The Lancet Infectious Diseases has expressed concern regarding the endorsement of use of hydroxychloroquine by the Indian Government. The endorsement comes despite a dearth of evidence regarding its specific use against COVID-19 – the disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), commonly simply referred to as the coronavirus.
The Indian Council of Medical Research (ICMR), under the Ministry of Health and Family Welfare, has recommended the use of chemoprophylaxis with hydroxychloroquine (consisting of 400 mg twice on day one, followed by 400 mg once a week thereafter) for people deemed to be “high risk.” This refers to asymptomatic healthcare workers treating patients with suspected or confirmed COVID-19 and for asymptomatic household contacts of confirmed cases. Hydroxychloroquine is a medicine used in the treatment of infectious diseases such as malaria.
As stated by The Lancet in an online correspondence, “even for treatment of diagnosed cases, only one small study reported faster nasopharyngeal viral clearance, with no data for clinical improvement. This evidence, or the lack thereof, hardly justifies state-endorsed, widespread use of hydroxychloroquine for prophylaxis.”
Hydroxychloroquine, available as both a brand-name and generic medication is a commonly used medication for both prevention and treatment of malaria. India is a major manufacturer of the medication and, since its endorsement by US President Donald Trump, the demand for the medication has elevated considerably.
Al Jazeera published an article whose headline even suggested hydroxychloroquine “has become a tool of India’s diplomacy.” This is arguably in-keeping with India’s reputation as a global pharmacy, given its voluminous exports of medicines overseas (particularly to developing countries). India is reportedly in the process of supplying anti-malarial drug hydroxychloroquine to 55 coronavirus-hit countries as grants as well as on commercial basis according to official sources quoted Thursday last week.
President Trump has expressed a particular interest in the drug, requesting that Indian Prime Minister Narendra Modi allow the sale of hydroxychloroquine tablets ordered by the US to treat the growing number of coronavirus patients in the US. In response, Modi lifted the ban on exports of the drug.
Trump responded on Twitter “extraordinary times require even closer cooperation between friends. Thank you India and the Indian people for the decision on [hydroxychloroquine]. Will not be forgotten! Thank you Prime Minister @NarendraModi for your strong leadership in helping not just India, but humanity, in this fight!” Modi responded in kind, tweeting “times like these bring friends closer. The India-US partnership is stronger than ever. India shall do everything possible to help humanity’s fight against COVID-19. We shall win this together.”
Irrespective of the use of hydroxychloroquine as an implement of diplomacy or foreign policy, it is important to remember that its use is in the context of public health and that, for state-sanctioned consumption, there must be a robust body of scientific evidence to back it up. It is unsurprising, therefore, that concerns have been expressed as of yet concerning the absence of such evidence. A second paper published in The Lancet described the current clinical data as “far from convincing”. They elaborate in detail the criticisms of the original study that sparked the interest in the medication to begin with
“The first study reported by Philippe Gautret and colleagues, which indicated that hydroxychloroquine might be effective, had several limitations: a small cohort of patients, with only twenty participants who received hydroxychloroquine (six of whom received azithromycin) and sixteen controls included in the final analysis; a very short observation period (six days); absence of randomisation, raising concerns about selection bias and imbalance of baseline characteristics in the intervention and control groups; and no report of effects on clinical evolution (six [seventeen percent] patients were asymptomatic and only eight [22 percent] had pneumonia).”
They note that subsequent studies simply neglected to have a control group at all. Such small-scale studies with less than rigorous methodology are far from convincing. This throws cold water on the idea of – as many countries have done – taking up hydroxychloroquine as the potential saviour against the global coronavirus pandemic.
The Wire notes that statements made by Dr Raman Gangakhedkar, the chief epidemiologist of the ICMR, regarding hydroxychloroquine have been conflicting. He mentioned in a video published by ANI News that because there was so little evidence of the drug’s efficacy against COVID-19, the ICMR was recommending it only as a prophylactic to doctors and contacts of lab-confirmed patients. However, the ICMR has suggested the use of hydroxychloroquine as treatment for COVID-19 patients in intensive care units (ICUs).
There are no current published studies assessing the use of hydroxychloroquine as a prophylactic. Studies such as those noted above have found some — albeit mixed — evidence regarding its use as a treatment, though nothing to indicate that the medication would be useful in a preventative sense.
Whether it could operate as a prophylactic is dubious, and may even vary from person to person. Hydroxychloroquine may impair a healthy person’s ability to fight off the coronavirus via inhibition of an immune system molecule called interferon alpha. For some, this may mean its use as a prophylactic actually negatively affects them. For others, the opposite may be true. Inhibition of interferon alpha could actually help many who suffer from an over-aggressive immune response (called a cytokine storm) to the virus that triggers coronavirus, reducing excessive inflammation.
Even the use of hydroxychloroquine among healthcare workers could be called into question by data produced by the ICMR themselves. While positive effects are at this stage still undergoing testing, the ICMR found that “healthcare workers having an average age of 35 years took these drugs and ten percent reported abdominal pain, six percent reported nausea and 1.3 percent reported hypoglycemia.”
The use of hydroxychloroquine has suffered from great expectations and short deadlines. In theory, as a relatively commonly used medicine and inexpensive in its generic form, it could be the ideal counter to coronavirus, especially in low-to-middle income countries. However, its use, as of yet, is based on only partial evidence that does not even fully support the conclusion seemingly reached by governments across the globe. A treatment, and indeed a hope, is vitally needed in the face of the pandemic, but it is important to wait for the evidence.