Do successful tuberculosis vaccines need to be immunoregulatory rather than merely Th1-boosting?

Tuberculosis vaccine candidates are entering clinical studies in areas where BCG fails. This is a high-risk strategy. We suggest that geographical variation in the efficacy of BCG is related to the presence in developing countries of a cross-reactive background Th2-like response, probably attributable to exposure of mother and infant to helminths and environmental mycobacteria. Such Th2-like activity can stop Mycobacterium tuberculosis from being pushed into a latent state by the Th1 response, impair bactericidal functions and cause toxicity of TNF-alpha and pulmonary fibrosis. A successful vaccine, rather than driving a Th1 response, might need to suppress this pre-existing subversive Th2-like component. (c) 2005 Elsevier Ltd. All rights reserved

Emerging viral respiratory tract infections—environmental risk factors and transmission

This article is made available for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.The past decade has seen the emergence of several novel viruses that cause respiratory tract infections in human beings, including Middle East respiratory syndrome coronavirus (MERS-CoV) in Saudi Arabia, an H7N9 influenza A virus in eastern China, a swine-like influenza H3N2 variant virus in the USA, and a human adenovirus 14p1 also in the USA. MERS-CoV and H7N9 viruses are still a major worldwide public health concern. The pathogenesis and mode of transmission of MERS-CoV and H7N9 influenza A virus are poorly understood, making it more difficult to implement intervention and preventive measures. A united and coordinated global response is needed to tackle emerging viruses that can cause fatal respiratory tract infections and to fill major gaps in the understanding of the epidemiology and transmission dynamics of these viruses

Potential of immunomodulatory agents as adjunct host-directed therapies for multidrug-resistant tuberculosis

Treatment of multidrug-resistant tuberculosis (MDR-TB) is extremely challenging due to the virulence of the etiologic strains of Mycobacterium tuberculosis (M. tb), the aberrant host immune responses and the diminishing treatment options with TB drugs. New treatment regimens incorporating therapeutics targeting both M. tb and host factors are urgently needed to improve the clinical management outcomes of MDR-TB. Host-directed therapies (HDT) could avert destructive tuberculous lung pathology, facilitate eradication of M. tb, improve survival and prevent long-term functional disability. In this review we (1) discuss the use of HDT for cancer and other infections, drawing parallels and the precedent they set for MDR-TB treatment, (2) highlight preclinical studies of pharmacological agents commonly used in clinical practice which have HDT potential, and (3) outline developments in cellular therapy to promote clinically beneficial immunomodulation to improve treatment outcomes in patients with pulmonary MDR-TB. The use of HDTs as adjuncts to MDR-TB therapy requires urgent evaluation

Hepatitis C: global epidemiology and strategies for control

It is estimated that globally there are approximately 100 million persons with serological evidence of current or past HCV infection, and that HCV causes about 700 000 deaths each year. The prevalence of infection is the highest in lower and middle income countries, in which a significant number of past infections were caused by iatrogenic transmission and sub-optimal injection safety. In contrast, in developed countries, infections are caused mainly by high-risk exposures and behaviours among specific populations, such as persons who inject drugs. Recently, new direct antiviral activity (DAA) oral drugs with high rates of cure over short duration, which are well tolerated, have made chronic hepatitis C a curable condition. The extraordinary clinical performance of DAAs and recent substantial price reductions and expansion in access in resource-limited settings has provided new impetus for potential control and elimination of hepatitis C as a public health threat. We review the global epidemiology of HCV and the opportunities for preventative and treatment interventions to achieve global control of HCV infection. We also summarize the key elements of the World Health Organization's first-ever global health sector strategy for addressing the viral hepatitis pandemic

Infectious diseases epidemic threats and mass gatherings: refocusing global attention on the continuing spread of the Middle East Respiratory syndrome coronavirus (MERS-CoV)

Media and World Health Organization (WHO) attention on Zika virus transmission at the 2016 Rio Olympic Games and the 2015 Ebola virus outbreak in West Africa diverted the attention of global public health authorities from other lethal infectious diseases with epidemic potential. Mass gatherings such as the annual Hajj pilgrimage hosted by Kingdom of Saudi Arabia attract huge crowds from all continents, creating high-risk conditions for the rapid global spread of infectious diseases. The highly lethal Middle Eastern respiratory syndrome coronavirus (MERS-CoV) remains in the WHO list of top emerging diseases likely to cause major epidemics. The 2015 MERS-CoV outbreak in South Korea, in which 184 MERS cases including 33 deaths occurred in 2 months, that was imported from the Middle East by a South Korean businessman was a wake-up call for the global community to refocus attention on MERS-CoV and other emerging and re-emerging infectious diseases with epidemic potential. The international donor community and Middle Eastern countries should make available resources for, and make a serious commitment to, taking forward a “One Health” global network for proactive surveillance, rapid detection, and prevention of MERS-CoV and other epidemic infectious diseases threats

Population Differences in Death Rates in HIV-Positive Patients with Tuberculosis.

SETTING: Randomised controlled clinical trial of Mycobacterium vaccae vaccination as an adjunct to anti-tuberculosis treatment in human immunodeficiency virus (HIV) positive patients with smear-positive tuberculosis (TB) in Lusaka, Zambia, and Karonga, Malawi. OBJECTIVE: To explain the difference in mortality between the two trial sites and to identify risk factors for death among HIV-positive patients with TB. DESIGN: Information on demographic, clinical, laboratory and radiographic characteristics was collected. Patients in Lusaka (667) and in Karonga (84) were followed up for an average of 1.56 years. Cox proportional hazard analyses were used to assess differences in survival between the two sites and to determine risk factors associated with mortality during and after anti-tuberculosis treatment. RESULTS: The case fatality rate was 14.7% in Lusaka and 21.4% in Karonga. The hazard ratio for death comparing Karonga to Lusaka was 1.47 (95% confidence interval [CI] 0.9-2.4) during treatment and 1.76 (95%CI 1.0-3.0) after treatment. This difference could be almost entirely explained by age and more advanced HIV disease among patients in Karonga. CONCLUSION: It is important to understand the reasons for population differences in mortality among patients with TB and HIV and to maximise efforts to reduce mortality