Tuberculosis could be eliminated by 2045, researchers suggest

By Dr Deepu

A new study by researchers  suggests that “increased investment in evidence-based interventions to diagnose, treat, and prevent tuberculosis (TB), especially in high-burden countries, could help end TB” by the year 2045. These interventions should not only “be scaled up, but greater investment and research is needed to develop new methods of diagnosis, treatment, and prevention around the world, [researchers] reported.” Additionally, they suggest that “responsibility for investing in TB programs should be shared between domestic allocation in these countries, as well as external funding through increased developmental assistance.”

The authors mentioned that”to reach these goals, global investment in TB research and development will need to increase to at least $2 billion per year during the next 4 years”.

With the goals of treating 40 million people and preventing 30 million new cases from 2018-2022, the United Nations held its first-ever "high-level meeting" about TB,in September 2018

A TB-free world is possible by 2045 if "increased political will and financial resources" are targeted towards areas where they are needed most, as stated in the report

 In India, the country with the highest burden of TB,  "unavoidable tuberculosis deaths" will cost the country at least $32 billion each year over the next 30 years, even with "optimal implementation of existing tools." The authors also have mentioned that the savings from averting a TB death can be three times the costs in certain countries.

Tuberculosis was declared a global emergency by WHO in 1993. Then, about a third of the world’s population was infected with the bacteria that cause tuberculosis, and the disease was responsible for an estimated 3 million deaths each year. Today, around a quarter of the world’s population has a tuberculosis infection, which causes about 1·6 million annual deaths, making it the leading infectious killer of our time. Although progress has been made in reducing the global burden of tuberculosis in the past 25 years, it has occurred at a frustratingly slow rate. Declines in tuberculosis mortality are not keeping pace with reductions in deaths from other infectious diseases of global importance such as HIV and malaria, and the world is not on track to meet targets set out in the Sustainable Development Goals and the WHO End TB Strategy.

The findings were published in The Lancet.

Are WHO approved nucleic acid amplification tests causing large-scale "false identification" of rifampicin-resistant tuberculosis?

By Dr Deepu

The nucleic acid amplification tests (NAATs): Line probe assay and GeneXpert (Xpert) have evolved as the primary tool for identification of rifampicin (RIF)-resistant (RR) tuberculosis (TB) worldwide, primarily because of the ease and speed. They rechecked RR isolates identified by NAATs from presumptive RR TB cases belonging to South India by the Revised National TB Control Program, India using multiple RIF concentrations on Bactec MGIT system and compared the mutation patterns with the resistance levels.
Researchers state that they used standard protocol for Bactec MGIT system as given by the manufacturer modified for the multiple RIF concentrations. All the retests were done in a certified BSL3 laboratory.
Astonishingly they found that there is a mismatch of up to 20% (RIF breakpoint 0.5 mg/L); the NAATs probably overidentifying RR TB. Half of the cases with mismatch showed a sub-breakpoint rise in resistance level (0.125 mg/L to 0.5 mg/L RIF).
They finally concluded by stating probable reasons for the mismatch are "sub-breakpoint low-level resistance mutants," hetero-resistant bacterial populations, and other inherent test limitations along with the low RR TB prevalence in South India (<5%) among "presumptive multidrug-resistants." They also quoted, could be due to the incomplete selection pressure by an inadequate RIF exposure caused by various factors including a low-RIF dosage being used widely and poor Directly observed treatment.
They concluded"To prevent the false diagnosis of RR TB in a massive scale when using NAATs, we may need to enforce a carefully targeted testing approach and a phenotypic susceptibility testing with multiple RIF concentrations for confirmatory purposes".
Find the full text article here

Researchers find genes linked to development of active TB.

By Dr Deepu

Researchers in Seattle and South Africa have identified markers in the blood of infected people that may predict those at high risk for developing an active  and potentially fatal form of the disease.

A signature pattern of 16 genes, detected in analysis of samples from more than 6,000 South African adolescents, may one day help create a test to identify and treat people likely to develop active TB  more than a year before they get sick.

Research shows, Inexpensive Urine Test For Tuberculosis Reduced Risk Of Death Among HIV-Positive Hospital Patients In Africa.

By Dr Deepu

HIV-associated tuberculosis is difficult to diagnose and results in high mortality. Frequent extra-pulmonary presentation, inability to obtain sputum, and paucibacillary samples limits the usefulness of nucleic-acid amplification tests and smear microscopy.Therefore  a urine-based, lateral flow, point-of-care, lipoarabinomannan assay (LAM) and the effect of a LAM-guided anti-tuberculosis treatment initiation strategy on mortality was assessed.
This inexpensive urine test for tuberculosis reduced the risk of death among HIV-positive hospital patients in Africa, where the combined effect of the two diseases is a leading cause of mortality.” Researchers found, “in a randomized controlled trial in four counties,” that “the test was associated with a 17% relative risk reduction in all-cause mortality after 8 weeks, possibly because TB treatment was started more quickly and in more patients.”

The findings were published online in The Lancet.

X Ray - Tuberculosis

By Dr Deepu
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RNTCP comes out with daily regimen for drug sensitive TB

By Dr Deepu

RNTCP India has come out with a new recommendation to use daily ATT in treatment of drug sensitive tuberculosis.

The Revised National Tuberculosis Control Programme (RNTCP) was launched in India in 1997 

based on World Health Organization endorsed Directly Observed Treatment Short-Course (DOTS) 

strategy, employing the thrice weekly treatment regimen.

The Standards for TB Care in India, 2014, which were jointly laid down by Ministry of Health &  Family Welfare, Government of India and World Health Organization, in consultation with experts, based on available evidences and WHO Treatment of TB Guidelines (2010), state that ‘all patients should be given daily regimen. The initial phase should consist of two months of 

Isoniazid (H), Rifampicin (R), Pyrazinamide (Z), and Ethambutol (E). The continuation phase should consist of three drugs, Isoniazid (H), Rifampicin (R) and Ethambutol (E) given for at least 

four months’. The National Technical Working Group (NTWG) on TB/HIV (2013) has recommended use of daily 

regimen using Fixed Dose Combination (FDC) first line TB treatment for PLHIV patients. 

Considering the above, the National Expert Committee to examine type of drug regimen for drug sensitive TB has recommended RNTCP to move towards introducing daily regimen for drug sensitive Tuberculosis in India.

The link to download the guidelines is given below. Please visit the link to download.

Download here

WHO Calls On India To Increase Funding To Fight TB

By Dr Deepu

Reuters (11/19, Kalra) reports that the World Health Organization said that the global fight to end a tuberculosis epidemic by 2030 hinges on India increasing funding to control the disease. Reuters notes that the country accounts for over 20 percent of global TB cases.

        Combating TB is a daunting task in India due to widespread insanitary conditions, poverty and a lack of public hospitals. Low public awareness and social stigma attached to the killer disease also hinder eradication efforts.

India also needs to upgrade laboratories to better detect the disease - the government last year tracked down 25,000 of the WHO's estimated 47,000 multi-drug resistant TB cases that, Raviglione said, was "not sufficient" but better than before.

    TB killed 1.1 million people globally last year, for the first time rivaling HIV/AIDS as a leading cause of death from infectious diseases.

"If India doesn't invest on TB, then there will be very little progress at the global level," said Raviglione.

Global Plan to End TB to Save Over 10 Million Lives

By Dr Deepu

The world is losing its battle with tuberculosis, which is now the biggest infectious killer globally, causing 1.5 million deaths every year, according to the new GlobalPlan to End TB 2016-2020, which was released Nov. 20 by the Stop TB Partnership. The plan’s targets, called 90-(90)-90, are aiming for 90 percent rates in the three areas of: TB diagnosis, care for vulnerable populations, and treatment. New tools are needed for successful implementation, and the Global Plan calls for an additional $9 billion to create a vaccine, rapid diagnostic tests, and drug regimens (including for drug-resistant TB). The plan will be shared with high-level politicians from around the world at the 46th Union World Conference on Lung Health in Cape Town, South Africa, in December.

Plombage - An Obsolete Technique of Historical Importance in treating TB

By Dr Deepu

Chest X Ray of Plombage using Lucite Balls

CT Thorax of the same Patient

Plombage was a surgical method used prior to the introduction of anti-tuberculosis drug therapy to treat cavitary tuberculosis of the upper lobe of the lung. The term derives from the Latin word "plumbum" (lead) and refers to the insertion of an inert substance in the pleural space. The technical medical term for plombage is extraperiosteal or extrapleural pneumonolysis.

The underlying theory of plombage treatment was the belief that if the diseased lobe of the lung was physically forced to collapse, it would heal quickly. There were positive results in tuberculosis therapy following plombage in the decades of the 1930s, 40s and early-50s. However, with the introduction of drugs which were effective in destroying the tuberculosis bacterium (Mycobacterium tuberculosis), plombage treatment fell into disfavor. In addition, complications of plombage began to appear in patients who had been so treated. These complications included hemorrhage, infection and fistulization  of the bronchus, aorta, esophagus and skin.

The technique involved surgically creating a cavity underneath the ribs in the upper part of the chest wall and filling this space with some inert material. A variety of substances were typically used and included air, olive or mineral oil, gauze, paraffin wax, rubber sheeting or bags and Lucite balls. The inserted material would force the upper lobe of the lung to collapse.

NEJM LINKS FOR LUCITE BALLS

link1

Link2

Two Medications May Be Effective Against XDR-TB, New Research Reveals

By Dr Deepu

MedPage Today (7/16, Smith) reports that researchers found that “a drug being studied as a treatment for extensively drug-resistant tuberculosis (XDR-TB) had durable efficacy in a small trial.” One “year after the end of treatment with linezolid (Zyvox), combined with a background regimen, 27 of 38 patients had negative results on sputum culture, according to Clifton Barry III, PhD, of the National Institute of Allergy and Infectious Disease in Bethesda, Md., and colleagues.” Meanwhile, “in another brief report, investigators said post-hoc analysis of three trials of the investigational drug delamanid – a mycobacterial cell wall synthesis inhibitor – suggests it, too, is effective against XDR-TB.” The findings were published in the New England Journal of Medicine.

Here are the link to the published article.

1.http://www.nejm.org/doi/full/10.1056/NEJMc1415332

2.http://www.nejm.org/doi/full/10.1056/NEJMc1500286