Impact of comorbidities on the serological response to COVID-19 vaccination in a Taiwanese cohort.

BACKGROUND/AIMS: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is one of the best policies to control COVID-19 pandemic. The serological response to COVID-19 vaccination in Taiwanese patients with different comorbidities is elusive. METHODS: Uninfected subjects who received 3 doses of mRNA vaccines (BNT162b2 [Pfizer-BioNTech, BNT] and mRNA-1273 [Moderna]), viral vector-based vaccines (ChAdOx1-S (AZD1222, AZ) or protein subunit vaccines (Medigen COVID-19 vaccine) were prospectively enrolled. The SARS-CoV-2-IgG spike antibody level was determined within three months after the 3rd dose of vaccination. The Charlson Comorbidity Index (CCI) was applied to determine the association between vaccine titers and underlying comorbidities. RESULTS: A total of 824 subjects were enrolled in the current study. The proportions of CCI scores of 0-1, 2-3 and > 4 were 52.8% (n = 435), 31.3% (n = 258) and 15.9% (n = 131), respectively. The most commonly used vaccination combination was AZ-AZ-Moderna (39.2%), followed by Moderna-Moderna-Moderna (27.8%). The mean vaccination titer was 3.11 log BAU/mL after a median of 48 days after the 3rd dose. Factors associated with potentially effective neutralization capacity (IgG level ≥ 4160 AU/mL) included age ≥ 60 years (odds ratio [OR]/95% confidence interval [CI]: 0.50/0.34-0.72, P < 0.001), female sex (OR/CI: 1.85/1.30-2.63, P = 0.001), Moderna-Moderna-based vaccination (compared to AZ-AZ-based vaccination, OR/CI: 6.49/3.90-10.83, P < 0.001), BNT-BNT-based vaccination (compared to AZ-AZ-based vaccination, OR/CI: 7.91/1.82-34.3, P = 0.006) and a CCI score ≥ 4 (OR/CI: 0.53/0.34-0.82, P = 0.004). There was a decreasing trend in antibody titers with increasing CCI scores (trend P < 0.001). Linear regression analysis revealed that higher CCI scores (ß: - 0.083; 95% CI: - 0.094-0.011, P = 0.014) independently correlated with low IgG spike antibody levels. CONCLUSIONS: Subjects with more comorbidities had a poor serological response to 3 doses of COVID-19 vaccination.

A people-centered decentralized outreach model toward HCV micro-elimination in hyperendemic areas: COMPACT study in SARS Co-V2 pandemic.

OBJECTIVES: Gaps in linkage-to-care remain the barriers toward hepatitis C virus (HCV) elimination in the directly-acting-antivirals (DAA) era, especially during SARS Co-V2 pandemics. We established an outreach project to target HCV micro-elimination in HCV-hyperendemic villages. METHODS: The COMPACT provided "door-by-door" screening by an "outreach HCV-checkpoint team" and an "outreach HCV-care team" for HCV diagnosis, assessment and DAA therapy in Chidong/Chikan villages between 2019 and 2021. Participants from neighboring villages served as Control group. RESULTS: A total of 5731 adult residents participated in the project. Anti-HCV prevalence rate was 24.0% (886/3684) in Target Group and 9.5% (194/2047) in Control group (P < 0.001). The HCV-viremic rates among anti-HCV-positive subjects were 42.7% and 41.2%, respectively, in Target and Control groups. After COMPACT engagement, 80.4% (304/378) HCV-viremic subjects in the Target group were successfully linked-to-care, and Control group (70% (56/80), P = 0.039). The rates of link-to-treatment and SVR12 were comparable between Target (100% and 97.4%, respectively) and Control (100% and 96.4%) groups. The community effectiveness was 76.4% in the COMPACT campaign, significantly higher in Target group than in Control group (78.3% versus 67.5%, P = 0.039). The community effectiveness decreased significantly during SARS Co-V2 pandemic in Control group (from 81% to 31.8%, P < 0.001), but not in Target group (80.3% vs. 71.6%, P = 0.104). CONCLUSIONS: The outreach door-by-door screen strategy with decentralized onsite treatment programs greatly improved HCV care cascade in HCV-hyperendemic areas, a model for HCV elimination in high-risk marginalized communities in SARS Co-V2 pandemic.

A modelling assessment of short- and medium-term risks of programme interruptions for gambiense human African trypanosomiasis in the DRC.

Gambiense human African trypanosomiasis (gHAT) is a deadly vector-borne, neglected tropical disease found in West and Central Africa targeted for elimination of transmission (EoT) by 2030. The recent pandemic has illustrated how it can be important to quantify the impact that unplanned disruption to programme activities may have in achieving EoT. We used a previously developed model of gHAT fitted to data from the Democratic Republic of the Congo, the country with the highest global case burden, to explore how interruptions to intervention activities, due to e.g. COVID-19, Ebola or political instability, could impact progress towards EoT and gHAT burden. We simulated transmission and reporting dynamics in 38 regions within Kwilu, Mai Ndombe and Kwango provinces under six interruption scenarios lasting for nine or twenty-one months. Included in the interruption scenarios are the cessation of active screening in all scenarios and a reduction in passive detection rates and a delay or suspension of vector control deployments in some scenarios. Our results indicate that, even under the most extreme 21-month interruption scenario, EoT is not predicted to be delayed by more than one additional year compared to the length of the interruption. If existing vector control deployments continue, we predict no delay in achieving EoT even when both active and passive screening activities are interrupted. If passive screening remains as functional as in 2019, we expect a marginal negative impact on transmission, however this depends on the strength of passive screening in each health zone. We predict a pronounced increase in additional gHAT disease burden (morbidity and mortality) in many health zones if both active and passive screening were interrupted compared to the interruption of active screening alone. The ability to continue existing vector control during medical activity interruption is also predicted to avert a moderate proportion of disease burden.

Update of transmission modelling and projections of gambiense human African trypanosomiasis in the Mandoul focus, Chad.

BACKGROUND: In recent years, a programme of vector control, screening and treatment of gambiense human African trypanosomiasis (gHAT) infections led to a rapid decline in cases in the Mandoul focus of Chad. To represent the biology of transmission between humans and tsetse, we previously developed a mechanistic transmission model, fitted to data between 2000 and 2013 which suggested that transmission was interrupted by 2015. The present study outlines refinements to the model to: (1) Assess whether elimination of transmission has already been achieved despite low-level case reporting; (2) quantify the role of intensified interventions in transmission reduction; and (3) predict the trajectory of gHAT in Mandoul for the next decade under different strategies. METHOD: Our previous gHAT transmission model for Mandoul was updated using human case data (2000-2019) and a series of model refinements. These include how diagnostic specificity is incorporated into the model and improvements to the fitting method (increased variance in observed case reporting and how underreporting and improvements to passive screening are captured). A side-by-side comparison of fitting to case data was performed between the models. RESULTS: We estimated that passive detection rates have increased due to improvements in diagnostic availability in fixed health facilities since 2015, by 2.1-fold for stage 1 detection, and 1.5-fold for stage 2. We find that whilst the diagnostic algorithm for active screening is estimated to be highly specific (95% credible interval (CI) 99.9-100%, Specificity = 99.9%), the high screening and low infection levels mean that some recently reported cases with no parasitological confirmation might be false positives. We also find that the focus-wide tsetse reduction estimated through model fitting (95% CI 96.1-99.6%, Reduction = 99.1%) is comparable to the reduction previously measured by the decline in tsetse catches from monitoring traps. In line with previous results, the model suggests that transmission was interrupted in 2015 due to intensified interventions. CONCLUSIONS: We recommend that additional confirmatory testing is performed in Mandoul to ensure the endgame can be carefully monitored. More specific measurement of cases, would better inform when it is safe to stop active screening and vector control, provided there is a strong passive surveillance system in place.

Predicted Impact of COVID-19 on Neglected Tropical Disease Programs and the Opportunity for Innovation.

Due to the COVID-19 pandemic, many key neglected tropical disease (NTD) activities have been postponed. This hindrance comes at a time when the NTDs are progressing towards their ambitious goals for 2030. Mathematical modelling on several NTDs, namely gambiense sleeping sickness, lymphatic filariasis, onchocerciasis, schistosomiasis, soil-transmitted helminthiases (STH), trachoma, and visceral leishmaniasis, shows that the impact of this disruption will vary across the diseases. Programs face a risk of resurgence, which will be fastest in high-transmission areas. Furthermore, of the mass drug administration diseases, schistosomiasis, STH, and trachoma are likely to encounter faster resurgence. The case-finding diseases (gambiense sleeping sickness and visceral leishmaniasis) are likely to have fewer cases being detected but may face an increasing underlying rate of new infections. However, once programs are able to resume, there are ways to mitigate the impact and accelerate progress towards the 2030 goals.