Challenges in modeling complexity of neglected tropical diseases: a review of dynamics of visceral leishmaniasis in resource limited settings.

OBJECTIVES: Neglected tropical diseases (NTD), account for a large proportion of the global disease burden, and their control faces several challenges including diminishing human and financial resources for those distressed from such diseases. Visceral leishmaniasis (VL), the second-largest parasitic killer (after malaria) and an NTD affects poor populations and causes considerable cost to the affected individuals. Mathematical models can serve as a critical and cost-effective tool for understanding VL dynamics, however, complex array of socio-economic factors affecting its dynamics need to be identified and appropriately incorporated within a dynamical modeling framework. This study reviews literature on vector-borne diseases and collects challenges and successes related to the modeling of transmission dynamics of VL. Possible ways of creating a comprehensive mathematical model is also discussed. METHODS: Published literature in three categories are reviewed: (i) identifying non-traditional but critical mechanisms for VL transmission in resource limited regions, (ii) mathematical models used for dynamics of Leishmaniasis and other related vector borne infectious diseases and (iii) examples of modeling that have the potential to capture identified mechanisms of VL to study its dynamics. RESULTS: This review suggests that VL elimination have not been achieved yet because existing transmission dynamics models for VL fails to capture relevant local socio-economic risk factors. This study identifies critical risk factors of VL and distribute them in six categories (atmosphere, access, availability, awareness, adherence, and accedence). The study also suggests novel quantitative models, parts of it are borrowed from other non-neglected diseases, for incorporating these factors and using them to understand VL dynamics and evaluating control programs for achieving VL elimination in a resource-limited environment. CONCLUSIONS: Controlling VL is expensive for local communities in endemic countries where individuals remain in the vicious cycle of disease and poverty. Smarter public investment in control programs would not only decrease the VL disease burden but will also help to alleviate poverty. However, dynamical models are necessary to evaluate intervention strategies to formulate a cost-effective optimal policy for eradication of VL.

Evaluation of socioecological factors on health behaviors and weight change during major life event: A cross-sectional study using data collected during the COVID-19 pandemic.

Background: Socioecological factors are associated with key health behaviors that are critical for weight management, and major life events may disrupt engagement in these behaviors. However, the influence of socioecological factors on health behaviors in the midst of major life events is not clear and is difficult to study due to the random and sporadic nature of their occurrence. The COVID-19 pandemic provided a unique opportunity to study a major life event and its impacts on diet, physical activity, and body weight. Objective: This cross-sectional study aimed to investigate associations between socioecological factors (environmental, interpersonal, and individual) and self-reported weight change during a major life event using data collected during the COVID-19 pandemic, and whether the associations were mediated through self-reported changes in eating and physical activity behaviors. Methods: Participants self-reported socioecological factors, weight change, and changes in eating behaviors (EB) and physical activity (PA) via online questionnaires between December 2020 and October 2021. Changes in EB and PA were measured using scales with higher scores reflecting more positive changes during the COVID-19 pandemic. Results: Participants (n = 1283) were mostly female (84.9%) with age 52.1 ± 14.1 years (mean ± SD) and BMI of 32.9 ± 8.2 kg/m2. Stronger healthy eater and exercise identities (individual factors) were associated with higher EB scores (EBS) and PA scores (PAS), respectively (p's < 0.00001). Less discouragement for healthy eating by family/friends (interpersonal factor) was associated with higher EBS (p = 0.002). Higher EBS and PAS were associated with weight loss. The indirect effect of healthy eater identity (-0.72; 95% CI: -0.90, -0.55) and discouragement for diet (0.07; 95% CI: 0.03, 0.12) on weight change through EBS were significant, as was the indirect effect of exercise identity (-0.25; 95% CI: -0.35, -0.15) on weight change through PAS. Conclusions: Stronger identities and less discouragement from family/friends may support health promoting behaviors and weight loss during a major life event, as well as identify additional behavioral targets for lifestyle interventions. Clinical Trial Registration: IWCR was registered at ClinicalTrials.gov (NCT04907396).

SARS-CoV-2 Transmission Potential and Policy Changes in South Carolina, February 2020 - January 2021.

INTRODUCTION: We aimed to examine how public health policies influenced the dynamics of coronavirus disease 2019 (COVID-19) time-varying reproductive number (R t ) in South Carolina from February 26, 2020, to January 1, 2021. METHODS: COVID-19 case series (March 6, 2020, to January 10, 2021) were shifted by 9 d to approximate the infection date. We analyzed the effects of state and county policies on R t using EpiEstim. We performed linear regression to evaluate if per-capita cumulative case count varies across counties with different population size. RESULTS: R t shifted from 2-3 in March to <1 during April and May. R t rose over the summer and stayed between 1.4 and 0.7. The introduction of statewide mask mandates was associated with a decline in R t (-15.3%; 95% CrI, -13.6%, -16.8%), and school re-opening, an increase by 12.3% (95% CrI, 10.1%, 14.4%). Less densely populated counties had higher attack rates (P < 0.0001). CONCLUSIONS: The R t dynamics over time indicated that public health interventions substantially slowed COVID-19 transmission in South Carolina, while their relaxation may have promoted further transmission. Policies encouraging people to stay home, such as closing nonessential businesses, were associated with R t reduction, while policies that encouraged more movement, such as re-opening schools, were associated with R t increase.

Plasma Hepatitis E Virus Kinetics in Solid Organ Transplant Patients Receiving Ribavirin.

Hepatitis E virus (HEV) infection causes chronic hepatitis in solid organ transplant (SOT) recipients. Antiviral therapy consists of three months of ribavirin, although response rates are not optimal. We characterized plasma HEV kinetic patterns in 41 SOT patients during ribavirin therapy. After a median pharmacological delay of three (range: 0-21) days, plasma HEV declined from a median baseline level of 6.12 (3.53-7.45) log copies/mL in four viral kinetic patterns: (i) monophasic (n = 18), (ii) biphasic (n = 13), (iii) triphasic (n = 8), and (iv) flat-partial response (n = 2). The mean plasma HEV half-life was estimated to be 2.0 ± 0.96 days. Twenty-five patients (61%) had a sustained virological response (SVR) 24 weeks after completion of therapy. Viral kinetic patterns (i)-(iii) were not associated with baseline characteristics or outcome of therapy. A flat-partial response was associated with treatment failure. All patients with a log concentration decrease of plasma HEV at day seven of >15% from baseline achieved SVR. In conclusion, viral kinetic modeling of plasma HEV under ribavirin therapy showed, for the first time, four distinct kinetic profiles, a median pharmacologic delay of three days, and an estimated HEV half-life of two days. Viral kinetic patterns were not associated with response to therapy, with the exception of a flat-partial response.

Severity of liver disease affects HCV kinetics in patients treated with intravenous silibinin monotherapy.

BACKGROUND: HCV kinetic analysis and modelling during antiviral therapy have not been performed in decompensated cirrhotic patients awaiting liver transplantation. Here, viral and host parameters were compared in three groups of patients treated with daily intravenous silibinin (SIL) monotherapy for 7 days according to the severity of their liver disease. METHODS: Data were obtained from 25 patients, 12 non-cirrhotic, 8 with compensated cirrhosis and 5 with decompensated cirrhosis. The standard-biphasic model with time-varying SIL effectiveness (from 0 to final effectiveness [εmax]) was fitted to viral kinetic data. RESULTS: Baseline viral load and age were significantly associated with the severity of liver disease (P<0.0001). A biphasic viral decline was observed in most patients with a higher first phase decline in patients with less severe liver disease. The εmax was significantly (P≤0.032) associated with increasing severity of liver disease (non-cirrhotic εmax [se]=0.86 [0.05], compensated cirrhotic εmax=0.69 [0.06] and decompensated cirrhotic εmax=0.59 [0.1]). The second phase decline slope was not significantly different among groups (mean 1.88 ±0.15 log10 IU/ml/week, P=0.75) as was the rate of change of SIL effectiveness (k=2.12/day [se=0.18/day]). HCV-infected cell loss rate (δ [se]=0.62/day [0.05/day]) was high and similar among groups. CONCLUSIONS: The high loss rate of HCV-infected cells suggests that sufficient dose and duration of SIL might achieve viral suppression in advanced liver disease.

Evaluating treatment of hepatitis C for hemolytic anemia management.

The combination therapy of antiviral peg-interferon and ribavirin has evolved as one of the better treatments for hepatitis C. In spite of its success in controlling hepatitis C infection, it has also been associated with treatment-related adverse side effects. The most common and life threatening among them is hemolytic anemia, necessitating dose reduction or therapy cessation. The presence of this side effect leads to a trade-off between continuing the treatment and exacerbating the side effects versus decreasing dosage to relieve severe side effects while allowing the disease to progress. The drug epoietin (epoetin) is often administered to stimulate the production of red blood cells (RBC) in the bone marrow, in order to allow treatment without anemia. This paper uses mathematical models to study the effect of combination therapy in light of anemia. In order to achieve this we introduce RBC concentration and amount of drug in the body as state variables in the usual immunological virus infection model. Analysis of this model provides a quantification of the amount of drug a body can tolerate without succumbing to hemolytic anemia. Indirect estimation of parameters allow us to calculate the necessary increment in RBC production to be > or =2.3 times the patient's original RBC production rate to sustain the entire course of treatment without encountering anemia in a sensitive patient.