There isn’t enough clinical research being done in Africa. Less than 2.5% of all clinical trials in the world are done on the continent. This is why South Africa’s involvement in one of the COVID-19 vaccine trials is so important. The country’s effort is being led by Professor Shabir Madhi. The Conversation Africa’s health and medicine editor Ina Skosana spoke to him about the process, and what can be expected. This is an edited version of a podcast, which you can listen to here.
How does the trial work?
The study that we embarked on in South Africa is for a vaccine that was developed by the Jenner Institute at the University of Oxford. It’s what is known as a non-replicating vector base COVID-19 vaccine.
The study came about when I reached out to the principal investigator at the University of Oxford whom I’ve known for over 20 years to find out if there was any interest on their part to include South Africa as part of the clinical development plan of the vaccine. The short answer was yes, provided we conducted the study on our own, including raising the funding to conduct the study.
The agreement with Oxford University preceded a subsequent agreement that they’ve entered into with AstraZeneca, the pharmaceutical company responsible for the further clinical development of the vaccine and future manufacturing. Pre-clinical studies of this vaccine candidate, including in non-human primates, have demonstrated initial evidence of the safety of this vaccine, as well as its ability to protect against COVID-19 disease.
Why South Africa?
The main reason is that the legacy of vaccines shows that they don’t necessarily work similarly across different populations. So if we want to be one of the early adopters, in terms of implementing vaccination against COVID-19 as part of our immunisation programme, we really need to generate data applicable to the local context.
A number of past vaccines have been shown to be highly efficacious in high income settings. But when they’ve gone on to be evaluated in low and middle income settings, they were found to be much less efficacious and, at times, not efficacious at all.
So if we want to make informed decisions at an early stage about whether these vaccines are going to be of benefit to people in South Africa, it’s critical that we undertake the clinical evaluation during the start of the entire programme, rather than at the latter stage. Waiting for results to come in from other studies would just lead to a lag in terms of the timing when vaccines would be introduced in South Africa as well as other low and middle income countries.
This has been the experience for many other life saving vaccines where it has taken between five and 20 years between their availability in high income countries and low middle income countries.
How are participants chosen for the trial?
Participation is completely voluntary.
Participants typically come to inquire about the study at clinics. We sit down with them and explain what the study is all about. What are the criteria for joining, what the expectations are of the volunteers because the study has quite intense expectations in terms of being able to come for regular visits. And they obviously need to be agreeable that when they do participate in the study, if they do develop signs and symptoms suggestive of COVID-19, that they would come forward to be investigated. This is critical for us to be able to determine whether this vaccine protects against COVID-19.
In addition, we would do some blood tests which ensures that they don’t have any sort of medical conditions that we would want to exclude.
If they’re found to be eligible, we randomly allocate them to one of two groups. Half will receive the vaccine, and the other half a control substance, which in our case, is a placebo. This is important for two reasons. The first is that it allows us to provide robust data in terms of the safety profile of the vaccine. And the control group enables us to determine whether the vaccine actually does have any impact in protecting against COVID-19.
Is there any reason people should be sceptical of the trial?
The short answer is no. The narratives that Africans are being used as guinea pigs is fundamentally incorrect. Rather a case of us wanting to generate robust scientific data to be able to make informed decisions about whether those vaccines actually do protect South Africans – and possibly Africans more generally – against developing COVID-19.
What are the next steps?
Right now we busy enrolling into the clinical trial. We’ve just reached the 200 mark out of the 2000 participants that we plan to enrol. We expect to have completed enrollment of all the volunteers over the next three to four weeks.
After that we will keep in touch with all of the participants at least every two weeks, including weekly SMS messages to determine whether or not experiencing any signs or symptoms of COVID-19. And if they are they will be asked to come in to be investigated to determine whether they are infected or not.
The endgame of the study is twofold. One is obviously to evaluate the safety of the vaccine, which is something that is ongoing almost on a daily basis.
The second part is that once we have about 42 individuals that have developed COVID-19 at least about a month after they’ve received the first dose of either the vaccine or the placebo we will then be able to do an analysis to determine whether the vaccine actually does protect against COVID-19. Specifically we will be testing if the vaccine efficacy is at least 60%; that is by being vaccinated your risk for developing COVID-19 will be reduced by at least 60% if not more.
We anticipate that we will probably be able to provide an answer as to whether this vaccine works and protects against COVID-19 by the end of November this year. In the worst case scenario it might take us a bit longer probably into the second quarter of next year.
What about managing expectations?
It’s very exciting to be involved in the sort of clinical development of the vaccine. But we need to be guarded in terms of our expectations as to what the result will be.
The fact that we’re embarking on a clinical trial doesn’t mean that we’re going to have a vaccine that’s going to protect against COVID-19.
Only about 10% of vaccines that go into clinical trials are eventually licensed for use. Right now there’ are approximately 200 vaccines that are being developed for COVID-19. It would be a huge accomplishment if, over the next 12 to 18 months, we are successful showing that even one out of every 20 (5%) of the vaccines that go into human studies are safe and provide some protection against COVID-19.
So even though there’s a huge amount of work taking place around vaccines, at least for the next 12 months the only tools that we’ve got available to us to try to protect people is adherence to physical distancing, the wearing of face masks in public spaces, avoiding mass gatherings, and making sure that you’re in adequately ventilated settings when in public spaces.
Coffee is the second-most traded commodity in the world, behind only petroleum, and has become a mainstay of the modern diet. Believed to have originated in Ethiopia, coffee was used in the Middle East in the 16th century to aid concentration.
But did you know it also sparked a social revolution in Britain in the 17th century? Here are eight facts about the history of coffee…
Coffee may have been discovered by ‘excited goats’
Legend has it that Kaldi, a lonely goat herder in ninth-century Ethiopia, discovered the energising and invigorating effects of coffee when he saw his goats getting excited after eating some berries from a tree. Kaldi told the abbot of the local monastery about this and the abbot came up with the idea of drying and boiling the berries to make a beverage. He threw the berries into the fire, whence the unmistakable aroma of what we now know as coffee drifted through the night air. The now roasted beans were raked from the embers, ground up and dissolved in hot water: so was made the world’s first cup of coffee.
The abbot and his monks found that the beverage kept them awake for hours at a time – just the thing for men devoted to long hours of prayer. Word spread, and so did the hot drink, even as far afield as the Arabian peninsula.
A Yemenite Sufi mystic named Ghothul Akbar Nooruddin Abu al-Hasan al-Shadhili also has a claim to the discovery of coffee: he is said to have spotted berry-eating birds flying over his village unusually energetically. On tasting some jettisoned berries he too found himself unusually alert.
It was brewed by a saint from Mocha
An alternative story has us believe that coffee was first discovered by a sheik named Omar, disciple to the Sufi mystic cited above. While in exile from Mocha (Arabia Felix in present-day Yemen), Omar, who was famous for his ability to cure the sick through prayer, lived in a desert cave near Ousab. Somewhat hungry, Omar one day chewed some berries only to find them bitter. He roasted them but this only made them hard; finally he tried boiling them, resulting in a fragrant brown liquid which, in an instant, gave him unnatural and exceptional energy and allowed him to stay awake for days on end. His ‘miracle discovery’ was held in such great awe that he was allowed to return home to Mocha and elevated to the sainthood while coffee percolated throughout the Arab world.
By the 16th century, coffee was the beverage of choice in Persia, Egypt, Syria and Turkey, its reputation as the ‘wine of Araby’ boosted no end by the thousands of pilgrims visiting the holy city of Mecca each year from all over the Muslim world. Yemeni merchants took coffee home from Ethiopia and began to grow it for themselves. It was prized by Sufis in Yemen who used the drink to aid concentration and as a spiritual intoxicant. They also used it to keep themselves alert during their nighttime devotions.
From the Middle East the popularity of coffee soon spread through the Balkans, Italy and to the rest of Europe, east to Indonesia and then west to the Americas, largely through the Dutch.
Coffee forged a social revolution
Coffee was so powerful a force that it forged a social revolution. Coffee was drunk in the home as a domestic beverage but, more significantly, it was also drunk in the ubiquitous public coffee houses – qahveh khaneh – which sprang up in villages, towns and cities across the Middle East and east Africa.
These coffee houses soon became all the rage and were the place to go to socialise. Coffee drinking and conversation were complemented by all manner of entertainment: musical performances, dancing, games of chess and, most crucially, gossiping, arguing and discussing the breaking news of the day (or night). These coffee houses soon became known as ‘schools of the wise’, the place you went to if you wanted to know what was going on in your world. The link between coffee and intellectual life had been established.
It was believed that coffee is ‘sinful’
Coffee, like alcohol, has a long history of prohibition, attracting fear and suspicion and religious disquiet and hypocrisy. Had the zealots (of all religions) got their way then there would not be very many coffee houses open today.
Coffee drinking was banned by jurists and scholars meeting in Mecca in 1511. The opposition was led by the Meccan governor Khair Beg, who was afraid that coffee would foster opposition to his rule by bringing men together and allowing them to discuss his failings. Thus was born coffee’s association with sedition and revolution. It was decreed sinful (haraam), but the controversy over whether it was intoxicating or not raged on over the next 13 years until the ban was finally rescinded in 1524 by an order of the Ottoman Turkish Sultan Selim I, with Grand Mufti Mehmet Ebussuud el-İmadi issuing a fatwa allowing coffee to be drunk again. Beg was executed for his troubles by command of the Sultan himself, who further proclaimed coffee to be sacred. In Cairo there was a similar ban in 1532; coffee houses and coffee warehouses there were ransacked.
Coffee was known as ‘the devil’s cup’
It did not take long for coffee to travel the short distance to the European mainland where it was landed first in Venice on the back of the lucrative trade the city enjoyed with its Mediterranean neighbours. Initially, however, coffee met with the suspicion and religious prejudice it had suffered in the Middle East and Turkey.
The word on the street, filtering back from intrepid European travellers to the mysterious and mystical lands of the east, was of an equally mysterious, exotic and intoxicating liquor. To Catholics it was the ‘bitter invention of Satan’, carrying the whiff of Islam, and it seemed suspiciously like a substitute for wine as used in the Eucharist; in any event, it was outlawed.
Such was the consternation that Pope Clement VIII had to intervene: he sampled coffee for himself and decreed that it was indeed a Christian as well as a Muslim drink. On tasting it he wittily declared: “This devil’s drink is so delicious… we should cheat the devil by baptising it!” From then on, coffee has been dubbed the devil’s drink, or the devil’s cup.
Coffee came to England in the mid-17th century
According to Samuel Pepys, England’s first coffee house was established in Oxford in 1650 at The Angel in the parish of St Peter in the east, by a Jewish gentleman named Jacob, in the building now known as The Grand Cafe. London’s first coffee house opened in 1652 in St Michael’s Alley, near St Michael at Cornhill’s churchyard. It was run by Pasqua Rosée, a Greek man who in 1672 also set up a coffee stall in Paris. Pepys visited the London coffee house on 10 December 1660: “He [Col. Slingsby] and I in the evening to the Coffee House in Cornhill, the first time that ever I was there, and I found much pleasure in it, through the diversity of company and discourse.”
Coffee houses became ‘the first internet’
For Pepys – and for many other literate men – the coffee house was his newspaper, his internet. In his diaries he refers to the latest news of the conflict with the Dutch, “the comet seen in several places” (15 December 1664) and the “threat of the plague growing upon us… and of remedies against it” (24 May 1665). In his entry for 3 November 1663 Pepys refers to diverse discussions on the Roman Empire, the difference between being awake and dreaming, and a discourse on insects.
By 1675 there were more than 3,000 coffee houses in England alone. Some even had bed and breakfast for overnight guests. Many seemed to follow the Turkish coffee house business model, if their exotic names are anything to go by: there were up to 57 different Turk’s Head coffee houses; The Jerusalem Coffee-house; various types of the Blackamoor or Ye Blackmore’s Head; The Oriental Cigar Divan; The Saracen’s Head (of Dickens fame); The Africa and Senegal Coffee-house; The Sultaness; The Sultan’s Head; Solyman’s Coffee House and Morat Ye Great.
Coffee was claimed to be a 17th-century ‘Viagra’
Unless they were prostitutes, women were excluded from coffee houses and they let their resentment be known: in An Essay in Defence of the Female Sex in 1696, an indignant Mary Astell wrote: “A coffee house habitué is someone who lodges at home, but he lives at the coffee-house. He converses more with newspapers, gazettes and votes, than with his shop-books, and his constant application to the publick takes him off all care for his private home. He is always settling the nation, yet cou’d never manage his own family.”
Astell was merely chiming with all the other wives left at home with their chores and cups of tea; in 1674 there had been the vitriolic The Women’s Petition Against Coffee, in which wives argued that their husbands were forever absent from the home and family, neglecting their domestic duties – “turning Turk”, and all for “a little base, black, thick, nasty, bitter, stinking nauseous puddle water”.
Coffee, she said, “made men as unfruitful as the deserts whence that unhappy berry is said to be brought, so much so that the offspring of our mighty ancestors would dwindle into a succession of apes and pigmies”. She was referring here to erectile dysfunction brought on by the “noxious puddle”.
These claims were further outlined in the 1663 The Maiden’s Complaint Against Coffee pamphlet. Men’s Answer to the Women’s Petition Against Coffee was the retort – it protested that it was “base adulterate wine” and “muddy ale” that made men impotent. Coffee, on the other hand, was the Viagra of the day, making “the erection more vigorous, the ejaculation more full, add[ing] a spiritualascendency to the sperm”. Pfizer could never have found a better opinion leader.
Paul Chrystal is the author of Coffee: A Drink for the Devil, published by Amberley Publishing, 2016.
This article was first published by History Extra in October 2016