Modeling The Epidemiological Impact Of Human Hookworm Infection

Background: Chronic hookworm infection affects an estimated 576 to 740 million people worldwide. Despite mass drug administration efforts, the morbidity associated with this soil-transmitted helminth remains a significant public health issue. Due to inter- and intra- community heterogeneity in susceptibility to infection, mathematical modeling can serve as an effective and efficient tool for investigating hookworm transmission in different settings and for guiding policymakers to consider new treatment and prevention strategies. Methods: Here we developed an age-structured, compartmental S-I model to identify epidemiological parameters for hookworm infection and to assess rates of attributable anemia within the population of Zanzibar. The model was first used to address the relative contributions of age group (adults versus children) and infection intensity status (high versus low) in transmission. The Markov chain Monte Carlo (MCMC) method was implemented to generate negative binomial distribution parameters for describing population-level parasite aggregation. Gibbs sampling and data on prevalence of hookworm infection were used in a subsequent MCMC to parameterize the overall model and account for uncertainty. Maximum likelihood point estimates for force of infection and natural recovery were derived from the 10,000 posterior distributions generated. Empirical data on average hemoglobin levels for given fecal egg count categories were included in the analysis to give distributions for the relative risk of moderate-to-severe anemia (hemoglobin \u3c 90 g/L) among infected versus susceptible individuals. Results: Using maximum likelihood estimates for the negative binomial distribution parameters, it was determined that children prone to high intensity hookworm infections were 4.9 times as infectious as children prone to lower intensity infection; high intensity infection adults were considered to be 4.7 times as infectious as low intensity infection adults. Model predictions with and without uncertainty were consistent in estimating that approximately 10% of the infected child population experienced moderate-to-severe anemia attributable to hookworm infection. Conclusion: The present model provides a population-level compartmental model framework for assessing hookworm-attributable morbidity independent of assumptions about worm burden thresholds. To evaluate the effectiveness of different intervention strategies at reducing the incidence of infection and rates of hookworm-attributable anemia, the current epidemiological model can be extended structurally to include treatment and vaccine parameters

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The HIV pandemic continues to impose enormous morbidity, mortality and economic burdens across the globe. Simultaneously, innovations in antiretroviral therapy, diagnostic approaches and vaccine development are providing novel tools for treatment-as-prevention and prophylaxis. We developed a mathematical model to evaluate the added benefit of an HIV vaccine in the context of goals to increase rates of diagnosis, treatment, and viral suppression in 127 countries. Under status quo interventions, we predict a median of 49 million [1st and 3rd quartiles 44M, 58M] incident cases globally from 2015 to 2035. Achieving the UNAIDS 95–95–95 target was estimated to avert 25 million [20M, 33M] of these new infections, and an additional 6.3 million [4.8M, 8.7M] reduction was projected with the 2020 introduction of a 50%-efficacy vaccine gradually scaled up to 70% coverage. This added benefit of prevention through vaccination motivates imminent and ongoing clinical trials of viable candidates to realize the goal of HIV control

Data-driven analyses of behavioral strategies to eliminate cysticercosis in sub-Saharan Africa

The multi-host taeniosis/cysticercosis disease system is associated with significant neurological morbidity, as well as economic burden, globally. We investigated whether lower cost behavioral interventions are sufficient for local elimination of human cysticercosis in Boulkiemdé, Sanguié, and Nayala provinces of Burkina Faso. Province-specific data on human behaviors (i.e., latrine use and pork consumption) and serological prevalence of human and pig disease were used to inform a deterministic, compartmental model of the taeniosis/cysticercosis disease system. Parameters estimated via Bayesian melding provided posterior distributions for comparing transmission rates associated with human ingestion of Taenia solium cysticerci due to undercooking and human exposure to T. solium eggs in the environment. Reductions in transmission via these pathways were modeled to determine required effectiveness of a market-focused cooking behavior intervention and a community-led sanitation and hygiene program, independently and in combination, for eliminating human cysticercosis as a public health problem (<1 case per 1000 population). Transmission of cysticerci due to consumption of undercooked pork was found to vary significantly across transmission settings. In Sanguié, the rate of transmission due to undercooking was 6% higher than that in Boulkiemdé (95% CI: 1.03, 1.09; p-value < 0.001) and 35% lower than that in Nayala (95% CI: 0.64, 0.66; p-value < 0.001). We found that 67% and 62% reductions in undercooking of pork consumed in markets were associated with elimination of cysticercosis in Nayala and Sanguié, respectively. Elimination of active cysticercosis in Boulkiemdé required a 73% reduction. Less aggressive reductions of 25% to 30% in human exposure to Taenia solium eggs through sanitation and hygiene programs were associated with elimination in the provinces. Despite heterogeneity in effectiveness due to local transmission dynamics and behaviors, education on the importance of proper cooking, in combination with community-led sanitation and hygiene efforts, has implications for reducing morbidity due to cysticercosis and neurocysticercosis

Effectiveness of UNAIDS targets and HIV vaccination across 127 countries

The HIV pandemic continues to impose enormous morbidity, mortality and economic burdens across the globe. Simultaneously, innovations in antiretroviral therapy, diagnostic approaches and vaccine development are providing novel tools for treatment-as-prevention and prophylaxis. We developed a mathematical model to evaluate the added benefit of an HIV vaccine in the context of goals to increase rates of diagnosis, treatment, and viral suppression in 127 countries. Under status quo interventions, we predict a median of 49 million [1st and 3rd quartiles 44M, 58M] incident cases globally from 2015 to 2035. Achieving the UNAIDS 95–95–95 target was estimated to avert 25 million [20M, 33M] of these new infections, and an additional 6.3 million [4.8M, 8.7M] reduction was projected with the 2020 introduction of a 50%-efficacy vaccine gradually scaled up to 70% coverage. This added benefit of prevention through vaccination motivates imminent and ongoing clinical trials of viable candidates to realize the goal of HIV control

Retrospective Analysis of the 2014-2015 Ebola Epidemic in Liberia.

The 2014-2015 Ebola epidemic has been the most protracted and devastating in the history of the disease. To prevent future outbreaks on this scale, it is imperative to understand the reasons that led to eventual disease control. Here, we evaluated the shifts of Ebola dynamics at national and local scales during the epidemic in Liberia. We used a transmission model calibrated to epidemiological data between June 9 and December 31, 2014, to estimate the extent of community and hospital transmission. We found that despite varied local epidemic patterns, community transmission was reduced by 40-80% in all the counties analyzed. Our model suggests that the tapering of the epidemic was achieved through reductions in community transmission, rather than accumulation of immune individuals through asymptomatic infection and unreported cases. Although the times at which this transmission reduction occurred in the majority of the Liberian counties started before any large expansion in hospital capacity and the distribution of home protection kits, it remains difficult to associate the presence of interventions with reductions in Ebola incidence

Unraveling the effects of the Ebola experience on behavior choices during COVID-19 in Liberia: a mixed-methods study across successive outbreaks

Background: The burden of the COVID-19 pandemic in terms of morbidity and mortality differentially affected populations. Between and within populations, behavior change was likewise heterogeneous. Factors influencing precautionary behavior adoption during COVID-19 have been associated with multidimensional aspects of risk perception; however, the influence of lived experiences during other recent outbreaks on behavior change during COVID-19 has been less studied. Methods: To consider how the direct disease experience (“near misses”) and behavior change during the 2014–2016 Ebola virus disease (EVD) outbreak may have impacted behavior change during the early waves of the COVID-19 outbreak in West Africa, we analyzed data from a mixed-methods study that included a phone-based survey and in-depth interviews among vaccinated Liberian adults. Logistic regression via generalized estimating equations with quasi-likelihood information criterion (QIC)-based model selection was conducted to evaluate the influence of the interaction between and individual effects of the outbreak (EVD and COVID-19) and the “near-miss” experience on adoption of individual precautionary behaviors. Thematic analysis of interview transcripts explored reasons for differential behavior adoption between the two outbreaks. Results: At the population level, being a “near miss” was not associated with significantly different behavior during COVID-19 versus Ebola; however, overall, people had lower odds of adopting precautionary behaviors during COVID-19 relative to during Ebola. Participants who report near miss experiences during Ebola were significantly more likely to report having a household member test positive for COVID-19 (p<0.001). Qualitatively, participants often reflected on themes around more proximal and personal experiences with Ebola than with COVID-19; they also commented on how EVD led to better preparedness at the systems level and within communities for how to behave during an outbreak, despite such awareness not necessarily translating into action during COVID-19. Conclusions: The results suggest that perceived proximity and intensity to disease threats in space and time affect behavioral decisions. For successive disease threats, comparisons of the present outbreak to past outbreaks compound those effects, regardless of whether individuals were directly impacted via a “near-miss” experience. Measures, such as risk communication and community engagement efforts, that gauge and reflect comparisons with previous outbreaks should be considered in response strategies to enhance the adoption of precautionary behavior

Interruption of tuberculosis detection and care during the Ebola virus disease epidemic (2014–2015) in Liberia: time-series analyses for 2013–2017

Objective Interrupted time-series analyses, using 5 years of routinely collected health information system data, were conducted to estimate the magnitude of impact of the 2014–2015 Ebola virus disease (EVD) epidemic and determine trends in tuberculosis (TB) care services in Liberia. Methods A segmented linear regression model was used to generate estimates and predictions for trends for three TB service indicators before, during, and after EVD, from January 2013 to December 2017. Results It was found that the number of presumptive TB cases declined significantly at the start of the EVD outbreak, with an estimated loss of 3222 cases (95% confidence interval (CI) −5691 to −752; P = 0.014). There was also an estimated loss of 709 cases per quarter post-EVD (95% CI −1346 to −71; P = 0.032). However, over the post-EVD period, quarterly increases were observed in the proportion of smear-positive to presumptive cases (1.45%, 95% CI 0.38% to 2.5%; P = 0.011) and the proportion of treatment success to TB cases evaluated (3.3%, 95% CI 0.82% to 5.79%; P = 0.013). Conclusions These findings suggest that the EVD outbreak (2014–2015) negatively affected TB care services. Rigorous quantitative analyses can be used to assess the magnitude of interruption and advocate for preparedness in settings with limited healthcare capacity

Unmet needs and behaviour during the Ebola response in Sierra Leone: a retrospective, mixed-methods analysis of community feedback from the Social Mobilization Action Consortium

Background: The west African Ebola epidemic (2014–15) necessitated behaviour change in settings with prevalent and pre-existing unmet needs as well as extensive mechanisms for local community action. We aimed to assess spatial and temporal trends in community-reported needs and associations with behaviour change, community engagement, and the overall outbreak situation in Sierra Leone. Methods: We did a retrospective, mixed-methods study. Post-hoc analyses of data from 12 096 mobiliser visits as part of the Social Mobilization Action Consortium were used to describe the evolution of satisfied and unsatisfied needs (basic, security, autonomy, respect, and social support) between Nov 12, 2014, and Dec 18, 2015, and across 14 districts. Via Bayesian hierarchical regression modelling, we investigated associations between needs categories and behaviours (numbers of individuals referred to treatment within 24 h of symptom onset or deaths responded to with safe and dignified burials) and the role of community engagement programme status (initial vs follow-up visit) in the association between satisfied versus unsatisfied needs and behaviours. Findings: In general, significant associations were observed between unsatisfied needs categories and both prompt referrals to treatment and safe burials. Most notably, communities expressing unsatisfied capacity needs reported fewer safe burials (relative risk [RR] 0·86, 95% credible interval [CrI] 0·82–0·91) and fewer prompt referrals to treatment (RR 0·76, 0·70–0·83) than did those without unsatisfied capacity needs. The exception was expression of unsatisfied basic needs, which was associated with significantly fewer prompt referrals only (RR 0·86, 95% CrI 0·79–0·93). Compared with triggering visits by community mobilisers, follow-up visits were associated with higher numbers of prompt referrals (RR 1·40, 95% CrI 1·30–1·50) and safe burials (RR 1·08, 1·02–1·14). Interpretation: Community-based development of locally feasible, locally owned action plans, with the support of community mobilisers, has potential to address unmet needs for more sustained behaviour change in outbreak settings

Liberia adherence and loss-to-follow-up in HIV and AIDS care and treatment: A retrospective cohort of adolescents and adults from 2016–2019

Background Antiretroviral therapy (ART) is a lifesaving intervention for people living with HIV infection, reducing morbidity and mortality; it is likewise essential to reducing transmission. The “Treat all” strategy recommended by the World Health Organization has dramatically increased ART eligibility and improved access. However, retaining patients on ART has been a major challenge for many national programs in low- and middle-income settings, despite actionable local policies and ambitious targets. To estimate retention of patients along the HIV care cascade in Liberia, and identify factors associated with loss-to-follow-up (LTFU), death, and suboptimal treatment adherence, we conducted a nationwide retrospective cohort study utilizing facility and patient-level records. Patients aged ≥15 years, from 28 facilities who were first registered in HIV care from January 2016 –December 2017 were included. We used Cox proportional hazard models to explore associations between demographic and clinical factors and the outcomes of LTFU and death, and a multinomial logistic regression model to investigate factors associated with suboptimal treatment adherence. Among the 4185 records assessed, 27.4% (n = 1145) were males and the median age of the cohort was 37 (IQR: 30–45) years. At 24 months of follow-up, 41.8% (n = 1751) of patients were LTFU, 6.6% (n = 278) died, 0.5% (n = 21) stopped treatment, 3% (n = 127) transferred to another facility and 47.9% (n = 2008) were retained in care and treatment. The incidence of LTFU was 46.0 (95% CI: 40.8–51.6) per 100 person-years. Relative to patients at WHO clinical stage I at first treatment visit, patients at WHO clinical stage III [adjusted hazard ratio (aHR) 1.59, 95%CI: 1.21–2.09; p <0.001] or IV (aHR 2.41, 95%CI: 1.51–3.84; p <0.001) had increased risk of LTFU; whereas at registration, age category 35–44 (aHR 0.65, 95%CI: 0.44–0.98, p = 0.038) and 45 years and older (aHR 0.60, 95%CI: 0.39–0.93, p = 0.021) had a decreased risk. For death, patients assessed with WHO clinical stage II (aHR 2.35, 95%CI: 1.53–3.61, p<0.001), III (aHR 2.55, 95%CI: 1.75–3.71, p<0.001), and IV (aHR 4.21, 95%CI: 2.57–6.89, p<0.001) had an increased risk, while non-pregnant females (aHR 0.68, 95%CI: 0.51–0.92, p = 0.011) and pregnant females (aHR 0.42, 95%CI: 0.20–0.90, p = 0.026) had a decreased risk when compared to males. Suboptimal adherence was strongly associated with the experience of drug side effects–average adherence [adjusted odds ratio (aOR) 1.45, 95% CI: 1.06–1.99, p = 0.02) and poor adherence (aOR 1.75, 95%CI: 1.11–2.76, p = 0.016), and attending rural facility decreased the odds of average adherence (aOR 0.01, 95%CI: 0.01–0.03, p<0.001) and poor adherence (aOR 0.001, 95%CI: 0.0004–0.003, p<0.001). Loss-to-follow-up and poor adherence remain major challenges to achieving viral suppression targets in Liberia. Over two-fifths of patients engaged with the national HIV program are being lost to follow-up within 2 years of beginning care and treatment. WHO clinical stage III and IV were associated with LTFU while WHO clinical stage II, III and IV were associated with death. Suboptimal adherence was further associated with experience of drug side effects. Active support and close monitoring of patients who have signs of clinical progression and/or drug side effects could improve patient outcomes