The epidemiologic impact and cost-effectiveness of new tuberculosis vaccines on multidrug-resistant tuberculosis in India and China.

BACKGROUND: Despite recent advances through the development pipeline, how novel tuberculosis (TB) vaccines might affect rifampicin-resistant and multidrug-resistant tuberculosis (RR/MDR-TB) is unknown. We investigated the epidemiologic impact, cost-effectiveness, and budget impact of hypothetical novel prophylactic prevention of disease TB vaccines on RR/MDR-TB in China and India. METHODS: We constructed a deterministic, compartmental, age-, drug-resistance- and treatment history-stratified dynamic transmission model of tuberculosis. We introduced novel vaccines from 2027, with post- (PSI) or both pre- and post-infection (P&PI) efficacy, conferring 10 years of protection, with 50% efficacy. We measured vaccine cost-effectiveness over 2027-2050 as USD/DALY averted-against 1-times GDP/capita, and two healthcare opportunity cost-based (HCOC), thresholds. We carried out scenario analyses. RESULTS: By 2050, the P&PI vaccine reduced RR/MDR-TB incidence rate by 71% (UI: 69-72) and 72% (UI: 70-74), and the PSI vaccine by 31% (UI: 30-32) and 44% (UI: 42-47) in China and India, respectively. In India, we found both USD 10 P&PI and PSI vaccines cost-effective at the 1-times GDP and upper HCOC thresholds and P&PI vaccines cost-effective at the lower HCOC threshold. In China, both vaccines were cost-effective at the 1-times GDP threshold. P&PI vaccine remained cost-effective at the lower HCOC threshold with 49% probability and PSI vaccines at the upper HCOC threshold with 21% probability. The P&PI vaccine was predicted to avert 0.9 million (UI: 0.8-1.1) and 1.1 million (UI: 0.9-1.4) second-line therapy regimens in China and India between 2027 and 2050, respectively. CONCLUSIONS: Novel TB vaccination is likely to substantially reduce the future burden of RR/MDR-TB, while averting the need for second-line therapy. Vaccination may be cost-effective depending on vaccine characteristics and setting.

Curving Tuberculosis: Current Trends and Future Needs.

Tuberculosis (TB) presents new challenges as a global public health problem, especially at a time of increasing threats to some particular patients due to Human Immunodeficiency Virus (HIV) infection and multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis. The World Health Assembly strives to reduce TB deaths by 95% and to decrease TB incidence by 95% by 2035. However, new approaches are necessary in order to attain these objectives. Such approaches include active ascertainment of cases in high risk populations, increasing the availability of accurate point-of-care testing, rapid detection of drug resistance, novel vaccines, and new prophylaxis and treatment regimens (particularly for MDR and XDR TB). The ultimate objective of those programs is to develop highly effective drug regimens that can achieve high cure rates regardless of strains' resistance patterns.

In vitro mycobacterial growth inhibition assays: A tool for the assessment of protective immunity and evaluation of tuberculosis vaccine efficacy.

Tuberculosis (TB) continues to pose a serious global health threat, and the current vaccine, BCG, has variable efficacy. However, the development of a more effective vaccine is severely hampered by the lack of an immune correlate of protection. Candidate vaccines are currently evaluated using preclinical animal models, but experiments are long and costly and it is unclear whether the outcomes are predictive of efficacy in humans. Unlike measurements of single immunological parameters, mycobacterial growth inhibition assays (MGIAs) represent an unbiased functional approach which takes into account a range of immune mechanisms and their complex interactions. Such a controlled system offers the potential to evaluate vaccine efficacy and study mediators of protective immunity against Mycobacterium tuberculosis (M.tb). This review discusses the underlying principles and relative merits and limitations of the different published MGIAs, their demonstrated abilities to measure mycobacterial growth inhibition and vaccine efficacy, and what has been learned about the immune mechanisms involved.

Drug-resistant TB: deadly, costly and in need of a vaccine.

TB is an underappreciated public health threat in developed nations. In 2014, an estimated 9.6 million TB cases and 1.5 million deaths occurred worldwide; 3.3% of these cases resulted from multidrug-resistant tuberculosis (MDR-TB) and extensively drug-resistant tuberculosis (XDR-TB) strains. These figures underestimate the economic burden associated with MDR-TB and XDR-TB, as the cost of treating disease caused by these strains can be 9-25 times higher than treating drug-susceptible TB. Developing new drugs, improved diagnostics and new TB vaccines are critical components of a strategy to combat TB in general, and drug-resistant TB in particular. Because Mycobacterium tuberculosis (MTB) has demonstrated a capacity to develop resistance to drugs developed to combat it, it is unlikely that drug-resistant MTB would be 'resistant' to vaccines capable of preventing disease or established infection with drug-sensitive MTB strains. Accordingly, the development of TB vaccines represents an important long-term investment in preventing the spread of drug-resistant TB and achieving WHO's goal of ending the global TB epidemic by 2035. Our current understanding of the epidemiology of drug-resistant TB and the interventions needed to limit its spread, reviewed in this article, illustrates the need for increased financial support for developing new TB drugs, diagnostics and vaccines to meet the WHO goal of TB elimination by 2035.

Optimal control for a tuberculosis model with reinfection and post-exposure interventions.

We apply optimal control theory to a tuberculosis model given by a system of ordinary differential equations. Optimal control strategies are proposed to minimize the cost of interventions, considering reinfection and post-exposure interventions. They depend on the parameters of the model and reduce effectively the number of active infectious and persistent latent individuals. The time that the optimal controls are at the upper bound increase with the transmission coefficient. A general explicit expression for the basic reproduction number is obtained and its sensitivity with respect to the model parameters is discussed. Numerical results show the usefulness of the optimization strategies.

Cost-effectiveness of novel vaccines for tuberculosis control: a decision analysis study.

BACKGROUND: The development of a successful new tuberculosis (TB) vaccine would circumvent many limitations of current diagnostic and treatment practices. However, vaccine development is complex and costly. We aimed to assess the potential cost effectiveness of novel vaccines for TB control in a sub-Saharan African country--Zambia--relative to the existing strategy of directly observed treatment, short course (DOTS) and current level of bacille Calmette-Guérin (BCG) vaccination coverage. METHODS: We conducted a decision analysis model-based simulation from the societal perspective, with a 3% discount rate and all costs expressed in 2007 US dollars. Health outcomes and costs were projected over a 30-year period, for persons born in Zambia (population 11,478,000 in 2005) in year 1. Initial development costs for single vaccination and prime-boost strategies were prorated to the Zambian share (0.398%) of global BCG vaccine coverage for newborns. Main outcome measures were TB-related morbidity, mortality, and costs over a range of potential scenarios for vaccine efficacy. RESULTS: Relative to the status quo strategy, a BCG replacement vaccine administered at birth, with 70% efficacy in preventing rapid progression to TB disease after initial infection, is estimated to avert 932 TB cases and 422 TB-related deaths (prevention of 199 cases/100,000 vaccinated, and 90 deaths/100,000 vaccinated). This would result in estimated net savings of $3.6 million over 30 years for 468,073 Zambians born in year 1 of the simulation. The addition of a booster at age 10 results in estimated savings of $5.6 million compared to the status quo, averting 1,863 TB cases and 1,011 TB-related deaths (prevention of 398 cases/100,000 vaccinated, and of 216 deaths/100,000 vaccinated). With vaccination at birth alone, net savings would be realized within 1 year, whereas the prime-boost strategy would require an additional 5 years to realize savings, reflecting a greater initial development cost. CONCLUSIONS: Investment in an improved TB vaccine is predicted to result in considerable cost savings, as well as a reduction in TB morbidity and TB-related mortality, when added to existing control strategies. For a vaccine with waning efficacy, a prime-boost strategy is more cost-effective in the long term.

Advancing TB vaccines to Phase I clinical trials in the US: regulatory/manufacturing/licensing issues.

This article discusses the steps required to file an investigational new drug (IND) application to the United States Food and Drug Administration (FDA) and begin a Phase I trial of a new tuberculosis vaccine in the US. Many different groups play a role in bringing a new vaccine to market. But it is the researcher who begins the process by converting an idea into a new vaccine construct. Awareness of certain chemistry, manufacturing, and control (CMC) issues on the part of the researcher who develops the investigational vaccine can prevent later problems that might cause the vaccine to be unapprovable or fail to meet regulatory requirements for eventual licensure. CMC information included in an IND is described.

[Assessment of the risk of tuberculosis among health care personnel in Meknes]. / Evaluation du risque tuberculeux chez le personnel de santé à Meknès.

Tuberculosis has long been a concern for those responsible for the health of hospital personnel. Several studies of healthcare professionals who work in Morocco with patients with tuberculosis have shown annual incidence rates approximately ten times higher than those for the general population. This survey of the risk of tuberculosis among healthcare personnel (109 subjects with high and 118 with intermediate exposure to tuberculosis) and a control population (124 teachers) showed a positive correlation between the diameter of the tuberculin induration and intensity of exposure (significant difference between the highly exposed versus those with intermediate or no exposure). The risk of occupational tuberculosis was greater among the highly exposed healthcare workers. The involvement of occupational medicine units in health training in national public health programs and especially in programs combating tuberculosis must be a high-priority activity, because studies show that tuberculin conversion rates diminish significantly when programs of tuberculosis sensitization (information, education and communication), prevention (vaccination), and control (screening and treatment) are widely available to healthcare professionals, even those who have direct and constant with patients with tuberculosis.

Tuberculose: um fantasma que volta a assustar / Viva Legal

Explica o que é a tuberculose, como pode ser prevenida, mostra alguns de seus sintomas mais freqüentes e o tratamento adequado. Conta a história do surgimento da tuberculose e da descoberta da bactéria causadora da doença, o bacilo de Koch. Esclarece como ocorre a transmissão, cita os sintomas mais freqüentes e ressalta que, apesar de existirem remédios eficazes, a tuberculose continua sendo um grave problema de saúde pública, uma vez que o bacilo é muito resistente aos medicamentos. Explica que é possível prevenir a tuberculose com a vacina BCG, que previne as formas mais graves da doença e deve ser aplicada em todas as crianças logo após o nascimento