PreprintPDF Available

Hydroxy-Chloroquine: Chemoprophylaxis of Malaria and not a Silver Bullet versus COVID-19

Preprints and early-stage research may not have been peer reviewed yet.
Hydroxy-Chloroquine: Chemoprophylaxis of Malaria and not a Silver Bullet versus COVID-19
ISSN (Print): 2521-8514 ISSN (Online): 2521-8484
RADS J. Pharm. Pharm. Sci.
Hydroxy-Chloroquine: Chemoprophylaxis of Malaria and
not a Silver Bullet versus COVID-19
Irshad Hussain
Institute of Pharmacy, SMBB Medical University Larkana, Pakistan
Article info.
Received: July 14, 2020
Accepted: July 23, 2020
Funding Source: Nil
Conflict of Interest: Nil
Cite this article: Hussain I. Hydroxy-
Chloroquine: Chemoprophylaxis of Malaria
During the Pandamic Covid-19. RADS J
Pharm Pharm Sci. 2020; 8(1):65-67.
*Address of Correspondence Author:
Introduction: The world has been facing the pandemic COVID-19. This
article highlights the importance of Hydroxychloroquine (HCQ) and
Chloroquine (CQ) in the chemoprophylaxis of malaria during the pandemic
Objective: To derive logical conclusion about the indicated use of HCQ/CQ in
malaria during the pandemic COVID-19.
Methods: Relevant research articles were retrieved. The online reports,
research articles from google, google scholar and PubMed databases were
searched and analyzed.
Results: HCQ and CQ are indicated for Malaria and its prophylaxis. The
drugs are not silver bullets versus the COVID-19. The available clinical data
till the end of July 2020 can be sufficient for the health authorities of various
countries to stop using HCQ/CQ to treat COVID-19 patients. The drugs are
indicated for malaria instead. Malaria, a potentially deadly parasitic disease
in the poorest countries which cannot even afford its preventive measures
with HCQ/CQ and other drugs. Misuse of available drugs of Malaria can
worsen the disease in the Africa and some Asian countries. The World
Health Organization has recommended continuing chemo-prophylactic
efforts for malaria during the COVID-19 crisis. Malaria and COVID-19 have
certain common symptoms such as fever, headache and body pain which
doubles the risk through misleading diagnosis by considering COVID-19
patients as malaria patients and vice versa. WHO has recommended the
mass distribution of antimalarial drugs for these counties, so that malaria
could not make COVID-19 more deadly.
Conclusion: Use of CQ/HCQ may be continued for the chemoprophylaxis of
Malaria during the pandemic COVID-19 and the drugs may not be considered
as Silver bullet for COVID-19. Directions of FDA and WHO may be complied
regarding use of CQ/HCQ.
Key words: HCQ, Hydroxychloroquine, CQ, Chloroquine,
Chemoprophylaxis of Malaria, COVID-19
This manuscript highlights the need to continue
the conventional use of hydroxychloroquine for
the chemoprophylaxis of malaria during the
COVID-19 pandemic by discussing the current
controversies developed with the use of drugs to
manage COVID-19 by certain countries based on
insufficient clinical information and by the
excessive influence of certain government officials
those otherwise could not develop an effective
strategy to minimize the threats of COVID-19 since
Hydroxy-Chloroquine: Chemoprophylaxis of Malaria and not a Silver Bullet versus COVID-19
ISSN (Print): 2521-8514 ISSN (Online): 2521-8484 66
RADS J. Pharm. Pharm. Sci.
the alarming outbreak from Wuhan., in China.
Malaria, a life-threatening parasitic disease of the
poorest countries (mainly the African region),
those, that cannot even afford its preventive
measures / prophylactic drugs. The African region
carries up to 90% of the global burden of malaria
[1]. Causative agent of the disease is plasmodium
parasite that is transmitted by female
anopheles mosquito (vector of malaria). It affects
more to children than adults. Due to malaria, an
estimated 0.405 million deaths worldwide were
reported in 2018. Symptoms of malaria are
fever, chills, headache, anemia, respiratory distress,
multiple organ failure and even deaths in the
absence of treatment [2]. Seasonal prophylaxis
and malaria prevention campaigns, provide the
community with a preventive dose of
antimalarials such as hydroxychloroquine (HCQ)
or chloroquine (CQ) and other medicines if a
resistant strain of plasmodium is confirmed.
WHO has already recommended preventive
measures against malaria. Although advanced
research drugs for malaria are also currently
available, but quinine derivatives are still used for
the prevention and control of malaria [3]. Current
pandemic caused by the novel SARS-Cov-2
has wreaked havoc in the lives of people from
almost all countries with the main symptoms of hot
fever, cough, shortness of breath and sore throat,
etc [4]. WHO has recommended continuing
chemo preventive efforts for malaria during COVID-
19. WHO has also closely monitored trials of
quinine derivatives for the prevention and
treatment of COVID-19 [5]. COVID-19 and malaria
have certain common symptoms such as fever,
headache and body pain that can double the risk of
misleading diagnosis. WHO has therefore
recommended mass distribution of anti-malaria
drugs in the poor countries, so that malaria could
not make COVID-19 more deadly [6]. Effects of
Chloroquine were studied versus
COVID-19 in vitro. [7]. Randomized controlled trials
were needed to better assess the clinical efficacy of
CQ / HCQ in COVID-19 [8]. There is available in-
vitro data related to efficacy of CQ / HCQ against
viruses such as HIV and SARS-Cov-1 [9,10]. The
Indian Ministry of Health had approved the use
of HCQ in the chemoprophylaxis of COVID-19
for asymptomatic healthcare workers in COVID-
19 and for family members of confirmed
cases of COVID-19, the approval with the
prescription of a licensed practitioner. The
Indian Ministry of Health had ignored the
requirements of essential clinical evidences
mandatory for such approvals. There were no
enough clinical trials to assess the efficacy of the
use of C Q/HC Q in COVID-19, as stated by
WHO. Several counties in the Middle East had
also authorized the use of HCQ in COVID-19 [11,
12]. Since the start of the COVID-19 epidemic in
Wuhan, the Chinese had attempted to trial HCQ
to minimize the symptoms of COVID-19 patients,
and such use has been reported in a multicenter
clinical trial in China [13]. Use of HCQ to minimize
symptoms of COVID-19 was also announced by the
president of United States. The president was
criticized by the relevant international health
agencies because advocating the use of CQ/HCQ
without sufficient clinical information was not
scientific. Under such circumstances, the Food
and Drug Administration (FDA) announced HCQ's
emergency approval for use in serious COVID-
19 patients in hospital settings and has now
restricted use for clinical trials in hospital settings
only, although, FDA had revoked this use. Being one
of the main producers of HCQ, India had sent
donations of HCQ stocks to 30 countries,
including SAARC countries (except Pakistan),
mentioning the requests for assistance by those
counties, particularly in the United States where
the death toll was alarming. Surprisingly, India was
also pushed by the United States president for
consequences in the event of non-supply of HCQ
In such a scenario of seasonal malaria, COVID-19
pandemic and the risks of co-infections, the author
on the basis of recent clinical evidences suggests to
support a campaign to administer the CQ / HCQ
prevention dose for malaria, among the population
at high risk of malaria.
1. Malarial prophylaxis to reduce doubling the risk of
misleading diagnosis of considering a malaria patient
as a COVID-19 patient. Malarial prophylaxis cannot
make COVID-19 more deadly by preventing the
possibility of co-infection of COVID-19 and malaria.
2. Reducing the prevalence of malaria and minimizing
the crowd of suspects at COVID-19 testing centers,
as similar symptoms of fever and headache can
increase the concerns of malarial victims to confirm it
by reaching test centers thus increasing the
probability that only COVID-19 patients will reach the
Hydroxy-Chloroquine: Chemoprophylaxis of Malaria and not a Silver Bullet versus COVID-19
ISSN (Print): 2521-8514 ISSN (Online): 2521-8484 67
RADS J. Pharm. Pharm. Sci.
test centers and hence preventing the wastage of test
kits and other resources.
FDA has revoked the emergency use authorization
(EUA) of CQ/HCQ in the COVID-19. There are
serious safety issues with the use of these drugs
mainly heart rhythm problems.. The drugs having no
benefit in decreasing the probability of death rate and
propelling the recovery [15]. WHO has also stopped
the use of CQ/HCQ in international clinical trial of
WHO based on the interim results of drug use as
compared to the standard of care. [16]. In such
circumstances the use of CQ/HCQ may be continued
in approved indications especially the prophylaxis of
Malaria during the pandemic COVID-19
1. Breman, JG., et al. 2001. The Intolerable Burden
of Malaria: A New Look at the Numbers. Journal of
Tropical Medicine and Hygiene. American Society
of Tropical Medicine and Hygiene. 64(1),
sheets/detail/malaria (accessed 14 April 2020).
3. Steffen, R., et al. 1990. Malaria chemoprophylaxis
among European tourists in tropical Africa: use,
adverse reactions, and efficacy. Bull World Health
Organ. 68(3), 313322.
4. Date Accessed 15 April 2020.
and-the-covid-19-pandemic. (Accessed 15 April
who (Accessed 15 April 2020).
7. Jia Liu., et al. 2020. Hydroxychloroquine, a less
toxic derivative of chloroquine, is effective in
inhibiting SARS-CoV-2 infection in vitro. Cell
Discovery. 6;16.
8. Kerstin Frie., Kome Gbinigie., 2020. Chloroquine
and hydroxychloroquine: Current evidence for their
effectiveness in treating COVID-19. CEBM.
9. Chauhan, A., Tikoo, A., 2015. The enigma of the
clandestine association between chloroquine and
HIV1 infection. HIV medicine. 16(10), 585-590.
10. Vincent., et al.. 2005. Chloroquine is a potent
inhibitor of SARS coronavirus infection and
spread. Virology journal,. 2(1). 69.
11. (Accessed
17 April 2020).
12. Secretary (Health and family welfare). Advisory on
the use of Hydroxy-chloroquine as prophylaxis for
SARS-CoV-2 infection. March 2020. Ministry of
Health and family welfare, Nirman Bhawan, New
13. Jianjun Gao., et al., 2020. Chloroquine phosphate
has shown apparent efficacy in treatment of
COVID-19 associated pneumonia in clinical
studies. Biosce Trends. 16;14(1):72-73. DOI:
nl_politics. (Accessed 15 April 2020).
15. safety-and-
outside hospital setting-or (Date accessed 30 July
who-discontinues hydroxychloroquine-and-
(Date accessed 30 July 2020.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License
(, which permits unrestricted use, distribution, and reproduction in any medium, provided
the original work is properly cited.
ResearchGate has not been able to resolve any citations for this publication.
Full-text available
Severe acute respiratory syndrome (SARS) is caused by a newly discovered coronavirus (SARS-CoV). No effective prophylactic or post-exposure therapy is currently available. We report, however, that chloroquine has strong antiviral effects on SARS-CoV infection of primate cells. These inhibitory effects are observed when the cells are treated with the drug either before or after exposure to the virus, suggesting both prophylactic and therapeutic advantage. In addition to the well-known functions of chloroquine such as elevations of endosomal pH, the drug appears to interfere with terminal glycosylation of the cellular receptor, angiotensin-converting enzyme 2. This may negatively influence the virus-receptor binding and abrogate the infection, with further ramifications by the elevation of vesicular pH, resulting in the inhibition of infection and spread of SARS CoV at clinically admissible concentrations. Chloroquine is effective in preventing the spread of SARS CoV in cell culture. Favorable inhibition of virus spread was observed when the cells were either treated with chloroquine prior to or after SARS CoV infection. In addition, the indirect immunofluorescence assay described herein represents a simple and rapid method for screening SARS-CoV antiviral compounds.
The coronavirus disease 2019 (COVID-19) virus is spreading rapidly, and scientists are endeavoring to discover drugs for its efficacious treatment in China. Chloroquine phosphate, an old drug for treatment of malaria, is shown to have apparent efficacy and acceptable safety against COVID-19 associated pneumonia in multicenter clinical trials conducted in China. The drug is recommended to be included in the next version of the Guidelines for the Prevention, Diagnosis, and Treatment of Pneumonia Caused by COVID-19 issued by the National Health Commission of the People's Republic of China for treatment of COVID-19 infection in larger populations in the future.
The antimalarial drug chloroquine (CQ) dampens the immune system and is used in the treatment of autoimmune disorders. CQ also shows antiviral activity against nonenveloped and enveloped viruses, including HIV-1. Persistent immune activation in chronic HIV-1infection leads to CD4 T-cell depletion. CQ is envisioned to attenuate immune activation and virus activity in HIV-1-infected patients. The role of CQ in immune activation and virus activity is discussed here. To elucidate the effect of CQ on immune activation, a retrospective review of published clinical trials, in vivo experimental studies in animals, and the most relevant in vitro observations in HIV-1-infected cells, together with observations from our own laboratory studies, was carried out and the findings discussed. In a few clinical studies and animal experiments, CQ was ineffective in decreasing immune activation and HIV-1 infection. In vitro, CQ markedly increased HIV-1 infection in astrocytes and other non-CD4 cells. The use of CQ in HIV-1-infected patients is questionable. The evidence for a dampening of immune activation by CQ is inconclusive. © 2015 British HIV Association.
In order to determine knowledge, attitudes and practices towards malaria prophylaxis, as well as its side-effects and efficacy, a self-administered questionnaire was distributed to European travellers on return flights from tropical Africa to Europe. Between 1985 and 1988 the questionnaire was completed by 44,472 passengers (80.1% of those on board) on 242 flights. A follow-up questionnaire was completed by 42,202 (94.9%) of the same travellers 3 months later. Almost all knew about the risk of malaria, but 10% relied solely on advice from nonmedical sources. While 55.6% had taken at least one measure against mosquito bites, only 4.5% adopted three such measures (used repellents and insecticides and wore long clothing after dusk). Compliance with chemoprophylaxis use was reported by 57.0% of travellers who spent less than 3 months in Africa, compared with 29.2% who stayed 3-12 months. Depending on the antimalaria regimen taken, 11-44% of the travellers experienced adverse effects, while four deaths were attributed to the chemoprophylaxis. The incidence of malaria per month of exposure for travellers who took no chemoprophylaxis was 15.2 per 1000 in East Africa and 24.2 per 1000 in West Africa. In East Africa, the prophylactic efficacy of the currently recommended antimalaria regimens (relative to that of no chemoprophylaxis) was zero for a chloroquine dosage of 300 mg base per week (4 malaria fatalities), 64.1% for a chloroquine dosage of 600 mg base per week (P = 0.03), and 94.0% for mefloquine (P = 0.003).
Chloroquine and hydroxychloroquine: Current evidence for their effectiveness in treating COVID-19
  • Kerstin Frie
  • Kome Gbinigie
Kerstin Frie., Kome Gbinigie., 2020. Chloroquine and hydroxychloroquine: Current evidence for their effectiveness in treating COVID-19. CEBM.
Advisory on the use of Hydroxy-chloroquine as prophylaxis for SARS-CoV-2 infection
Secretary (Health and family welfare). Advisory on the use of Hydroxy-chloroquine as prophylaxis for SARS-CoV-2 infection. March 2020. Ministry of Health and family welfare, Nirman Bhawan, New Delhi-110008.