Tuberculosis

Can mRNA vaccine tech take on tuberculosis?

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Dr. Adenov, Kazakhstan’s director of the National TB Program, with a patient. Researchers are pushing to capitalise on the success of mRNA technology against COVID-19 and are aiming to develop an mRNA vaccine to be used against TB.

Speed read

  • Clinical trials of an mRNA vaccine for TB are set to begin this year
  • TB kills around 1.5 million people a year, mostly in developing countries
  • Research funding remains a major obstacle to progress

 

A successful mRNA vaccine for tuberculosis could be rapidly developed and save more than 1 million lives every year, say hopeful global health advocates.

Researchers are pushing to capitalise on the success of mRNA technology against COVID-19 by exploring whether the platform could be effective against tuberculosis, the world’s second most deadly infectious disease.

TB is a disease of poverty, but it is curable and preventable. Caused by the bacteria Mycobacterium tuberculosis, TB spreads from person to person through the air. TB bacteria can live for longer in rooms with no fresh air or sunlight, and poor living conditions and overcrowding increase the risk of becoming infected.

“The mRNA technology has progressed over the years and actually leap-frogged during the COVID-19 pandemic. It is the right time now to use mRNA technology for developing a new and effective vaccine for TB.”

Suvanand Sahu, deputy executive director, Stop TB Partnership

The disease primarily affects people in developing countries, and there were an estimated 10 million new TB cases and 1.5 million deaths in 2020, according to the World Health Organization. Eight countries accounted for two-thirds of total TB cases, including India, China, Indonesia, Nigeria and South Africa.

The only licenced TB vaccine, Bacillus Calmette–Guérin (BCG), is a century old. It is a live attenuated vaccine – a living but weakened version of the disease-causing organism is used – that protects young children, but provides inconsistent protection for adults and adolescents.

Scientists are pushing for greater funding and political commitment to back the research and development needed to create an effective mRNA TB vaccine.

Clinical trials

The “unprecedented speed” by which COVID-19 vaccines were developed, licensed and introduced provides an example for tuberculosis vaccine research and development, members of the Tuberculosis Vaccine Roadmap Stakeholder Group said in a February review in The Lancet Infectious Diseases.

“New platforms have been successfully deployed that might have useful applications for tuberculosis, in particular the mRNA technology,” the group said.

Exploration of mRNA technology for TB is not new. A 2004 study by researchers in the United Kingdom showed that an mRNA vaccine had “modest but significant protection” against Mycobacterium tuberculosis for mice.

In July, the German biotechnology company BioNTech announced that clinical trials of its mRNA vaccine for TB, developed with the Bill & Melinda Gates Foundation, will begin in 2022. BioNTech’s clinical trials will begin “just about two years after the programme was initiated”, according to the pharmaceutical developer.

Suvanand Sahu is the deputy executive director of the Stop TB Partnership, which has more than 2,000 partner organisations including governments, international organisations and patient groups. Sahu, a medical doctor and public health specialist with more than 18 years’ experience in TB, said other groups around the world were also working on mRNA vaccines against the disease.

He tells SciDev.Net that the scientific teams that developed the mRNA vaccines for COVID-19 are best placed to rapidly repurpose the technology for a TB vaccine.

mRNA vaccine viability 

The BCG vaccine was introduced in 1921 and, as yet, no other vaccine against tuberculosis has been licenced. “BCG is 100 years old and reliably protects only against severe forms of childhood TB,” Sahu tells SciDev.Net. “Clearly, [it is] not the tool that will interrupt TB transmission and help end TB.”

The importance of leveraging mRNA platforms for accelerated vaccine development has become “self-evident”, the Global Forum on TB Vaccines, held virtually in April 2021, heard. BioNTech’s Mustafa Diken told the forum how the mRNA vaccine technology used for COVID-19 could be tailored to fight TB.

As of October 2021, there were more than a dozen candidate vaccines undergoing clinical trials, according to the Tuberculosis Vaccine Initiatives pipeline tracker, including five that are in phase III trials. None of the current candidates use the mRNA platform.

TB Vacc dev path

Patrick Tippoo, executive director of the South Africa-based African Vaccine Manufacturing Initiative, tells SciDev.Net that it is theoretically possible to develop an mRNA vaccine to prevent tuberculosis. But, he says, in practice it will depend on whether scientists can identify the most appropriate vaccine antigen targets. “The correct vaccine targets need to be identified and this has been elusive to date,” Tippoo says.

The WHO’s new mRNA technology transfer hubs have raised optimism that the time has come to find a new vaccine for TB. The WHO said that the mRNA technology transfer hubs would empower low- and middle-income countries to produce their own vaccines, medicines and diagnostics, and the technology could also be used to develop vaccines for other priority diseases such as TB, malaria and HIV.

“We strongly believe that the mRNA technology can be used for developing a TB vaccine,” says Sahu, who was part of the group that launched India’s polio eradication initiative in 1997.

He says that the 2004 mRNA vaccine trialled on mice did not progress to human trials due to lack of funding and a perception that “getting an mRNA vaccine will be too difficult”. However, Sahu says, “the mRNA technology has progressed over the years and actually leap-frogged during the COVID-19 pandemic. It is the right time now to use mRNA technology for developing a new and effective vaccine for TB.”

Funding and access

Multidrug-resistant TB is a growing public health crisis and a global health security threat, increasing the urgent need for a safe and effective vaccine. With a sharper focus on the disease and speedier vaccine development times, TB advocates are calling for greater financial support to take on this killer disease.

Funding for research and development remains a serious obstacle: the total funding for tuberculosis research in 2019 was US$901 million, “far below” the WHO target of at least US$2 billion per year. The global health body has called for TB research and development funding to double.

Mel Spigelman, president and chief executive officer of the US and South Africa-based Global Alliance for TB Drug Development, says: “Tremendous scientific advances in TB testing, treatment, and prevention are possible. [However], the limiting factor to date has been a profound scarcity of research funding.”

TB advocates want to begin conversations about funding, access and affordability to avoid the inequality that has plagued the roll-out of COVID-19 vaccines. With the possibility of an mRNA vaccine for TB, issues relating to patents and vaccine-production capacity in developing countries become prominent.

Sarah Fortune, however, wants to keep the focus squarely on research and development for the time being. “While I understand the urge to worry about whether a vaccine will be affordable…I think this diverts focus from the more immediate problem, which is whether a protective vaccine for TB is biologically possible,” says Fortune, professor and chair of the department of immunology and infectious diseases at Harvard TH Chan School of Public Health in Boston.

“We want everyone to lean into this problem because we fundamentally do not know how to build a better TB vaccine and it is killing a million people a year.”

Intestinal Tuberculosis

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A 36-year-old woman presented to the emergency department with a 1-day history of severe abdominal pain and a 2-week history of fever and cough. She had no known medical history and worked as a physician. On physical examination, diffuse, severe abdominal tenderness with rebound and guarding was observed. Computed tomography of the chest showed a miliary pattern of pulmonary nodules and subdiaphragmatic free air, which prompted urgent transfer to the operating room. On gross pathological examination, six perforations were seen in the terminal ileum (Panel A). Intestinal resection of the distal ileum with an ileostomy was performed. Histopathological examination showed submucosal necrotizing granulomatous inflammation (Panel B; the asterisk indicates a granuloma). Cultures and real-time polymerase-chain-reaction testing of peritoneal fluid and intestinal tissue revealed Mycobacterium tuberculosis. A diagnosis of disseminated tuberculosis with tuberculous ileitis was made. Testing for human immunodeficiency virus was negative. In intestinal tuberculosis, the ileocecal area is the most commonly involved region, and infection there may initially be misdiagnosed as appendicitis or inflammatory bowel disease. This patient completed 9 months of antituberculous therapy and underwent ileostomy closure 6 months after her initial operation. At a follow-up visit 12 months after her initial presentation, she had completely recovered.

Shorter Treatment for Nonsevere Tuberculosis in African and Indian Children

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Abstract

BACKGROUND

Two thirds of children with tuberculosis have nonsevere disease, which may be treatable with a shorter regimen than the current 6-month regimen.

METHODS

We conducted an open-label, treatment-shortening, noninferiority trial involving children with nonsevere, symptomatic, presumably drug-susceptible, smear-negative tuberculosis in Uganda, Zambia, South Africa, and India. Children younger than 16 years of age were randomly assigned to 4 months (16 weeks) or 6 months (24 weeks) of standard first-line antituberculosis treatment with pediatric fixed-dose combinations as recommended by the World Health Organization. The primary efficacy outcome was unfavorable status (composite of treatment failure [extension, change, or restart of treatment or tuberculosis recurrence], loss to follow-up during treatment, or death) by 72 weeks, with the exclusion of participants who did not complete 4 months of treatment (modified intention-to-treat population). A noninferiority margin of 6 percentage points was used. The primary safety outcome was an adverse event of grade 3 or higher during treatment and up to 30 days after treatment.

RESULTS

From July 2016 through July 2018, a total of 1204 children underwent randomization (602 in each group). The median age of the participants was 3.5 years (range, 2 months to 15 years), 52% were male, 11% had human immunodeficiency virus infection, and 14% had bacteriologically confirmed tuberculosis. Retention by 72 weeks was 95%, and adherence to the assigned treatment was 94%. A total of 16 participants (3%) in the 4-month group had a primary-outcome event, as compared with 18 (3%) in the 6-month group (adjusted difference, −0.4 percentage points; 95% confidence interval, −2.2 to 1.5). The noninferiority of 4 months of treatment was consistent across the intention-to-treat, per-protocol, and key secondary analyses, including when the analysis was restricted to the 958 participants (80%) independently adjudicated to have tuberculosis at baseline. A total of 95 participants (8%) had an adverse event of grade 3 or higher, including 15 adverse drug reactions (11 hepatic events, all but 2 of which occurred within the first 8 weeks, when the treatments were the same in the two groups).

CONCLUSIONS

Four months of antituberculosis treatment was noninferior to 6 months of treatment in children with drug-susceptible, nonsevere, smear-negative tuberculosis. (Funded by the U.K. Medical Research Council and others; SHINE ISRCTN number, ISRCTN63579542. opens in new tab.)

Discussion

The SHINE trial evaluated the duration of antituberculosis treatment in children with nonsevere, drug-susceptible tuberculosis who were living in countries with a high burden of tuberculosis, where nearly 90% of cases of tuberculosis in children occur.19 The trial showed the noninferiority of 4 months as compared with the standard 6 months of treatment, with the upper boundary of the 95% confidence interval being below the prespecified margin of 6 percentage points. Consistency of results across all the analyses, including a key secondary analysis in a subgroup of children who were adjudicated to have tuberculosis at baseline, was observed. Participants had a good response to treatment with few adverse drug reactions, most of which occurred before 4 months, during the period when the two trial groups had the same treatment regimen.

Shortening treatment for drug-susceptible tuberculosis is a key goal for both adults and children. Early trials showed that it was possible to shorten the treatment duration in adults with culture-negative disease.20-22 A meta-analysis of treatment-duration trials involving adults showed that 4-month drug regimens were efficacious in adults with paucibacillary tuberculosis who had disease with a sputum-smear grade of less than 2+ (<1 acid-fast bacillus per field) or noncavity disease.23 Recently, the Tuberculosis Trials Consortium Study 31/AIDS Clinical Trials Group A5349 trial showed the noninferiority of a 4-month rifapentine-based regimen containing moxifloxacin, as compared with the 6-month standard regimen, for all forms of drug-susceptible tuberculosis (including cavity disease) in adults and adolescents.24 Challenges remain in terms of the availability of child-friendly formulations of rifapentine and moxifloxacin, data on doses in children, and cost. However, our results show that a new regimen with new drugs is not necessary for the shortening of treatment in the majority of children with drug-susceptible tuberculosis, since such treatment shortening can be accomplished with the affordable, child-friendly, fixed-dose combinations that are already available.25

This trial showed the feasibility of identifying children with nonsevere disease. We used a pragmatic approach by following routine screening procedures and reviewing chest radiographs to assess the severity of respiratory tuberculosis. Despite perceived difficulties of obtaining respiratory samples in children, such challenges were overcome with appropriate training, and samples were successfully obtained for tuberculosis testing in all 1204 children who underwent randomization. The trial included children with HIV infection as well as those without HIV infection, with consistent results.

Most children with tuberculosis have paucibacillary and nonsevere disease with low rates of microbiologic tuberculosis confirmation in routine care. To ensure the applicability of our results to clinical practice and the spectrum of disease that is most prevalent in children, we did not limit the trial to bacteriologically confirmed tuberculosis. We adapted the pediatric consensus algorithm for diagnosis of intrathoracic tuberculosis13 to both intrathoracic tuberculosis and peripheral lymph-node tuberculosis and used independent expert review and central reading of chest radiographs, with blinding to the treatment assignments, to ensure objective categorization of tuberculosis status. The end-point review committee, whose members were unaware of the randomized group assignments, reviewed tuberculosis outcomes to minimize the effect of treatment assignment on adjudication.

Our trial had several strengths. It was well-powered, and we observed 94% adherence (to the receipt of ≥80% of the doses) in the assigned groups and 95% retention of trial participants, findings that increase confidence in the results. We assumed in the sample-size calculation that 8% of the participants in the 6-month group would have an unfavorable status, and we observed this result in 7% of the participants overall in the trial. However, events in 3% of the participants occurred after month 4, when the trial groups were receiving different durations of the treatment, which we had not anticipated when we designed the trial.

The trial also has several limitations. One limitation is that this trial was open-label, which had the potential to result in more frequent treatment extensions in the 4-month group, contributing to more unfavorable outcomes in this group. Despite this possible disadvantage in the 4-month group, the results showed consistently that the 4-month regimen was as good as the 6-month regimen. Another limitation relates to the generalizability of our results to settings where chest radiographs are not available for characterizing nonsevere tuberculosis.

Our inclusion criteria for the trial required smear microscopy to be undertaken to rule out more severe forms of respiratory tuberculosis. With the current rollout of rapid molecular diagnostic tests replacing smear microscopy,26 this may pose a challenge to implementation on the basis of the trial results. However, smear-grade and Xpert semiquantitative results have been shown to be correlated.27 In our trial, most Xpert results from respiratory samples were negative and the few positive Xpert samples had low or very low semiquantitative results, which suggest that the trial findings can be extrapolated to settings where Xpert is replacing smear testing and that children with negative, low, or very low positive values on Xpert testing can be categorized as having nonsevere tuberculosis. It will be useful in future implementation studies to explore treatment shortening in all children who are treated for nonsevere, drug-susceptible tuberculosis, regardless of smear or Xpert results.

In this trial, we found that 4 months of antituberculosis treatment was noninferior to 6 months of therapy in children with drug-susceptible, nonsevere, smear-negative tuberculosis. The results suggest that a stratified medicine approach as an alternative to the one-size-fits-all strategy of treatment for presumptive drug-susceptible tuberculosis could be implemented in children with nonsevere tuberculosis.

Source: NEJM

GENE-XPERT gives early diagnosis in early c

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Abstract

Introduction: Gene-Xpert, a CBNAAT (catridge based nucleic acid amplification test) is a widely accepted diagnostic test for Tuberculosis. This test is a rapid diagnostic test for Tuberculosis detection as well as Rifampicin resistance in direct smear negative cases. Due to of non availability and lack of cost effectiveness it is still not common in devoloping countries like India.

Aims and Objective: To compare the Gene-Xpert result with sputum smear microscopy and culture report.

Methods: This was a prospective study conducted from July 2014 to June 2015.Bronchial washings, sputum,pleural samples(pleural fluid,pleural biopsies),tissue biopsy and other samples from patients of suspected Tuberculosis were sent for direct smear/culture for AFB as well as Gene-Xpert.

Results: A total of 415 samples were analysed, among which 163 was Bronchial washings ,71 were Sputum,Pleural samples was 98 and others ( biopsies / FNAC and body fluids) were 83.Gene-Xpert was detected positive in 67 samples (BAL-30,Sputum-15,Pleural samples-4,Others-18). Rifampicin resistence was detected in 15 samples and 2 samples had indeterminate result. Of the 67 patients who had detected positive in Gene-Xpert, 28 samples were positive for direct smear and 40 samples had shown growth of AFB in culture. Only one sample(sputum) in 415 show AFB in direct smear but was negative for Gene-Xpert .Culture growth for mycobacterium tuberculosis was seen positive in 7 which were negative in Gene-Xpert.

Conclusion: Gene Xpert is an excellant clinical tool for detection of Mycobacterium Tuberculosis in early stage where the direct smear is negative as well as in early detection of Rifampicin resistance.

Covid-19’s Devastating Effect on Tuberculosis Care — A Path to Recovery

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The Covid-19 pandemic has had devastating effects on every aspect of global health, but tuberculosis services have been disproportionately affected.1 According to the World Health Organization (WHO) Global Tuberculosis Report 2021, case notifications have plummeted because of pandemic-related disruptions in services.2 For the first time in more than a decade, tuberculosis mortality has increased.2

Even as high-income countries roll out Covid-19 vaccine boosters and stockpile millions of vaccine doses, many low- and middle-income countries are struggling to obtain vaccines. Whereas 76% of people in high-income countries have received at least one Covid-19 vaccine dose, as of the end of December 2021, the rate was only 8% in low-income countries. Because of vaccine inequity, new variants of SARS-CoV-2 (such as omicron) are emerging and particularly affect countries with low vaccine coverage and high rates of poverty and tuberculosis.

The WHO (where two of us work) estimates that nearly 10 million people developed tuberculosis in 2020.2 Only 5.8 million cases were diagnosed and reported, however, which reflects an 18% decrease from 2019. This decrease was concentrated in 16 countries, with Asian countries (especially India, Indonesia, the Philippines, and China) seeing the largest reductions in case reporting.2 These countries all had major Covid-19 outbreaks and health care service disruptions.Global Trends in the Estimated Number of Tuberculosis Deaths and Tuberculosis Mortality, 2000 to 2020.

Tuberculosis deaths have increased because of reduced access to care.2 In 2020, there were roughly 1.5 million tuberculosis deaths worldwide, representing the first year-over-year increase in tuberculosis deaths since 2005 (see figure).2 Other negative pandemic-related effects include a 15% reduction in the number of people treated for drug-resistant tuberculosis, a 21% decrease in people receiving preventive treatment for tuberculosis infection, and a decrease (from $5.8 billion to $5.3 billion) in global tuberculosis spending between 2019 and 2020.2

Given these setbacks, progress toward the 2022 targets established by the United Nations (UN) high-level meeting on tuberculosis is off track. Reductions in tuberculosis incidence have dramatically slowed. This trend is expected to worsen, driven by ongoing Covid-19 surges in low- and middle-income countries.2 India and Indonesia, for example, had delta-variant surges in 2021, with millions of excess deaths and severe disruptions to essential health services. The emergence of the omicron variant poses a new threat, especially to countries in southern Africa that are experiencing massive Covid-19 surges on top of already high tuberculosis and HIV coinfection burdens.

Without an effective tuberculosis vaccine for adults, treatment is the primary form of disease control. Because so many tuberculosis cases have been missed during the past 2 years, increased transmission is expected. WHO modeling suggests that the pandemic’s effects on tuberculosis incidence and mortality in 2020 will be exacerbated in 2021 and beyond, in some cases throughout all 16 countries that were considered.2

These projections don’t account for exacerbations in the social determinants (extreme poverty and malnutrition, for example) that fuel the tuberculosis epidemic. In 2020, the Covid-19 pandemic pushed 100 million people into poverty, and the UN estimates that developing economies will have pandemic-related losses of $12 trillion through 2025. Nearly 20% of global tuberculosis incidence is attributable to undernutrition.2 In countries with high tuberculosis burdens, such as India, the population attributable fraction for undernutrition is higher — more than 50% in many Indian states3 — and malnutrition and poverty could be important tuberculosis drivers in coming years.

The path to recovery will require both immediate, short-term steps and longer-term actions. First, ending the Covid-19 pandemic quickly is critical for rebuilding tuberculosis services and other essential health services. No country can keep new variants in check without high Covid-19 vaccine coverage. Without global vaccination, health care systems in low- and middle-income countries will collapse. We believe people working in the tuberculosis field should support the WHO plan — which was also included in the Group of 20 Rome leaders’ declaration — to vaccinate 70% of all countries’ populations by mid-2022. To achieve this goal, high-income countries will need to immediately redistribute surplus vaccine doses and meet their pledges to the Covid-19 Vaccines Global Access (COVAX) program. Waiving intellectual-property rights and sharing vaccine know-how is essential so that countries can produce their own vaccines. The WHO has created a multilateral mechanism to address regional inequities in vaccine manufacturing, with the first mRNA technology–transfer hub established in South Africa and spokes in many countries.

Second, we need to highlight the worsening tuberculosis epidemic. Real-time Covid-19 dashboards are widely available, and governments respond immediately to new data. Tuberculosis programs can learn from this approach. Investments in digital data systems, connected diagnostics, and digital treatment-support tools could make tuberculosis data more visible and accessible. Communities could use these data to hold governments accountable and advocate for increased funding. During the pandemic, the WHO has published monthly tuberculosis-notification data and offered modeling estimates to guide countries’ recovery efforts. Such rapid reporting should become the new normal, and real-time tuberculosis data should be available everywhere.

Third, improving case detection is an urgent priority.4 Doing so will necessitate leveraging mobile-phone–based apps and digital tools to improve patient education, triage, and referrals and contact screening. Targeted active-case–finding initiatives, guided by precision public health (i.e., predictive analytics and mapping of hotspots), could help identify people with undiagnosed tuberculosis. This approach will require learning from Covid-19 testing experiences by bringing tuberculosis testing closer to where people live and work and engaging communities, private providers, and community-based health workers and civil-society organizations.4

Every country has scaled up its molecular-testing capacity for Covid-19, and this capacity could be used for tuberculosis testing, in combination with validation of simpler, nonsputum samples. Better integration of tuberculosis and Covid-19 testing is also necessary. Because of the need to provide medical care during lockdowns, substantial advances have been made in digital health, remote service provision, ultra-portable digital x-ray systems with artificial-intelligence–based reading software, use of digital technologies for promoting medication adherence, and use of e-pharmacies in combination with home delivery of medicines.4 These systems could be leveraged for tuberculosis on a large scale, including scale-up of preventive therapy for tuberculosis.

In the longer term, only by establishing multisectoral collaborations involving personal, societal, and health system interventions will we end the global tuberculosis epidemic by 2035.1 Achieving this goal will require addressing the social determinants of tuberculosis infection and mortality; reducing stigma and other barriers to seeking care; promoting the use of masks, improved ventilation, and other airborne infection–control measures; and ensuring that health care workers have adequate personal protective equipment.

Another long-term strategy involves increasing investment in the development of new tuberculosis tools, taking advantage of the scientific advances that rapidly produced Covid-19 vaccines, diagnostics, and drugs. Development of a simple, point-of-care tuberculosis test, an improved tuberculosis vaccine, and ultra-short drug regimens is critical.

These efforts will require increased funding. Even as more than $100 billion has been invested in developing Covid-19 vaccines, leading to more than a dozen vaccines being authorized within 1 year after the WHO declaration of Covid-19 as a Public Health Emergency of International Concern, the century-old bacille Calmette–Guérin vaccine is still used for tuberculosis. Investments in new tuberculosis vaccines amount to barely $0.1 billion per year, and overall research and development investments reached only $0.9 billion in 2020, as compared with an estimated need of $2 billion.2 New platforms such as mRNA and viral vectors that have proven successful for Covid-19 vaccines could be leveraged to develop tuberculosis vaccines, and clinical trials must be accelerated.

Tuberculosis should be included in the pandemic preparedness and response agenda, which will probably be the focus of international government attention and increases in health spending moving forward. Investments in social protection and universal health coverage would mitigate the Covid-19 pandemic’s effects and help avert the next crisis. Progress toward the UN’s Sustainable Development Goals (SDGs) would be beneficial for tuberculosis and other poverty-related diseases. Conversely, failure to achieve the SDGs’ tuberculosis-mortality target by 2030 would result in substantial health and economic losses.5

We believe world leaders should commit to vaccinating people globally to help end the Covid-19 pandemic. They should also reaffirm their commitment to ending the tuberculosis epidemic, work harder to mitigate the effects of the pandemic, and address the social, environmental, and economic determinants of tuberculosis infection and mortality.

Multicomponent Strategy with Decentralized Molecular Testing for Tuberculosis

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Abstract

BACKGROUND

Effective strategies are needed to facilitate the prompt diagnosis and treatment of tuberculosis in countries with a high burden of the disease.

METHODS

We conducted a cluster-randomized trial in which Ugandan community health centers were assigned to a multicomponent diagnostic strategy (on-site molecular testing for tuberculosis, guided restructuring of clinic workflows, and monthly feedback of quality metrics) or routine care (on-site sputum-smear microscopy and referral-based molecular testing). The primary outcome was the number of adults treated for confirmed tuberculosis within 14 days after presenting to the health center for evaluation during the 16-month intervention period. Secondary outcomes included completion of tuberculosis testing, same-day diagnosis, and same-day treatment. Outcomes were also assessed on the basis of proportions.

RESULTS

A total of 20 health centers underwent randomization, with 10 assigned to each group. Of 10,644 eligible adults (median age, 40 years) whose data were evaluated, 60.1% were women and 43.8% had human immunodeficiency virus infection. The intervention strategy led to a greater number of patients being treated for confirmed tuberculosis within 14 days after presentation (342 patients across 10 intervention health centers vs. 220 across 10 control health centers; adjusted rate ratio, 1.56; 95% confidence interval [CI], 1.21 to 2.01). More patients at intervention centers than at control centers completed tuberculosis testing (adjusted rate ratio, 1.85; 95% CI, 1.21 to 2.82), received a same-day diagnosis (adjusted rate ratio, 1.89; 95% CI, 1.39 to 2.56), and received same-day treatment for confirmed tuberculosis (adjusted rate ratio, 2.38; 95% CI, 1.57 to 3.61). Among 706 patients with confirmed tuberculosis, a higher proportion in the intervention group than in the control group were treated on the same day (adjusted rate ratio, 2.29; 95% CI, 1.23 to 4.25) or within 14 days after presentation (adjusted rate ratio, 1.22; 95% CI, 1.06 to 1.40).

CONCLUSIONS

A multicomponent diagnostic strategy that included on-site molecular testing plus implementation supports to address barriers to delivery of high-quality tuberculosis evaluation services led to greater numbers of patients being tested, receiving a diagnosis, and being treated for confirmed tuberculosis.

Fast, Cheap Testing for Tuberculosis? Soon It May Be Possible

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Diagnosing a lung disease like tuberculosis with a urine test may seem illogical, but a group of American researchers is now a step closer to that goal.

Scientists at George Mason University have improved by at least 100 times the accuracy of testing for a sugar shed by tuberculosis bacteria, meaning that a simple dipstick urine test may soon become possible.

The researchers’ study was published last month in Science Translational Medicine.

Tuberculosis kills about 1.7 million people a year, according to the World Health Organization — more than are killed now by AIDS. While many people carry inactive bacteria, about 10 million fall ill annually and develop coughs that transmit the infection.

If they could be found and treated sooner, more would be cured and the spread would slow.

For decades, tuberculosis was diagnosed by chest X-rays, skin or blood tests, or by reading sputum samples under a microscope. But the W.H.O. has condemned skin and blood tests as inaccurate, X-rays detect only advanced damage, and microscopy requires trained pathologists.

Since 2010, detection has been revolutionized by GeneXpert machines, which take two hours to make the diagnosis. They not only find bacterial DNA in sputum but can tell if the strain is impervious to a common antibiotic, which suggests that the patient has multi-drug-resistant disease.

 

But the machines are expensive, even at discounts offered to poor countries, and it is hard for weak patients and children to hock up lung mucus. (Some clinics have sealed “cough rooms” where salt mist is blown deep into lungs to trigger coughing fits.) Urine is easier to obtain.

In tests on about 100 hospitalized Peruvians, half of whom were known to have tuberculosis, the new test proved about as accurate as GeneXpert machines, said Alessandra Luchini, a nanoparticle scientist at George Mason’s molecular biology center and co-author of the study. (The new test, however, does not measure drug resistance.)

The team hopes to adapt the new technique to clamp onto other tuberculosis-related molecules and come up “with a rapid test similar to a pregnancy test,” Dr. Luchini said.

Scientific Study of Surfer Butts Reveal Drug-Resistant Bacteria in the Oceans

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Surfers are known to brave bad weather, dangerously sized waves, and even sharks, for the perfect ride. But, it seems another danger of surfing has been lying in plain sight all along: ocean waters are full of drug-resistant bacteria — and surfers are most at risk.

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In a study published this weekend in the journal Environmental International, a team of researchers from the University of Exeter found that regular surfers and bodyboarders are four times as likely as normal beach-goers to harbor bacteria with high likelihoods of antibiotic resistance. This is because surfers typically swallow ten times more seawater during a surf session than sea swimmers.

The cheekily named Beach Bums study, carried out with the help of UK charity Surfers Against Sewage compared rectal swabs from 300 participants and found that 9 percent of the surfers and bodyboarders (13 of 143) harbored drug-resistant E. coli in their systems, compared to just 3 percent of non-surfers (four of 130).

World Health Organization Anti-Microbial Resistance
The World Health Organization is concerned about drug resistance.

The World Health Organization has warned that widespread drug resistance may render antibiotics useless in the face of otherwise easily treatable bacterial infections, meaning that just as in the age before Penicillin, diseases like tuberculosis, pneumonia, blood poisoning, gonorrhea, food– and water-born illnesses as well as routine medical procedures that can lead to infection, including joint replacements and chemotherapy, could once again be fatal.

 Indeed, a 2016 report commissioned by the British government estimated that, by 2050, infections stemming from antimicrobial resistance could kill one person every three seconds.

Solutions to an impending drug resistance epidemic have largely focused on prescriptions and use, but there is an increasing focus on the role of the environment in transmitting drug-resistant bacteria strains. The Beach Bums study adds important insight into how sewage, run-off, and pollution that makes its way into the oceans spread the drug-resistant bacteria.

“We are not seeking to discourage people from spending time in the sea,” says Dr. Will Gaze of the University of Exeter Medical School, who supervised the research. “We now hope that our results will help policy-makers, beach managers, and water companies to make evidence-based decisions to improve water quality even further for the benefit of public health.”

Though the study’s purpose is not to alarm beachgoers — or surfers — Dr. Anne Leonard, who led the research, tells Inverse that the risk for anti-drug resistance may actually be lower in the United Kingdom, which “has invested a great deal of money in improving water quality at beaches, and 98 percent of English beaches are compliant with the European Bathing Water Directive. The risk of exposure to and colonization by antibiotic resistant bacteria in seawater might be greater in other countries which have fewer resources to spend on treating wastewater to improve water quality.”

For surfers on this side of the pond, check out the free app available for Apple and iOS, Swim Guide, for updated water quality information on 7,000 beaches in Canada and the U.S.

WHO issues ethics guidance to protect rights of TB patients

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New tuberculosis (TB) ethics guidance, launched today by the World Health Organization (WHO), aims to help ensure that countries implementing the End TB Strategy adhere to sound ethical standards to protect the rights of all those affected.

TB, the world’s top infectious disease killer, claims 5 000 lives each day. The heaviest burden is carried by communities which already face socio-economic challenges: migrants, refugees, prisoners, ethnic minorities, miners and others working and living in risk-prone settings, and marginalized women, children and older people.

“TB strikes some of the world’s poorest people hardest,” said Dr Margaret Chan, WHO Director-General. “WHO is determined to overcome the stigma, discrimination, and other barriers that prevent so many of these people from obtaining the services they so badly need.”

Poverty, malnutrition, poor housing and sanitation, compounded by other risk factors such as HIV, tobacco, alcohol use and diabetes, can put people at heightened risk of TB and make it harder for them to access care. More than a third (4.3 million) of people with TB go undiagnosed or unreported, some receive no care at all and others access care of questionable quality.

The new WHO ethics guidance addresses contentious issues such as, the isolation of contagious patients, the rights of TB patients in prison, discriminatory policies against migrants affected by TB, among others. It emphasizes five key ethical obligations for governments, health workers, care providers, nongovernmental organizations, researchers and other stakeholders to:

  • provide patients with the social support they need to fulfil their responsibilities
  • refrain from isolating TB patients before exhausting all options to enable treatment adherence and only under very specific conditions
  • enable “key populations” to access same standard of care offered to other citizens
  • ensure all health workers operate in a safe environment
  • rapidly share evidence from research to inform national and global TB policy updates.

From guidance to action

Protecting human rights, ethics and equity are principles which underpin WHO’s End TB Strategy. But it is not easy to apply these principles on the ground. Patients, communities, health workers, policy makers and other stakeholders frequently face conflicts and ethical dilemmas. The current multidrug-resistant TB (MDR-TB) crisis and the health security threat it poses accentuate the situation even further.

“Only when evidence-based, effective interventions are informed by a sound ethical framework, and respect for human rights, will we be successful in reaching our ambitious goals of ending the TB epidemic and achieving universal health coverage. The SDG aspiration of leaving no one behind is centred on this,” said Dr Mario Raviglione, Director, WHO Global TB Programme.

“The guidance we have released today aims to identify the ethical predicaments faced in TB care delivery, and highlights key actions that can be taken to address them,” he added.

World TB Day is an opportunity to mobilize political and social commitment for further progress in efforts to end TB. This year, World TB Day signals new momentum at the highest levels with the announcement of the first ever Global Ministerial Conference on Ending TB, which will be held in Moscow in November 2017.

“The Global Ministerial Conference will highlight the need for an accelerated multisectoral response to TB in the context of the Sustainable Development Goals,” said Dr Ren Minghui, Assistant Director-General HIV/AIDS, Tuberculosis, Malaria and Neglected Tropical Diseases. “It will emphasize that global action against antimicrobial resistance must include optimized care, surveillance and research to address MDR-TB urgently”.

The Conference will inform the UN General Assembly high-level meeting on TB which will be held in 2018.

Source:WHO

Antibiotics resistance could kill 10 million a year by 2050

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A British government-commissioned review has found that resistance to antibiotics could account for 10 million deaths a year and hit global gross domestic product by 2.0 to 3.5 percent by 2050

A British government-commissioned review has found that resistance to antibiotics could account for 10 million deaths a year and hit global gross domestic product by 2.0 to 3.5 percent by 2050

London (AFP) – A British government-commissioned review has found that resistance to antibiotics could account for 10 million deaths a year and hit global gross domestic product by 2.0 to 3.5 percent by 2050.

The Review on Antimicrobial Resistance said surgeries that have become widespread and low-risk thanks to antibiotics, such as caesarean sections, could become more dangerous without urgent action.

The review announced by British Prime Minister David Cameron was led by Jim O’Neill, former chief economist at US investment bank Goldman Sachs, and included British senior public health experts.

It found the region with the highest number of deaths attributable to antimicrobial resistance would be Asia with 4.7 million, followed by Africa with 4.1 million, while there would be 390,000 in Europe and 317,000 in the United States.

For comparison, the review estimated that the second-biggest killer, cancer, would account for 8.2 million deaths a year by 2050.

“The damaging effects of antimicrobial resistance are already manifesting themselves across the world,” the report said.

“Antimicrobial-resistant infections currently claim at least 50,000 lives each year across Europe and the US alone,” it added.

The calculations were based on existing studies by the think tank Rand Europe and the consultancy KPMG.

It warned drug resistance was not “a distant and abstract risk” and called for “a major intervention to avert what threatens to be a devastating burden on the world’s healthcare systems”.

The review emphasised the economic advantage of investment in tackling the problem early.

It said that three types of bacteria — the Klebsiella pneumonia, Escherichia coli (E. coli) and Staphylococcus aureus — were already showing signs of resistance to medicine.

Treatment of HIV, malaria and tuberculosis were broader public health issues in which resistance “is a concern”, the report said.

In the United States, antibiotic-resistant infections are associated with 23,000 deaths and two million illnesses each year.

The economic costs annually are as high as $20 billion (16 billion euros) in excess direct health care costs and $35 billion (28 billion euros) in lost productivity.