TB Clinic in South Africa. The country was one of the sites for the recent trials of the new MDR-TB regime.  South Africa  has one of the highest burdens of TB and of drug resistant TB in the world, with around 20,000 people diagnosed in 2015.

A first-ever clinical trial of a new, all-oral, treatment regime for multidrug-resistant tuberculosis (MDR-TB)  has stopped enrolling patients after initial data provided positive results that the new treatment could potentially save thousands of lives, as well as improving peoples’ quality of life.

Findings of the TB-PRACTECAL, Phase II/III clinical trial sponsored by Médecins Sans Frontières (MSF), were originally due to be reported in late 2021 or early 2022. 

But an independent data safety and monitoring board found that one of the regimens being studied in the trial – bedaquiline, pretomanid, linezolid and moxifloxacin –  has already shown itself to be superior to current care, which typically also involves the use of drug injections, since MDR TB is available to standard oral treatment formulations.  More patient data would be extremely unlikely to change the trial’s outcome, the safety board determined.

Findings Could Transform Treatment Of MDR-TB

MSF, in announcing the findings on Wednesday (World TB Day), said that it believes the regime could dramatically change clinical care standards, saying it would soon share the trial data with the World Health Organization (WHO), with full results being submitted to a peer reviewed journal in the coming months. 

“This will be the first ever multi-country, randomised, controlled clinical trial to report on the safety and efficacy of a six-month, all oral regimen for drug-resistant TB,” said Professor David Moore from the London School of Hygiene and Tropical Medicine and a member of the Trial Steering Committee. “The findings could transform the way we treat patients with drug-resistant forms of TB worldwide, who have been neglected for too long.”

 

Treatment for MDR-TB is commonly administered for 2 years or longer and involves daily injections for six months, according to the TB Alliance. Many second-line drugs are toxic and have severe side effects. However, the complexity and prohibitive cost of MDR-TB treatment means that few of the world’s MDR-TB patients actually receive proper treatment.

Study Tested Six-Month Oral Combination Regime 

The multi-country, randomized controlled trial involved testing the six-month regimen of bedaquiline, pretomanid, linezolid and moxifloxacin, against the locally accepted standard of care. At the time of the interim analysis 242 patients had been enrolled in seven trial sites across Belarus, South Africa and Uzbekistan.

MSF said that since the first patient enrollment in the TB-PRACTECAL trial in 2017, new treatments for MDR-TB have become available. 

“But lengthy regimens that patients struggle to complete are still the reality in many of the countries in which MSF works. The WHO’s current guidelines recommend treatment lasting nine to 20 months for patients with MDR-TB,” MSF said in its statement.

About one-quarter of the world’s population has a TB infection, with an estimated 10 million infections and 1.4 million TB deaths in 2019. Worldwide, TB is one of the top 10 causes of death and the leading cause from a single infectious agent (above HIV/AIDS). MDR-TB remains a public health crisis and a health security risk. Of the 465 people who developed rifampicin-resistant TB in 2019, 182, 000 died.

The current standard treatment for MDR-TB is arduous, lasting between nine to 24 months, exposes patients to serious side effects, and is only successful in about half of all cases. 

552 Patients Participated In Three Stages Of The TB-PRACTECAL Trial

Altogether some 552 MDR TB patients participated in three stages of the TB-PRACTECAL trial – a  multi-arm, multistage, open label, RCT which enrolled patients into three investigational regimens, comparing various combination treatments against the current standard of care. 

“Our hope is that rigorous data from TB-PRACTECAL will be reviewed by the WHO urgently and allow for the recommendation of this six-month regimen, which should translate into countries incorporating it into national treatment programmes,” said Professor Nargiza Parpieva, Country Coordinating Principal Investigator in Uzbekistan. 

“This could not only ultimately save many thousands more lives, but also vastly improve quality of life for those undergoing treatment. Patients on the trial tell us they no longer need to put their life on hold just to get cured.”

 

Image Credits: msf.

A recent University of Stellenbosch doctoral study found that many South African children with tuberculosis didn’t receive the necessary treatment because of challenges with diagnosis and reporting.

A recent doctoral study at the Desmond Tutu Tuberculosis Centre at Stellenbosch University (SU), South Africa has shown that hospital-based intervention could help address the tuberculosis hospital reporting gap.

The university said there were many children with tuberculosis that didn’t receive the necessary treatment because of challenges with diagnosis and reporting.

“In South Africa, thousands of children with TB fall through the cracks because they are either undiagnosed or diagnosed but unreported,” said Dr Karen du Preez from the Desmond Tutu TB Centre.

The Star newspaper in South Africa reports that a recent doctoral graduate in Paediatrics and Child Health said that to ensure proper diagnosis and reporting, TB programmes needed good monitoring and evaluation tools as well as reliable TB surveillance data for children.

Image Credits: University of Cape Town Lung Institute.

The author as a volunteer processing sputum samples for TB testing. Molecular-based diagnostic tools, such as the GeneXpert platform, have superseded sputum smear microscopy in terms of accuracy and are now very cost-effective for low- and middle-income countries.

Tuberculosis care is quintessentially colonial, even in 2021. While many countries have been emancipated from their colonizers, the heritage of the colonial mindset, culture and even entire economies is deeply embedded within high burden TB countries in the post-colonial era.  

A disease of poverty, TB has historically been terribly neglected. Although the number one infectious killer, raising funds for TB continued to be a challenge, as the disease failed to rank high as a priority once TB cases and mortality started to decline in wealthy countries. Colonizers deployed controversial strategies such as relegating infected people to sanatoria.  More recently, the DOTS (directly observed therapy, short-course) strategy was touted for its purported cost-effectiveness  – as agents of previous colonizers continued to drive the TB disease control agenda in poor economies.

From the pre-colonial to the post-colonial era, we continue to struggle for equitable partnerships with funders and global policy makers to truly make an impact.  This results in an ongoing divide between the global north and global south, where the south struggles to find a seat at the table to raise local TB voices for global change.  

All aspects of TB work have colonial roots, including research, technical assistance, monitoring programs, policy making, and service delivery.  These are all undergirded by choices, made by individuals not infrequently brandishing the agenda of the donors, rather than considering what is best for the recipients.  These choices manifest themselves in whom to fund, which groups to support, and which programs to criticize.  As we mark World TB Day, the objective of this piece is to reflect on and unravel some key areas through the lens of a TB implementer from a low-income setting. 

Disclosures: I am a physician, working in global public health representing the global south. I work in TB, interested mainly in multidrug-resistant forms of TB. I have survived ocular TB and it pains me that we continue to struggle to make progress in TB care.

National TB Strategies: A Question of Ownership

Reviewing TB case files in Afghanistan

No doubt, without external TB funding (through funders such as the Global Fund to Fight AIDS, Tuberculosis and Malaria), low-and-middle-income-countries (LMICs) would not have gotten as far as they have in TB prevention and control. However, for interventions and projects to succeed and demonstrate sustained value, the relationship between donors and implementers needs to be far more equitable.

For example, country strategic plans are still firmly guided by external stakeholders, funders and global TB policy makers; in most cases by the same groups which provide financing. In some LMICs, the national strategic plans are written by ‘external consultants.’  Both these options limit and deter local input, context and ownership. The lack of trust in local capacity smacks of a particular kind of professional arrogance that erodes the foundation of what should be a successful north-south partnership.  

I have had the benefit of sitting at both sides of the table. I have seen up close the harsh reality that leaves key implementers from low-income settings being excluded from participating in developing national strategic plans. To be fair, ensuring a higher level of inclusion is not the donor’s responsibility alone. Country level stakeholders – the government and influential local partners – need to ensure their people are represented at the table. Unfortunately, decades of dependence on external funding, fragmented local governance structures, and political agendas, relegate participatory engagement to a distant priority. Thus, a system that supports the objectives of a few perpetuates a bilateral colonial mindset.

TB Technical Assistance: Fostering & Relying Upon Local Expertise 

Joint external TB monitoring mission in Indonesia

We in the global south continue to self-sabotage local voices by not leveraging home-grown resources – thus  undermining our ability to build local capacity and sustain growth. 

For example, countries discriminate against their own experts (whom they could use at minimal to no cost). Instead, they are willing to pay exorbitant costs for technical assistance to TB experts/consultants from low TB burden, high income settings.

As a personal example, I have provided TB technical assistance to countries in Asia and Africa. In that same context, I also have tried to engage with the government of my own country of birth (Pakistan) to support and assist them at different times through the last decade. I assume it is my gender and my ‘brown’ Pakistani heritage that does not make me, and others like me, able enough advisors in comparison to the privileged, white males from the west (and expensive professionals at that). 

When these technical experts from the global north arrive in poor high burden TB countries to advise on all aspects of our programmes- how to diagnose patients, what clinical protocols to use, how to design regimens- the relationship is too often that of a master and underling, rather than that of professional colleagues.

I have had the unfortunate personal experiences of listening to an ‘expert’ criticize my clinical colleagues at local NGOs in Asia, in areas we knew far more than them.  In one case, a foreign expert’s opinion on the TB program was to insist that this high-TB burden country use smear microscopy (an insensitive test) as a primary diagnostic test, when we have better and more sensitive, rapid diagnostic technology (GeneXpert) available. His lack of understanding about the relatively low cost of contemporary methods when applied nationally would lead to an outmoded and possibly dangerous recommendation.

One would need several chapters, if not a book, to compile such examples and challenges implementers have to face.  It is obvious that consultants from high-income countries do not make the same suggestions in their own high-resource settings.  Far from challenging this behaviour, however, we generally accept it.  I am outraged at the way my own colleagues in the south listen to this bullying behaviour without objection- even welcoming these pearls of foreign wisdom while paying for the pleasure of receiving them.  And, I am beyond concerned at the global health actors responsible for employing and perpetuating this kind of behaviour.

TB Research: A Mixed Bag With No Vaccine Yet In Sight

Field visit at a TB clinic Karachi, Pakistan

Over the last year, $US 5 billion has been spent to develop COVID-19 vaccines. Although heartening to see manufacturers, international funders, academics and researchers collaborating to fight a pandemic, it is frightening to realize that we have never prioritized a new TB vaccine, ostensibly due to limited funding. In fact, there is just one- the BCG vaccine– now a century old. This is a reflection of how the world functions.  As we look back at innovations in diagnostics and treatment, conditions never truly received attention until (and if) they hit the west.  HIV and COVID-19 are just two of the examples.

Unfortunately, TB is a disease of the poor, so if one need funds for research, monies are not easy to locate.  Compounding this overall scarcity, academics and researchers from the global north generally have easier access to whatever research funding is available.

Even so, in the research arena, at least, disease colonialism is less on display.  I recognize the TB researchers based in the global north who have helped their colleagues in the south by leveraging their position for good: providing visibility to their colleagues and collaboratively generating evidence to inform policy.  I have known some wonderful academics in the north who collaborate with local implementers, supporting them and valuing their contribution towards research. There may be still a lot of work to bring about a fully equitable relationship in TB research, but we at least have a model upon which we can build. 

However, while there is improved collaboration at the level of the individual researchers – and even between individual academic institutions – the donor organisations’ mindset has undermined, at times, this fundamentally sound model. The big organizations have pushed TB research towards priorities that appear to be innovative but are in fact shortsighted.  The desires of funders to obtain quick results has led to misplaced priorities – such as focusing on models for scale-up of new TB diagnostics, which may leave other areas of research into TB treatment (and more importantly MDR-TB treatment) negligently under-funded.

Even here, donors use colonial-style tactics that create divisions between collaborators. These may include micromanagement, threats to pull out funding, and as discussed elsewhere, use of a monitoring and evaluation methodology under which longer-term, locally-owned programs are doomed to fail.

For example, I have observed individuals from international donor organisations deciding the fate of grants by performing TB research audits without appropriate technical or research qualifications. As another example, when a longer-term investment is necessary to see results, donors  will sometimes utilise these audits to justify ‘cutting their losses’, because they cannot openly object to the value of the research.

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The above are a few personal experiences and while they highlight my own frustration with TB care, I hope that they will continue an important discussion. I wish to motivate people to ask for more transparency, raise their collective voices, and advocate on behalf of the global south. And, not just humbly request a seat at the table but demand restructuring of a system that benefits a few.  A sustainable, mutually respectful and equitable path forward dictates a new way of doing business.

Paul Farmer said it well: “The idea that some lives matter less is the root of all that is wrong in this world.”  

Dr Uzma Khan

Uzma Khan is a physician and public health professional working in TB control in LMICs. A native of Pakistan and currently residing in Canada, Khan has extensive experience in overseeing, implementing and conducting MDR-TB research, and has provided technical assistance to TB programs in Asia and Africa. She holds a medical degree as well as a Masters in Epidemiology from the Harvard School of Public Health. Her interests are health equity, advocacy and policy especially in the time of COVID-19. She tweets @imuzk

 

Image Credits: Uzma Khan.

The Wellcome trust is pledging up to US $100 million (£70m/€80m) to accelerate Covid-19 research and development to ensure science keeps pace with the virus.

The funding will help advance treatments and vaccines and SARS-CoV-2 tracking research in low and middle income countries.

Announcing the funding on Wednesday, the trust said the rise and spread of COVID-19 meant new vaccines and treatments were needed along with better global systems to identify and track changes in the virus.

Jeremy Farrar, Director of Wellcome, announced massive funding on Wednesday to accelerate Covid-19 research and development.

Jeremy Farrar, Director of Wellcome, said: “More funding is vital to develop the range of treatments and vaccines the world needs – and to make sure these, and those we already have, are fairly and equally available in all countries. The job for science is a long way from done – either to exit this crisis or ensure the world can keep Covid-19 in check long-term”.

The trust said international funding was not keeping pace with global research needs. The ACT-Accelerator faces a $22.1billion global funding gap. 

Divya Shah, Wellcome’s Epidemics Research Lead, said: “Virus mutations threaten the effectiveness of the Covid-19 tools we have worked so hard to develop. We need to build capacity for genomic sequencing globally to identify new variants and map their spread to inform public health measures and further research”.

The US $100 milion package follows $80m (£60m/€70m) Wellcome pledged in 2020 for treatments, research and capacity building in low- and middle-income countries. The US $80 million included up to $50m in seed funding for the Covid-19 Therapeutics Accelerator.

 

Image Credits: Wellcome Trust.

Manual screening of patients will be accelerated with the use of new AI which makes the screening process more efficient – significantly reducing the time taken to make a diagnosis.

NEW DELHI – Reversing decades of negative messages, the World Health Organisation is once again endorsing the use of X-rays as a TB screening tool  in lower-income countries – this time in conjunction with the use of new artificial intelligence programmes that can read digital x-rays and identify suspected TB cases more accurately. 

For community-level screening of TB, the WHO has ranked the tools that could be used. The guideline says that if resources are available, the state should first use chest X-rays at the community level since an abnormal chest X-ray is very likely to be a TB-positive case. However, patients with abnormal chest X-rays have to undergo rapid molecular diagnostics to confirm TB. The other tools that can be used are deploying rapid molecular tests at community level, or screening of symptoms.  

The WHO guidelines also give a huge boost to computer-aided AI detection software and said that it can better interpret the digital X-rays, and triage suspected cases, more accurately than human X-ray readers. 

The new AI makes the screening process more efficient, and significantly reduces the time taken to make a diagnosis. The WHO has said that they would release a more detailed guideline this month, coinciding with World TB day, on Wednesday (March 24).

The move has been welcomed by TB experts as a tried-and-true means of screening – which was effectively used by countries for over a century, but falling by the wayside in recent decades. 

“This is huge,” said Salmaan Keshavjee Director, Harvard Medical School Center for Global Health Delivery. “It can find more people with potential disease. It was the approach that was used in Western countries since the early 20th century, so it’s more than 100 years old.”

In December last year, the WHO released the Rapid Communication on Systematic Screening for Tuberculosis recommended for community-wide screening, and particularly for HIV-positive people, pediatric contacts of TB patients, among others. The WHO released a consolidated guideline on systematic screening of TB recently which includes the use of chest X-ray and artificial intelligence. 

“This Rapid Communication is being issued to help national TB programmes and other stakeholders prepare for the changes that will be introduced with the new guidelines on TB screening.” the WHO said in its statement.

10 Million People Annually Diagnosed with TB – Mostly In Asia & Africa 

Globally, an estimated 10 million people fell ill with TB in 2019. Eight countries accounted for two-thirds of the global total including India, Indonesia, China, Philippines, Pakistan, Nigeria, Bangladesh and South Africa. India has the highest TB burden among these nations and accounts for 26% of the global total number of TB cases.

Many lower-income countries, including India still use smear microscopy as the first line of testing for most of the population. Smear microscopy involves simply looking for the bacteria through the microscope, a method which misses about half of TB-positive patients. The more sensitive diagnostic test- that is the Cartridge-based Nucleic Acid Amplification test or CB-NAAT — is mostly used for those who are sputum-positive to detect resistance to one TB drug- rifampicin. 

“We miss too many people with TB, and a relatively simple test like X-ray might help us find more people with TB. And AI-based software like Computer-aided detection software could help us do that, even when trained radiologists are not there for example in the rural or remote areas,” said Madhukar Pai from McGill University in Montreal, Canada.

Messaging On X-Ray Went Off The Tracks  

When TB programmes evolved, X-rays were a mainstay of diagnosis. Historically, miniature radiography for mass TB screening activities was widely used in high-income countries throughout the 20th century. 

In the early 90s, the WHO declared TB a global emergency. It advocated TB programmes to follow Directly Observed Treatment Short-course or DOTS. DOTS categorically recommended a limited use of X-ray, mostly as a supplemental diagnosis if sputum microscopy failed. 

This meant that patients who were not sputum-positive had to wait for chest X-rays to be ordered but continued to have TB symptoms, depending on who was treating them. 

“But the messaging was off the track. The idea was to say X-ray could be a diagnostic tool, but not a confirmatory tool. But somewhere along the line, doing X-ray was a sin, and only bad doctors use X-ray,” said Shibu Vijayan, Global TB Technical Director at PATH. The organisation engages the private sector in diagnosing and treating tuberculosis. 

The guidelines reflected a differential treatment for those in the lower and middle income countries and higher income countries, say some global health experts like Keshavjee. 

“DOTS did not recommend it  (use of X-ray) because they saw it as being too expensive.  It’s always been known that it is more effective. So they are correct to come back to it finally,” he said.

It was during the TB prevalence studies in countries such as Vietnam, Kenya and Zambia that found chest X-rays were detecting more patients, as compared to sputum microscopy.

 “It was found that around 40% of those surveyed with X-ray shadows and were positive for TB did not have any symptoms at all. That’s how experts asked for X-ray to be brought back,” said Vijayan. 

The focus is now, however, on using X-ray as a screening tool, and not a diagnostic tool, per se.

“We now know that X-rays are good for triage or screening, to find out who needs further confirmatory testing. So, someone with TB symptoms could get an X-ray, and if that is abnormal, then CBNAAT could be done. So, the current focus is really on screening, not diagnosis. For diagnosis, WHO still endorses rapid molecular tests,” said Pai.

Lower Cost Digital X-Rays & AI Been Game Changers

WHO has once again endorsed the use of X-rays as a TB screening tool  in lower-income countries.

The game changer has been the relatively low cost of digital X-rays and artificial intelligence programmes that enhance the efficiency of the screening process.

Friends for International TB Relief (FIT) in Vietnam has been conducting chest X-rays screenings across the country, even in remote parts. It works with multiple global agencies focusing on implementing TB and HIV programmes in Vietnam. 

“I think my organisation in Vietnam has shown that chest X-ray screenings can be done anywhere,” said Andrew Codlin from FIT. 

“The new portable X-ray machines are the size of digital cameras, something that you can put in the backpack and walk up the hill.  We have done screening campaigns in a remote island, in mountainous areas. We also had a screening camp during a cyclone with water running through the streets,” he said.

“If there is commitment, and the right buy-in from the political establishment, it is not difficult to scale up screening campaigns,” Codlin said.

Qure.ai  is a computer-aided technology that can detect abnormalities in the chest X-ray and is used in 20 countries. It is particularly useful in mass screening camps.

“Our product -qXR processes the X-rays that are recorded in a cloud. The health worker can see the report within a minute of taking the X-ray in an app,” said Prashant Warrier, founder of Qure.ai. In case of an abnormal X-ray, the patient’s sputum sample can then be sent for rapid molecular diagnostics.

In Nagpur, a city in West India, PATH helped run a pilot programme with a local nonprofit, Disha Foundation using chest X-ray with a computer-aided detection software called Qurei in the private sector. 

In India, more than half of the TB patients are treated in the private sector. Presumptive TB patients were provided a free X-ray under this pilot. If the patient had an abnormal X-ray, the sputum samples would be sent for rapid molecular testing in a medical college there. 

“When patients do not feel better, they switch doctors. The quick turnaround of the AI technology helps retain patients in the programme and ensure they take treatment,” said Lucky Richardson Masih, operations manager, Disha Foundation in Nagpur. 

The organisation works with local private doctors in Nagpur’s slums in providing the patients with approved diagnostic facilities and treatment. They tied up with PATH for this project in 2019.

The use of radiological screening and AI resulted in a 13% additional TB cases being detected, said Vaishnavi Jondhale, Operations Manager, Path Mumbai.

Warrier claimed that the product can find more cases, and is far more sensitive than a radiologist reading X-ray reports. The cost works out cheaper as well.

Codlin explained how AI is more sensitive. 

 “If a human reader reports 100 abnormal chest X-rays, perhaps 10 would be positive for TB.  If we use qXR it will report 50 abnormal chest X-rays for 10 TB positive cases will be found. We are effectively using fewer CBNAAT tests and resources that way,” he said.

 

 

 

 

Image Credits: Andrew Codlin.

Dag-Inge Ulstein, Norway’s Minister of International Development.

In a decisive act of global solidarity, Norway has offered almost a third of its allocation of COVAX vaccines to poorer countries, according to Dag-Inge Ulstein, Norway’s Minister of International Development.

Norway has only fully vaccinated about 5% of its population – 260,000 people – and unlike many other European countries, it has not stockpiled vaccines and is mainly depending on COVAX for vaccines.

However, it decided to allow COVAX to redistribute 700,000 out of its 1.9 million vaccine doses to lower-income countries despite domestic pressure not to, Ulstein told the Access to COVID-19 Tools (ACT) Accelerator facilitation council meeting on Tuesday.

“People are asking: ‘Why give vaccines away when we need them here?’ And this is a good question, representing an obvious dilemma. But the answer is equally simple: the virus crosses borders. This is not a local outbreak. And this combination of solidarity and self-interest gives me no choice but to stand firmly in the face of domestic criticism,” said Ulstein. 

‘Colossal Task Force’ on Vaccine Manufacturing

He also expressed Norway’s support for a “colossal task force on expanding vaccine production” co-led by the World Health Organization (WHO) and the Coalition on Epidemic Preparedness Innovation (CEPI) to “do better” and expand beyond COVAX’s initial target of vaccinating 20% of the global population by the end of the year.

Earlier, CEPI CEO Richard Hatchett had announced that his organisation was setting up a task force to address vaccine manufacturing and invited all interesting parties to join.

Highlighting global achievements, Hatchett reported that, in little over a year, “we have nine manufacturers that are scaling up rapidly across three technology platforms: inactivated vaccines. viral vector vaccines and mRNA vaccines.”

Between them, the manufacturers had administered 400 million vaccine doses – but only 30-million of these doses had gone to COVAX.

“The nine manufacturers envision manufacturing between 10 and 14 billion doses of vaccine in the coming year,” he added. “Those are very aspirational numbers, and they may be very difficult to achieve. But that is based on the capacity they already have. So I would argue that the immediate problem is supply chains: making sure that the critical inputs of material are provided.”

Soumya Swaminathan, WHO’s Chief Scientist

But Soumya Swaminathan, WHO’s Chief Scientist, said that many countries were still waiting for the first dose of vaccines to arrive “and it’s clear that there has been a mismatch between what manufacturers thought they would be able to produce and what they’ve actually been able to produce”. 

While there was an urgent need to address immediate bottlenecks, Swaminathan urged the global community to take a medium- to long-term approach to solving these problems.

“We need to think about the future and the possibility that we may need booster vaccines,” she said. “We may need vaccines regularly in order to deal with the emerging issue of the variants. We’re not sure about that as yet. But we need to prepare for repeated technologies and it is critical to increase the ability of all regions in the world to respond without being dependent on restricted global supply chains.” 

‘Global Hypocrisy’

Fifa Rahman, the NGO representative on the ACT Accelerator, said that low and middle income countries (LMICs) may only vaccinate 80% of their populations by 2024. 

However, the leaked text of a WHO draft resolution to strengthen local production of health technologies showed that some wealthy countries had deleted text that would enable technology transfer, said Rahman.

Fifa Rahman, NGO representative at the ACT Accelerator

“To sit here and talk about global solidarity and then to ask for the deletion of text and important provisions that would help LMICs get access to more vaccines is hypocrisy,” said Rahman. “We thus call upon the United States, Norway, the UK and Switzerland to withdraw their objections to the text.”

Rahman also criticised an over-reliance on industry to address the pandemic. Although the pharmaceutical industry claimed that it had the capacity to produce 14 billion doses by end of 2021, “according to an Airfinity document, industry developed delivered 96% fewer doses in 2020 than it had promised”, she said.

“Why are we blindly trusting that 2021 will be any different? We can’t take industries’ claims at face value. There’s too much at stake to rely on these aspirational projections as our route out of the biggest public health crisis of our generation,” said Rahman.

Instead, she proposed a mapping exercise on manufacturing capacity and expertise available in the global south to ensure viable vaccine manufacturing for entire continents.

Prioritise the Dose-Sharing

John Nkengasong, Director of Africa’s Centers for Disease Control (CDC), made two simple pleas: for any countries with excess doses of vaccines to “release them” to countries that do not have, and to “strengthen regional capabilities to manufacture vaccines across the world as part of our collective security”. 

Wellcome Trust Director Jeremy Farrar urged the ACT Accelerator not to “pretend that everything is going in the right direction”, but to develop a coordinated response to health system, regulatory and human resource challenges.

“We have to also push on with support for the diagnostics – critically, increasingly importantly – of the genomic surveillance globally, for the new variants of concern as they will continue to arise,” said Farrar.

Summarising various country and partner inputs, Ayoade Olatunbosun-Alakija, a member of the Africa Union Africa Vaccine Delivery Alliance, said that “we cannot have equitable outcomes without an equitable process”.

Olatunbosun-Alakija said countries had spoken about “prioritising the dose-sharing of existing vaccines” which meant that a “three-way conversation is required between countries, industry and COVAX to explore the potential sharing modalities”.

“There’s strong support for a task force to explore these options on the table and enforce the options where necessary,” she added.

 

Image Credits: ABC7 News.

Anthony Fauci, director of the US National Institute for Allergies and Infectious Diseases.

British-Swedish pharma company AstraZeneca may have included outdated information from their COVID-19 vaccine trial, the US National Institute of Allergy and Infectious Diseases (NIAID) said in a statement released Tuesday. 

The NIAID, part of the National Institutes of Health, urged AstraZeneca to work with the US  Data Safety and Monitoring Board (DSMB) to review the efficacy data to ensure up-to-date efficacy data can be made public as quickly as possible. 

The AstraZeneca US Phase III trial results published on Monday showed a 79% vaccine efficacy of preventing symptomatic COVID-19, and 100% efficacy at preventing severe disease and hospitalization. 

However, US health officials felt that the information was “outdated” and may have provided an incomplete view of the efficacy data. 

NIAID Director Anthony Fauci also discussed the issue during an appearance Tuesday morning on Good Morning America. 

“Because the fact is, this is likely a very good vaccine,” said Fauci. “It [just] wasn’t completely accurate.” 

Unforced Error

Fauci calls AstraZeneca’s “unforced error” something that will cause some people to doubt the vaccines and contribute to the ongoing vaccine hesitancy. 

“We essentially have to keep trying as hard as we can to get people to understand that there are safeguards in place,” he added, calling the DSMB’s ability to pick up on the discrepancy one example of a safeguard. 

While Fauci oversees the DSMB that assessed the trial results for AstraZeneca and other vaccine makers, he is not directly involved in its assessments. The final decision will be made by the US Food and Drug Administration (FDA), which will conduct their own review following the independent advisory committees. AstraZeneca plans to file with the FDA by mid-April, though their timeline relies on the DSMB clearing its trial results.  

AstraZeneca responded to the NIAID’s claims, saying in a statement that the numbers published on Monday were consistent and said it will “immediately engage with the DSMB to share our primary analysis with the most up to date efficacy data.” The company intends to issue results of the analysis within the next 48 hours.  

‘Stunned’ Health Experts Question AstraZeneca’s Credibility 

The national institute’s statement stunned experts, leaving them to question the pharma company’s credibility.  Dr Eric Topol, a clinical trials expert at Scripps Research in San Diego, called AstraZeneca’s response to the DSMB’s statement “unacceptable”. 

“They know exactly what is going on with respect to the time cutoff for primary analysis, which appears to be at odds with the independent Data and Safety Monitoring Board. It should not take 48 hours to sort out,” Topol tweeted on Tuesday.  

“Let’s see all the data, AstraZeneca,” Topol added, calling out the company. “Let’s be clear. This is not about the vaccine. It is about AstraZeneca, their own worst enemy, with an apparent breach on data dissemination. And where is the University of Oxford on this, their partner?” 

Topol had called the DSMB’s statement, which is supported by the National Institutes of Health, to be “unprecedented” in the history of large scale clinical trials. 

“I am rarely speechless. This turn of events has rendered me speechless. What a debacle,” said Helen Branswell, senior writer at Stat News.  

Branswell quoted the Washington Post, which said that the “AstraZeneca results were the equivalent of “telling your mother you got an A in a course, when you got an A in the first quiz but a C in the overall course.” 

Branswell added that, after this “extraordinary public rebuke of AstraZeneca by the DSMB”, the company team will “face tough, tough questioning.” 

Laurie Garrett, a former senior fellow at the Council on Foreign Relations, tweeted that the Board should “fire the entire AstraZeneca management team. “[The team] has made so many major blunders in launching the company’s COVID-19 vaccine that it will be a textbook study for decades in business schools and Communication departments.” 

The renewed skepticism for the pharma company in the US may counter the European Medicines Agency’s statement last week, which declared that the vaccine was safe, in spite of rare blood clotting events seen in Europe. 

 

Image Credits: Flickr, National Institutes of Health.

Escalating violence in Aleppo, northwest Syria, has claimed innocent lives and further devastated homes and one critical health facility.

Syria needs $US 78-million to vaccinate 20% of its population against COVID-19 by the end of this year, and its pandemic response is being challenged by a worsening humanitarian crises in the country, including continued attacks on health care facilities.

This is according to Akjemal Magtymova, the World Health Organisation (WHO) Representative in Syria, who told a media briefing on Tuesday that the country had only received half of the funding it had requested for this year and that additional assistance was needed to combat the virus and save lives.  

The briefing comes two days after the Al-Atareb Hospital in the Aleppo area was hit by artillery shelling from Syrian government forces, killing six people and injuring 17, including patients and medical personnel. 

The underground hospital, in an area controlled by forces opposed to the Syrian regime, sustained structural damages, resulting in the evacuation of all patients and staff, and the suspension of health services.  Hospitals and clinics in opposition-held areas have been repeatedly targeted, and destroyed in attacks by government forces – backed by Russia and Iran, according to a recent report by the International Rescue Committee. The attacks have continued despite a Russian-Turkish ceasefire covering rebel-held areas of northwest Syria, in effect since March 2020. Only 58 percent of hospitals remain fully functional, according to UN data.

“Thousands of people who depend on this hospital for basic and lifesaving health care are now deprived of this basic human right. Our thoughts and prayers are with the families of the victims,” said Ahmed Al-Mandhari, WHO Regional Director for the Eastern Mediterranean Region. 

Magtymova said funding is needed for creating mobile clinics, services, training, administration of vaccines, surveillance and dealing with side effects in the country whose health system and financial resources have been severely strained by war.

The country is expected to get its first delivery of AstraZeneca vaccines from COVAX within the next two to three weeks, allowing it to kick off a national COVID-19 vaccination programme starting with healthcare and frontline workers. Its immediate need is $7-million to vaccinate 2% of the population before the end of June.

Magtymova said WHO was working with dozens of different international and regional partners to address some of the country’s challenges, including funding, security issues and the fight against COVID-19. 

“We have worked hand in hand with our partners for coordinated efforts for COVID-19 preparedness and response against enhancing laboratory surveillance capacity, infection prevention and control points of the case management,” said Magtymova. “Most importantly is to maintain essential health services…and health care professionals are severely depleted.”  According to the IRC report, following a mass exodus of medical personnel, there remains just one Syrian doctor for every 10 000 civilians. 

COVID Adds To Multiple Healthcare Challenges in a Complex Environment

Describing the situation as “one of the most complex environments”, Magtymova said some of the challenges included “expanding public trust measures and achieving behaviour change, protecting health workers, security and access in ensuring continued use of essential health services, as well as establishing reliable supply chains”.

Some of the challenges at health care facilities include patients being treated in overcrowded rooms with no masks or social distancing and patients with abdominal wounds due to artillery strikes being treated in the same rooms as mothers with children. Some patients had to take detours of about six hours to get medical help due to hostilities and violence in their areas.

Magtymova added that while the pandemic was WHO’s priority, non-communicable diseases remain one of the major causes of mortality and morbidity with COVID-19 making people even more vulnerable. 

“Access to essential medicines have been severely compromised due to economic constraints. WHO sustains provision of life saving medicines to patients with diabetes, kidney diseases and failure, cancer, alongside with COVID-19 patients,” she said.

Giving an update on the situation in the northwest part of Syria, held by opposition forces, Mahmoud Daher, head of the WHO’s Gaza sub-office, said increased attacks on healthcare facilities were impeding the provision of critical health services.

“In Syria in general, and in northwest Syria, we have witnessed the attack on a hospital that was providing 5700 outpatient consultations, 375 hospital admissions and 160 major surgeries per month,” said Daher.

“This situation continues, and shows the fragility of that system that is prevailing in the northwest Syria. We are working with the international community and with the UN system in order to continue to provide health care services to the entire population. We are working under the United Nations Security Council Resolution to ensure that humanitarian assistance can continue despite the current volatile situation,” said Daher.

Syria’s COVID-19 real COVID-19 Numbers Are Much Higher than Official Data

On 26 March 2020, children in the town of Binnish, Syria, watch a member of the Syrian Civil Defence disinfect a former school building, now inhabited by displaced families, as part of measures to prevent the spread of COVID-19.

Syria has nine dedicated COVID-19 hospitals, 70 community care treatment centres for moderate to mild cases of the virus. Three laboratories have been established to detect and confirm COVID-19 cases. The country has registered 21, 260 COVID-19 cases, with 411 deaths.

Daher believes that investment from the international community, led by WHO, has contributed to the low numbers. He however warned that: “The situation is in need of all our efforts in order to contribute to humanitarian assistance, including radical services”.

As of 19 March, Syria had 21,000 COVID-19 cases reported in northwest Syria, more than 9,000 in the northeast and more than 17,000 in government-controlled Syria – the highest case fatality ratio is under government control territory. 

However, Magtymova believes that the numbers are not a true reflection of the COVID-19 situation, partly due to the country’s testing and record-keeping capabilities.

I do believe that the real numbers are much, much higher. The virus is not behaving differently in Syria. In fact, we are not aware of what kind of variants of the virus we are dealing with, because of the level of the capacities, but as WHO we have sent samples for sequencing to understand,” said Magtymova, adding that they were seeing a 100% bed occupancy level.

“Our epidemiological curve shows an increase in the new cases…which means that we are working in a very steep curve. And I have no reason to believe that, you know the situation of recorded cases is real. I’ve seen much more people with COVID-19, said Magtymova.

Magtymova concluded that the current infection patterns emerging in Syria and the looming third wave of the pandemic necessitates a more vigorous and urgent response.

 

Image Credits: Unicef.

WHO Director General Dr Tedros Adhanom Ghebreyesus

For the fifth week in a row, global COVID-19 cases have increased, with substantial increases in South-East Asia (49%) and the Western Pacific (29%), according to the World Health Organization (WHO).

India is driving up numbers in South-East Asia, while the Philippines and Papua New Guinea are responsible for the Western Pacific increases, according to Maria Van Kerkhove, WHO’s technical lead on COVID-19 speaking at the global body’s bi-weekly pandemic briefing.

Europe’s 12% increase was largely being driven by the spread of the B.117 variant “that was first identified in the UK, that is now starting to circulate in many countries in the eastern part of Europe,” said Van Kerkhove.

“The Americas and Africa have seen a slight decline in the last seven days, but overall, we’re seeing increasing cases and these are worrying trends in Europe and across a number of countries,” she added.

Brazilian Deaths Have Doubled in a Month

Despite a decline in the Americas, COVID-19 cases in Brazil have exploded with around 70,000 new cases a day and 2,000 deaths.

Describing Brazil’s cases as “accelerating really, really fast”, WHO Director General Dr Tedros Adhanom Ghebreyesus said that the global body was “especially worried about the death rate, which doubled in just one month from 7,000 to 15,000 a week”. 

However, Tedros was non-committal about giving Brazil’s new health minister – the fourth since the pandemic started – much advice other than that only “concerted effort of all actors that will reverse this upward trend”.

Van Kerhove reported that the ICU capacity has been running at over 80% in 25 of Brazil’s 27 federal units in the past week, and said that the P.1 variant prevalent in the country had increased the transmissibility of the virus.

“The country is under a heavy burden, but as you have heard us say many times before, Brazil has a lot of experience of dealing with not only COVID-19 but many infectious diseases,” she said.

WHO’s country staff are “working with the different federal levels in the state levels to support the country and to make sure that those who are needing care received the oxygen that they need”, and “vaccination is well underway”, added Van Kerkhove. 

Driving the increases

Van Kerkhove attributed the global increase to four main factors: pressure for countries to open up, difficulties in people and communities complying with “proven control measures”, uneven distribution of vaccines and the spread of variants, particularly B.117, B.1351 and P.1.

“If you have a combination of factors: of virus variants that transmit more easily, individuals who are fatigued and frustrated because we want this to be over, and are perhaps not being supported in carrying out the individual behavioral measures … to reduce our contact with others, and vaccination that is not yet reaching those who are most at risk – that is a very dangerous combination,” said Van Kerkhove.

Suppliers Can’t Keep Up With COVAX Orders

WHO special adviser and COVAX representative, Dr Bruce Aylward, said that “the facility can deliver that over 300 million doses” and “we’ve seen in the last couple of weeks some incredible work by t

“The procurement coordinators that are part of COVAX and UNICEF have been able to very rapidly put in place the purchase orders and very rapidly put the shipping pieces in place as well. 

“The problem that we have, quite frankly, is we simply cannot get enough vaccine to be able to keep up and the manufacturers are unable to keep up with our orders. We have two main suppliers to COVAX in this period, the Serum Institute of India, which got off to a great start but has had trouble now with its deliveries in March and April. And then AstraZeneca itself, the facility in Korea has also gotten off to a good start, but is having challenges keeping up with the rate of orders.,” said Aylward.

“We are hoping that both companies will be able to scale up and keep up with the rate of deliveries that we’re aiming for. But we’re still having some teething problems on the part of the suppliers that are trying to keep up with the demands that we’re making.”

Globally, 785 million people lack a basic drinking-water service and over half of the world’s population could be water-stressed by 2025.

COVID has highlighted deep-seated weaknesses in urban water and sanitation systems that are vital to health – but the pandemic has also underlined how improvements can hit back at the SARS-CoV2 virus – as well as reducing other traditional waterborne diseases. 

That was a key message at a seminar Monday on “Water and Sanitation in the City” – sponsored by the Geneva Cities Hub, UN Habitat, and Geneva Water Hub, on the occasion of World Water Day. It was the first in a series of ‘Geneva Urban Debates.’ 

“COVID in some ways has given us a huge opportunity in the water sector, because it has acted as an x-ray,” said Graham Alabaster, Chief of the Geneva Office of UN Habitat. 

He pointed to evidence that showed in cities where hygiene standards were improved so as to combat the spread of the SARS-CoV2 virus, the incidence of waterborne diseases has dropped significantly. “So we know that the ideas around hygiene and providing people with water and sanitation work,” Alabaster added.

On the right, Graham Alabaster, Chief of the Geneva Office of UN Habitat, and on the left, Kamelia Kemileva, Executive Manager of Geneva Cities Hub.

Water also is a a critical “engine for economic growth” and a precondition for development, said Sami Kanaan, Mayor of Geneva and the President of the Geneva Cities Hub. It is an issue that converges with health, poverty, climate change, education, and livelihoods. 

“Increasing access to safe drinking water and basic sanitation is a crucial step in eradicating growing poverty and reducing inequality in cities,” said Kanaan. 

The importance of accessing water and sanitation has been highlighted by the COVID pandemic, whereby one of the key infection prevention measures promoted from the beginning by WHO was effective handwashing and other good hygiene measures.

And yet, in many low- and middle-income cities, low-income households and neighbourhoods are often left without reliable access to clean water and must buy it from private vendors, paying up to five times as much as that paid by middle class residents. That makes uptake of hygiene messages for disease prevention all the more challenging.  

Over Half of World’s Population May Be Water-Stressed by 2025

By 2025, over half of the world’s population will be living in water-stressed areas. And some 68% of the global population is projected to be living in cities by 2050, making urban challenges around the universal provision of safe water and sanitation all the more daunting. 

At the same time, some cities have found innovative ways to meet growing demands, and sharing urban experiences across continents can help improve cities’ performance, the panelists underlined.  

The panelists highlighted the need to move beyond an approach to water and sanitation focused merely on service provision; instead attention also needs to be paid to broader assessments of water resources, the effective distribution of water, and sustainable financing for infrastructure. 

“We need an effective multi stakeholder framework, it must be an institutional will and institutional intention at the city level, with the support of the upper institutional levels,” said Kanaan. “Water management needs cooperation of all levels.”

Sami Kanaan, Mayor of Geneva and President of the Geneva Cities Hub, at the ‘Water & Sanitation in Cities’ event on Monday.

“Sustainable management of fresh water is a vital issue of this century at the center of health security, food security, energy security, and in short human security,” said François Münger, General Director of the Geneva Water Hub. 

Conference Featured Stories from Kenya, Tanzania, Nepal & Mauritania 

The conference featured good practices from cities in in Mauritania, Tanzania, Nepal and Kenya highlighting how public and public-private partnerships involved in managing urban water and sanitation had brought about change, in some of the following ways: 

Informal settlements in Dar-es-Salam, Tanzania.

Dar-es-Salaam in Tanzania – Only 10% of the city’s 7 million people have sewer connections or safe onsite septic tanks.  New approaches have revolved around “simplified sewerage” hookups, that involve laying small diameter pipes at a fairly flat gradient/slope to sewer ponds. The municipal water and sewerage utility provide technical support and finance, while households in the community provide space and labour to lay the pipes. A more recent pilot has connected households to a community-based waste water treatment plant (DEWAT) that produces biogas from the methane extracted from the sewage. The biogas then provides a clean and climate friendly fuel source for household cooking.

Nairobi, Kenya – Chronic water shortages affecting some 60% of the population have been traced to the conversion of wetlands and forests that form the watershed for the Tana River – into agriculture land. The unsustainable agricultural development has increased volumes of sedimentation that enter the river with rainfall, reducing the flow of the river and its watershed which supply 95% of the water for Nairobi’s population and causing blockages in water treatment facilities.

Several public and private partners joined to provide training and tools to over 25,000 farmers upstream on river and soil conservation and to restore forest land. These efforts have benefited farmers, by increasing agricultural yields by over US$3 million per year, and city residents, with 27 million more litres of water available every day for the city’s water needs.

The steps involved in the Upper Tana Nairobi Water Fund project in Kenya.

Dhulikhe, Nepal –  A national sanitation and hygiene campaign was launched in 2010, leading to the prioritisation of investment in sanitation facilities and increasing access to sanitation for the majority of households. In the country’s Dhulikhel municipality, the local government passed a ‘’one house, one tap’’ policy with the goal of providing safe drinking water to every household in the city. The plan arranged for every resident to get 65 liters of water per day. 

Dhulikhel also joined Banepa and Panauti, all in the Kavre district, to collaborate and manage drinking water in an integrated manner. The project identified and mapped existing drinking water sources and established Water Supply User Committees to represent and engage local communities in governmental water supply schemes and improve investment in the needs of communities.

Health Impacts of Poor Access to Clean Water and Sanitation 

Long before COVID, diarrhoea was estimated to kill some 829,000 people a year, as a result of unsafe drinking water and poor sanitation, according to the World Health Organization. Contaminated drinking water – which may be due to the encroachment of sewage or industrial pollutants into drinking water resources – is estimated to cause 485, 000 diarrhoeal deaths each year.

Many neglected tropical diseases (NTDs), which infect millions of people worldwide, are water or hygiene-related and are most often found in places with unsafe drinking water, poor sanitation, and insufficient hygiene practices.

Some of the biggest challenges occur in fast-growing cities, where sprawling informal settlements often develop on the periphery, without adequate water and sanitation infrastructure planning – leaving only ad hoc approaches. 

Poor sanitation in informal settlements disproportionately impacts women and girls, with an estimated 335 million girls attending schools without access to safe latrines, not to mention water and soap for hygiene. Deprived of adequate sanitation and hygiene facilities, adolescent girls may just avoid school on days when they are menstruating.  

Improved water, sanitation and hygiene has the potential to prevent at least 9.1% of the global disease burden and 6.3% of all deaths, according to the US Centers for Disease Control and Prevention.

Image Credits: UNHCR, Geneva Cities Hub, Geneva Cities Hub.