 worldwide. Methods Using data on the number of confirmed cases of COVID-19 and air travel data between countries, we applied a stochastic meta-population model to estimate the global spread of COVID-19. Pearson's correlation, semi-variogram, and Moran's Index were used to examine the association and spatial autocorrelation between the number of COVID-19 cases and travel influx (and arrival time) from the source country. Results We found significant negative association between disease arrival time and number of cases imported from Italy (r = −0.43, p = 0.004) and significant positive association between the number of COVID-19 cases and daily travel influx from Italy (r = 0.39, p = 0.011). Using bivariate Moran's Index analysis, we found evidence of spatial interaction between COVID-19 cases and travel influx (Moran's I = 0.340). Asia-Pacific region is at higher/extreme risk of disease importation from the Chinese epicentre, whereas the rest of Europe, South-America and Africa are more at risk from the Italian epicentre. Conclusion We showed that as the epicentre changes, the dynamics of SARS-CoV-2 spread change to reflect spatial proximities

Increasing the frequency of hand washing by healthcare workers does not lead to commensurate reductions in staphylococcal infection in a hospital ward

Hand hygiene is generally considered to be the most important measure that can be applied to prevent the spread of healthcare-associated infection (HAI). Continuous emphasis on this intervention has lead to the widespread opinion that HAI rates can be greatly reduced by increased hand hygiene compliance alone. However, this assumes that the effectiveness of hand hygiene is not constrained by other factors and that improved compliance in excess of a given level, in itself, will result in a commensurate reduction in the incidence of HAI. However, several researchers have found the law of diminishing returns to apply to hand hygiene, with the greatest benefits occurring in the first 20% or so of compliance, and others have demonstrated that poor cohorting of nursing staff profoundly influences the effectiveness of hand hygiene measures. Collectively, these findings raise intriguing questions about the extent to which increasing compliance alone can further reduce rates of HAI. In order to investigate these issues further, we constructed a deterministic Ross-Macdonald model and applied it to a hypothetical general medical ward. In this model the transmission of staphylococcal infection was assumed to occur after contact with the transiently colonized hands of HCWs, who, in turn, acquire contamination only by touching colonized patients. The aim of the study was to evaluate the impact of imperfect hand cleansing on the transmission of staphylococcal infection and to identify, whether there is a limit, above which further hand hygiene compliance is unlikely to be of benefit. The model demonstrated that if transmission is solely via the hands of HCWs, it should, under most circumstances, be possible to prevent outbreaks of staphylococcal infection from occurring at a hand cleansing frequencies <50%, even with imperfect hand hygiene. The analysis also indicated that the relationship between hand cleansing efficacy and frequency is not linear - as efficacy decreases, so the hand cleansing frequency required to ensure R0<1 increases disproportionately. Although our study confirmed hand hygiene to be an effective control measure, it demonstrated that the law of diminishing returns applies, with the greatest benefit derived from the first 20% or so of compliance. Indeed, our analysis suggests that there is little benefit to be accrued from very high levels of hand cleansing and that in most situations compliance >40% should be enough to prevent outbreaks of staphylococcal infection occurring, if transmission is solely via the hands of HCWs. Furthermore we identified a non-linear relationship between hand cleansing efficacy and frequency, suggesting that it is important to maximise the efficacy of the hand cleansing process

Transmission Dynamics of Methicillin-Resistant Staphylococcus aureus in a Medical Intensive Care Unit in India

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a global pathogen and an important but seldom investigated cause of morbidity and mortality in lower and middle-income countries where it can place a major burden on limited resources. Quantifying nosocomial transmission in resource-poor settings is difficult because molecular typing methods are prohibitively expensive. Mechanistic statistical models can overcome this problem with minimal cost. We analyse the transmission dynamics of MRSA in a hospital in south India using one such approach and provide conservative estimates of the organism's economic burden. Methods and Findings: Fifty months of MRSA infection data were collected retrospectively from a Medical Intensive Care Unit (MICU) in a tertiary hospital in Vellore, south India. Data were analysed using a previously described structured hidden Markov model. Seventy-two patients developed MRSA infections and, of these, 49 (68%) died in the MICU. We estimated that 4.2% (95%CI 1.0, 19.0) of patients were MRSA-positive when admitted, that there were 0.39 MRSA infections per colonized patient month (0.06, 0.73), and that the ward-level reproduction number for MRSA was 0.42 (0.08, 2.04). Anti-MRSA antibiotic treatment costs alone averaged $124/patient, over three times the monthly income of more than 40% of the Indian population. Conclusions: Our analysis of routine data provides the first estimate of the nosocomial transmission potential of MRSA in India. The high levels of transmission estimated underline the need for cost-effective interventions to reduce MRSA transmission in hospital settings in low and middle income countries. © 2011 Christopher et al