Possible changes in the transmissibility of trachoma following MDA and transmission reduction: implications for the GET2020 goals

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Complex Ecological Dynamics and Eradicability of the Vector Borne Macroparasitic Disease, Lymphatic Filariasis

The current global efforts to control the morbidity and mortality caused by infectious diseases affecting developing countries--such as HIV/AIDS, polio, tuberculosis, malaria and the Neglected Tropical Diseases (NTDs)-have led to an increasing focus on the biological controllability or eradicability of disease transmission by management action. Here, we use an age-structured dynamical model of lymphatic filariasis transmission to show how a quantitative understanding of the dynamic processes underlying infection persistence and extinction is key to evaluating the eradicability of this macroparasitic disease.We investigated the persistence and extinction dynamics of lymphatic filariasis by undertaking a numerical equilibrium analysis of a deterministic model of parasite transmission, based on varying values of the initial L3 larval density in the system. The results highlighted the likely occurrence of complex dynamics in parasite transmission with three major outcomes for the eradicability of filariasis. First, both vector biting and worm breakpoint thresholds are shown to be complex dynamic entities with values dependent on the nature and magnitude of vector-and host specific density-dependent processes and the degree of host infection aggregation prevailing in endemic communities. Second, these thresholds as well as the potential size of the attractor domains and hence system resilience are strongly dependent on peculiarities of infection dynamics in different vector species. Finally, the existence of multiple stable states indicates the presence of hysteresis nonlinearity in the filariasis system dynamics in which infection thresholds for infection invasion are lower but occur at higher biting rates than do the corresponding thresholds for parasite elimination.The variable dynamic nature of thresholds and parasite system resilience reflecting both initial conditions and vector species-infection specificities, and the existence of hysteresis loop phenomenon, suggests that eradication of filariasis may require taking a more flexible and locally relevant approach to designing elimination programmes compared to the current command and control approach advocated by the global programme

Improving our forecasts for trachoma elimination: What else do we need to know?

The World Health Organization (WHO) has targeted trachoma for elimination as a public health concern by 2020. Mathematical modelling is used for a range of infectious diseases to assess the impact of different intervention strategies on the prevalence of infection or disease. Here we evaluate the performance of four different mechanistic mathematical models that could all realistically represent trachoma transmission. We fit the four different mechanistic models of trachoma transmission to cross-sectional age-specific Polymerase Chain Reaction (PCR) and Trachomatous inflammation, follicular (TF) prevalence data. We estimate 4 or 3 parameters within each model, including the duration of an individual's infection and disease episode using Markov Chain Monte Carlo. We assess the performance of each models fit to the data by calculating the deviance information criterion. We then model the implementation of different interventions for each model structure to assess the feasibility of elimination of trachoma with different model structures. A model structure which allowed some re-infection in the disease state (Model 2) was statistically the most well performing model. All models struggled to fit to the very high prevalence of active disease in the youngest age group. Our simulations suggested that for Model 3, with annual antibiotic treatment and transmission reduction, the chance of reducing active disease prevalence to < 5% within 5 years was very low, while Model 2 and 4 could ensure that active disease prevalence was reduced within 5 years. Model 2 here fitted to the data best of the models evaluated. The appropriate level of susceptibility to re-infection was, however, challenging to identify given the amount and kind of data available. We demonstrate that the model structure assumed can lead to different end points following the implementation of the same interventions. Our findings are likely to extend beyond trachoma and should be considered when modelling other neglected tropical diseases

Enhanced antibiotic distribution strategies and the potential impact of facial cleanliness and environmental improvements for the sustained control of trachoma: a modelling study.

BACKGROUND: Despite some success in controlling trachoma with repeated mass drug administration (MDA), some hyperendemic regions are not responding as fast as anticipated. Available data suggests that individuals with higher bacterial infection loads are less likely to resolve infection following a single dose of treatment, and thus remain a source of re-emergent infection following treatment. We assessed the potential impact of a new double-dose antibiotic distribution strategy in addition to enhanced facial cleanliness (F) and environmental improvements (E). METHODS: Using a within-community mathematical model of trachoma transmission we assessed the impact of a new double-dose antibiotic distribution strategy given 2 weeks apart, with and without enhanced F&E. We compared the annual double-dose strategy to single-dose annual MDA treatment in hyper-, meso- and hypoendemic settings, and to biannual MDA at 6-monthly intervals in hyperendemic communities. RESULTS: The findings from our mathematical model suggest that implementing the new double-dose strategy for 5 years or less was predicted to control infection more successfully than annual or 6-monthly treatment. Infection was controlled more readily if treatment was combined with enhanced F&E. The results appeared robust to variation in a number of key epidemiological parameters. To have long-term impact on transmission, enhanced F&E is essential for high transmission settings. CONCLUSION: Our current findings are based on simualtion modelling only, due to lack of epidemilogical data, however they do suggest that the  annual double-dose treatment strategy is encouraging for trachoma control. In high transmission settings, both MDA and enhanced F&E are needed for sustained control

Factors Associated With Measles Transmission in the United States During the Postelimination Era.

Importance: Measles cases and outbreaks continue to occur in the United States after the introduction of measles from endemic settings. Objective: To discern the factors associated with measles transmission in the United States after measles had been eliminated. Design, Setting, and Participants: This cross-sectional study was conducted from January 1, 2001, to December 31, 2017, in the United States among US residents and international visitors with confirmed measles. A maximum likelihood algorithm that uses the observed dates of rash onset and the known distribution of the serial interval (time between symptom onset in related consecutive cases) was applied to outbreak notification data to estimate the effective reproduction number (R), or the mean number of new infections generated per case. Transmissibility was assessed by comparing R based on the characteristics of primary and secondary cases of measles. Exposures: Measles virus. Main Outcomes and Measures: Effective reproduction number (R), or the mean number of successful transmission events per case of measles (ie, the mean number of persons to whom each patient with measles spreads measles). Results: A total of 2218 individuals with confirmed measles cases (1025 female, 1176 male, and 17 sex not reported; median age, 15 years [range, 0-89 years]) reported from 2001 to 2017 were evaluated. Among patients who received no doses of measles vaccine, R was 0.76 (95% CI, 0.71-0.81); among patients who received 1 dose of measles vaccine, R was 0.17 (95% CI, 0.11-0.26); among patients who received 2 doses or more of measles vaccine, R was 0.27 (95% CI, 0.17-0.39); and among patients with unknown vaccination status, R was 0.52 (95% CI, 0.44-0.60). Among patients born before 1957, R was 0.35 (95% CI, 0.20-0.58), and among those born on or after 1957, R was 0.64 (95% CI, 0.61-0.68). R was higher when primary and secondary cases of measles were patients aged 5 to 17 years (0.36 [95% CI, 0.31-0.42]) compared with assortative transmission in other age groups (<1 year, 0.14 [95% CI, 0.10-0.20]; 1-4 years, 0.25 [95% CI, 0.20-0.30]; 18-29 years, 0.19 [95% CI, 0.15-0.24]; 30-49 years, 0.15 [95% CI, 0.11-0.20]; ≥50 years, 0.04 [95% CI, 0.01-0.10]). Conclusions and Relevance: The findings of this study support having high targets for 2-dose measles vaccine coverage, particularly among school-aged children in the United States

Estimating Household and Community Transmission of Ocular Chlamydia trachomatis

Trachoma is a major cause of blindness worldwide and results from ocular infection with the bacterium Chlamydia trachomatis. Mass distribution of antibiotics in communities is part of the strategy to eliminate blindness due to trachoma. Targeted treatment of infected households could be more efficient, but the success of such a strategy will depend on the extent of transmission of infection between members of the same household and between members of the community. In this work, we estimated the magnitude of household and community transmission in four populations, two from The Gambia and two from Tanzania. We found that, in general, transmission of the bacteria within households is very efficient. In three of the four populations, persistent infection within households was predicted by the high level of household transmission (a phenomenon observed in longitudinal studies of trachoma). In all of the studied populations, individuals who live in households with more individuals contribute more to the number of new infections in the community than those who live with fewer individuals. Further studies are required to identify and examine household-targeted approaches to treatment

A MultiCenter analysis of factors associated with hearing outcome for 2,735 adults with cochlear implants

While the majority of cochlear implant recipients benefit from the device, it remains difficult to estimate the degree of benefit for a specific patient prior to implantation. Using data from 2,735 cochlear-implant recipients from across three clinics, the largest retrospective study of cochlear-implant outcomes to date, we investigate the association between 21 preoperative factors and speech recognition approximately one year after implantation and explore the consistency of their effects across the three constituent datasets. We provide evidence of 17 statistically significant associations, in either univariate or multivariate analysis, including confirmation of associations for several predictive factors, which have only been examined in prior smaller studies. Despite the large sample size, a multivariate analysis shows that the variance explained by our models remains modest across the datasets (R2 = 0.12–0.21). Finally, we report a novel statistical interaction indicating that the duration of deafness in the implanted ear has a stronger impact on hearing outcome when considered relative to a candidate’s age. Our multicenter study highlights several real-world complexities that impact the clinical translation of predictive factors for cochlear implantation outcome. We suggest several directions to overcome these challenges and further improve our ability to model patient outcomes with increased accuracy.The collection of the VUMC dataset was supported by a research project grant no. NIH NIDCD R01 DC13117 (principal investigator: Gifford).http://journals.sagepub.com/home/tiadm2022Speech-Language Pathology and Audiolog