european commission
Katalin Cseh a Hungarian MEP associated with the  Renew Europe Group.
EP Plenary session – Preparation of the European Council meeting of 25 and 26 March 2021 and Digital Green Certificate

European Parliament members (MEPs) expressed overwhelming support for a coronavirus-related “Digital Green Certificate” to ease travel within the European Union, voting by a more than two-thirds majority to accelerate approval by the summer.  

But parliamentarians also warned that all efforts to recover from COVID-19 will be void unless Europeans are vaccinated more quickly. 

“We need to speed up vaccination – that is the only light at the end of the tunnel,” said Katalin Cseh a Hungarian MEP associated with the  Renew Europe Group, on the opening day of a two-day debate at the European Union Summit  happening today and tomorrow on the “Digital Green Certificate”.

“We need to increase production capacities to set up more ambitious targets for deliveries to work together with manufacturers, and also to ramp up production,” said Cseh. 

“Only vaccines can offer us a way out of the crisis; we need to do our utmost to help boost vaccine production and ensure more transparency, predictability, and supply of the vaccines, so that we can speed up the vaccination campaigns across the EU,” said Ana Paula Zacarias of Portugal. 

The majority of the MEPs who took the floor said the Digital Green Certificate proposed by the European Commission on 17 March, would support the much-needed recovery of the travel and tourism sector. 

With 468 votes in favor, 203 against, and 16 abstentions, MEPs took advantage of an urgency procedure (Rule 163), which allows for faster parliamentary scrutiny of the Commission’s proposals. The MEPs will next mandate negotiations over the proposal, to be considered during the parliament’s next plenary session (26 – 29 April). 

Certificate To Offer Proof of COVID Vaccination, Recovery Or Negative Test Result
digital green certificate
The stages of the Digital Green Certificate System in practice.

The certificate would be free of charge, in digital or paper format, with a QR code to help ensure security and authenticity.  It would offer proof that a person has either been vaccinated, received a negative test result, or recovered from COVID-19, and has antibodies. 

Other key provisions are that the certificate will be recognized in every EU member state, and it will pave the way for the establishment, or re-establishment, of  full freedom of movement inside the EU during the COVID-19 pandemic. 

“The Commission will build a gateway to ensure all certificates can be verified across the European Union, and will support member states in the technical implementation of certificates,” said Commission Vice-President Maroš Šefčovič. Šefčovič said the Commission aims to have the system in place by June. 

MEPs Call For Legal Action Over AstraZeneca Vaccine Delays & Unreported  Doses 
AstraZeneca vaccine

In terms of speeding up Europe’s vaccine rollout, the MEPs focused most of their fire on the recent AstraZeneca delays in vaccine deliveries. 

Concerns over the failure of the company to meet its EU commitments have been compounded by the  recent discovery of almost 30 million undelivered AstraZeneca doses stashed  in an Italian factory. 

During the debate,  several MEPs speakers called for legal action against the manufacturer.  

Iratxe Garcia Perez, Group of the Progressive Alliance of Socialists and Democrats in the European Parliament, Spain, called the reports about AstraZeneca’s undelivered doses “the straw that broke the camel’s back.” 

“We’re not talking about the fact that they are not complying with their commitments and the contracts. Basically, they’re laughing at us in our faces,” she said. 

The AstraZeneca vaccines were discovered by Italian police in a raid of a factory in Anagni, a town near Rome.  Italian government officials were reportedly unaware of the vaccine stash until the EU’s internal market commissioner, Thierry Breton, launched an investigation, and then tipped off Italian police, according to the Italian newspaper La Stampa

Some EU sources said that the jabs had initially been bound for the UK – before being  blocked by Italy after the country introduced new rules on vaccine exports, EU sources told the paper. 

However, in a statement on Wednesday, AstraZeneca said that 16 million of the vaccine doses were simply awaiting quality control to be disbursed to EU countries.  

Another 13 million doses were manufactured outside of the EU, and then brought to the plant for the “fill and finish” process of putting the vaccine into vials, the company said. These doses are awaiting shipment to low and middle-income countries, in the framework of the WHO co-sponsored COVAX global vaccine rollout initiative, which is supported by the EU. 

“It is incorrect to describe this as a stockpile. The process of manufacturing vaccines is very complex and time consuming. In particular, vaccine doses must wait for quality control clearance after the filling of vials is completed,”  the company said.  

Garcia Perez and other MEPs, however, blamed  AstraZeneca for still moving too slowly on the EU vaccine deliveries. 

“[We] have to act firmly and take actions against a pharmaceutical company because they are undermining the prestige of other companies that are meeting their obligations. So I would urge the Commission to get down to work and do something about this flagrant attack against the commitments that the company undertook, “ said Garcia Perez. 

Independence From Pharma, Though Not Through Export Ban 
Martin Schirdewan, of The Left Group in the European Parliament, Germany.

Although several MEPs called for legal action against AstraZeneca to restrain it from exporting vaccines to the UK and elsewhere in the world, others warned that an export ban could result in further delays in Europe’s vaccine rollout. 

“Export bans can lead to retaliatory measures and that could lead to lower production of vaccines in the EU. We could end up in the worst possible situation where nobody benefits,” said Martin Schirdewan, of The Left Group in the European Parliament, Germany.

Schirdewan, however, called on the European Commission to “give up all contracts with the pharmaceutical companies and release the patents to produce the vaccines.” 

“We have made ourselves dependent on the pharmaceutical companies. We have made ourselves dependent on a market that regulates nothing, shown clearly by AstraZeneca stockpiling 29 million doses in Italy that have just been accidentally discovered.” 

“Let’s create a joint European strategy that we can use to combat the virus. Let’s coordinate healthcare, let’s deal with the social and economic consequences of this pandemic for our populations.” 

 

Image Credits: Jan Van De Vel, European Commission, gencat cat/Flickr, Alexis Haulot.

rapid antigen test
A new study suggests that administration to travelers of a rapid antigen test upon arrival at their destination, may be just as effective as quarantine requirements, to stop imports of COVID-19 cases.

A new study published by a consortium of UK-based airline industry interests suggested that administration to travelers of a rapid antigen test upon arrival at their destination, may be just as effective as quarantine requirements, to stop imports of COVID-19 cases.

The study, which reviewed case studies of airport testing procedures elsewhere, claims that a single on-arrival antigen test is as effective as a ten-day-self isolation period in reducing imported cases of COVID-19, while testing after five-seven days of quarantine may catch as many as 90% of cases. Specifically, it found that: 

  • Air passenger testing after five days of quarantine in Iceland is between 83% and 90% effective. 
  • Testing after seven days in Toronto and Paris is between 84% and 90% effective. ​
  • Single tests on arrival in Canada (Toronto-Pearson Airport), France (Paris-Charles de Gaulle Airport), Jersey and Iceland detected between 54% and 76% of infected travellers.

“Real world evidence supports a significant reduction in current UK 14-day quarantine policy,” claimed the studies authors who also disputed a previously published Public Health England (PHE) paper that  had concluded  airport testing would identify only ‘7%’ of virus cases.

The study was prepared for a consortium of British airlines interests, including Virgin Atlantic, Heathrow Airport, and the International Airlines Transportation Association. 

“We believe that international travel can safely restart at scale, using a risk-based, phased easing of testing requirements and border restrictions, that follows the scientific evidence,” Virgin Atlantic’s chief executive Shai Weiss said, upon publication of the review.

Britain has currently banned all foreign travel, except for essential work, education, or health reasons. The ban, along with the current quarantine requirement, was supported by the PHE paper. The new study finds that this significantly underestimates the effectiveness of passenger testing.  

The study has been submitted to Britain’s Global Taskforce, which is set to review how and when travel should restart on 12 April. 

Image Credits: Wikimedia Commons: Nemo.

 

African health officials appeal for more COVID vaccines after current supplies run out in some countries

About 10 African countries have yet to receive any doses of a COVID vaccine, while at least one country, Rwanda, has already run out of the doses that it received through the WHO co-sponsored COVAX facility, said WHO’s African Regional Office on Thursday, citing this as evidence of the vaccine inequalities that continue to mark the battle against the pandemic.  

“It is unfair. I believe that some high income countries are looking to vaccinate their entire populations while others, including most countries in our region, are struggling to reach a significant proportion of at-risk populations,” said Dr Richard Mihigo, Immunization and Vaccines Development Program Coordinator at WHO’s African Regional Office, speaking at a WHO/AFRO press briefing on Thursday.

Under the COVAX initiative, countries are supposed to receive some 20% of their COVID-19 vaccine needs, with the shipment of the doses officially beginning in Accra, Ghana, just weeks ago.  So far, some 7.7 million doses have been administered in 32 African countries through COVAX or national initiatives, the WHO African region officials said.  And some 44 countries have received vaccines through COVAX or other channels.  

At the same time, however, some 10 countries have not received any vaccines at all, and have no idea when the next shipments will be, while other countries are already running out of the doses that they received. 

Rwanda Already Used Its COVAX Vaccine Supplies

Rwanda, for instance,  received about 240,000 doses of the Oxford/AstraZeneca COVID-19 vaccine through the WHO co-sponsored COVAX Facility on March 3. It received a further 103,000 doses of the Pfizer vaccine, as the first African country to administer the vaccine that requires ultracold storage. 

But only 20 days after it commenced vaccination, Rwanda has already administered all of its doses. Rwandan government officials said they did not know when the next shipment will be received, especially since the new guidelines that prioritise India and Europe over the rest of the world, delay vaccine deliveries to Africa. Rwanda has a population of about 13 million and needs to vaccinate 7.8 million people to achieve herd immunity.

“When the COVID vaccine was made available, we already had a programme that was built from the community to national level, so we just plugged into the existing system, and that made it easier and faster to make it happen,” said Dr Sabin NSanzimana, director of the Rwanda Biomedical Centre, at the WHO briefing, describing the country’s experience. “And the thing is that, deploying a vaccine rapidly, without waiting is the best way you can actually stop the progression of this virus.”

However, that success has now been tinged with anxiety as Rwanda awaits more vaccine doses to arrive.

And while countries like Rwanda are rapidly and impressively vaccinating their people against COVID-19 with the very limited doses available, they are largely helpless regarding getting additional doses, said Dr John Nkenkasong, Director of the Africa Centres for Disease Control and Prevention. 

Speaking at a back-to-back Africa CDC briefing, Nkenkasong urged global leaders to pursue equitable access to vaccines, saying:  “There is absolutely no need, absolutely no need for us as a world, as humanity, to go into a vaccine war to fight this pandemic. We’ll all be losers. 

John Nkenkasong, Director of the Africa Centres for Disease Control has appealed for equitable distribution of COVID-19 vaccines, saying there was no need for a vaccine war.

“I remain hopeful that the power of humanity will prevail,”  Nkenkasong added, “I strongly believe that we should continue to be our neighbour’s keeper and the only way we do that is to exercise that strong sense of solidarity and coordination and with common wisdom. I remain hopeful that wisdom will prevail over time.”

Worries That Serum Institute Doses Will Be Kept In India or Diverted To  European Union   

Officials also are worried about the news that AstraZeneca vaccine doses produced by the Serum Institute of India, Africa’s main vaccine supplier either directly and through COVAX, may be kept in India or diverted to the European Union. 

The Oxford/AstraZeneca vaccine is the main vaccine that African countries are receiving through the COVAX  initiative – as well as through bilateral deals. And most of those doses are produced by the Serum Institute. 

In February, however, Adar Poonawalla, CEO of vaccine producer, Serum Institute of India (SII), announced his company had been directed to prioritise the needs of India, currently undergoing a surge in COVID cases. 

“SII has been directed to prioritise the huge needs of India and along with that balance the needs of the rest of the world. We are trying our best,” Poonawalla said on Twitter 

That was confirmed by a GAVI announcement Thursday, which stated that some 90 million doses due to be supplied to COVAX in March and April may not be delivered – as a result of the Indian government’s decision to divert doses domestically.  

In addition, Africa CDC officials fear that Africa COVID-19 vaccines produced in Europe could also be threatened by new guidelines issued by the European Commission that limit the export of coronavirus vaccines to countries outside the bloc. The guidelines stipulate that the EU countries may curb the exportation of vaccines for six weeks to destinations with fewer COVID cases or higher vaccination rates – although the restrictions explicitly exclude exports to low-income countries that are participating in COVAX. 

Ursula von der Leyen, president of the European Commission, justified the guidelines and said the world is in the crisis of the century and the commission is not ruling anything out. 

“I’m not ruling out anything for now, because we have to make sure that Europeans are vaccinated as soon as possible. Human lives, civil liberties and also the prosperity of our economy are dependent on that, on the speed of vaccination, on moving forward,” Leyen said.

Threats to Africa’s vaccine plans

Also speaking at today’s briefing, Anthony Costello, Professor of Global Health and Sustainable Development, University College London, supported the call for speedier delivery of vaccines to Africa and said the continent’s plan to vaccinate 60% of its citizens by mid-2022 can only be achieved if there is quick access to doses of the vaccines. 

While expecting access to improve before the end of 2021, Costello said the continent needs to vaccinate about 35% of its citizens before the end of the year and this would require about 800 million doses of COVID-19 vaccines.

“If you’re going to reach a 60% target of vaccinating the continent by the middle of next year, which I think is the aim, then, in this year, if you want to reach 35% of the African population, you’re going to need 800 million doses. Let’s say the population of Africa is 1.2 billion, you’re probably going to need to vaccinate 727.5 million people by the middle of next year, that’s going to mean you’ll need almost 1.5 billion doses (of Oxford/AstraZeneca COVID-19 vaccine), so that’s a huge challenge,” Costello said.

Costello expressed confidence that Africa’s health infrastructure  was adequate to ensure a speedy roll-out if the doses became available. “I’m pretty confident that Africa can get there because I think the immunisation infrastructure in Africa is generally not bad. The figures have come up dramatically over the past 10 or 15 years. I think Africa’s public health structure is often better than Europe, to be honest,” he said.

Earlier this month, Africa CDC also announced plans to hold a major conference in April to discuss the local production of vaccines, as one avenue to address the continent’s vaccine shortages. 

Speaking at the time, William Kwabena Ampofo, Chairperson of African Vaccine Manufacturing Initiative, called for a “roadmap” to increase vaccine production that will facilitate immunization of childhood diseases and enable Africa to control outbreaks of highly infectious pathogens

 

Image Credits: Johnson & Johnson, WHO African Region .

3D print of a spike protein on the surface of SARS-CoV-2, enabling the virus to enter and infect human cells.

NEW DELHI – Scientists have sequenced a new “double variant” of the coronavirus first identified  in India – along with a handful of other variants of concern that are appearing during the second biggest wave of the virus since the pandemic began.

The new double variant, bearing two significant mutations in the coronavirus spike protein, dubbed E484Q+L452R, could be associated with higher infectivity and with a capacity to evade antibodies, government experts have warned. Alone or together, the mutations E484Q and L452R “have been found in about 15-20% of samples and do not match any previously catalogued VOCs”,said the Ministry of Health and Family Welfare in a press release, 

The two variants both appear to “confer immune escape and increased infectivity”, the Ministry said; immune escape refers to the ability of a variant to evade immunity conferred by a prior infection

The government also said that there is not yet sufficient evidence to establish a link between the new mutation and the surge of COVID-19 cases occurring now in some states of India. India reported 53,476 new cases in the last 24 hours, of which 31,855 are from Maharashtra.  “The variants of concern and a new double mutant variant..have not been detected in numbers sufficient to either establish a direct relationship or explain the rapid increase in cases in some states,” the press statement issued by India’s Ministry of Health and Family Welfare.

The double mutation has been found mostly in the Western state of Maharashtra which is seeing a massive surge in COVID-19 cases. Several cities in Maharashtra including Mumbai and Pune had massive number of cases in the first wave of the pandemic last year. However, since mid-February, the state has seen a massive spike of cases yet again. 

“We have seen this double mutant E484Q+L452R in 206 samples in Maharashtra and a varied number in Delhi. In Nagpur, we found a substantial number of samples with this mutation- about 20%. But, the data so far does not show that the surge is related to this mutant,” said Dr Sujeet Kumar Singh, Director of India’s National Centre for Disease Control, speaking at a press conference on Wednesday.

Nagpur is one of the cities in Maharashtra which saw the beginning of the surge of  Covid-19 cases in India from mid-February. 

Variant of ‘Interest’, Not Yet ‘Concern’ According to WHO Criteria

Speaking at the press briefing, however, Singh also downplayed the significance of the double mutation at this point. 

He said that according to WHO criteria, the double mutation could be called a “variant of interest”, but it has not yet been  established as a “variant of concern” in the same way as the variants first identified in the United Kingdom, Brazilian and South Africa – also circulating in India. 

The WHO has established three classifications for the identification of SARS-CoV2 mutations, including variants under investigation, variants of interest and variants of concern. 

Singh said that further investigations of the Indian mutations are underway. “Only when the variant has public health impact, increases severity of the disease does it become cause of concern,” explained  Singh of the classifications. 

In an interview with Health Policy Watch, Dr Shahid Jameel, chair of the scientific advisory committee of the Indian SARS-CoV-2 Consortium on Genomics (INSACOG), echoed that message. The consortium is a group of 10 laboratories that carry out genomic sequencing and analysis of circulating COVID-19 viruses. The consortium tests international travellers, their contacts, and   community samples. It has so far tested more than 10,000 cases.

“We do not need to worry about the double mutation, but we have to be concerned,” Jameel said. “Both these mutations allow the virus to infect better and evade antibodies. But we do not know how much it will affect the surge on the ground.” 

Variants of greatest concern are typically associated with a higher viral load,  increased transmissibility and  also “immune escape” – referring to variants that can evade immunity conferred by a prior infection

The Genomic Consortium is primarily concerned with variants that carry mutations in the characteristic spike protein of the coronavirus, which eases the virus’s way into cells, allowing it to infect individuals with COVID-19. On that spike protein, one region of greatest interest is the “receptor binding domain”, said Jameel.  

In the cases of mutations that facilitate “immune escape”  changes occur in that receptor binding domain, Jameel explained: “In the [spike protein’s] receptor binding domain, there is a path called the ‘receptor binding motif’. It contacts the cell, and from there the virus is able to enter the cell. However, antibodies [built from previous infection or immunization] can prevent its binding to the cell. 

“If the virus changes the process slightly, so that it is not recognised by antibodies it is able to enter cells more effectively,” said Jameel.

Another variant associated with “immune escape” -N44OK- also has been found in the country’s southern states of Kerala and Telangana. This variant, however, has also been reported in 16 other countries including the United Kingdom, Denmark, Singapore, Japan and Australia. 

Sequencing Is Simple – Linkage to Community Spread Is More Difficult

“While sequencing is simple, linking the sequences to community spread depends on various reports and the kinds of samples taken,” said Jameel. “To link it epidemiologically is time consuming and difficult. The mutant strain will be figured out in time, but the important thing is to stop the spread of the virus,” said Jameel.

Even in Nagpur, the cases are spreading in areas of the city that were relatively unaffected in the first wave last year, and that the population in these areas were susceptible to the virus.

A nation-wide survey showed only one out of 5 people have been exposed to the virus. But in cities such as Mumbai, Pune, Delhi the sero-surveillance shows high levels of high levels of sero-positive cases, of more than 50%.

“The most important thing to remember is that viruses will not mutate if they are not allowed to replicate. Therefore, we have to only suppress the chain of transmission to stop mutations of the virus. Testing, quarantine, and containment will limit the spread of the virus,” said Dr Vinod Paul, chairperson of India’s Covid-19 task force.

Mutations Will Not Affect India’s Vaccination Drive

These variants should  not, however, impact India’s vaccination drive, other government officials have said . “It is well established by research studies in literature and published literature, that both the vaccines that are available in our country are effective against both the UK and Brazil variants. The research regarding the South African variant is ongoing at the moment,” Balram Bhargava, director general of Indian Council of Medical Research (ICMR), said.

More than 50 million people have been vaccinated with one dose so far in the country. Much has been said about the slow pace of vaccination in the country covering only about 3% of the population. 

In the first drive of vaccination which started in January, the government only allowed healthcare workers to take the vaccine. In March, the government started the vaccination drive for people above 60 years old and people above 50 years old with co-morbidities. It has now announced that those who are 45-years and more are eligible for the vaccine.

Covid-19’s Second Wave in India

Since mid-February COVID-19 cases have been steadily rising in India. From an average of about 12,000 cases a day at the time, more than 40,000 are getting reported in the last few days.

Just six states in India – the western states of Maharashtra and Gujarat, the central state of Chhattisgarh, the northern state of Punjab and the southern states of Kerala and Karnataka –  have accounted for some 80.63% of the new cases reported in the last 24 hours, said India’s Health Ministry.

Along with any locally emerging variant, another major concern is the high number of samples identified with the UK variation (B.1.1.7) in the northern state of Punjab. The Punjab government said that 81% of the samples examined between January and early March have been found to be from that coronavirus lineage. The explanation for that is likely to be international travel – insofar as the UK is home to a large Punjabi diaspora. 

In the press conference, Singh attributed the rise in cases to the large number of people that were not infected in the first wave, and have not been vaccinated either, and so they are still  susceptible to COVID-19. With a year of the pandemic, pandemic fatigue has set in and people are perhaps lax about COVID appropriate behaviour, he said. 

Image Credits: Flickr – NIAID.

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.