The October 2020 Global TB report reviews TB control strategies and United Nations (UN) targets set in the political declaration at the September 2018 UN General Assembly high-level meeting on TB held in New York. Progress in TB care and prevention has been very slow. In 2019, TB remained the most common cause of death from a single infectious pathogen. Globally, an estimated 10.0 million people developed TB disease in 2019, and there were an estimated 1.2 million TB deaths among HIV-negative people and an additional 208, 000 deaths among people living with HIV. Adults accounted for 88% and children for 12% of people with TB. The WHO regions of South-East Asia (44%), Africa (25%), and the Western Pacific (18%) had the most people with TB. Eight countries accounted for two thirds of the global total: India (26%), Indonesia (8.5%), China (8.4%), the Philippines (6.0%), Pakistan (5.7%), Nigeria (4.4%), Bangladesh (3.6%) and South Africa (3.6%). Only 30% of the 3.5 million five-year target for children treated for TB was met. Major advances have been development of new all oral regimens for MDRTB and new regimens for preventive therapy. In 2020, the COVID-19 pandemic dislodged TB from the top infectious disease cause of mortality globally. Notably, global TB control efforts were not on track even before the advent of the COVID-19 pandemic. Many challenges remain to improve sub-optimal TB treatment and prevention services. Tuberculosis screening and diagnostic test services need to be ramped up. The major drivers of TB remain undernutrition, poverty, diabetes, tobacco smoking, and household air pollution and these need be addressed to achieve the WHO 2035 TB care and prevention targets. National programs need to include interventions for post-tuberculosis holistic wellbeing. From first detection of COVID-19 global coordination and political will with huge financial investments have led to the development of effective vaccines against SARS-CoV2 infection. The world now needs to similarly focus on development of new vaccines for TB utilizing new technological methods.
To the Editor-The current outbreak of COVID-19 in India, which started in early March 2021, has created a new world record even beyond the outbreaks in the UK, the United States and Brazil. Prior to March 2021, less than 0.7% of the Indian population was infected with COVID-19. This current second wave took only 2 months to infect an additional ~0.36% of the population, and India is now recording over 0.4 million new cases per day (as of 23 April 2021). The true number is probably even higher, with some estimates putting the number of daily new cases at over 1 million, more than five times the officially recorded number 1 .The sudden surge in COVID-19 cases in India coincides with high prevalence of more-transmissible variants, associated with diagnostic test failures and antibody escape 2 . These coronavirus SARS-CoV-2 variants of concern-B.1.1.7 (501Y.V1), B.1.351 (501Y.V2) and B.1.1.28.1 (501Y.V3; also known as P.1)-were observed during the sudden surge in COVID-19 cases in the UK, South Africa and Brazil, respectively, with subsequent local transmission across the world 2,3 (Fig. 1a).In India, the frequency of 501Y.V1 is higher than that of 501Y.V2 and 501Y.V.3 (Fig. 1b). The recently designated variant of concern B.1.617 and variant of interest B.1.618 have also been gaining attention in India 3 (Fig. 1a-c). Variant B.1.617.1 shows co-occurrence of three key mutations in sequence encoding the viral spike protein: L452R, E484Q and P681R. L452R raised concerns in the United States as part of the California variants B.1.427 and B.1.429 and conferred resistance to the neutralizing monoclonal antibodies X593 and P2B-2F6 4 . E484Q shares antibody-escape features similar to those of mutation E484K, seen in variants 501Y.V2, 501Y.V3 and B.1.618 2 . P681R may enhance processing by host proteases by extending the polybasic 'RRAR' motif, which results in a greater viral load and the potential for increased transmission. Another similar variant of concern, B.1.617.2, with mutations L452R, T478K and P681R, is highly prevalent in the state of Gujrat in India 3 . There was enrichment for the mutation T478K or T478R when SARS-CoV-2 was subjected to weak neutralizing antibodies, which indicates this mutation may lead to antibody escape.
The pathophysiological functions of proline-glutamic acid (PE)/proline-proline-glutamic acid (PPE) family of proteins of Mycobacterium tuberculosis are not well understood. In this study, we demonstrate that one of the PPE proteins, PPE18 can stimulate macrophages to secrete IL-10, known to favor a Th2 type response. The recombinant PPE18 was found to specifically interact with the TLR2 leading to an early and sustained activation of p38 MAPK, which is critical for IL-10 induction. In silico docking analyses and mutation experiments indicate that PPE18 specifically interacts with the leucine rich repeat 11 approximately 15 domain of TLR2 and the site of interaction is different from that of a synthetic lipopeptide Pam(3)CSK(4) known to activate predominantly ERK 1/2. When PMA-differentiated THP-1 macrophages were infected with a mutant Mycobacterium tuberculosis strain lacking the PPE18, produced poorer levels of IL-10 as compared with those infected with the wild-type strain. In contrast, an M. smegmatis strain overexpressing the PPE18 induced higher levels of IL-10 in infected macrophages. Our data indicate that the PPE18 protein may trigger an anti-inflammatory response by inducing IL-10 production.
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