Effects of the Beijing genotype on latent tuberculosis infection, TB disease risk, and clustering of TB cases.

BACKGROUND: The Beijing genotype of Mycobacterium tuberculosis (Mtb) has sparked debate regarding its virulence and transmissibility. This study contributes to this discussion by assessing its effect on the risk of latent tuberculosis infection (LTBI), active tuberculosis (TB) disease among contacts, and clustering of known TB cases. METHODS: We conducted a retrospective cohort study using the records of 4457 culture-confirmed TB patients and their contacts (20,448) reported to the Florida Department of Health between 2009 and 2023. Univariate and multivariate analyses were used to evaluate the effect of the Beijing strain on LTBI, active TB risk among contacts, and case clustering. RESULTS: Our study revealed no significant difference in transmissibility between the Beijing and non-Beijing genotypes among contacts. LTBI prevalence was 19.9%, slightly higher in non-Beijing than Beijing genotypes (20.2% vs. 15.5%, p < 0.001). The prevalence of active TB was 1.8%, with no significant difference between the Beijing and non-Beijing genotypes (1.4% vs. 1.8%, p = 0.296). Increased LTBI risk was associated with older age, male sex, Hispanic ethnicity, multidrug-resistant TB exposure, household exposure, and a longer exposure duration. Active TB risk was higher for males, HIV-positive individuals, and contacts with more prolonged exposure to index cases. The Beijing genotype was associated with increased TB case clustering (aOR = 1.98, 95%CI: 1.53, 2.55, p < 0.001) as compared to the non-Beijing genotypes. US birthplace (aOR = 2.75, 95%CI: 2.37, 3.19, p < 0.001), pulmonary disease (aOR = 1.27, 95%CI: 1.04, 1.56, p < 0.020), cavitary TB (aOR = 1.25, 95% CI: 1.08, 1.44, p < 0.003), previous year alcohol use (aOR = 1.68, 95%CI: 1.38, 2.04, p < 0.001), and recreational drug use (aOR = 1.32, 95%CI: 1.04, 1.67, p < 0.024) were also associated with an increased risk of TB case clustering. CONCLUSION: While the Beijing genotype did not increase the risk of LTBI or active TB among contacts, it showed a higher tendency for case clustering. Hence, interventions should prioritize populations where this genotype is prevalent.

Factors Associated With the Discontinuation of Two Short-Course Tuberculosis Preventive Therapies in Programmatic Settings in the United States.

Background: The objective of this study was to investigate timing and risk factors for discontinuation of short-course tuberculosis preventive therapy (TPT) comparing directly observed 3-month isoniazid/rifapentine (3HP) vs self-administered 4-month rifampin (4R). Methods: This was a subanalysis of a 6-month health department cohort (2016-2017) of 993 latent tuberculosis infection (LTBI) patients initiating 3HP (20%) or 4R (80%). Time at risk of TPT discontinuation was compared across regimens. Risk factors were assessed using mixed-effects Cox models. Results: Short-course TPT discontinuation was higher with 4R (31% vs 14%; P < .0001), though discontinuation timing was similar. Latino ethnicity (hazard ratio [HR], 1.80; 95% CI, 1.20-2.90) and adverse events (HR, 4.30; 95% CI, 2.60-7.30) increased 3HP discontinuation risk. Social-behavioral factors such as substance misuse (HR, 12.00; 95% CI, 2.20-69.00) and congregate living (HR, 21.00; 95% CI, 1.20-360.00) increased 4R discontinuation risk. Conclusions: TPT discontinuation differed by regimen, with distinct risk factors. Addressing social determinants of health within TPT programs is critical to enhance completion rates and reduce TB disease risk in marginalized populations.

Central Nervous System Tuberculosis: Risk Factors for Mortality in a Propensity Score-Matched Case-Control Study.

Background: Despite advancements in tuberculosis (TB) control and treatment in the United States (US), patients with central nervous system TB (CNS-TB) continue to experience significantly higher mortality rates than those without CNS-TB. This raises concerns regarding clinical management and the need for a deeper understanding of the risk factors contributing to these deaths. This study aimed to determine the predictors of mortality in patients with CNS-TB. Methods: We conducted a retrospective 1:2 propensity score-matched case-control study. Cases were TB patients diagnosed with TB of the meninges, brain, spinal cord, or peripheral nerves, as documented in the Florida Department of Health (FDOH) TB registry, between 2009 and 2021. Controls were TB patients without CNS-TB, also reported in the FDOH TB registry during the same timeframe. We employed conditional logistic regression models to investigate the factors contributing to mortality in cases compared with controls. Results: We analyzed data from 116 cases and 232 matched controls. Patients with CNS-TB had a 5.69-fold higher risk of death than those without CNS-TB (adjusted odds ratio [aOR], 5.69 [95% confidence interval {CI}, 2.91-11.6]). Increased risk of death was associated with human immunodeficiency virus (HIV) coinfection (aOR, 1.93 [95% CI, .82-4.37]) and diabetes (aOR, 3.13 [95% CI, 1.28-7.47]). Miliary TB and non-HIV immunosuppression were significantly associated with being a case, while cavitary TB was less likely to be associated with being a case. Conclusions: Clinical management should prioritize screening and close monitoring of patients with HIV coinfection and diabetes to improve patient outcomes.

Critical assessment of the impact of vaccine-type and immunity on the burden of COVID-19.

The COVID-19 pandemic continues to have a devastating impact on health systems and economies across the globe. Implementing public health measures in tandem with effective vaccination strategies have been instrumental in curtailing the burden of the pandemic. With the three vaccines authorized for use in the U.S. having varying efficacies and waning effects against major COVID-19 strains, understanding the impact of these vaccines on COVID-19 incidence and fatalities is critical. Here, we formulate and use mathematical models to assess the impact of vaccine type, vaccination and booster uptake, and waning of natural and vaccine-induced immunity on the incidence and fatalities of COVID-19 and to predict future trends of the disease in the U.S. when existing control measures are reinforced or relaxed. The results show a 5-fold reduction in the control reproduction number during the initial vaccination period and a 1.8-fold (2-fold) reduction in the control reproduction number during the initial first booster (second booster) uptake period, compared to the respective previous periods. Due to waning of vaccine-induced immunity, vaccinating up to 96% of the U.S. population might be required to attain herd immunity, if booster uptake is low. Additionally, vaccinating and boosting more people from the onset of vaccination and booster uptake, especially with the Pfizer-BioNTech and Moderna vaccines (which confer superior protection than the Johnson & Johnson vaccine) would have led to a significant reduction in COVID-19 cases and deaths in the U.S. Furthermore, adopting natural immunity-boosting measures is important in fighting COVID-19 and transmission rate reduction measures such as mask-use are critical in combating COVID-19. The emergence of a more transmissible COVID-19 variant, or early relaxation of existing control measures can lead to a more devastating wave, especially if transmission rate reduction measures and vaccination are relaxed simultaneously, while chances of containing the pandemic are enhanced if both vaccination and transmission rate reduction measures are reinforced simultaneously. We conclude that maintaining or improving existing control measures, and boosting with mRNA vaccines are critical in curtailing the burden of the pandemic in the U.S.

The impact of age structure and vaccine prioritization on COVID-19 in West Africa.

The ongoing COVID-19 pandemic has been a major global health challenge since its emergence in 2019. Contrary to early predictions that sub-Saharan Africa (SSA) would bear a disproportionate share of the burden of COVID-19 due to the region's vulnerability to other infectious diseases, weak healthcare systems, and socioeconomic conditions, the pandemic's effects in SSA have been very mild in comparison to other regions. Interestingly, the number of cases, hospitalizations, and disease-induced deaths in SSA remain low, despite the loose implementation of non-pharmaceutical interventions (NPIs) and the low availability and administration of vaccines. Possible explanations for this low burden include epidemiological disparities, under-reporting (due to limited testing), climatic factors, population structure, and government policy initiatives. In this study, we formulate a model framework consisting of a basic model (in which only susceptible individuals are vaccinated), a vaccine-structured model, and a hybrid vaccine-age-structured model to assess the dynamics of COVID-19 in West Africa (WA). The framework is trained with a portion of the confirmed daily COVID-19 case data for 16 West African countries, validated with the remaining portion of the data, and used to (i) assess the effect of age structure on the incidence of COVID-19 in WA, (ii) evaluate the impact of vaccination and vaccine prioritization based on age brackets on the burden of COVID-19 in the sub-region, and (iii) explore plausible reasons for the low burden of COVID-19 in WA compared to other parts of the world. Calibration of the model parameters and global sensitivity analysis show that asymptomatic youths are the primary drivers of the pandemic in WA. Also, the basic and control reproduction numbers of the hybrid vaccine-age-structured model are smaller than those of the other two models indicating that the disease burden is overestimated in the models which do not account for age-structure. This result is confirmed through the vaccine-derived herd immunity thresholds. In particular, a comprehensive analysis of the basic (vaccine-structured) model reveals that if 84%(73%) of the West African populace is fully immunized with the vaccines authorized for use in WA, vaccine-derived herd immunity can be achieved. This herd immunity threshold is lower (68%) for the hybrid model. Also, all three thresholds are lower (60% for the basic model, 51% for the vaccine-structured model, and 48% for the hybrid model) if vaccines of higher efficacies (e.g., the Pfizer or Moderna vaccine) are prioritized, and higher if vaccines of lower efficacy are prioritized. Simulations of the models show that controlling the COVID-19 pandemic in WA (by reducing transmission) requires a proactive approach, including prioritizing vaccination of more youths or vaccination of more youths and elderly simultaneously. Moreover, complementing vaccination with a higher level of mask compliance will improve the prospects of containing the pandemic. Additionally, simulations of the model predict another COVID-19 wave (with a smaller peak size compared to the Omicron wave) by mid-July 2022. Furthermore, the emergence of a more transmissible variant or easing the existing measures that are effective in reducing transmission will result in more devastating COVID-19 waves in the future. To conclude, accounting for age-structure is important in understanding why the burden of COVID-19 has been low in WA and sustaining the current vaccination level, complemented with the WHO recommended NPIs is critical in curbing the spread of the disease in WA.

Effect of mixed strain infections on clinical and epidemiological features of tuberculosis in Florida.

Mixed infections with genetically distinct Mycobacterium tuberculosis (MTB) strains within a single host have been documented in different settings; however, this phenomenon is rarely considered in the management and care of new and relapse tuberculosis (T.B.) cases. This study aims to establish the epidemiological and clinical features of mixed infections among culture-confirmed T.B. patients enrolled in tuberculosis care at the Florida Department of Health (FDOH) and measure its association with T.B. mortality. We analyzed de-identified surveillance data of T.B. cases enrolled in T.B. care from April 2008 to January 2018. Mixed MTB infection was determined by the presence of more than one Copy Number Variant (CNV) in at least one locus, based on the genotype profile pattern of at least one isolate using 24-locus Mycobacterial Interspersed Repetitive Unit-Variable Number Tandem Repeat (MIRU-VNTR). The prevalence of mixed MTB infections among the 4944 culture-confirmed TB cases included in this analysis was 2.6% (129). Increased odds of mixed infections were observed among middle-aged patients, 45-64 years (AOR = 2.38; 95% CI: 0.99, 5.69; p = 0.0513), older adults 65 years and above (AOR = 3.95; 95% CI: 1.63, 9.58; p = 0.0023) and patients with diabetes (OR = 1.77; 95% CI: 1.12, 2.80; p = 0.0150). There was no significant association between mixed infections and death. Our study provides insight into the epidemiological and clinical characteristics of patients with mixed MTB infections, which is essential in the management of T.B. patients.