Off-label drug use during the COVID-19 pandemic in Africa

Although rejected by the World Health Organization, the human and even veterinary formulation of ivermectin has widely been used for prevention and treatment of COVID-19. In this work we leverage Twitter to understand the reasons for the drug use from ivermectin supporters, their source of information, their emotions, their gender demographics, and location information, in Nigeria and South Africa. Topic modelling is performed on a Twitter dataset gathered using keywords ‘ivermectin’ and ‘ivm’. A model is fine-tuned on RoBERTa to find the stance of the tweets. Statistical analysis is performed to compare the stance and emotions. Most ivermectin supporters either redistribute conspiracy theories posted by influencers, or refer to flawed studies confirming ivermectin efficacy in vitro. Three emotions have the highest intensity, optimism, joy and disgust. The number of anti-ivermectin tweets has a significant positive correlation with vaccination rate. All the provinces in South Africa and most of the provinces of Nigeria are pro-ivermectin and have higher disgust polarity. This work makes the effort to understand public discussions regarding ivermectin during the COVID-19 pandemic to help policy-makers understand the rationale behind its popularity, and inform more targeted policies to discourage self-administration of ivermectin. Moreover, it is a lesson to future outbreaks.

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1.  Background

‘Off-label’ or ‘expanded drug use’ refers to an unapproved use of a drug, that is to say, any use beyond what regulatory agencies have reviewed and authorized to be marketed in a country, as indicated on the product label. Self-administration of unauthorized drugs can pose serious health problems and represents a global public health concern. Self-administration of off-label drugs has become very widespread for treating SARS-CoV-2 during the COVID-19 pandemic [1]. Although several substances such as nirmatrelvir/ritonavir, dexamethasone, remdesivir, and molnupiravir gained approval or conditional approval for mild or severe cases of COVID-19, other medications such as hydroxychloroquine (HCQ), chloroquine (CQ), lopinavir/ritonavir, ruxolitinib, colchicine, doxycycline and ivermectin have been strongly rejected by the World Health Organization (WHO), since randomized controlled trials indicated that they had no clinical efficacy in prevention or treatment of coronavirus, and were rather harmful [2,3]. HCQ/CQ use was found to be associated with a rise in the risk of ventricular arrhythmias and subsequent death of hospitalized patients [2,3].

With the emergence of new SARS-CoV-2 variants, ivermectin gained the most popularity among all the different unapproved drugs. shows the total number of tweets on prohibited drugs used during the COVID-19 pandemic for the whole world. It can be observed that HCQ and CQ were popular at the beginning of the pandemic but lost attention afterwards. However, the volume of the tweets on ivermectin dramatically increased, especially during the third and fourth waves of COVID-19, and it still remains high. Other drugs did not gain that much attention on Twitter during the COVID-19 pandemic.

Ivermectin may have antiviral properties against RNA viruses such as SARS-CoV-2 in vitro. However, the dosage required to reach in vitro efficacy is very toxic to the human body [4]. Ivermectin toxicity includes symptoms such as ataxia, weakness, decreased consciousness, confusion, hallucinations, gastrointestinal distress, nausea, vomiting, diarrhoea, hypotension, seizure, coma and death [5,6]. Therefore, it was not approved for treatment or prevention of COVID-19. Unfortunately, this did not stop the distribution of the drug through black markets [7,8]. Due to shortages of the human formulation of ivermectin, people even consumed ivermectin intended for livestock [9]. Consequently, during the COVID-19 pandemic, hospitalizations caused by veterinary form and overdosage of human form of ivermectin increased [10]. Moreover, as a result, those who were in need of ivermectin (e.g. for parasites, for their farm animals/pets) found it hard to have access to the drug [11]. Above all, false anecdotes of ivermectin success discouraged people from taking vaccines [12]. In this work, we study social media to understand the reasons that have caused people to believe in ivermectin and their feelings towards it.

People are increasingly using social media platforms to discuss their beliefs, experiences, and opinions. With the lockdown measurements during the COVID-19 pandemic, even more time was spent on social media platforms [13]. Therefore, social media is broadly used in different areas of research, especially the COVID-19 pandemic [14]. Although social media has widely been studied for different aspects of the COVID-19 pandemic such as macroeconomic consequences [15], indicator prediction [16], mental health problems [17], misinformation [18], and vaccine hesitancy [19], few papers have used it to understand mass opinions on ivermectin. Diaz et al. [20] have studied ivermectin from a political point of view. Topic modelling and sentiment analysis were performed on tweets related to ivermectin and posted from the United States. The results show that the overall sentiment of the tweets was negative. However, tweets from democrats had more negative polarity compared to tweets from republicans. In [21] a dataset of tweets posted from the United States, the United Kingdom, Canada and India were analysed. Most of the users posting the tweets were health practitioners, scientists/researchers, or executives. Three main topics were identified from the tweets: one of these was ‘Pierre Kory’, an American critical care physician who advocated off-label use of various drugs as treatments for COVID-19, including ivermectin, described as a ‘wonder drug’ with ‘miraculous effectiveness’ against COVID-19. The other two topics were ‘early treatment’, and ‘be brave and keep fighting against COVID19’. Gouveia et al. [22] pointed out the high volume of tweets and searches on Google trends regarding ivermectin, HCQ and CQ in Latin American countries. Koss & Bohnet-Joschko [23] found ivermectin to be one of the most discussed supplements used for COVID-19 prophylaxis and treatment, on social media.

In [24] authors found that there was an increase in purchasing ivermectin from December 2020 to January 2021 in the United States and Canada, and this was statistically in line with the number of posts on ivermectin in social media platforms and the number of searches for ivermectin in Google trends. Authors in [25] studied the posts from Peru related to ivermectin on Facebook. Their results show that most of the posts are rumours that support ivermectin efficacy against COVID-19. In [26] Google trends were examined and topic modelling was performed on Facebook posts to understand ivermectin popularity in Romania. They found that ivermectin was a topic of public concern, as the top voices initiating the conversations were not only anti-vaccine influencers, but also mainstream personalities. Of interest, authors in [27] found a negative correlation between the number of ivermectin Google searches and vaccination rates. They also found that the number of searches on ivermectin is higher in locations that have lower vaccination rates. In [28] posts from South Africa were studied to show that social media is a driver to medicine use, despite availability of scientific evidence. The results show that posts related to ivermectin and HCQ efficacy against COVID-19 had positive sentiments, in general. In [29] four medications, namely, HCQ, ivermectin, molnupiravir and remdesivir, were compared using tweets posted from the United States. They concluded that HCQ and ivermectin are highly politicized and under conspiracy theories, hearsay and celebrity effects. Republicans supported ivermectin and HCQ more than democrats. While the general population supported HCQ and ivermectin, people with healthcare backgrounds opposed it.

Although papers mentioned above provide rich information on public opinions regarding ivermectin, none of them have properly studied the reasons ivermectin has gained so much popularity and the general feelings towards it. In this paper, we fill in the gap by performing topic modelling and emotion analysis on tweets related to ivermectin to understand ivermectin-supporters' reasoning and emotions. Additionally, most of the studies in this area have used publicly available datasets. In this research we use Twitter API academic researcher account which guarantees to return all the tweets available for a certain query to study the aspect [30]. Our dataset is freely available from [31]. Our contribution to this work is four-fold:

• (1)

  To understand assertions made for supporting ivermectin, and their sources.

• (2)

  To understand feelings and emotions towards ivermectin being unapproved by WHO and prohibited by responsible health agencies.

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• (3)

  To understand the distribution of public opinions and emotions across gender and different locations.

• (4)

  To provide an extensive Twitter dataset on unapproved drug use during the COVID-19 pandemic that future studies could build up on [ 31 ].

Natural language processing (NLP) is a machine learning tool for analysing text. Different NLP tasks are performed to conduct this study. Topic modelling is used to comprehend the different discussions related to ivermectin on Twitter. Stance is the state of a tweet being pro-ivermectin, anti-ivermectin or neutral [29]. We train a model based on transformers to find the stance of the tweets. Then, the stances of the tweets in each topic are identified, and the emotions of each stance are realized. Next, the emotions of the stances and topics for men and women, and for different locations in Nigeria and South Africa are studied. Understanding the demography of pro-ivermectin individuals could be useful in messaging campaigns to reduce the harms of off-label drug use. Nigeria and South Africa are the two African countries that were heavily affected by the ivermectin confusion during the COVID-19 pandemic [32,33]. As this project clarifies the rationale behind ivermectin use for COVID-19, it can help decision-makers inform more targeted policies for promoting safe medication use. Moreover, it is a lesson for future epidemics.