The mobile station, which opened Friday in a large city park, allows Israeli citizens and residents over the age of 60 to walk in and be vaccinated on the spot.

BREAKING – Israel’s Ministry of Health on Tuesday approved the administration of Moderna’s COVID-19 vaccine, making it the first country outside of North America to greenlight the US-based startup’s candidate.

The announcement by Moderna said that deliveries of the vaccine to Israel would begin already in January – sharply advancing a schedule that was originally to have begun in March.

“First deliveries are expected to begin shortly,” the press release stated, noting that “Israel is the third country for which Moderna has received authorization for its COVID-19 vaccine” following the US and Canada on 18 and 23 December 2020 respectively. The European Union (EU), Singapore, UK and Switzerland are also reviewing the candidate.

Moderna’s vaccine is based upon a novel mRNA technology similar to that being used by Pfizer/BioNTech, already being deployed in a number of countries worldwide.

The vaccine was approved against the specter of mounting COVID-19 infections in Israel, despite the massive vaccine campaign already underway: more than 1 million people have an initial Pfizer vaccine dose.

Israel’s average rates of new infections, are among the highest in the world currently, with Switzerland holding one of the highest rates in western Europe.

While the campaign has placed Israel at the top of the list of vaccine doses administered per-capita, it is racing against time to beat back infection rates by vaccinating more people.

Israel’s average rates of new infections – which are among the highest in the world currently – are running at about 66 people per 100,000, as compared to 64 per 100,000 in the United States and 82 per 100,000 in the United Kingdom.

Israel has secured around 6 million doses of Moderna’s vaccine. Together with another large order secured from Pfizer, the two vaccines should be sufficient to vaccinate most of the country’s 9 million residents even before a locally-developed vaccine – currently in Phase 2 trials – becomes available, most likely in the summer.

Switzerland Delay of Moderna Vaccine Approval – Doses in Visp Can Ship Immediately To Israel

Ironically, the Moderna vaccine will be imported to Israel from the Swiss-based firm Lonza, where hundreds of thousands of vaccine doses were already in production in December at the company’s manufacturing facility in Visp.

In light of the Swiss and European delays in approving the Moderna vaccine, ready-to-use vaccines can be shifted to Israel for the time being, which is eager to get its order right away.

Swiss approval of the Moderna vaccine by the national regulatory authority, Swissmedic, has lagged behind that of the Pfizer counterpart, which was approved by Swissmedic in December.

That is despite the fact that the expert panel of the US Food and Drug Administration gave the Moderna vaccine an even higher vote of confidence than it did the Pfizer candidate, when it reviewed both vaccines in meetings only a week apart last month.

While the US and China have already rolled out more than 4.5 million doses of COVID-19 vaccines, and Israel and the UK have reached or exceeded the one million mark, the rest of Europe is moving much more slowly.

Switzerland’s slow start to its vaccination campaign has been the subject of sharp criticism.

And among European countries, the number of vaccines administered by Switzerland have so far been negligible. Only half of the country’s Cantons have even begun their campaigns – which major efforts only set to kick off in some regions, such as the heavily populated and heavily infected Canton of Vaud, bordering Geneva, next week.

The slow Swiss start to its own national rollout has become a growing focus of criticism, particularly in light of Switzerland’s high infection rates. At about 40 new cases per 100,000, Switzerland has a new infection rate that is one of the highest in western Europe outside of the United Kingdom.

“In another ten days, all of the Israeli population over the age of 60 will have been vaccinated  – our vaccination programme is a fiasco that is costing lives every day and will continue to destroy still for months our economy,” Swiss lawmaker Philippe Natermod, vice president of the Swiss Freel Democratic Party, (PLR) and a member of the Swiss Federal Council, lamented in a recent Tweet.

Last week, in an exclusive interview with Health Policy Watch, a senior scientist at the University of Lausanne also complained about the unnecessary loss of lives as well as lifelong cases of COVID-related disability that would occur as a result of the delayed vaccine rollout.

“The Department of Health doesn’t seem to understand that in just three weeks of delay, with 4,000 new infections per day, 100 will die everyday. That means in three weeks, more than 2,000 people will die unduly,” said Dr Pierre Goloubinoff, a biologist who has been doing research on COVID-19 treatments, as a result of the pandemic.

“If we could do a vaccine blitz, and vaccinate all of the high-risk population in a month, in terms of the economy it would be completely liberating.”

Switzerland has also been criticised for carrying out far too few tests to adequately chart the spread of coronavirus.

Switzerland has ordered approximately 13 million COVID-19 doses: 4.5 million doses from Moderna, 5.3 million from AstraZeneca, and 3 million of the Pfizer/Biontech vaccine.

But in the absence of a Swissmedic approval of the Moderna vaccine, only the Pfizer vaccine doses are approved for use. And only 107,000 doses of that vaccine have been delivered so far.

Vaud’s Health Minister Rebecca Ruiz told Swiss Radio RTS that regional authorities  have also been left to fend for themselves in terms of setting up an adequate vaccination infrastructure – after requesting help from the army to set up mobile vaccination units. “But our request was refused, so we are left to our own devices”, she pointed out.

In a series of messages conveyed by the Swiss Mission in Geneva to UN international organizations, Swiss health authorities said that the initial phases of the vaccine campaign would be focused on people over the age of 75 living in care homes, as well as health workers, in light of the limited vaccine supplies.

The statements also pointedly stated that the vaccine campaign is of unprecedented logistical complexity.

Image Credits: Our World in Data, Our World in Data.

The administration of the Pfizer COVID-19 vaccine in mid-December.

The United Kingdom’s decision to delay the second dose of the Pfizer/BioNTech COVID-19 vaccine being rolled out en masse in the nation is a risky strategy – not only for those getting the vaccine, but also in terms of the longer-term public health impacts such delays could have in terms of future SARS-CoV2 mutations, some experts are warning. 

Administering a weakened vaccine formulation, as a result of long delays between the required two vaccine doses could open the door for the more rapid evolution of SARS-CoV virus, including mutations resistant to the vaccines only just now being deployed en masse, several leading virologists have said.  

They spoke in the wake of Britain’s decision on 30 December to postpone the administration of the second dose of the two-dose Pfizer vaccine by as much as 4 to 12 weeks, so that more first doses could be administered right away. 

Delaying the second dose has the potential to generate resistant spike variants that evade the antibody responses induced by vaccines, tweeted Paul Bieniasz, a British-American virologist at Rockefeller University. 

“Generating a pool of hosts with just the right amount of neutralizing antibody to apply selection pressure, but also maintain sufficient levels of partially antibody-resistant virus to allow onward transmission is key here…If we let immunity wane for a little while, say 4 to 12 weeks, we just might hit the sweet spot” to generate vaccine-resistant SARS-CoV2 variants, Bieniasz added. 

While the UK’s novel attempt to provide some form of broad population immunity as fast as possible is laudable, the experts says, potential negative impacts on the mutation of the virus, and thus on vaccine effectiveness, could offset the benefits. 

“The most credible arguments…are: a) the possibility that ‘partial immunity’ will spawn harmful mutations; b) concern that delay means more people won’t return for 2nd dose; c) whether change in vaccine schedule will lead to more vaccine hesitancy,” said Bob Wachter, chair of the Department of Medicine at University of California at San Francisco, in another series of Tweets. 

UK Was First In Pfizer Rollout – But Stretched Resources Leave It Hunting For More Doses

The United Kingdom was the first country in the West to issue an emergency authorization for the Pfizer vaccine, followed by the launch of the mass vaccination campaign on 8 December, beginning with health workers and older people. So far, the vaccine has been administered to about 1 million people nation-wide through the National Health Service, with second shots due three weeks later.

The total number of doses of COVID-19 vaccines administered globally, as of January 4.

The decision to prioritize the administration of the first dose to as many at-risk individuals as possible over providing the two doses according to the recommended schedule was made amid the spread of a variant strain of SARS-CoV2 with a higher rate of transmission and higher viral load. 

These measures were justified as “allow[ing] more people to benefit from the protection provided from the first dose during the roll out phase,” states the updated UK guidelines “Greenbook.”  An accompanying statement by the Joint Committee on Vaccination and Immunisation (JCVI), makes the case, saying that in the case of the Pfizer vaccine, vaccine efficiency would still be at least 70% and possibly as high as 90%, from about two weeks after the first dose, based on models of the clinical trials undertaken so far.    

But with the absence of clear data on the length that protection from the first dose lasts, Britain’s decision could have dangerous ramifications, leaving millions of people with incomplete or waning immunity, other independent experts pointed out. 

“There are good reasons for giving the second dose. It is likely that the second dose is needed to generate long lived and strong immunity,” tweeted Florian Krammer, professor at the Department of Microbiology at the Icahn School of Medicine at Mount Sinai in New York City. “But it will likely also drive affinity maturation of antibodies. This will make the antibodies stronger, and potentially will allow them to better cope with new variants.” 

Moncef Slaoui, head of the US Government’s Operation Warp Speed rollout of COVID vaccines in the US, also criticized Britain’s decision in an interview with CBS “Face the Nation,” saying: “We always said that these vaccines would be developed on the basis of science and all decisions would be made transparently on the basis of data. Changing the decisions made…which was to give two doses of vaccine – the second dose gives you ten times higher immune response than the first – without any data, I think would not be responsible.” 

Meanwhile, Pfizer and BioNTech warned in a joint statement released on Monday that “the safety and efficacy of the vaccine has not been evaluated on different dosing schedules as the majority of trial participants received the second dose within the window specified in the study design.”

Mixing and Matching Of Vaccines also Emerges as an Issue

Last week British regulators also became the first to approve a vaccine developed by AstraZeneca and Oxford University, which is also a two dose regimen – based on a more conventional adenovirus vector technology, and also more temperature resilient than the sensitive Pfizer mRNA vaccine, which requires ultra cold storage.   

British regulators have also suggested that they might allow for the mixing of different vaccine brands, as well, in some situations. According to the UK’s updated vaccination guidelines, in cases “where the same vaccine is not available, or if the first product received is unknown, it is reasonable to offer one dose of the locally available product to complete the schedule.” 

But while the guidelines offer vaccine mixing and matching as an option, this should only take place on very rare occasions and “every effort should be made to give [the patient] the same vaccine,” stressed Mary Ramsay, head of immunizations at Public Health England.  

The US media, meanwhile, has overplayed the impacts of the “mix and match” vaccine option as a part of UK vaccine strategy, Fiona Godlee, editor of The BMJ was reported to have said in a letter to the New York Times. Godlee stressed that the strategy was not a recommendation, but rather a strategy of last resort, the BBC reported. Godlee demanded that the New York Times print a correction to its previous article, which had stated that: “Britain Opens Door to Mix-and-Match vaccinations, Worrying Experts”.

Image Credits: Flickr – Province of British Columbia, Our World in Data.

Dr VG Somani, Drugs Controller General of India (DCGI), has said that two COVID vaccines have been approved for emergency use. He refused to take questions from the press following the announcement, however.

Delhi – India’s chief drug regulator approved two COVID-19 vaccines for “restricted emergency use” in the country on Sunday, opening the doors for a mass vaccination campaign against COVID to begin in one of the world’s largest countries, and a lower middle-income country at that.

However, some watchdog groups said that the review process leading up to the government’s approval had lacked transparency – and in the case case of one locally-developed vaccine, Phase 3 trials had not been completed.

The approved vaccines include the AstraZeneca-Oxford vaccine, to be manufactured at large scale in India by the Serum Institute, and an indigenous vaccine developed by India’s Council for Medical Research, and to be produced by the Hyderabad company Bharat Biotech.

While the AstraZeneca vaccine was also approved last week in the United Kingdom, Indian government approval of the Bharat Biotech vaccine came before Phase 3 trials had even been completed, prompting criticism over a lack of efficacy data.  The fact that Bharat Biotech has not completed its Phase 3 trials, means that India will now join the ranks of China and Russia as the only countries to have approved vaccines without Phase 3 clinical trial data.

The Drugs Controller General of India (DCGI), Dr VG Somani, said that the drug regulatory body approved the vaccines after “adequate examination”. Approval of the two vaccines was recommended by an expert committee of doctors who examined data from the clinical trials.

The Indian government plans to first immunise 30 million healthcare workers. In this first phase, the government also plans to immunise about 270 million people above the age of 50, and those younger with comorbidities. The vaccine will be given free of cost as promised by India’s Health Minister, Dr Harsh Vardhan.

While the Serum Institute vaccine was granted permission for restricted use in emergency situations “subject to certain regulatory conditions”, the Bharat Biotech vaccine was approved “as abundant precaution, in clinical trial mode.” The Bharat Biotech vaccine was developed the Indian Council for Medical Research, a government research body.

No Phase 3 Trial Data

While the AstraZeneca approval relied upon Phase 3 data gathered abroad, India’s Serum Institute has not yet submitted complete data from the AstraZeneca trials being conducted in India, critics also said. Scientists and other experts questioned the meaning of the approval of the Bharat Biotech vaccine while still in “clinical trial mode”. They warned that a hasty approval process could stoke vaccine hesitancy or even fuel anti-vaccine sentiments.

Phase 3 trials are usually double-blinded, with one arm of the trial participants receiving the vaccine, and the other arm getting a placebo. In case of the COVID-19 vaccine trials, the two arms are compared to see which group had participants that did not suffer from COVID-19. The extent of protection provided in the vaccine group determines its efficacy.

In terms of the AstraZeneca vaccine, the DCGI relied on the safety, efficacy and immunogenicity (the ability to induce immune responses) data generated on 23,745 adult participants from the UK and Brazil which showed vaccine efficacy of 70.42%, the govenrment statement said. The efficacy results were published in The Lancet earlier in December. The Serum Institute in India is still conducting a bridge trial with 1,600 participants in India.

In case of the Bharat Biotech vaccine, the company’s founder Krishna Ella said in a press conference on Monday that the company will be able to submit phase 3 trial data by March 2021.  Under the government authorization, members of the public being administered the vaccine will be tracked and monitored as if they are in a trial. However, critics said that ethically, that could be problematic, insofar as a placebo arm for the trial could not realistically be maintained:

“Once the vaccine has been authorised, it’s unethical to continue Phase 3 and give placebo to participants. You cannot continue clinical trials,” said Dr Amar Jesani, an independent researcher and bioethicist pointed out.

According to the DCGI, Bharat Biotech’s Phase 3 trial has already recruited 22,500 participants so far and was “found to be safe” – although it provided no further details. Other media reports, meanwhile, contradicted that statement, saying that not enough volunteers had even been registered for Phase 3 trials of the vaccine.

The controversy quickly took on political tones as some leaders from opposition parties also questioned the local vaccine’s approval ahead of the completion of Phase 3 trials.

An Indian government official retorted meanwhile, that the opposition’s comments were “disgraceful” and an attempt to politicise the vaccine approvals.

Opaque Approval Process – Indian Watchdog Group Calls for Vaccine Transparency

AstraZeneca’s India trial has already been a subject of controversy.  In October 2020, a trial participant from Chennai, in southern India, sent a legal notice to Serum Institute seeking Rs 5 crores (or approximately US$ 684,000) as compensation, claiming he had suffered serious neurological impairment following one dose of the vaccine.

Serum Institute threatened to counter-sue the trial participant calling the allegations in the notice “malicious and misconceived”, and it was subsequently reported that the adverse event was not vaccine-related.

Dr Jesani flagged that while the trial stopped after a serious adverse event was reported in the UK, the same did not happen in India. That and other issues related to a reproted lack of transparency have stirred debates in the media about about the way in which the local arm of the AstraZeneca trial was conducted and monitored.

And while the US Food and Drug Administration (FDA) live-streamed the 8 hour proceedings that led to the emergency authorization of the Pfizer-BioNTech vaccine, the process in India has been comparatively opaque. The government has provided no criteria by which the vaccines were reviewed. Only a few lines of text described the meeting held to approve the vaccines.

Although DCGI Dr Somani’s statement was published live, he also refused to take any questions from the press.

The All India Drug Action Network (AIDAN), a public health watchdog, demanded that authorities provide more information on the process that had led to the clearances of the two vaccines for restricted emergency use.

“We are baffled to understand what scientific logic has motivated the top experts in the SEC to approve this vaccine posthaste,” it said in a statement.

The statement further demanded the drug controller clarify the legal provisions under which the two vaccines were approved, and asked the regulator to share the “detailed rationale for the decision along with disclosure of the data, evidence and information” reviewed by the expert panel and drug controller.

“There is a stronger case for transparency in the pandemic because of the accelerated process of vaccine regulatory approval. Globally a norm has set in with vaccine companies sharing trial data even through publications and pre-prints in the interest of public disclosure. We have unfortunately not made enough progress in India on the transparency front,” said Malini Aisola, co-convenor of AlDAN.

Image Credits: Flickr – Trinity Care Foundation.

Healthcare workers in Nigeria fight to maintain vaccination services during the COVID-19 pandemic.

Ibadan, Nigeria. Several Nigerian states were unable to carry out preventative yellow fever campaigns late last year because of the COVID-19 pandemic, leaving thousands of people at risk of developing the disease as the country now faces a new winter yellow fever outbreak, Health Policy Watch learned.

In early November, Nigeria’s Center for Disease Control (NCDC) received several reports of a yellow fever-like illness affecting people in 4 states: Delta, Enugu, Bauchi and Benue. The NCDC quickly confirmed the illness was yellow fever.

As of Christmas Eve, 17 deaths and 101 confirmed cases had been reported from 13 Nigerian states, with the 4 states that had first reported the infection, accounting for about 85% of cases.

Rising Epicurve of yellow fever cases in Nigeria
Epicurve of yellow fever cases in Nigeria, by epidemiological week (Epi-Week).

Yellow fever, which is 10 times deadlier than COVID-19, causes headache, muscle pain, nausea and jaundice (from which it takes its name). It is entirely vaccine-preventable, with immunity lasting a lifetime once someone has been vaccinated.

Speaking to Health Policy Watch, NCDC’s Head of Epidemiology Dr Jafiya Abubakar disclosed that Delta and Benue States were part of a cluster of states that were supposed to have undergone a preventive yellow fever vaccination campaign in November – which was then delayed.

“They were supposed to have it earlier but because of the COVID outbreak, it wasn’t held. It was planned for November even before the [current] outbreak,” he said.

Nigeria, Africa’s most populous country, is one of several on the African continent to routinely see outbreaks of yellow fever, an acute viral disease transmitted by mosquitoes, which is entirely preventable with a vaccine, but otherwise kills about half of those who become seriously ill. It is endemic to tropical areas of Africa and Central and Southern America.

Abubakar also revealed that Nigeria had previously mapped yellow fever risk across all 36 states, phasing them into clusters to prioritise vaccination.

Map of Nigeria showing states and local government areas with yellow fever outbreak
Map of Nigeria showing states and local government areas with yellow fever outbreak.

He confirmed that Delta and Benue have since had the preventive vaccination campaign, with Bauchi’s to be held this month. According to WHO, the vaccine provides effective immunity within 10 days for 80-100% of people vaccinated, and within 30 days for more than 99% of people vaccinated.

Abubakar attributed Nigeria’s yellow fever outbreak to the existence of a “critical mass of people that are not immunised”.

Nigeria’s Fraught History with Yellow Fever

In April 2018, WHO Director General Dr Tedros Adhanom Ghebreyesus joined UNICEF representatives in Nigeria’s capital, Abuja, to launch the joint Eliminate Yellow Fever Epidemics (EYE) Strategy.

The strategy aims to rid the continent of these circulating outbreaks by 2026 by introducing the yellow fever vaccine into routine immunization programmes. With support from Gavi, the Vaccine Alliance, EYE aims to vaccinate around 1.4 billion people in Nigeria and 40 other high-risk countries around the world by 2026.

“The eligible age group for the vaccination campaign is from 9 months to 44 years. These are the ages that have been noticed to have missed out in initial vaccination campaigns,” Abubakar said.

The Risk of An Endemic Threat As the Continent Faces Its Second COVID Wave

With the emergence of a yellow fever outbreak roughly coinciding with the onset of a second wave of COVID-19 infections, Abubakar flagged how vital it is to maintain an adaptive response to the pandemic – maintaining and strengthening other critical public health services alongside COVID response.

Throughout the pandemic, Nigeria has aimed to implement and utilise equipment, structures and support systems that can be adapted to multiple public health emergencies.

Nigeria’s Emergency Operations Centers (EOCs), which predated the COVID pandemic, have made a coordinated national response much easier to mount, in comparison to some other African and Western countries, as they work with state governments to allocate resources systematically for emergency purposes.

According to Abubakar, the NCDC will continue to follow in this direction, and it has now activated EOCs in 30 states to facilitate quick yellow fever case finding during the COVID pandemic.

“These centers are hubs: they are coordination centers where the teams have been trained on how to manage emergencies and crisis,” Abubakar told Health Policy Watch. “The multidisciplinary team is also multisectoral and contains all the partners.

“For every outbreak, we use our resources together — human, financial and other resources and things that are required — collaboratively to respond to the outbreak. That is what we are doing. We cannot, just because we are in a pandemic, ignore outbreaks of other diseases and interventions that are needed by our communities.”

PCaregivers must be reminded that yellow fever vaccination is offered at no cost for children under 9 months across the country, Abubakar said.

To avert future yellow fever outbreaks, the NCDC official said more efforts and resources need to be committed to enlightening the general public on the urgent need to be vaccinated, especially as vaccines are available for free for certain age groups across the country.

“We need to encourage caregivers and parents that yellow fever vaccination is given for free [to of children under 9 months] in all our health facilities. They should take advantage of that to ensure that their kids are protected against yellow fever,” Abubakar said.

Image Credits: Twitter: @WHOAFRO, NCDC.

Italy launched its COVID-19 vaccine drive on Sunday, 27 December along with several other European Union countries

As European COVID-19 vaccine campaigns got underway with celebratory first jabs into the arms of citizens in half a dozen countries, some seasoned observers were still wondering if the pace of vaccine roll-outs will move fast enough to outpace the continuing high levels of infection and fatality – now being fuelled by a new mutant SARS-CoV-2 virus strain taking hold on the continent.   

Among the 27 countries of the European Union, Germany, Greece, France, Italy, Spain and Poland were among the first to begin administering shots on Sunday – after receiving the first dispatches of the EU’s order for  some 200 million doses of the Pfizer vaccine, which has been delivered region-wide.  However, some countries were already behind, with the Netherlands not due to start vaccinating until 8 January.

European leaders ranging from Italy’s Prime Minister Giuseppe Conte and Spain’s Pedro Sánchez, to European Commission president Ursula Van der Leyen have heralded the recent moves, expressing hope that the vaccines will be transformational for the continent, which has suffered some of the world’s highest infection and death tolls in the year since the pandemic began. 

“Today, we start turning the page on a difficult year,” von der Leyen, the European Commission president wrote in a Twitter post on Saturday. “The  #EUvaccinationdays are a touching moment of unity. Vaccination is the lasting way out of the pandemic. ”

Regulatory Delays Followed by Holidays Hamper Initial Rollout

While Switzerland was in fact the first country in continental Europe to administer a COVID vaccine on 23 December – the start has been largely symbolic. In the intervening period of Christmas and New Year’s holidays, only a few more vaccines have been administered in the Confederation – with more serious efforts only set to get underway in mid-January.  Further dampening enthusiasm was the death of one of the first vaccine recipients, a 91-year old woman in the Canton of Lucerne, just five days after receiving the vaccine – although Swiss authorities said that the timing had been “a coincidence.“

COVID vaccine doses administered in total, by country

But the chain of events have also left some observers worried that delays seen so far could have a lasting impact on the vaccine’s rollout in Switzerland – a country where death rates have been comparatively high throughout the pandemic, and are even more so right now. 

“Israel has vaccinated over 700,000 people and what has Switzerland done so far?” asked Dr. Pierre Goloubinoff, a biologist at the University of Lausanne who has worked in both countries, including collaborations on COVID therapies, in an interview with Health Policy Watch. 

“As of 29 December, there were 6 vaccinations in Canton of Geneva and a few dozen, maximum, in Fribourg and the Valais. At this rate Switzerland will be vaccinated in 250 years.  

“The Department of Health doesn’t seem to understand that in just three weeks of delay, with 4000 new infections per day, 100 will die everyday. That means in three weeks, more than 2000 people will die unduly.”

“If we could do a vaccine blitz, and vaccine all of the high-risk population in a month, in terms of the economy it would be completely liberating,” he said.

Already high Swiss infection and death rates, compounded by the spread of a new mutant strain of the virus originating in the United Kingdom, and which is even more infectious, hold the potential to create more havoc for health systems and economies – just as countries try to regain normalcy, he warned.  

For the moment, COVID vaccines being rolled out still appear to be effective against the mutant virus strains that have surfaced recently in South Africa as well as the UK.  However extensive spread of those strains will also create new opportunities for still further mutations – which could then increase risks that vaccine efficacy could be reduced.

Vaccine Conservatism & Christmas Hamper Swiss Rollout Efforts

In comparison to Israel, a country similar in size to Switzerland, and nearly identical COVID infection rates, Switzerland’s average mortality rate throughout the pandemic has been roughly double – Goloubinoff noted in a provocative Facebook post last week which made the comparisons very directly:

Facebook post last week by University of Lausanne biology researcher Pierre Golubinoff, complaining about Switzerland’s slow pace of vaccines
 Pressing ‘Restart’ – In Slow Motion?

That, he says, reflects broader shortcomings in the non-pharmaceutical approaches tried so far. But even so, the introduction of COVID vaccines should mark a moment when every country can press “restart” on their efforts to combat the virus, he observed: 

“My general prediction was that the vaccines are going to totally change the situation because they are efficient.  They decrease the risks dramatically; it makes the difference between someone like me having a 1 in 50 chance of being hospitalized and a 1 in 100 chance of dying to having a 1 in tens of thousands chance,” said Goloubinoff who is 64.  

However, even when vaccine campaigns do finally get underway in mid-January, he fears that Switzerland is not adequately geared up well for the kind of rapid blitz that is needed now. 

“Switzerland had a year to get organized, to say that we are stuck now because we were not ready, is of the stupidest reasoning,” bemoaned Goloubinoff. “We have a great infrastructure but we are not prepared for pandemic response.” 

Although Switzerland, like Israel, has procured enough vaccines in principle to immunize its entire population, the initial deliveries of the Pfizer vaccine will be in far smaller quantities – with only 357,000 doses due to be available by the end of January 2021.

And that is only enough to vaccinate about 178,500 people in the month of January – when Israel is vaccinating the same number of people in just one or two days [see related story]. 

Eventually, the Moderna vaccine should bolster vaccine availability – particularly since Moderna’s global manufacturing, Lonza, is based in the Valais town of Visp. 

However, Swissmedic has not yet approved the Moderna vaccine.  And that is despite the fact that it was approved on 18 December by the United States Food and Drug Administration with even fewer reservations than those that accompanied that of the FDA’s approval of Pfizer’s mRNA vaccine – which Swissmedic greenlighted earlier in the month.

“I suspect Swissmedic has not made a determination on Moderna because the experts were not asked by the Conseil Féderal to work on an emergency basis during their Christmas holidays,” said Goloubinoff, wryly. 

The damage of vaccine delays, whether due to holidays, supply chain gaps, or an overall lack of preparedness will be cumulative, not only in terms of mortality, but also in terms of long-term disabilities being experienced by younger people suffering from ‘Long COVID’, Goloubinoff says. 

He cited the recent experience of one of his PhD students, aged 35 who became ill with COVID this autumn and nearly died: “He’s still walking with a stick, is very, very weak, and able to carry out maybe half of the intellectual load that he was doing before.”

Official Swiss Vaccine Communications Provide No Timetables

As it stands now, the initial vaccine rollout will be extremely limited. A Swiss Mission missive, sent to UN employees in the Geneva area last week, announced that Geneva’s vaccine drive, beginning on 28 December, would include people aged 75 and older living in care homes, and some hospital staff.

“As more vaccines are delivered by the Confederation, the campaign will be expanded to people aged 65-74 years of age, as well as to people with clinically diagnosed pre-existing conditions under 65 years of age,(e.g. cardiac illness, obesity, etc.),” the notice, dated 22 December, states.  As for anyone under the age of 65, the rollout date remains undetermined.

A circular from the Canton of Vaud sets the first date for vaccinations two weeks later, on 11 January. There too, the initial phase of immunizations will be limited to people aged 75 living in care facilities, along with health care workers.

The circular also hastens to underline the complexity of the vaccine task being faced, stating: “this vaccination campaign is without precedent in terms of its logistical chalenges, which include conservation of three types of vaccines [Pfizer, Moderna and AstraZeneca] at different temperatures.  In addition, certain products have to be mixed before the injection, and then they all have to be injected in the 5-6 hours after having been placed in ambient temperature conditions. Finally, everyone who wishes to be vaccinated has to go two times, within an interval of four weeks.”

Other Health Policy Watch queries yielded no further clarity regarding vaccination schedules:  “We haven’t yet received word of when we will be receiving the vaccine,” said the head of an outpatient clinic at a hospital in the Canton of Vaud.

In response to another query, a Swiss Department of Health spokesperson also had no further details about timetables, stating only: “The vaccine doses are arriving in a staggered manner, as they do in every country. We expect to have everyone vaccinated by early summer who wants to be,” the spokesperson said.   

That remains in stark contrast to countries like Israel, which are vaccinating everyone 60 and older right now – and soon to move onto teachers and younger people with chronic health conditions. Among the 700,000 people vaccinated so far, there has been one widely reported death in a man aged 70 suffering from multiple health conditions. However, as one prominent Israeli health expert pointed out, among people aged 60 and over, some 700 a week die on average in any case from causes unrelated to COVID.

In the United States Lack of Public Health Infrastructure Inhibits Vaccine Delivery 

On the other side of the Atlantic, frustrations about a slow pace of vaccine rollout also are surfacing in the United States, the Boston-based, Stat News reported this week.

Although the Trump administration has shipped more than 11 million doses of the Pfizer and Moderna vaccines to locales around the country, only 2.1 million people have received their shots since the drive began on 14 December, according to the US Centres for Disease Control (CDC).  

“We are below where we want to be,” Anthony Fauci, director of the National Institute of Allergy and Infectious Diseases, was quoted as saying on CNN. “Not being responsible myself for the rollout, I can’t personally guarantee that we’re going to catch up. I hope we do.”

In the case of the US, the biggest stumbling block appears  to be the lack of budget and coherent public health infrastructure for administering the vaccines – after they are received. 

While outgoing President Donald Trump aggressively invested in, and pushed for Operation Warp Speed’s vaccine R&D – he left the critical field operation underfunded. State and local public health officials have waited for months for  more than $US 8 billion that they said would be needed to develop the infrastructure needed to administer vaccines, while the Trump administration provided only $US 340 million. The coronavirus stimulus package passed by the Congress shortly before Christmas and signed by the US president on Sunday, finally allocated the full amount that had been requested.  

Along with a shortage of funds, the US health system is fragmented between a host of public and private health insurance providers – which make a single coherent campaign of the kind being launched in other countries, such as the UK, Europe, Israel, Bahrain, even more challenging. 

“There appears to be no investment or plan in the last mile,” tweeted Ashish Jha, dean of the Brown University School of Public Health. “No effort from Feds to help states launch a real vaccination infrastructure. Did the Feds not know vaccines were coming? Shouldn’t planning around vaccination sites, etc not have happened in October or November?”

United Kingdom Approves AstraZeneca/Oxford Vaccine – Good News For Low- and Middle-Income Countries

There was was good news in the United Kingdom, however, where the adenovirus-based COVID vaccine jointly developed by AstraZeneca and the University of Oxford, became the third to receive regulatory approval by a globally recognized agency, on Tuesday, 30 December.

Approval of the AstraZeneca vaccine by the Medicines and Healthcare products Regulatory Agency (MHRA) will allow the UK to redouble its aggressive vaccine efforts – while it directly faces the threat of the SARS-CoV2 virus variant on home turf.

On Tuesday, 53,135 new Covid cases were recorded in the UK – the highest single day rise since mass testing began, BBC reported. The UK has ordered 100 million doses of the AstraZeneca vaccine – enough to vaccinate 50 million people – or roughly 75% of its population.  

That is in addition to the Pfizer vaccine, which the UK’s National Health Service was the first to rollout already beginning on 8 December.   With ample supplies now available, the NHS aims to open vaccine campaigns to a much wider swathe of the general public, ramping up the pace of vaccinations to as many as two million people a week.

The UK regulatory approval of the AstraZeneca vaccine also marks an important milestone for low- and middle-income countries – as the vaccine’s modest cold-chain requirements permit storage in a conventional refrigerator making it easier to administer in resource-constrained settings.

Some 3 billion doses of the AstraZeneca vaccine are due to be manufactured in 2021 including  in India and Brazil – with some supplies also being procured and distributed even more widely through the WHO co-sponsored COVAX facility. 

Even so, while vaccine hoarding, vaccine nationalism and inequitable distribution of vaccines remain huge global issues to be surmounted – the problems already being experienced by high income countries seemingly awash in vaccines, may be seen as warning signal to other nations that are only just now starting to plan their vaccine campaigns. 

And the message is this: once you have secured an adequate vaccine supply – that is still only the beginning of the journey.

 

Image Credits: Euoropean Commission , Our World In Data .

Just-vaccinated – Client walks out of Maccabee Health Fund’s night station in Jerusalem’s Arena conference center

Jerusalem – The huge neon sign over the city’s football stadium flashed over the highway and into the night. “Jerusalem is vaccinating” – it proclaimed. 

Across from the stadium, in a giant Arena that in normal times hosts conferences and trade shows, a steady stream of older people – some in wheelchairs, moving with walkers or assisted by family members or caregivers, were entering the big hall at 8 pm to get their first shot of the Pfizer’s Covid vaccine.

The arena has been turned into an impromptu vaccine station for one of Israel’s four public health funds – Maccabee.  It features a large, airy waiting room with numbers flashing across a big screen – and 8 vaccination stands down a hallway where people were immunised within minutes behind a flimsy curtain and then ushered back to wait 15 minutes to insure no allergic reaction 

It’s a scene that is being repeated all over Israel – including at some drive in vaccine facilities-  as the country goes into vaccine overdrive. 

“It was just like an A&W drive-thru,” marveled 65-year-old retired teacher Deborah Sullum, who was vaccinated at a drive-in facility in the coastal city of Haifa just last week together with her husband, a medical doctor. “You roll down your window, place your order with your magnetic Maccabee (health fund) card.  At the second station, you get your injection and at the third station you wait in the parking lot for 15 minutes to make sure there are no allergic reactions. Super efficient.”  

As of Tuesday evening, 29 December, some 643,000 people received their first vaccine, making Israel, with nearly 9 million people,  the country with the highest rate of COVID vaccine coverage per capita in the world, and third highest in absolute terms, just beyind the United Kingdom, China and the United States.  As of Wednesday morning, 30 December, that reached and then exceeded 700,000 vaccines, as numbers mounted by the hour.  

With most health care workers and over 20% of people over the age of 60 already having received their first shot, the aim is now to become the first country in the world to vaccinate its entire vulnerable population. Immunizations of teachers and younger people with chronic health conditions are slated to begin next week.  While over 100,000 vaccines a day are being administered already, the goal is to reach 150,000 vaccinations daily. If that pace is sustained, then some 2.25 million people may already be immunized with the full two-dose course of the Pfizer vaccine by the end of January, or about one-quarter of the entire population.

“Jerusalem is vaccinating – maintain hygiene” proclaims a sign over west Jerusalem’s Teddy football stadium
Hype, Efficiency & Creative Chaos  

Of course the process, which kicked off on December 19th with the televised vaccination of Prime Minister Benjamin Netanyahu and Health Minister Yuli Edelstein, hasn’t been entirely smooth going. 

The initial days also saw chaotic moments of long and crowded vaccine queueing in some hastily erected health fund stations – along with well publicized moments of queue jumping, which is almost a national sport in tiny, crowded Israel. 

There has been vigorous media coverage examining which one of Israel’s four public health funds are providing the best and the worst vaccine services – including where people have been getting appointments immediately or after delays of a few weeks. In some cases, wannabe vaccine candidates were able to register online.  In others, they had to call a hotline dozens of times just to make an appointment, some people complained.

Despite the hiccups, the strenous advance preparations, media hype and hopes that vaccines will help return a semblance of normalcy to life have helped propel the campaign – and vaccine acceptance to unexpected heights. 

Vaccine response rates have compared well in progressive, higher income areas of Israel’s central region – and more low-income rural areas on its periphery. It  has lagged in some smaller, and more conservative, Bedouin and Palestinian communities where vaccine hesitancy is higher, but the general assumption is that those pockets of doubt will be overcome by the otherwise huge turnouts seen.  

Vaccines are being administered at stretches of 12 hours a day – even in some cases on the Jewish Sabbath. The demand is so great that lines of younger people and those with chronic conditions, who don’t yet qualify to get vaccinated officially, form outside of some of the larger vaccine stations toward the end of the evening, just before closure, with people aiming to get doses that would otherwise be thrown out – because they won’t survive overnight without the ultra-cold storage that they require. 

Intense media coverage of how many vaccines are arriving, and what health funds and cities are outperforming in terms of vaccine coverage, has added to the hype.

 

The camapign has also been a morale booster, placing the efficiency and muscle of Israel’s four public health funds that provide universal health coverage front and centre on full display.  Although beyond the strength of the health system, there are other obvious ingredients to success. Those include the country’s small size, high-level political commitment despite incessant political infighting – and the ability to pay for a big vaccine supply right away.

Reportedly Israel, which opted to buy the Pfizer/BioNTech COVID vaccine relatively late in the game, paid a premium price of  US$ 28 per dose as compared to the US$ 19.50 paid by the United States and US$18.34 paid by the European Union. But along with the higher price, the deal,  reportedly sealed in a series of late night phone calls between Netanyahu and Pfizer’s CEO Albert Bourla, also included a schedule of rapid, high-volume deliveries.  As a result, Israel will have already received 3.8 million doses of the Pfizer vaccine by the end of this month – out of a total order of 9 million doses. 

Add to that six million doses of Moderna’s vaccine, which is based on a simlar mRNA technology, Israel already has enough vaccines to cover most of its population, as well as ensure a steady supply so that immunizations can proceed uninterrupted over the first four months of 2021.  And that is without considering a domestic vaccine that it is currently in Phase 2 trials.   

Covid vaccination doses administered per 100 people as of 30 December, 2020

Interestingly enough, Israel has not been the only country in the region to have advanced so quickly – while Europe has seen delays due to a more cautious process of regulatory approvals followed by Christmas and New Year’s holidays.

Bahrain, a tiny Gulf country with just 1.7 million people, currently ranks second in the world behind Israel, in terms of COVID vaccine coverage, per capita. 

That rollout also has included Bahrain’s sizeable population of foreign workers who comprise half of the resident population – setting a precedent for other countries in the region where hundreds of thousands of Pakistanis, Bangladeshis, Filipinos and other foreign workers keep oil-based economies operating smoothly.  

Bahrain’s rapid rollout has been built upon pillars similar to Israel’s  – early approval of the Pfizer vaccine by the country’s independent regulator’s; and thanks partly to that, Pfizer commitments of rapid delivery of large quantities of vaccine doses; and an excellent public and private health system which is also patronized by people from around the Gulf.  

Vaccine Nationalism & Vaccine Geopolitics   

The Israeli campaign has not been without criticism – it also reflects the pockmarks of the area’s broader regional disputes. Most of the nearly 3 million Palestinians in the Israeli-occupied West Bank and another 2 million people in Hamas-controlled Gaza, are not part of the vaccine drive – despite soaring rates of infection and serious illness. It’s a vivid illustration of the global differences between the world’s vaccine “haves” – and “have nots”.  In the Israeli context, it’s also an example of how the geopolitics of vaccine nationalism are intertwined here with other deepseated national and territorial conflicts.

Israel has said that the Palestinian Authority, is responsible for procuring its own vaccines for West Bank Palestinians – as it typically does for routine childhood vaccinations – often obtained in bulk through discounted UN procurement deals.  But health activists say that leaving the matter to the budget-strapped PA is self-defeating – insofar as tens of thousands of Palestinians work in Israel – and continued high infection rates in the West Bank will inevitably spill over. 

And precisely because Israel doesn’t recognize the Palestinian Authority as a national entity – large areas of the West Bank aren’t even under the PA’s control  – then Israel still holds ultimate responsibility for ensuring Palestinian access to COVID vaccines, legal and human rights advocates also point out.  

“You don’t have to be a licensed lawyer to understand the absurdity of a position by which [Israel claims that the West Bank] territory belongs to the Jewish people when it comes to settlement, exploitation and annexation, but that when its non-Jewish residents are ill, the territory is Palestinian,” opined human rights lawyer Sari Bashi, in a 2 December op-ed in the liberal national daily, Ha’aretz; she argued that Israel should purchase vaccines for Palestinians as well.  

Universal Health Coverage – Almost 

Then again, the nature of the vaccine distribution, is not precisely etched around national identity either. Rather it is anchored in the Israeli system of national health funds. Those funds do not cover Israelis living abroad. They do include hundreds of thousands of Palestinians in disputed East Jerusalem, who can thus obtain the COVID vaccines right away. 

At the same time, the remaining 2.2 million or so Palestinians living in the West Bank on the other side of the army checkpoints and stark concrete barriers that mark Israeli-defined Jerusalem city limits, must rely upon the health services of the Palestinian Authority – which doesn’t yet have access to any COVID vaccines.

Foreign residents and workers living in Israel, on the other hand, generally belong to Israeli health funds and are eligible to get the vaccine under the same criteria as Israeli citizens  – with foreign caregivers of elderly Israelis getting first priority this week.

The situation is less clear, however, for Israel’s approximately 30,000 African asylum seekers, most of whom fled war-torn Sudan and Eritrea a decade or more ago, slipping into the country via Israel’s border with Egypt, after a tortuous trip through the Sinai desert, but have never been granted formal refugee status by Israel’s Interior Ministry. 

While in principle, asylum seekers are supposed to be covered with health insurance by their employers – in fact they have limited access to medical care.  Some employers duck the rules, while those who are unemployed or unable to work because they are chronically ill, fall into an insurance void. Human rights advocates are hopeful that they may soon be able to make an arrangement, however, whereby vulnerable asylum seekers may also be immunized.  

Palestinian Authority Ordering Russia’s Sputnik Vaccine  

In terms of the current lack of Palestinian access to the vaccines, Israel’s deputy health minister Yoav Kish told Israel’s Kan Radio station last week that “should we see that Israel’s demands have been met and we have additional capability, we will certainly consider helping the Palestinian Authority.”    

However, the Palestinian Authority, which typically procures its own vaccines anyway for routine immunizations, is not waiting for Israel. 

Earlier this month, one PA health official Osama al-Najjar announced  that four million doses of the Russian Sputnik vaccine would be delivered in early 2021.

“We will begin to inoculate those most at risk [for the coronavirus],” al-Najjar said in an interview with Voice of Palestine Radio. Outside of Russia, only Argentina and Belarus have have so far approved the Sputnik vaccine, whose Phase 3 clinical trial results have not yet been fully completed – or independently reviewed. . 

The PA also hopes to vaccinate one-fifth of Palestine’s people under the WHO co-sponsored COVAX facility, starting with healthcare workers, another senior Palestinian health official, Ali Abed Rabbo told the Associated Press last week.

“The remainder will depend on Palestine purchasing from the global supply, and we are working with several companies,” Rabbo said, naming Pfizer, Moderna, AstraZeneca, as other potential candidates, along with the Russian Sputnik vaccine. 

Israel also eyeing Sputnik

The Palestinians are not the only ones eyeing Sputnik; some prominent Israelis have also given the Russian vaccine a nod. Zeev Rothstein,  Director General of Jerusalem’s prestigious Hadassah-Hebrew University Medical Center, said last month that the hospital had secured an agreement to purchase 1.5 million doses of the vaccine from Russia  – with the aim of becoming a regional vaccine distributor. However so far, the hospital, which also has a branch in Russia, has not secured official Israeli Ministry of Health approval for the move.  

Along with the imported vaccine options, an Israeli-developed one-dose COVID vaccine just began Phase 2 trials this week; if all goes well, Phase 3 trials will begin in the spring. With some 10 million doses of that vaccine slated for potential production, it’s possible that in the end, Israel might become a net exporter of COVID vaccines. The question, however, is how much time it may take?

Said an Israeli Ministry of Foreign Affairs spokesperson in Geneva: “Israel, at this point, has made vaccine agreements with both Pfizer and Moderna, and plans to obtain vaccines for all its citizens. 

“At the same time, Israel is part of the COVAX facility, WHO’s instrument to insure that all citizens of the world will be safely vaccinated equitably. 

“Understanding that pandemics know no borders, Israel has strengthened its cooperation with the Palestinian Authority in order to prevent, mitigate and address the spread of the virus in the region. 

“The ongoing cooperation includes consultations, training and information sharing, cooperation with Palestinian medical teams, and delivery of COVID-19-related PPE.  We encourage the international community and donor countries to help the PA with all aspects of dealing with the COVID-19, including access to vaccines.”

Image Credits: Our World In Data .

Health care workers sensitize a Kenyan community to COVID-19 precautions.

In early January 2020, as our Health Policy Watch team returned to work just after the New Year’s break, our production editor who had returned from a visit to her mother in China, called me to say in a mildly worried tone: “Hi Elaine, there is a strange virus circulating in Wuhan. I thought you should know.”

Within just several weeks, we watched and wrote, and probed and wrote, as the first cases of the “novel coronavirus” spread like wildfire in the city of ten million people, to other parts of China, and then hip-hopping to Thailand, Singapore, the French Alps, an office in Germany, small communities in northern Italy, cruise ships, and beyond.

Journalists crowded into the press room at Geneva’s WHO headquarters to get briefings on the spreading virus – until we understood that it was no longer safe to do so because the virus had also arrived at our doorstep.

As COVID-19 captured headlines in media around the world, there has been new recognition of how important health is to social and economic development. But while a single virus came to dominate almost every aspect of our lives – from how we work, order food or do drug discovery – we realized that, as a media outlet specializing in health policy reporting, we need to constantly be getting “under the hood” of this fast-moving story.

This includes examining the diverse ways in which the pandemic has manifested itself in different parts of the world. And through the lens of COVID-19, we can gain new insights into a range of other thorny health issues that haven’t gone away – including HIV/AIDS, tuberculosis, non-communicable diseases, drug-resistant pathogens, air pollution, climate change, and more.

Health Policy Watch’s Kerry Cullinan interviewed Professor Kelly Chibale,, founder and director of the Holistic Drug Discovery and Development (H3D) Centre at the University of Cape Town (UCT), who is studying how African populations metabolize drugs – an issue that goes beyond COVID-19.

In the same way that polaroid glasses allow you to see beneath the sunlight’s glare over water to appreciate the fish, the coral reefs – and also the plastic debris otherwise concealed – COVID-19 has given us a new lens through which we can see much better.

We can see how well health systems are functioning – or not; the racial and socio-economic inequalities that can hinder public health crisis response – and the importance of evidence-based political leadership.

We can appreciate how climate change and ecosystem degradation are increasing pandemic risks and threatening decades of hard-won health gains. Armed with greater awareness, we can strengthen the debate about how to clear away the systemic, long-term threats we face – along with the pandemic.

New Support from The Wellcome Trust

In line with that vision and mission, we are pleased to announce new support from the Wellcome Trust. This will enable us to redouble efforts to report on all aspects of the pandemic by bringing on new reporters from the Global South, in turn fostering a more balanced health policy dialogue.

Social distancing and mask measures at a KFC outlet in Ibadan – Health Policy Watch’s Paul Adepoju looked at how Nigerians are coming to terms with COVID.

As we head into 2021, we expect that COVID-19 will continue to dominate the news for some time. And we will continue writing about pandemic trends and responses, new drug innovations, and the rollout of long-awaited COVID vaccines.

But we will also explore the broader health issues, through the “COVID-19 lens” that has sharpened our insights into the challenges we face, and how we can rebound and recover – in even better shape.

One key to this is a more balanced dialogue between policymakers and the public as well as between voices in the north and south. The new support we gain from the Wellcome Trust will help us to  build  out our “network approach” to journalism – to link global and regional health policy debates, bridge ideological divides and bring more developing country media voices into the circuit of our coverage.

As Will Hall, Wellcome’s Global Policy and Advocacy Manager told us: “New digital platforms, such as Health Policy Watch, bring fresh perspectives to debates, including from low- and middle-income countries.

“We are pleased to support them in this effort to amplify the voices of journalists in the global south across interconnected health challenges.”

COVID-19 Pandemic Relief Services, New Delhi. Health Policy Watch’s Menaka Rao and Jyoti Pande Lavakare explored how COVID-19 cases rose this autumn, along with air pollution levels.
About our Team

Our small and nimble team is based in Geneva, a global health hub that is home to the World Health Organization and dozens of global health organizations. We operate under the auspices of the non-profit, Global Policy Reporting Association – which has been providing media services for over 15 years.

We already have reporters corresponding from Nairobi, Ibadan, Delhi and Cape Town, as well as from New York City and London. And in 2021, we will be building out our team further into English-speaking parts of Africa; southeast Asia, western Pacific and Latin America and the Caribbean.

Menaka Rao, Delhi
Jyoti Pande Lavakare, environmental health
Kerry Cullinan, Cape Town
Paul Adepoju, Ibadan

 

 

 

 

 

 

Says Kerry Cullinan, our Africa editor: “Health Policy Watch ensures that the voices and experiences of African policy-makers, health workers and patients are heard by global decision-makers in Geneva, providing a unique platform for an exchange of views and news.”

We will be boosting our columnists to provide “Inside Views” from a diversity of regions, disciplines and perspectives.   We urge you to get in touch with us by email or @HealthPolicyW with your ideas for stories and op-eds.

Wellcome Trust – a new supporter of Health Policy Watch reporting in the Global South

Finally, we retain as a core value that of accurate, evidence-based and independent reporting. With regards to the latter, we appreciate the complete editorial freedom accorded to us under the terms of the Wellcome Trust support.

After the dark days of 2020, we sincerely hope that the New Year may indeed see further milestones in strengthening health systems, supporting health workers, and reducing the terrible burden of the pandemic on peoples, societies and economies. Sincere wishes for a brighter, and COVID-free, 2021!

Elaine Ruth Fletcher
Editor-in-Chief

Image Credits: WHO African Region, Photo : Victoria Nthenge/Trocaire, Kerry Cullinan, P Adepoju/HP-Watch, Belur Math, Howrah, Jyoti Pande Lavakare, Courtesy of Kerry Cullinan.

The US COVID-relief package confirmed a US $4 billion investment in Gavi, the Vaccine Alliance.

Just 2 weeks ago, the World Health Organization (WHO) issued a plea to countries to honor their donor pledges to support its COVAX vaccine procurement scheme to equitably distribute at least a portion of forthcoming COVID-19 vaccines to countries around the world. Without donor support, the globall vaccine procurement facility that over 180 countries have joined, risked “becoming no more than a noble gesture”, the WHO warned.

Shortly after the warnings, commitments of some US$ 2.4 billion by eight high-income countries ended the immediate crisis. 

And now, after a vote by the United States Congress, the funding prospects for COVAX in 2021 are looking even brighter. The US COVID-19 relief package – agreed upon on Sunday night, after a near-five-month-long gridlock – has earmarked a US$ 4 billion investment for Gavi, The Vaccine Alliance, which along with WHO, is a co-sponsor of the COVAX initiative.

GAVI launched the COVAX Facility in collaboration with WHO – with the aim of immunizing at least 20% of peple in all countries, prioritizing those at highest risk, regardless of income or development levels. It aims to distribute 2 billion doses by the end of 2021, including to 92 low- and middle-income countries (LMICs) that cannot afford to pay on their own.

While donor commitments made in recent weeks led to last week’s announcement of procurement deals for nearly 2 billion vaccine doses – enough to vaccinate about 1 billion people, the new US aid should help the campaign go further yet.  It will provide much needed support to health systems to actually carry out the vaccine campaigns – as well as enabling the purchase of further doses required to meet the 20% vaccination goal.

The US investment also represents a domestic about-face after months of almost exclusively “America First” rhetoric and policies on the pandemic from lame duck President Donald Trump; the move by Congress acknowledges that, in fact, a global vaccine drive also will help hasten the end of the pandemic. 

USGLC President & CEO Liz Schrayer

As Liz Schrayer, President and CEO of the US Global leadership Coalition (USGLC), said in a statement: “As the virus is spreading anywhere in the world, Americans are not safe, and that means our current global response is simply not enough.

“There’s no denying this year-end agreement was difficult and hard-fought to address many critical domestic needs. At the same time, hundreds of lawmakers from both sides of the aisle have spoken out in recent months that failing to invest in a global response comes at our own peril.”

“More must still be done to address the indirect impacts of the pandemic, particularly the damage its done to stabilization efforts in fragile states and on the food security of vulnerable populations around the world,” said House Foreign Affairs Committee Lead Republican Michael McCaul.

Schrayer also said that this “critical step in the right direction” would “directly impact America’s health and economic recovery”.

COVAX: A Tough Funding Year

The COVAX facility was launched to ensure equitable distribution of the COVID-19 vaccine.

Despite remaining largely uninvolved in the drafting of the Congressional bill, Trump told reporters Wednesday morning that Congress’ coronavirus relief bill “really is a disgrace” – for reasons including the several billion dollars in foreign aid.

He said: “Congress found plenty of money for foreign countries, lobbyists and special interests, while sending the bare minimum to the American people who need it. It wasn’t their fault. It was China’s fault.”

He capped his remarks with a call to raise the one-off payment to be made to most Americans from US$600 to US$2,000.

Whether Trump’s remarks were merely rhetorical, or not, they followed in line with his previous announcements in April to suspend US funding to the World Health Organization, followed by his July announcement of a US withdrawal from the global health body, altogether. The US moves highlighted the delicate nature of the Organization’s resource base, which relies heavily on voluntary donations from member states as well as other charities. Until April, the US was the biggest single donor to WHO, providing about US$400 million in 2019, and accounting for around 15% of its annual budget. WHO’s programme budget for the two-year 2020-21 period amounts to about US$5.84 billion a year.

While the monies are being directed to Gavi, and not WHO, the bi-partisan approval by Congress of the COVID global vaccine aid, as part of domestic COVID bailout measures, suggests the winds of change that are blowing, ahead of the inauguration of US president-elect, Joe Biden. And while Biden will still have to win the approval of the Republican-controlled Senate for other domestic and global public health spending initiatives, some things can also be done by executive order. For instance, Biden has declared his intention to rejoin the Paris Climate Agreement as well as halting the process of withdrawl from the WHO, which was only supposed to take effect in July, 2021.

Image Credits: Ennoti/Flickr, USGLC/Flickr, CIO Look/Flickr.

Wuhan residents lining up outside a drugstore to buy masks in January. From the beginning of the outbreak, masks were required by Chinese authorities to reduce person-to-person transmission – WHO only issued a recommendation months later.

The redacted WHO report on Italy’s pandemic response, “An Unprecedented Challenge” contained a brief timeline of events in the early days of the SARS-CoV-2 outbreak in China, which a number of WHO officials sought to amend or suppress even before the entire report was recalled.

In fact, the so-called “China box” on the outbreak’s early days, which had been vetted by several experts, contained a narrative of sensitive key events – including the fact the genome sequence was posted publicly by scientists the week before the official report by Beijing of the genome sequence to WHO – which have either been omitted or muted in the official WHO timeline of the COVID-19 pandemic, which was updated just last week.

Straightforward Narrative – With  Bombshell Implications – Ruffling Feathers In Beijing or Washington?  

The intent of the “China box” – the name gaven to a box-out in the report – of no more than 300 words, was straightforward: to present a terse, factual narrative of the pandemic’s onset in Wuhan and beyond. 

However, just ahead of the report’s publication, a controversy over the fine print of the “China box” text erupted among WHO officials, Health Policy Watch has learned. And it was in fact concerns over that box, which directly led to the report’s withdrawal from the WHO website on 14 May, a day after it had been published online. 

The chain of events raises further questions over whether the entire document’s recall may not only have been linked to the feathers it might ruffle in Rome, but also those in Beijing.  

China Box Timeline Drawn From Original WHO Reports – Which Were Later ‘Amended’   
The China box: excerpted from the suppressed WHO report, “An unprecedented challenge”

The report’s “China box” provided a cursory, but unvarnished narrative of the early days of the SARS-Cov-2 virus spread, which was based on initial WHO epidemiological reports from January 2020 and other expert sources. But that WHO narrative has since seen several major revisions – including on 27 April, 29 June, and again on 15 December.  As a result, some of the facts to which the “China box” briefly refers – and verified by outside sources – have since been muted or even removed from the official WHO record.  

Examples include: the circumstances around the initial SARS-Cov2 genome sequencing; WHO statements downplaying the possibility of human-to-human virus transmission in connection with the first reported cases in Wuhan; and the first case reported outside of China in Thailand on 13 January- in someone with no link to the Wuhan seafood market – providing evidence of human to human transmission. Here below are the details of the “China box” account of events – and the revisions the record has since undergone: 

First Case Reports  & WHO Statement on “No Evidence” Of Human to Human Transmission 

The China box states that “As of 3 January, 2020 China had reached 44 cases, including 11 with severe systems; the Wuhan City Health Committee confirmed that 121 close contacts were under observation. WHO was told that there was no evidence of human to human transmission.” 

Indeed, WHO repeatedly referred to the lack of any evidence, or any clear evidence, of human-to-human transmission in the first three weeks of January, at WHO press conferences as well as in tweets, such as one on January 12. Only in the latter part of January, shortly before declaring a public health emergency of international concern, did WHO finally begin to concede that human to human transmission was occurring. The “China Box” narrative refers bluntly to this “inconvenient” fact of WHO’s earlier communications which downplayed transmission risks – communications that are now muted in the official WHO account. 

WHO Timeline Revisions: WHO “updates” of the pandemic timeline, in April, June and December, omit reference to WHO’s initial dismissals of human to human transmission risks. The latest WHO timeline, updated on 15 December 2020, begins the narrative on the transmission risks with a tweet from 19 January 2020, by WHO’s Western Pacific Regional Office, stating; “According to the latest information received and @WHO analysis, there is evidence of limited human-to-human transmission of #nCOV.”  

A little more than a week later, on 30 January, WHO declared the new coronavirus a public health emergency of international concern. The initial number of cases that had been reported in Wuhan as of 3 January 2020 (44 ill, 11 seriously)-  are not explicitly mentioned in the most recent 15 December timeline update either; the timeline refers simply to a “cluster of cases”. The case numbers are, however, still available online in the 5 January 2020 WHO Disease outbreak news.  

Publication Of the SARS-CoV-2 Genome Sequence

The China Box states: “On 7 January, the causative agent was identified by China as a novel strain of coronavirus and the genetic sequence was quickly made available.”

Early WHO accounts acknowledge that the virus had been isolated in the week of 7 January. A WHO disease outbreak report from 12 January stated: “The Chinese authorities identified a new type of coronavirus (novel coronavirus, nCoV), which was isolated on 7 January 2020.”

A 10 December post on virological.org, by an Australian researcher from the University of Sydney “on behalf of the consortium led by Professor Yong-Zhen Zhang, Fudan University, Shanghai” note that the sequence was available on an open-source data base called GenBank. This is echoed by direct postings from the University of Minnesota’s prestigious Center for Infectious Disease Research and Policy.

However, the fact that the virus sequence had first been posted independently online by a  group of Chinese researchers before it was shared by China officially with WHO on Saturday, 11 January became a subsequent point of political embarrassment. It is among the issues that has been raised by WHO critics, who say that there was intense backroom coordination between WHO and Beijing over the course of the pandemic narrative. 

Either way, the updated WHO timelines contain no reference to any independent sharing of the sequence by researchers in the week of 7 January – and the fact that the virus sequence was already available on an open source database by Friday, 10 January.  

Rather, the official WHO timeline begins with 11 January in one tweet, headlined “Breaking” noting that the virus had been made available to WHO. An earlier WHO report in “Disease Outbreak News, which has since been removed from the record, cites 12 January as the date in which the genetic sequence was officially shared by Chinese government officials.

The fact that the “China box” suggests that the virus was sequenced and publicly available earlier in that week – resurrects a politically sensitive issue that WHO and Beijing would both rather forget. That is the fact that China may have dallied in sharing the vital information with the global body – possibly doing so only after it had been made available ad-hoc by a group of Chinese researchers.   

First Case Report Outside China – Growing Evidence of Human-to-Human Transmission 

The China box states: “The first case outside of China was reported on 13 January in Thailand. There was a link to Wuhan, but not to the market in question, suggesting human-to-human transmission.”

The fact that the Thai case was the first abroad, and it also had no apparent link to the Wuhan seafood market, were both facts widely reported in the media as mounting evidence of the virus spread, and likely human-to-human transmission – including in this paper, which led a story on Wednesday, 15 January, stating “Human Transmission of New Coronavirus May be Occuring.”

Further evidence of human-to human transmission was indeed evident by Wednesday, as second case was reported in Thailand, as well as another infection in Japan – the latter in a man who had never visited the Wuhan seafood market thought to be the center of the outbreak. In addition, a commission of technical experts from Hong Kong, Macao and Taiwan, visited Wuhan on 13-14 January, confirming that they had found two family clusters of the virus, including a spouse who had not visited the market recently. Chinese links to the original Wuhan government report about the experts’ visit, as well as the statement by Wuhan authorities about the woman who may have been infected by her husband, which were linked to the Health Policy Watch story of 15 January, have since been deleted.  

In a WHO press briefing on 14 January, WHO’s Maria Van Kerkhove, admitted that “from the limited information that we have, it is possible that there is limited human-to-human transmission, especially among families who have close contact with one another.

However, the official, updated, WHO timeline account remains silent about the ways in which the Japanese and Thai cases had heightened concerns over human-to-human transmission – and ambivalent about those risks overall. A 14 January tweet by WHO continued to maintain that “Chinese authorities have found no clear evidence of human-to-human transmission of the novel #coronavirus (2019-nCoV) identified in #Wuhan, #China.” 

WHO’s official Disease Outbreak Report, posted 14 January. also maintained that: “To date, China has not reported any cases of infection among healthcare workers or contacts of the cases. Based on the available information there is no clear evidence of human-to-human transmission.” 

That same disease outbreak report also sounded another note of false reassurance, stating that: “No additional cases have been detected since 3 January 2020 in China.” 

Cases Increasing Exponentially & Health Workers Dying 

WHO statements to the contrary – cases were increasing exponentially in Wuhan in that period – but under the international health radar.  

And health workers were falling ill – including the Chinese whistleblower, Li Wenliang, who had alerted colleagues to the new infectious virus in a medical chat group on 30 December 2019, was hospitalized on 13 January, and died February 7.  At the same time in mid-January when WHO Director General was repeatedly praising China for its fast and efficient response, Wenliang and other Chinese doctors trying to get a grip on the emerging virus were being reprimanded and detained by authorities.  

Li Wenliang, doctor at Central Hospital of Wuhan, was one of the 8 people detained by police for spreading “rumors” about the new viral disease – from which he died on 7 February.

Even so, WHO resisted acknowledging the human to human transmission was occurring until a WHO mission visited China in the last part of January. 

On 19 January, WHO’s Western Pacific Regional Office (WPRO), which is responsible for China, tweeted that “there was evidence of limited human to human transmission”

On 21st January WHO/WPRO tweeted that “it is now clear that there is at least some human to human transmission”.

It wasn’t until 22 January that the WHO mission which had rushed to China issued a statement saying that “Data collected through detailed epidemiological investigation and through the deployment of the new test kit nationally suggests that human-to-human transmission is taking place in Wuhan” The WHO Mission added, however, that “more investigation was needed to understand the full extent of transmission of human-to-human transmission.” 

On the same day, WHO’s Second Situation Report on the novel coronavirus, reported a total of 314 cases, of which 270 were in Wuhan, 39 elsewhere in China, and four abroad in Thailand, Japan and South Korea. WHO’s Emergency Committee met and on 23 January failed to agree on declaring a public health emergency of international concern (PHEIC).  

Just one week later on 30 January, the number of confirmed cases globally had increased 25 fold to 7818, including 82 cases in 18 countries outside of China; no one could doubt that human-to-human transmission was occuring. And WHO would finally declare a Public Health Emergency of International Concern, this critical point of human transmission was still up for debate.

China Box Became a Lightning Rod For WHO Political Concerns 

Ultimately, insiders say, the China box became a lightning rod for the full set of WHO political concerns that were weighing down on the document. 

Key WHO China experts also were afraid that geopolitical sensitivities would be aroused by the facts that it cited – which were in the process of being buried by WHO official records, sources say. 

“Kindly pull the document off the web immediately. Consider this an emergency,“ said one internal email, seen by Health Policy Watch. 

One key correction was needed, in fact: unlike the narrative implied by WHO’s initial alert about the outbreak, in its 5 January 2020 “Disease Outbreak News” account, the Chinese authorities had not directly “informed” WHO’s China Country Office on 31 December 2019 about the outbreak; rather WHO learned about it from a Wuhan Municipal Health Commission press release. After the exact circumstances of the first alert were aired widely by media, WHO amended the account in its official timeline. 

But there were yet other, more politically-tinged objections to the text – including objections to a reference that the 13 January report of the infected person in Thailand was “suggesting human-to-human transmission.” While this, too, was widely reported in the media as one of the first examples of human-to-human transmission (the person in question had not been at the Wuhan Seafood Market), the text was perceived as “contradicting” 14 January statements by Director General Dr Tedros Adhanom Ghebreyesus downplaying the risks, the team was told.   

The fact that official WHO statements downplayed the human-to-human transmission risk in that period is very clear, as described in the official outbreak news reports and Twitter chains cited here. The record of Dr Tedros’s own statements is more elusive. A google search turned up a single tweet by @DrTedros on 5 January acknowledging the outbreak and noting WHO was in contact with Chinese authorities; another tweet 20 January announces the IHR Emergency Committee’s meeting. Dr Tedros’ first official statement on the WHO record about the novel coronavirus dates to 22 January, 2020, when he convened the IHR Emergency Committee. 

Text Revisions lead to Report Suppression 

Whether the issues raised by the China box touched on facts, political sensitivities – or a combination of both – the report’s lead coordinator, Francesco Zambon, based in WHO’s Venice Office, was asked to make textual revisions – and told he should also talk to the WHO Legal Department. In fact, it is WHO Legal – and not only the scientists – who have a final word on the elements of the coronavirus narrative that are published in WHO’s name – and those that are muted or ignored.  

Rather than see the objections proliferate further, the report’s lead author, Wim Van Lerberghe, who was focused on portraying the account in Italy and not in China, quickly offered to remove the sensitive box from the document altogether. Zambon and the writing team, at the WHO Venice Office, which was in charge of the publication, agreed. 

The team was particularly eager to resolve the issues over China – insofar as these were coming on top of objections raised by WHO’s Assistant Director General Ranieri Guerra, a former Italian Ministry of Health official, to the detailed Italy narrative that was the heart of the report.

Guerra, according to the emails and testimonies reported by Health Policy Watch on 15 December, wanted to remove or tone down phrases in the report that he perceived as shedding negative light on the Italian government response or even, as insiders say, on him personally. Notably, the record shows that Guerra wanted to amend a reference in the report to Italy’s national pandemic preparedness plan, so as to suggest that the 2006 plan had been updated in 2016 – when in fact it had not been. In this same period he was in charge of the Ministry’s   prevention initiatives  -which should have included updating the decade-old plan.  

On 14 May, the day after the report’s publication, it was removed from the WHO website – so that an amended version without the China box could be uploaded again – a process that was supposed to happen the same day. 

But the report on Italy’s pandemic response – An Unprecedented Challenge – never was republished.  

WHO’s official response 14 December states that: “Following publication, factual inaccuracies were found in the text and the WHO Regional Office for Europe removed the document from the website, with the intent to correct errors and republish it. 

“By the time corrections were made, WHO had established a new global mechanism – called the “Intra-action Review” – as a standard tool for countries to evaluate their responses and share lessons learned. The original document (“An unprecedented challenge”) was therefore never republished.”

In fact, the corrections to the China box were only supposed to take a couple of hours; the WHO Intra-action review process guidance to countries for conducting their own pandemic response reviews, was published over two months later – on 23 July, 2020.  

Asked on by Health Policy Watch to explain what factual inaccuracies at stake, a WHO spokesperson declined to comment, saying, “We are not going to discuss factual inaccuracies.” 

WHO Responds To China Box Story

In a response following the publication of this article, a WHO spokesperson provided Health Policy Watch with the following clarifications about the issues surrounding the China box controversy, and the WHO narrative around the early days of the outbreak:

“Regarding the issue itself of China box: The Italy report was removed to address concerns expressed by WHO’s China country office about ‘Box 1: How it started.’

“The report was never re-published, however, upon the decision of the WHO Regional Office for Europe for reasons unrelated to the China box. There are several inaccuracies in the China box in relation to the reporting of the outbreak and the characterization of human to human transmission:

“Having made a request to the authorities on 1 January 2020, WHO’s China country office received information on the cluster of cases of ‘viral pneumonia of unknown cause’ identified in Wuhan directly from Chinese officials on 3 January 2020 – not 31 December 2019 as the ‘How it started’ box says.

“WHO did learn of the outbreak on 31 December 2019 through its monitoring in two ways. Its Country Office in China picked up a media statement by the Wuhan Municipal Health Commission. WHO’s Epidemic Intelligence from Open Sources (EIOS) platform also picked up a media report on ProMED (a programme of the International Society for Infectious Diseases).

“The box says that “WHO was told that there was no evidence of human-to-human transmission” but our Disease Outbreak News from 5 January importantly nuances this statement with the word ‘significant’: ‘Based on the preliminary information from the Chinese investigation team, no evidence of significant human-to-human transmission and no health care worker infections have been reported.’

The box surfaces human-to-human transmission (H2H) as an issue but does not reference relevant and important WHO documents and statements from January, including:

  • 10 January: Guidance on infection prevention and control
  • 14 January: Press conference, which recognised H2H as a possibility; WHO tweet that preliminary investigations by the Chinese authorities had found “no clear evidence of human-to-human transmission”; WHO’s own risk assessment saying that additional investigation was needed into H2H.
  • 19 Jan: WHO Western Pacific Regional Office tweet that there was evidence of limited H2H.

WHO continues to refine the timeline of its activities from Day 1 of the outbreak. The interactive and text timelines are regularly updated to add recent activities and also amend earlier listings. We aim to state clearly when we have made a material change in a timeline.

The interactive timeline remains our main reference piece.”

________________________________________________

-Updated 29 December 2020

Third in a series. First two stories include: 

World Health Organization’s Censorship Of Report On Italy’s Pandemic Response Sets Dangerous International Precedent – Critics Say  

WHO Playbook For Responses To Media Queries On Suppressed Italian COVID-19 Report – Raises More Questions than Answers 

 

Image Credits: Flickr/Nicolò Lazzati, China News Service／中国新闻网, An unprecedented challenge, WHO 2020, Nandu News.

 

Kelly Chibale in the H3D laboratory in Cape Town

CAPE TOWN – A new antiretroviral drug was supposed to be a game-changer for South Africa, which has one of the largest HIV-positive populations in the world. The drug, dolutegravir, was cheap, had few side effects, and – most importantly – it suppressed the virus quickly.

But after a few months on the treatment, many African women began experiencing significant weight gain. A clinical study published in The Lancet in October this year showed that one in five were clinically obese after 96 weeks of treatment, running the risk of cardiovascular problems and diabetes.

These unexpected side effects were in patients that had been excluded from the initial clinical trials, as historically, medicines have been optimised for people in the Global North.

To address this bias and improve the treatment outcomes for millions of African people, Professor Kelly Chibale, founder and director of the Holistic Drug Discovery and Development (H3D) Centre at the University of Cape Town (UCT) in South Africa, is turning his attention to how African populations metabolize drugs.

Dosing regimens are optimised for Caucasians

One of the things Chibale is doing is ‘collecting’ livers. Specifically, he is assessing the livers of African patients for the African Liver Project, which is investigating the African microbiome – the microorganisms in various parts of the body or the combined genetic material of all the microbes, including bacteria and viruses, that live inside people on his continent.

“Africans account for 15% of the world’s population, and 25% of the global disease burden,” he says. “But they are involved in less than 2% of clinical trials that happen here.”

Dosing regimens – meaning the dosage and the frequency a medicine is taken – are optimized for the populations involved in the trial: typically caucasians.

This is a trend that exists across nearly all medical sciences, from treatment design to vaccine development. Although the COVID-19 crisis that has gripped the whole world has highlighted the need for diversity in clinical trial research, the conversation goes beyond COVID-19 and it is only just beginning. And even as awareness grows, three-quarters of COVID-19 treatment trials still exclude pregnant women.

“African patient responses to the medicines are varied and accompanied by suboptimal treatment outcomes in some instances,” adds Chibale, who is also the Neville Isdell Chair in African-centric Drug Discovery and Development and a professor of organic chemistry at UCT.

One of the reasons for such variable responses is down to genetic polymorphism: genetic differences in the activity of enzymes that metabolize drugs in the liver.

For example, for one of the five drug-metabolizing enzymes there is a variation between Africans and Caucasians in its gene coding. The liver is the major organ where metabolism occurs, and five drug-metabolizing enzymes in the liver are responsible for metabolizing 90% of all medicines.

People are either slow, normal or fast metabolizers. Slow metabolizers have too much of the drug in their system which leads to adverse effects, and likely poor patient adherence.

Ultra-fast metabolizers have suboptimal levels of the drug in their system, which leads to poor efficacy and disease-related morbidity.

In a number of cases where African patients have experienced unexpected side effects, the participants in the drug trials had normal or fast metabolisms, whereas the Africans were slower metabolizers. They experienced more drug toxicity because they were unable to process the drug fast enough.

Look at the drug efavirenz, a first-line treatment for HIV/AIDS, for example. Its main route of metabolism involves the cytochrome P450 2B6 (CYP2B6) enzyme. Mutations of this enzyme may lead to reduced metabolism leading to higher efavirenz exposures. These CYP2B6 mutations are more common in patients with African heritage.

“One way to address these variations is to have more clinical trials in Africa. Our people have to understand that taking part in clinical trials will help them,” Chibale rationalises. “It is a necessary sacrifice to be part of the solution. The safety of the medicines we take has been established because someone else sacrificed and took part in a clinical trial.”

Creating a liver ‘bank’

Kelly Chibale in the H3D laboratory in Cape Town

Chibale’s solution is to do more pre-clinical work even before getting to the clinical trials.

“In the past, 40% of the failures in clinical trials were due to suboptimal drug metabolism and pharmacokinetics, which is basically what the body does to the medicine,” he says.

“This was until the pharmaceutical industry realised that we needed to front-load drug metabolism and pharmacokinetics pre-clinical studies much earlier on, to gain an understanding of what the human body is likely to do to a drug,” says Chibale.

‘Front-loading’ involves incubating potential drugs with liver fractions that contain drug-metabolising enzymes. Researchers are then able to examine how human livers process the drugs. By the time drugs get to human trials, scientists are able to make much better predictions about what doses to use.

This is done in conjunction with laboratory test-tube testing the drug, then ethically on animals like rodents and non-human primates to understand its efficacy and safety.

Chibale aims to refine this further, developing tools that will help to identify which drugs are more likely to perform well in African patients, predict what the optimal human dose is likely to be in specific African populations, provide useful data for targeted clinical trial design and eventually for the establishment of better-directed dosing regimens.

The African Liver Project objectives include creating a unique and novel biobank of well-characterised African human liver tissue, generating liver cells (known as hepatocytes) and subcellular liver fractions, and investigating the metabolism of study drugs across different tissue in matching African populations in the same way as has been done for the Caucasian derived human livers and tissue.

This would create a platform for hypothesis testing before clinical trials are carried out.

The proposed in vitro (test tube) experiments would be cheaper to design and perform to get data that can be extrapolated to pharmacokinetics in humans using mathematical models.

To do this, the H3D team needs to get access to diverse African livers to see how their drug-metabolising enzymes work – but most of the liver fractions available have been donated by Caucasians in the Global North and need to be bought for large amounts of money from Western companies.

To address the lack of African liver fractions, the H3D Centre has formed a partnership with the UCT Liver Transplant Centre and has ethical approval to process African human liver tissue from discarded or diseased livers, and examine how the drug-metabolising enzymes present in the liver fractions process drugs.

But Chibale would love to have similar arrangements with liver transplant centres throughout the continent to increase the samples from which to derive robust data and because there are many genetic differences between populations on the continent.

“To do this at scale, we need more transplant hospitals in South Africa and other regions of Africa to collect enough samples. Then, with enough African-derived human liver tissue samples collected, we want to then start generating metabolism data, starting with existing medicines for any disease, whether it’s diabetes or cancer,” says Chibale.

“You know why? Because then this data can help any company really look at their own medicine that they’ve been giving out to African patients, and reformulate it in terms of the right dose,” says Chibale.

Studying the effects of antibiotics 

But drug-metabolising enzymes aren’t the only factors in determining how patients process drugs. Research has shown that the microorganisms that live in the body, including bacteria, viruses and fungi – known as the microbiome – are also important.

“Literally in the last decade, there has been an accumulation of evidence of the involvement of the gut microbiome in the metabolism of medicines, including having an impact on what happens in the liver,” says Chibale. “This means if we just optimise medicine for liver metabolism, we will not necessarily get it right. Why the microbiome is so important is, first of all, clearly genetic differences and there is overwhelming evidence of this.”

H3D’s more recent initiative, the African Gut Microbiome project, is aimed at investigating the impact of microorganisms found in various parts of the body on the metabolising of drugs. It is also aimed at studying the effect of antibiotics on the gut microbiome and the resultant changes in drug metabolism of a range of commonly used medicines.

The idea is that these initial in vivo (human) studies will inform subsequent studies around the African gut microbiome, with the goal of establishing relevant preclinical research tools that mimic those aspects of Africa-specific microbiomes that are involved in variable drug responses.

But socio-economic and physical environments in which patients live also affect how a patient can process drugs. The diet of a person has a major role to play in how the body functions, while the physical environment affects a person’s resilience.

Chibale’s centre is unique in that it is based at a university rather than being a stand-alone company or being part of a drug company. He hopes it can become an example for other parts of the world, such as South America.

Funding comes from a variety of sources from the South African government to philanthropic organisations and innovative pharmaceutical companies.

H3D has the strategic advantage for developing Africa-specific pharmaceutical research tools because of its location on the African continent providing easy access to African patients and researchers who are interested in addressing global health and health inequality issues.

Chibale has built a network of collaboration involving the chemistry, biology and pharmacology departments at the university, and has an 80-person staff, that includes post-doctoral scientists and students from all over the world.

It’s been a long journey for Chibale from a village in northern Zambia and townships in the Zambian Copperbelt, to a PhD at Cambridge University, then research positions at Liverpool University and the Scripps Research Institute in San Diego. For the past 24 years, he has been in Cape Town with his wife and three sons.

Always up for new lessons, Chibale confides that he has recently joined Twitter and realised that he needs to be part of the push-back against misinformation.

“Life is about taking risks and sacrifice. We can never achieve anything if we live in fear. Look what the world has been able to achieve in the face of COVID-19, a vaccine in an unprecedented time,” he says.

Image Credits: Kerry Cullinan.