US President, Donald Trump, in one of his daily press briefing on coronavirus, claimed the country’s Food and Drugs Authority has given approval for chloroquine and hydroxychloroquine to be used on COVID-19 patients.
The FDA rebutted the claim and rather indicated the President had directed it to carry out clinical trials.
Few days after Trump gave a thumbs-up to chloroquine and hydroxychloroquine as the new therapeutic ‘messiah’ to rescue COVID-19 victims and potential victims, there are reports of a rush for the old tablets in Nigeria and Ghana.
Chief Executive of Ghana’s second-largest hospital, Komfo Anokye Teaching Hospital, Dr Oheneba Owusu-Danso, urged restraint until clinical trials are conclusive on its efficacy.
“In situations like this, there’s a whole lot of desperation,” he observed. ‘’Nobody should do self-medication. Though some countries have reported on some success, Scientists will formally come out with this.”
While the Komfo Anokye CEO’s statement may be full of caution and doubt, the Pharmaceutical Society of Ghana (PSGH), erring on the side of caution, issued a statement asking its members not to sell hydroxychloroquine tablets to the public without a valid prescription as “there will be real COVID-19 patients who will need it to survive that battle, if it proves potent against the coronavirus.”
Is it suggestive Ghanaian pharmacists see hope in the new drug?
What is chloroquine?
The drug, discovered in the 1930s, has managed to make the World Health Organization’s essential drug list due to its effectiveness and safety.
Chloroquine was the frontline anti-malarial medication in Ghana until a malaria-causing strain known as Plasmodium falciparum mounted a defence against it.
That was a big blow to the malaria-endemic country like Ghana whose Ministry of Health had indicated the disease accounted for 40 per cent of all out-patient attendance in 1999.
A 2015 paper by the Kwame Nkrumah University of Science and Technology had found the resistance of 87 per cent in urban and peri-urban centres while in rural Ghana, it was 94 per cent.
Though a larger sample size is crucial, 20 out of 23 in peri-urban areas and 15 out of 16 in rural areas is enough testament to the level of resistance.
Several findings far predating the trend prompted the WHO in 2005 to intervene as a growing number of Africans had been found to have developed resistance.
However, in the quest of scientists to keep the soul of the drug, they came up with hydroxychloroquine, a more effective treatment for malaria.
“Chloroquine was found to be toxic and after that, they came up a derivative, hydroxychloroquine which is less toxic, therefore more tolerable. Meaning, the side effect was less,” said Dr Samuel Amoabeng Kontoh, Specialist Pharmacist at the Komfo Anokye Teaching Hospital.
How does chloroquine work?
At the latter part 2019, the Lancet reported a new type of pneumonia in the Chinese City of Wuhan. According to the report, over 2,800 cases were reported in mainland China, with 81 deaths.
John Hopkins University reports, as at 24 March 2020, more than 392,000 cases had been reported, though over 17,000 have died and more than 100,000 recovered.
Macao, Hong Kong and Taiwan also reported 19 cases. United States, France, Australia are not the only ones battered by imported cases; Africa has been hit. Ghana’s Health Ministry notes almost all cases have been imported.
Physicians who first came into contact with infected patients observed symptoms related to the virus known as SARS-CoV, responsible for the 2003 Severe Acute Respiratory Syndrome, SARS.
The Journal Nature’s finding finally confirmed the new virus to be a relative of SARS-CoV called SARS-CoV-2
Chloroquine, apart from its anti-malarial prowess, is effective against Rheumatoid Arthritis and lupus erythromatosis among others.
“Chloroquine is known to produce a slight suppression of the immune system so based on that it has been recommended for auto-immune diseases like Lupus erythromatosis,” explained Dr Noble Kuntworbe, a pharmaceutical Scientist at the Kwame Nkrumah University of Science and Technology.
Chloroquine’s success as an anti-malarial agent has largely been due to “its ability to attack the parasite at the stage where it invades the red blood cells,” Dr Kuntworbe noted. “These compounds are able to cross cell membranes and get accumulated in the red blood cells and, eventually, within the acid food vacuole of the parasite, which is like the stomach of the parasite.”
When the chloroquine compound gets to the acid food vacuole, they can’t come out, thereby, leading to parasite’s death.
The Journal of Virology, however, made a revelation of its anti-viral arsenal.
The 2005 study found hydroxychloroquine could surmount SARS-CoV.
In the investigation involving primate cells grown in culture, Chloroquine curbed the spread of the virus.
Viruses cannot multiply like bacteria but are propagated by cells they invade. A process known as replication.
Hydroxychloroquine inhibits the ability of a virus to replicate in two ways.
According to the same report, the drug enters compartments called endosomes within the cell membrane. Endosomes tend to be slightly acidic, but the chemical structure of the drug boosts their pH, making the compartments more basic.
Many viruses, including SARS-CoV, acidify endosomes in order to breach the cell membrane, release their genetic material and begin replication; chloroquine blocks this critical step.
“So it sort of reduces the ability of the virus to cause the host cell to replicate the viral particles,” Dr Kuntworbe summarized.
Secondly, the drug also prevents SARS-CoV from plugging into a receptor called angiotensin-converting enzyme 2 or ACE2, on primate cells.
When the virus inserts its spike protein into the ACE2 receptor, it sets off a chemical process that alters the structure of the receptor and allows the virus to infect. The spike protein is like a key whiles ACE2 is changed to act as the spike protein’s keyhole.
An adequate dose of chloroquine appears to undermine this process, so the spike protein is unable to fit in the ACE2, to open the door of viral replication.
How would it fare?
The Center for Disease Control and Prevention identifies there is no vaccine or specific antiviral treatment for Covid-19.
Treatment of symptoms, quarantine and supportive services have been some of the interventions.
The Chinese Science and Technology Ministry had reported a drug developed in Japan had shown promise in treatment outcomes.
It reports improvement in lung condition of 91 out of 340 patients treated with the drug, favipiravir, in Wuhan.
The Science magazine reports the WHO has launched a global mega trial of the four most promising coronavirus treatments.
Chloroquine and hydroxychloroquine are high on the list.
Before the trial begins, however, results from a clinical trial from Shanghai Public Health Clinical Center in China on use of the hydroxychloroquine for Covid-19 has suffered a set-back.
The controlled study found no significant health outcomes between patients who received conventional care and those who took the drug.
The 5-day investigation involved 30 patients in two groups of 15 each.
They were given 400mg of chloroquine. Interestingly, one of the patients whose condition had gotten worse was on the dosage.
Though the meagre sample size is not enough to put it at par with a WHO study, this might give it a lead. Is it also possible different dosages might birth encouraging outcomes?
A Marseille, France report sought to juggle with a different dosage of 600 mg.
36 patients who took part in the ten-day research were administered 3 times per day with hydroxychloroquine and antibiotic Azithromycin.
Of the 26 patients who received the drug, data of 20, according to the report published in the International Journal of Antimicrobial Agents, had encouraging results. However, the journal’s Editor-in-Chief, J.M. Rolain, is one of the authors. This and the fact that it is yet to make a cut in a medical journal makes the study’s authenticity somehow questionable.
Already, the Economic Community of West African States (ECOWAS) has given approval for hydroxychloroquine to be used on COVID-19 patients.
However, the 5 to 7-day treatment is for patients with mild symptoms.
In a large-scale trial published in the Canadian Medical Association Journal, zinc was found to be effective at treating common cold, also caused by a virus.
The results published in 2011, showed “those receiving zinc had a shorter duration of cold symptoms.”
In a 2010 report published in the journal, PLoS Pathogen, zinc was found to inhibit coronavirus in the lab.
Recent reports from South Korea suggest hydroxychloroquine and zinc combination has successfully been used on COVID-19 patients.
“Chloroquine helps to increase the cellular uptake of zinc; and zinc is known to interfere with the RNA of the virus, which affects replication,” Dr Kuntworbe explained.
While we await the verdict of the WHO, and results from ECOWAS, three other drugs have been considered alongside the duo.
Two HIV drug combinations, lopinavir and ritonavir; same combination plus a virus-crippling agent and an experimental antiviral agent, remdesivir, which prevents viruses from building new genes, are the other agents.
The use of blood plasma from recovering patients to treat ailing ones have been successful in recent times. Infectious diseases like Influenza and measles were fought with century-old therapy.
In 2014 when the world health body was deliberating on vaccines and therapies for fighting the Ebola outbreak, the use of plasma treatment came up for discussion.
“There was consensus that the use of whole blood therapies and convalescent blood serums needs to be considered as a matter of priority,” the report noted.
Findings from the Journal of Infectious Diseases noted the therapy was successful with Ebola patients.
Reports of China’s success at treating COVID-19 patients with the method probably prompted the U.S. FDA to consider plasma treatment as a viable means of relieving Covid-19 patients.
Side effect fears
Though chloroquine’s side effects have included mild nausea and occasional stomach cramps, one of the most dreaded of all the side effects, according to many people I spoke with, is chloroquine-induced itching known as pruritus.
“I couldn’t sleep the whole night, Yusif, a mechanic, told me. “It was after I was made to swallow piriton before it could go down,” he recalled.
“I can’t tolerate chloroquine at all,” Franklin, a media manager, wouldn’t hide his fear about the drug.
Their misgivings reflect a 1988 study involving 1,152 participants in Ghana.
The findings in Ghana Medical Journal says 44.8 per cent of respondents reported itching after taking chloroquine.
“Black people are known to be sensitive or experience this itching condition as compared to white population,” Dr Kuntworbe asserts.
Clinicians, in recent times, have sought to lessen this reaction by combining chloroquine with drugs called antihistamines, known to quell the allergic reactions. Those who have been put on these combinations, I spoke with, have not been impressed.
“The itching went down, but not that much,” both Yusif and Franklin pointed out.
Though the study also found 78 per cent of respondents “felt that the antihistamine helped their itching,” the benefit, however, was not quantified.
They again found nearly 1 in 2 of offspring itch, if both parents are itching as opposed to 1 in 10 when neither parent itches.
The report of “a genetic basis for chloroquine-induced pruritus, in addition, a pathway leading to male preponderance in off-springs (sic) of respondents who itch has been established,” perhaps, will give researchers cues to work with to manage in administering of the drug, if approved.
After Donald Trump’s endorsement, two cases of chloroquine poisoning have been reported in Nigeria.
“On a more serious note, Chloroquine can result in cardiac arrest,” Dr. Kuntworbe clarified. “Which is the main cause of death as a result of chloroquine toxicity.”
“Across the nation, all pharmacies are aware of the directive not to sell chloroquine or hydroxychloroquine to people without a valid prescription. At the moment, hydroxychloroquine is not at the licensed over-the-counter shops, only at the pharmacies,” Dr Kontoh assured.
In Ghana, the Centre of Awareness Peace Mission has been in the news for its herbal-based dietary supplement, COA FS. The preparation branded as an immune booster has been touted to fight HIV AIDS.
The Executive President, Prof. Samuel Ato-Duncan, was reported to have said some Chinese are using his drug to treat Covid-19, a claim he later refuted.
“We wish to state that COA FS is not a cure for coronavirus,” he told a press conference.
Ghana’s premier medical research centre, Noguchi Memorial Institute for Medical Research has confirmed receiving the COA FS for clinical trials. Ahead of the procedure, there have been complaints about inadequate equipment.
Last week, Head of the institute, Prof. Kwabena Anang, sounded an alarm at the country’s lack of preparedness towards certifying even test kits for Covid-19.
“We have equipment that will cost us about $25,000 for just one certification,” he opened up to Evans Mensah on Joy FM’s Top Story. “Some of the equipment we’re using in testing COVID-19 also need this kind of certification,” he pointed out.
“We’re raising the issue with the Ghana Health Service and the Ministry of Health so that appropriate funding is made available so that we’ll not need to shut down any equipment,” Dr Annan added.
On the National Health Insurance Scheme, chloroquine and hydroxychloroquine are not included on the essential medicines list.
“Because of the issues of resistance, it was taken out of the essential drug list. Because it has other benefits, a few facilities have them, just in case a prescriber needs it to manage certain conditions. As for large scale, we don’t have it,” Dr Kontoh said.
Before chloroquine use was suspended fifteen years ago by Ghana’s Health Ministry, many pharmaceutical manufacturers were producing the syrup but Chief Executive of Aspee Pharmaceuticals Limited in Ejisu Ghana, Aboasu Amponsah-Kodua revealed, “It was at the time we started producing the tablet the ban came.”
On March 16, President Akufo-Addo met with pharmaceutical companies to strategize to produce hand sanitizers and drugs as part of Covid-19 response.
“I met with leaders of our country’s pharmaceutical and banking industries to discuss, at length, how best Ghana can begin to reduce her dependency on imports, in the wake of the Coronavirus pandemic,” the President posted on Facebook.
“We are far too dependent on the things made abroad, and imported by us for use. We should be making most of the things we use in Ghana, and needed to combat the spread of the pandemic, by ourselves. The pandemic has very severe consequences, but it also presents us with an opportunity. They say necessity is the mother of invention, and advisedly so,” he concluded.
Dr Kontoh is optimistic Ghana’s industries will stand up to the challenge when it comes to large-scale manufacture of the drug. He believes governments support is needed.
“As soon as the go-ahead comes from the FDA, I can guarantee our manufacturers are ready. Because it’s not a new drug, we’re not going to struggle at all. All they may need is support from the government,” he assured.
How accessible can it be?
According to the Ghana Living Standards Survey Round 7 report, 6.8 million Ghanaians live on 1 dollar or 5.7 cedis a day. My search at some pharmaceutical shops reveals a tablet of hydroxychloroquine costs between 2 cedis and 3 cedis.
Already, hand sanitizers which went for 4 cedis are reportedly being sold for 30 cedis in many parts of the country. It is a similar situation with Personal Protection Equipment.
“Nose mask which use to be about 50 pesewas is now something else,” David Danu posted on his WhatsApp status. “Three days ago, I got it for 3 cedis and today, 10 cedis. Some pharmacies told me 15 cedis. How do we expect people to buy it?”
Though the government has made several appeals and admonished people against the price hikes, the message has gone unheeded. Won’t it be the same when the drug is approved as a panacea?
Though Dr Kontoh is optimistic of Ghana’s ability to produce in large quantities when the need arises, a chemistry lecturer at the Kwame Nkrumah University of Science and Technology, Dr Lawrence Borquaye, in a Facebook post, expressed worry the situation will expose Ghana’s lack of support, especially, for research activities.
“Recent developments indicate that a number of drug leads are pointing in the right direction towards being a cure,” he wrote on his Facebook page. “The announcement that the pH regulator HCQ is in clinical trials is good news. Other drugs such as the adenosine mimic and chain terminator Remdesivir (RDV) and the RNA dependent RNA polymerase inhibitor Favilavir (FV) are also said to be doing well in clinical trials,”
“We don’t have the capacity to do the basic science needed to develop a cure,” Dr Borquaye revealed. “We pay scientists a research allowance of GH¢500 per annum.”
“However, let’s be proactive. How can we get enough HCQ or RDV or FV when the need arises? We need to work on this as a matter of urgency,” he stressed.
Dr Borquaye warned Ghana may lose the fight against the disease should it wait for the drug’s utmost approval.
“Though it’ll be a risk to procure raw materials for drug manufacture,” he told me via phone conversation, ‘’it’s a necessary risk because when it comes out it’s the cure, the countries supplying the materials would have to serve their people before us’’.
Fortunately, the Health ministry upon the Food and Drugs Authority’s recommendation included Chloroquine and hydroxychloroquine on the emergency drug list for Covid-19 patients.
“For hydroxychloroquine, no clinical trial has been conducted in Ghana. We’re using 200mg of hydroxychloroquine, 3 times daily for 14 days. There are studies to show that they can be of help in managing Covid-19 cases, that’s why we’ve authorized it for emergency use,” head of laboratory services, FDA, Eric Karikari Boateng explained.
He noted his outfit is undertaking a fast-track test on drugs that would be registered under emergency.
“We’re conducting a fast-track test on the drugs to ensure they conform to standards. This takes place within 2 to 3 days,” he said.
Ghana joins the likes of Togo and Senegal in the treatment of Covid-19 patients with Chloroquine and hydroxychloroquine. As our neighbour, Burkina Faso prepares for a clinical trial, Ghana, with some of its Covid-19 patients recovering, will be watched closely to cast one.
“It’s most likely Ghana might participate in the WHO mega trial known as solidarity trial,” Mr Boateng is optimistic.
The world is far ahead in coming out with a potent drug to tackle the new scare. Drugs that can slow or kill the virus could be lifesavers. Front line health workers who have been caught in the crossfire will be relieved.
Vaccines, drugs, drug combinations are under scrutiny. The virus has not only tested our healthcare system but will test our drug research and production capacity, as well.
It has become crucial we are not always known for clapping when the West pulls a dove from their magic box but we own the box itself.