The controversy around Hydroxychloroquine

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Hydroxychloroquine: A potentially effective remedy for Covid-19?

The use of Hydroxychloroquine to treat covid-19 is a huge discussion in France now. Our correspondent, Adnan Haider, who is currently in France, has told us about the discussions going on in France:

The coronavirus pandemic has recently wreaked havoc, causing several thousand deaths worldwide. Countries have moved from initial precautions to full containment. Europe has become the epicentre of the pandemic and has surpassed the three-thousand deaths recorded in China, there are more than 21,000 deaths worldwide with more than half a million cases recorded. The issue of the vaccine is on everyone’s mind and governments are organising to find the cure for this epidemic.

Recently, hydroxychloroquine has been the subject of debate in France. Indeed, this molecule used in the preventive and curative treatment of malaria and other pathological diseases is said to be “promising” in the media in France and raises the hopes of all French people, especially since its use has recently been authorised by the French government in hospitals for the patients most seriously affected by the virus. In a press conference, Donald Trump went as far as to call it a “gift from heaven”, encouraging people to rush to pharmacies where the drug was available over the counter.

Hydroxychloroquine and chloroquine are the derivatives of quinine. Quinine comes from Cinchona tree (Cinchona officinalis), a medicinal plant originally found in Peru and was used by indigenous people to fight chills and fever. It was brought to the West in 1633 and quickly gained economic and political importance as the extract of the cinchona bark was found to be the only effective treatment against malaria at the height of European colonisation. Its active ingredient was later isolated in 1820 and named quinine. Afterwards, quinine and its derivatives chloroquine and hydroxychloroquine were also made in laboratories. Quinine and its derivatives are well known anti-malarials and are used in certain inflammatory diseases. Contrary to some reports going around in social media, quinine and its derivatives are not related to black seed (Nigella Sativa).

Interestingly, these drugs have shown anti-viral activity in laboratory test studies since the late 1960s, but these findings were never actively pursued in clinical studies.

The reason hydroxychloroquine is so hopeful in France is because it was tested on patients with the coronavirus. Professor Didier Raoult, a French infectious disease expert and professor of microbiology, is a specialist in emerging tropical infectious diseases at the Faculty of Medicine at the University of Aix-Marseille and the IHU Méditerranée Infection.

On the evening of February 25, 2020, at the start of the coronavirus pandemic in France, Didier Raoult announced the “endgame” for the coronavirus, saying that hydroxychloroquine is “probably the cheapest and simplest treatment to treat the Covid coronavirus”. His position follows two Chinese communications: the first on 25 January reported great effectiveness, the second on 15 February, with positive preliminary results on a hundred patients. It is the subject of numerous warnings, due to many failures to treat other viruses following promising in vitro results, the lack of clinical data and contradictions, side effects, risks of overdose and known drug interaction problems.  The French Ministry of Health then stated that no rigorous study, published in an international peer-reviewed journal, had demonstrated the efficacy of chloroquine for the treatment of coronavirus.

On March 11, 2020, Didier Raoult became one of eleven experts chosen to be part of the COVID-19 Scientific Council, responsible for informing the decisions to be taken by the authorities to fight the pandemic in France. No longer participating in the meetings, he says he refuses to resign on March 24. He quickly positioned himself against the policy of low screening and dissociated himself from the containment measures taken in France, judging that the mortality due to the disease is insignificant in view of its low recorded lethality, which in his geographical area (PACA) concerns only two people over 87 years of age for 120 confirmed cases.

On 16 March 2020, he had broadcast a video to his students in which he announced the positive results of his own clinical study, which were published on 20 March. Indeed, the vast majority of patients tested were free of the virus after six days.

Initially other antivirals are selected for the first French clinical trial announced on March 11, since hydroxychloroquine was not selected. The justification given then was the risk of drug interaction with resuscitation treatments, side effects and the absence of hydroxychloroquine on the list of priority treatments recommended by the WHO. Nevertheless, on March 17, Health Minister Olivier Veran, judging the results of Didier Raoult and his team to be “promising”, immediately gave authorisation for other teams to undertake a larger trial “as soon as possible”.

On March 19, 2020, Donald Trump declared that he had “approved” the use of hydroxychloroquine which, according to him, “has shown very encouraging preliminary results” in the fight against Covid-19. In all likelihood he is referring to, and has been influenced by the work of Didier Raoult. He was immediately tempered by the FDA, which wants to take more time to evaluate this treatment and launch “an extended clinical trial” to see if science fully supports these claims.

On 20 March, 2020, the preliminary results of this trial were published as “Hydroxychloroquine and Azithromycin as a treatment of COVID-19: preliminary results of an open-label non-randomized clinical trial” as a non-peer-reviewed “pre-publication” on the MedRix website and in the International Journal of Antimicrobial Agents. Its protocol and publication methods have been strongly criticised by the scientific community, by the Scientific Advisory Board on Covid-19, and commented on the Pubpeer website. This also resulted in  hydroxychloroquine to be included in numerous clinical trials, including the European “discovery” clinical trial from which it was initially excluded.

Raoult’s team announced on March 22 that it would offer all infected patients a treatment combining hydroxychloroquine and the antibiotic azithromycin. The High Council of Public Health (HCSP) recommends that this molecule should not be used in this context, with the exception of serious hospital forms of the disease.

Despite all the bickering among the scientific community, the Faculty of Medicine at the University of Aix-Marseille, has opened its doors to anyone who wants to be tested, and even offers to treat coronavirus patients with hydroxychloroquine. Several mayors in France affected by the virus have consented to this treatment, such as Christian Estrosi, Mayor of Nice, who says he feels he is cured using Chloroquine.

Several countries have already started treating their patients with hydroxychloroquine. This is the case of Morocco, which has requisitioned all the stocks of Chloroquine produced by the country. Belgium is using it to treat its patients, as well as Algeria and other West African countries.

In Tunisia, a budget of 2.5 million dinars – 800,000 euros – is allocated to research on the use of the molecule in the treatment of Covid-19. The Minister of Health, Abdellatif Mekki, has authorised its experimental use in Tunisian hospitals.

Although some clinical studies have shown efficacy of hydroxychloroquine, it may be too early to draw conclusions because all such studies were non-randomised open label trials or case-series; such studies are methodologically weak and therefore conclusions drawn are very limited.

Only one randomised clinical trial of 30 patients has been published by a group in China which showed that hydroxychloroquine was no different from usual treatment. One possible reason for the lack of result is that the trial was too small.

Currently, many clinical trials are underway around the world on chloroquine and hydroxychloroquine and it will be several weeks before concrete results of its overall efficacy are available. Furthermore, it is not known if the use of hydroxychloroquine/chloroquine in non-symptomatic people will prevent and reduce the spread of COVID-19.

In most countries these drugs are available only via prescription and should only be taken under doctors’ supervision due to side-effects. One death has also been reported in USA following an overdose. The victim and his wife, she told NBC, ingested chloroquine phosphate used in fish tank cleaner after hearing hearsay that extolled the benefits of the drug at a press conference.

As for Professor Raoult, he is the subject of much criticism in France despite the fame of his exploits. Highly controversial in this crisis, the man is a highly recognised scientist, holder of the Inserm Grand Prize in 2010 and ranked among the world’s most influential researchers in 2015 by the medical journal Thomson Reuters. A misunderstanding is suspected between Professor Raoult and Agnès Bzyn, former French Minister of Health.

In any case, Professor Didier Raoult is increasingly supported by the population through social networks. Several videos denounce the lack of efficiency of the French government in the face of the crisis and praise Professor Raoult’s “quick and dirty” research in a time similar to war.

(A special thanks to Dr. Tauseef Khan)

Sources:

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