Best COVID-19 Outcomes | Outcomes

Markedly Lower Rates of Coronavirus Infection and Fatality in

Malaria-Endemic Regions – A Clue to Treatment?

Abstract

This comparative analysis of coronavirus infection and death among 2.4 billion persons

around the world demonstrates a wide (two orders of magnitude or one hundred-fold) disparity in

coronavirus fatality rates between well-developed and less-developed countries. The difference is

backward or counterintuitive. The current data demonstrates the surprising fact that those in more

affluent countries are about one hundred times more likely to become infected with coronavirus

infection and die. This effect is most apparent when these countries are compared to countries

with the highest rates of endemic malaria. It is known that the novel coronavirus, also known as

COVID-19, originated in Wuhan China and is transmitted from one country to another by travelers

from a coronavirus-infested area. It is also known that travelers to malaria-endemic countries are

likely to be taking antimalarial prophylaxis. There is also evidence that antimalarials, notably

hydroxychloroquine, may have some efficacy in the treatment of coronavirus. In light of these

facts, the mortality data presented here is highly probative for the hypothesis that prophylactic

antimalarial use by its incoming visitors markedly attenuates a country’s coronavirus fatality rate.

Keywords

coronavirus, COVID-19, mortality, antimalarial, decrease, Africa, death, disparity,

protective, treatment, malaria, SARS-CoV-2, epidemiology, statistics, migration, pharmacology

Introduction

Our world finds itself in the grip of a global pandemic caused by a novel coronavirus known

as SARS-CoV-2 or COVID-19. This worldwide coronavirus pandemic has turned medicine as we

know it upside down. Patients are told, “don’t come to the hospital.” “You don’t need to be

diagnosed.” “A test won’t change your treatment.” Take Tylenol (this has replaced the proverbial

two aspirin) and call the doctor, not in the morning, but later (when you experience hypoxic

respiratory failure or cytokine storm or multi-organ failure).

Always before, we strove to diagnose early and to initiate treatment early. Doctors were

trained to believe that when the diagnosis was made late and treatment was delayed, this was likely

to be harmful to the patient. It was a sign of poor medical practice. See for example, the package

insert for Tamiflu – the treatment for influenza virus. The insert states, “indicated for the treatment

of acute, uncomplicated influenza A and B in patients 2 weeks of age and older who have been

symptomatic for no more than 48 hours.” Antiviral therapy for influenza is to be started within

48 hours. This is the standard of care for the most treatable viral illness. But not with coronavirus.

Now, with coronavirus, everything is backward.

Generally, in the U.S. the focus has been on mitigation - social distancing, rather than a

cure. Sure, there is talk of a vaccine, but that is 18 months away. There is some increasing

discussion and some trials of Remdesivir

and other antiviral agents as well as plasma infusions

for late stage treatment. There have been some trials of hydroxychloroquine. Underlying the daily

televised ventilator wars is the fact that the lay public thinks there is a one-to-one correspondence

between a ventilator and a cure. This is medicine’s dirty dark secret in the age of coronavirus.

About two-thirds of COVID-19 patients placed on ventilators will succumb to the disease.

This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3586954

In fact, a recent study indicated that about 88% of COVID-19 patients placed in ventilators in New

York City succumbed to the disease.

Is there no place for traditional medical treatment, an oral

agent which, if started early, might alter the progression of the disease? In sum, we need a cure.

There is, of course, in some circles, talk of a cure. Is there a drug, which if given early

enough, might alter the progression of COVID-19? Is there an oral agent which would be effective

during the viral response or replication phase before the cytokine storm or host response phase?

There are, of course, a host of viral agents developed over the past forty years, many of which may

be given orally. Perhaps one of them might be effective. The most commonly touted possible

early/oral treatment is hydroxychloroquine, recently promoted by Dr. Raoult of the IHU-

Méditerranée Infection, Marseille, France. Dr. Raoult released a preliminary study of 80 patients

and then a study of 1,061 patients treated with hydroxychloroquine and azithromycin. The

mortality rate was reported to be 0.5%.

His report was criticized for small sample size and lack

of a control arm. The view that hydroxychloroquine might be effective against SARS is not new.

For example, in 2003, Boelaert, et. al. wrote in Lancet Infections Disease “the drug has an

exceptionally broad spectrum of antimicrobial activity that could be exploited in many infections.

Results obtained in the prophylaxis of Q fever indicate that chloroquine/hydroxychloroquine can

be successfully used in the clinical management of infections other than malaria.”

Many physicians are optimistic about the use of hydroxychloroquine. A study of 6,000

physicians by Sermo was widely criticized. A more recent survey by physician staffing group

Jackson & Coker found that 65% of physicians would prescribe hydroxychloroquine.

Unfortunately, at least in the U.S., the debate over the use of hydroxychloroquine has been fraught

with controversy. The data examined in this paper may impact this debate, albeit indirectly.

Methods

This study compares publicly available data pertaining to coronavirus infections of in 2.4

billion persons living in twelve different countries. The twelve countries are divided into three

groups: Group 1 - westernized countries (Italy, Spain and U.S.) with more mature health care

delivery systems and virtually no presence of malaria; Group 2 - South Asia (India, Pakistan, and

Bangladesh); and Group 3 - malaria-endemic sub-Saharan Africa (Nigeria, Congo, Mozambique

Uganda, Niger and Côte d'Ivoire).

Groups 2 & 3 consisted of less-developed countries with less

mature health care delivery systems and a variable presence of malaria in their country.

The data was obtained from Coronavirus COVID-19 Global Cases Dashboard from The

Center for Systems Science and Engineering (CSSE) at Johns Hopkins University Whiting School

of Engineering.

The data is summarized in the attached table. The data for the total number of

infections, number of deaths, overall fatality rate, deaths per million and relative risk (of death)

ratio from twelve different countries were analyzed in an attempt to measure and explain the noted

disparities.

The initial impetus for this study was the fact that unlike western countries, less affluent

and overcrowded countries in South Asia, like India, Pakistan and Bangladesh have experienced

As a preliminary matter, the basic socioeconomic data as to income and physician access for the twelve countries

was reviewed. The westernized countries have income approximately twenty-six times that of South Asia. The

westernized countries have income approximately thirty-seven times that of sub-Saharan Africa. The westernized

countries have approximately seven times more doctors than South Asia. The westernized countries have

approximately twenty-four times more doctors of sub-Saharan Africa.

This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3586954

notably less impact from the COVID-19 pandemic. These countries have infection rates much

lower than seen in the West with death rates less than one per million with population. The

relatively low death rates particularly in India and Bangladesh have been widely noted and the

source of much speculation. The reasons for the low infection and death rates seen in South Asia

will be analyzed below in the Discussion. Suffice it to say at this point, it was noticed that not

only were the three countries in South Asia less affluent and had less access to health care than the

West, these three countries all had some presence of malaria and one in particular, India, is the

world’s leading manufacturer of hydroxychloroquine, used to prevent and treat malaria. Because

of this association, the data analysis was expanded to include six of the world’s leading malaria-

endemic countries. They are Nigeria, Congo, Mozambique, Uganda, Niger, and Côte d'Ivoire.

Results

The data from the twelve different countries plus New York, were analyzed in an attempt

to determine the reasons for the unexpected, hundred-fold, inverse disparity in coronavirus

infection rates. COVID-19 is a worldwide infectious pandemic infecting about 1.3 million persons

in 185 countries and causing 92 thousand deaths to date. A primary purpose of this paper is to test

the hypothesis that better socioeconomic status and access to health care should result in less

infection and fewer deaths from the novel coronavirus known as SARS-CoV-2. That is to say,

better health care should decrease the morbidity and mortality of coronavirus. This hypothesis is

almost axiomatic and correlates to a great degree with the focus of the past decade or so on the

"social determinants of health," that is that “to a large degree, health is shaped by the conditions

in which people are born, grow, live, work, and age.”

The results, in particular the disparate fatality rates of the three groups are described below.

The results are summarized here in Table 1.

Table 1 - Discrepant Fatality Rates from Coronavirus Infections, updated 04/22/20

(this data was reviewed throughout the month of April, 2020 and the disparity persisted.)

This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3586954

The results are as follows. As of April 22, 2020, Italy has a population of 60 million with

183,957 cases and 24,648 deaths. Spain has a population of 46.7 million with 208,389 cases and

21,717 deaths. The United States has a population of 327 million with 825,306 cases and 45,075

deaths. India has a population of 1.35 billion with only 20,178 cases and 645 deaths. Pakistan has

a population of 220 million with 9,749 cases and 209 deaths. Bangladesh has a population of 160

million with 3,772 cases and 120 deaths. Nigeria has a population of 205 million with 782 cases

and 25 deaths. Congo has a population of 89 million with 359 cases and 25 deaths. Uganda has a

population of 45 million with 613 cases and no deaths. Mozambique has a population of 31 million

with 39 cases and no deaths. Côte d'Ivoire has a population of 25 Million with 916 cases and 13

deaths. Niger has a population of 22 Million with 657 cases and 20 deaths. In contrast, New York

State has a population of 19.8 million with 190,288 cases and 9,385 deaths.

As of this writing, India has a fatality rate of 0.000048%, Pakistan has a fatality rate of

0.000095%, and Bangladesh has a fatality rate of 0.000075%. Nigeria has a fatality rate of

0.000012%. Congo has a fatality rate of 0.000028%. Uganda has a fatality rate of zero.

Mozambique has a fatality rate of zero. Côte d'Ivoire has a fatality rate of 0.000059%. Niger has

a fatality rate of 0.000080%. The average national fatality rate of the six malaria-endemic

countries is 0.000030%. All six of these countries have national fatality rates of less than one case

per million.

Among the western countries, Italy has a fatality rate of 0.041% or 411 cases per million

and with a relative risk death from coronavirus is 2,402 times that of the six poor countries of sub-

Saharan Africa. Spain has a fatality rate of 0.047% or 465 cases per million and a relative risk of

death from coronavirus 2,719 times that of the six poor countries of sub-Saharan Africa. The

United States has an overall fatality rate of 0.014% or 338 cases per million and a relative risk 806

times that of the six poor countries of sub-Saharan Africa.

Overall, the Industrialized West has a population corrected coronavirus fatality rate

of approximately 1,059 times that of malaria-endemic, sub-Saharan Africa. This increased

coronavirus fatality rate in the west is highly significant statistically (p < 0.0001). The

increase infection rate may less certain due to variable availability of testing. Still, the

measured coronavirus infection rate in the Industrialized West is 416 times more than that

for sub-Saharan Africa. This measured difference is statistically significant (p < 0.0001).

The six malaria-prone countries of sub-Saharan Africa (Nigeria, Congo, Mozambique,

Uganda, Niger and Côte d'Ivoire – 0.3 deaths per million) have coronavirus fatality rates of about

half of that found in the three large countries of South Asia (India, Pakistan and Bangladesh – 0.7

deaths per million). At present, all of these less affluent counties have coronavirus fatality rates

less than one percent of the rates of the U.S. and other more affluent westernized countries.

Similarly, the infection rates of the six malaria-endemic countries are less than one percent of the

coronavirus infection rates seen in the West.

Obviously, this could be to relative lack of testing

in these countries. This is why a country’s death rate is the more valid measure.

The Westernized countries (Italy, Spain and U.S.) reviewed in their study had an overall coronavirus infection rate

of 0.2647%. The South Asian countries (India, Pakistan, and Bangladesh) had an overall infection rate of 0.0012%.

The malaria-endemic Sub-Saharan African countries (Nigeria, Congo, Mozambique, Uganda, Niger and Côte d'Ivoire)

had a similar overall infection rate of 0.0016%. Thus, the average raw coronavirus infection rate of the three

Westernized countries (Italy, Spain and U.S.) reviewed in the study was 189 times greater than the average raw

coronavirus infection rate of the nine less affluent countries (India, Pakistan, and Bangladesh, Nigeria, Congo,

This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3586954

Discussion

Analysis of this data is challenging. It changes daily if not hourly. The review of COVID-

19 infections in 2.4 billion persons demonstrates truly unexpected results. One unexpected pattern

consistently emerges. Otherwise less fortunate countries enjoy a protective effect against

coronavirus infection and death compared to the U.S. and Western European nations.

Conventional wisdom dictates that the coronavirus fatality rate would be much worse where

poverty and lack of access to healthcare prevails. One would expect those of lower socioeconomic

status with lesser access to health care would have increased morbidity and mortality from a viral

pandemic such as COVD-19. In fact, this is precisely what is seen within the U.S. itself but just

the opposite of what is seen in the rest of the world.

Many experts have expressed fear that because of cramped living quarters and overstressed

health systems, the coronavirus pandemic is likely to run rampant in countries in South Asia and

Africa. This study is, by no means, an effort to trivialize that risk. The data shows that, thus far,

this has simply not been the case. The Genetic Literacy Project notes, “A review of the world

maps of confirmed cases of the coronavirus and the fatalities that it has caused shows an unusual

anomaly: The world’s second most populated continent, Africa, has seen the fewest number of

confirmed cases per capita, 7080, through April 3, despite the fact that Africa has extensive trade

and travel relations with China, where the outbreak originated, and with Europe, a global hotspot.”

This analysis confirms that observation.

Many have noticed these relatively low rates of coronavirus infection and death,

particularly in India and Bangladesh. Some have said this fact proves that coronavirus is a hoax.

Others assert that this proves that coronavirus is not dangerous. Such careless proclamations

cannot be taken seriously in light of bodies stored in refrigerated semi-trailers outside New York

hospitals or buried in mass graves on Hart island. Nor can the trivialization of COVID-19 be

squared with the experience of any front-line physician practicing in an affected area. At this point

in time, based upon the data representing 2.4 billion people, the unexpected, hundred-fold, inverse

disparity in fatality rates is real.

What can explain this disparity? In Africa, it cannot be explained by expected social

determinants of health as commonly understood. It cannot be explained by poverty or poor access

to care. The average fatality rate per million in the three developed countries in this study is 338.

The average coronavirus fatality rate per million of the three large nations of South Asia was only

0.7 per million. The average coronavirus fatality rate per million in the six impoverished nations

with endemic malaria in sub-Saharan Africa is only 0.3 per million. Thus, death from coronavirus

is 800 times more likely in the U.S. than in some of the poorest nations in the world. This paper

attempts to understand that discrepancy.

The hypothesis that higher socioeconomic status and improved access to health care should

result in less infection and fewer deaths from the novel coronavirus known as SARS-CoV-2 seems

to be disproven. Better access to health care does not decrease the morbidity and mortality of

coronavirus worldwide. This apparent protective effect afforded by living in South Asia or sub-

Mozambique Uganda, Niger and Côte d'Ivoire). Conversely, the nine less affluent countries (India, Pakistan, and

Bangladesh, Nigeria, Congo, Mozambique, Uganda, Niger and Côte d'Ivoire) had average raw coronavirus infection

rates which were 99.5% less than the three more affluent Westernized countries (Italy, Spain and U.S.).

This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3586954

Saharan Africa screams out for explanation. An alternative hypothesis must be extended. This is

the purpose of this paper.

There are several possible explanations for the unexpected, hundred-fold, inverse disparity

in fatality rates associated with coronavirus. They are: 1) underreporting; 2) undertesting;

3) higher temperatures; 4) different genetic predispositions; and 5) some temporal anomaly.

The first possible explanation for the discrepancy in fatality rates is underreporting. There

is reason to believe that there may be underreporting of coronavirus deaths in China and maybe

even in Iran. It is far less reasonable to believe that there is underreporting by all nine of the less-

developed countries listed here in this study. For example, if India had a death rate similar to the

U.S. and highly affected Western European countries, it would have to be concealing and secretly

disposing about 300,000 corpses. Does anyone really think this is possible? There may be errors

in reporting, but it seems implausible that massive systemic underreporting or conspiracy to under

report could explain the disparities in the data reported here in this study.

Similarly, some have ascribed the discrepancy to under testing. Undertesting is no doubt

a problem around the world. But COVID-19 is often a fatal disease, and undertesting does not

stop an individual from dying. This is why death rates are a better marker than infection rates in

this global study.

The third possible explanation for the discrepancy in fatality rates is heat or climate. It is

argued that there is less progression of viral disease in warmer regions. This is seen with many

viral illnesses. This offers some hope for those living in western countries in temperate climates.

The susceptibility of coronavirus to warmer temperatures has generally been discounted by

experts. Hopefully, they will be proven wrong. Even if there is some truth to this theory,

temperature variation between countries does not seem to be able to explain the hundred-fold

differences in coronavirus fatality and infection rates seen here in this study.

Another alternative explanation offered might be some sort of racial or genetic protection

against coronavirus infection. Were this the case, it would mean that people of color and Blacks

in particular are less susceptible to coronavirus infection. Unfortunately, this seems not the case.

This hypothesis that Blacks are less susceptible to coronavirus infection seems to be distinctly

disproved by the American experience.

Black Americans seem to be “at higher risk, Surgeon General Dr. Jerome Adams said

during an appearance on CBS This Morning on Tuesday. That racial disparity has been evident in

early data on coronavirus deaths in Louisiana, Illinois, Michigan and New Jersey.”

This

disparity, of American Blacks being at higher risk of death from coronavirus, is seen for example

in Louisiana, a major US hotspot, which “was the first southern state to categorize Covid-19 deaths

by race. On Monday Governor John Bel Edwards announced that a shocking 70% of deaths were

among African Americans, despite making up only 33% of the state’s population.”

The unexpected result of this analysis is that, on a worldwide scale, at least in particular

African countries, it is simply not true that Blacks are more susceptible to coronavirus. This

analysis involved one-third of the world’s population. Two-thirds of the population studied were

non-westerners. Two hundred and eighty-six million with were black Africans. Based upon the

conventional wisdom, we would expect higher social economic status and more highly developed

health care systems to produce better outcomes. Here, the facts say otherwise. If the reported data

is accurate, it indicates that those in more westernized, highly developed countries are 400 times

more likely to die from coronavirus infection than residents of economically stressed countries

This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3586954

with less well-developed heath care delivery systems. The unmistakable fact to emerge from this

analysis is that, across that world, at this point in time, less affluent people of color, with less

access to health care, are 99.9% less likely to die of coronavirus than western Europeans and

Americans.

Finally, it is possible that the data may change. Perhaps this is just a temporal anomaly?

Perhaps the disparity is simply due to chance? Perhaps Africa and South Asia are simply behind

the western countries in the progression of their coronavirus pandemic. This seems unlikely as

Africa was exposed to travelers from China and Europe as well. Also, the introduction of

coronavirus to Africa came at exactly the same time as New York City, and it was predicted that

the coronavirus would be catastrophic for Africa. However, New York with its seven medical

schools, two hundred hospitals, thousands of doctors, hospitals built by the U.S. Government, and

even a one-thousand-bed hospital ship, has fared far worse in the coronavirus pandemic than any

country in Africa. The data may well change but for now, the data demonstrates the disparate

death rates.

The counterintuitive fatality rate from coronavirus in the regions studied is so marked there

must be some explanation. Underreporting seems unlikely and has not been proven. Differences

in climate or temperature do not clearly explain, and genetic differences should actually produce

the opposite effect. The hint of an additional and partially determinative factor is the fact that the

South Asian countries studied are known to have a significant presence of malaria. This seems to

be a common denominator. It may offer a clue.

To test the hypothesis that a country’s prevalence of malaria was somehow inversely

related to its prevalence of or susceptibility to coronavirus, the six malaria-endemic countries were

added to the study. There is no doubt that many residents of South Asia suffer from poverty and

lack of access to health care, especially when compared to western countries. The six sub-Saharan

African countries (Nigeria, Congo, Mozambique, Uganda, Niger and Côte d'Ivoire) were selected

for this study because of the malaria factor, because all six are thought to have a higher prevalence

of malaria overall than the three South Asian countries. The WHO’s World Malaria Report for

2019 states that “nineteen countries in sub-Saharan Africa and India carried almost 85% of the

global malaria burden.” These “six countries accounted for more than half of all malaria cases

worldwide.”

They are Nigeria (25%), the Democratic Republic of the Congo (12%), Uganda

(5%), and Côte d’Ivoire, Mozambique and Niger (4% each). With regard to socioeconomic status

and access to health care, the residents of the six sub-Saharan countries are even less fortunate.

The six sub-Saharan countries have approximately 31% lower per capita income and 66% fewer

physicians than the three South Asian countries (India, Pakistan, and Bangladesh).

However, the morbidity and mortality due to coronavirus in the six poorer and more

malaria-prone countries were actually better than even the larger, slightly more affluent, malaria

afflicted countries of South Asia. The incidence of coronavirus infection and death in these six

sub-Saharan countries is about 0.1% of that in well-developed, malaria-free countries.

Alternatively, given the present data, living in a less well-developed, less affluent, malaria-prone

country is associated with a 99.9% reduction in the probability of death due to coronavirus

infection. Thus, it is hypothesized that somehow the prevalence of malaria infection in a country

might somehow protect a country’s residents from coronavirus infection and death.

The evidence indicates that the presence of malaria in a country is somehow associated

with some protective effect against death from coronavirus. There seems to be three possible

causal mechanisms whereby a nation’s prevalence of malaria could be linked to the unexpected,

This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3586954

hundred-fold, inverse relationship to malaria suggested by the data. The first is some direct

interaction between coronavirus and malaria itself. We know that malaria can interact with other

diseases. There is a well described interaction between malaria and sickle cell anemia.

11,12,13

this point, there does not seem to be any evidence that such a direct interaction exists with

coronavirus.

The second causal mechanism whereby a nation’s prevalence of malaria could be linked to

its incidence of coronavirus infection and death could be the direct use of antimalarial agents to

directly treat the malaria present within the country – some sort of spill-over effect. We know that

there is a real need for an effective treatment of pandemic COVID-19. We know that there is a

much discussion and some early evidence that antimalarial agents, particularly

hydroxychloroquine, may be effective in the treatment of coronavirus infection. Unfortunately,

the current public debate is steeped in controversy.

There does seem to exist a third possibly related causal mechanism whereby a nation’s

malaria prevalence might be linked to its incidence of coronavirus infection and death. This third

possible mechanism might be the use of antimalarial prophylaxis in travelers entering the country.

To better understand this phenomenon, one must recall that coronavirus is introduced into a

country by travelers from other countries.

COVID-19 was first observed in Wuhan, China. It has now spread to one hundred eighty-

five countries worldwide. Coronavirus is spread from one country to another by travelers. A

major new genomic study just published by researchers at Mount Sinai in New York “found

evidence that the first COVID-19 cases in New York City originated in Europe.” The study found

that ‘COVID-19 in New York City "predominately arose through untracked transmission between

the United States and Europe, with limited evidence supporting direct introductions from China,

where the virus originated, or other locations in Asia.’"

The researchers found multiple,

independent but isolated introductions mainly from Europe and other parts of the United States.

Similarly, one of the first cases in Africa was thought to be transmitted by a Taiwanese woman on

a Nile River cruise.

Finally, “the first case of coronavirus in sub-Saharan Africa was believed

to have been introduced by an Italian citizen who entered the country on 24 February on a Turkish

Airlines flight from Milan via Istanbul.”

Thus, a country is seeded with coronavirus by its visitors. Once introduced by travelers,

coronavirus can then spread within a country by direct person-to-person transmission. Thus, the

incidence of coronavirus within a country would be expected to be lower if the visitor’s rate of

introduction of coronavirus could be decreased.

It is a fact that those traveling to sub-Saharan Africa are likely to be taking antimalarial

agents prophylactically. Even twenty years ago it was found that 95.4% used antimalarial

chemoprophylaxis.

More recently Ahluwalia et. al. found that those numbers may have slipped,

finding an adherence rate of only 89% for antimalarial prophylaxis.

So, while the prevalence of

antimalarial prophylaxis utilized by travelers to these malaria-endemic countries cannot be

precisely known, it is likely to be very high.

It is hypothesized that these same prophylactic antimalarial agents are also effective against

coronavirus as well. Thus, travelers taking a prophylactic antimalarial agent while entering are

less likely to introduce coronavirus into the country. This would explain the low rate of

coronavirus infection and death seen in the nine less affluent countries analyzed here. Travelers

entering the U.S. and western Europe are almost certainly not taking any form of malaria

This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3586954

prophylaxis. This would be consistent with the high rates of coronavirus transmission into these

countries by travelers. These observations thus suggest that antimalarial agents taken by those

traveling to Africa and South Asia may be effective as prophylaxis against infection and death due

to coronavirus. This would translate to a low or initially low infection rate for those countries.

The question as to the use of antimalarial agents as prophylaxis against coronavirus

infection has been at least initially raised. In fact, a U.S. Coronavirus Task Force expert was asked

about this directly. He was asked if some antimalarial agent (in this case hydroxychloroquine) had

some use as a prophylaxis against COVID-19?

Q: And to Dr. Fauci, if I could. Dr. Fauci — this was explained yesterday —

there has been some promise with hydroxychloroquine as potential therapy for

people who are infected with coronavirus. Is there any evidence to suggest that, as

with malaria, it might be used as a prophylaxis against COVID-19?

DR. FAUCI: “No. The answer is no. And the evidence that you’re talking about,

John, is anecdotal evidence.

This was right about the time the U.S. FDA Commission loosened the restrictions of the

use of hydroxychloroquine. So, the assertion that there is “no” evidence is not exactly correct.

One may say the evidence is weak or inconclusive, but it is inaccurate to say that there is no

evidence that the prophylactic use of antimalarial agents is not effective. At least one source

reports that “India itself advocates health care workers take the drug regularly as a preventive

measure.”

Finally, the evidence presented herein comes from an entirely different perspective

yet strongly suggests that some antimalarial agents may inhibit the transmission of coronavirus.

This comparative analysis involving 2.4 billion patients across the world suggests that

antimalarial agents may be the reason for the disparate infection and fatality rates and may have a

role in the prophylaxis against coronavirus infections as well as malaria. If this hypothesis proves

to be correct, it means the prophylactic administration of some yet to be precisely identified

antimalarial agent could be up to 99% effective in averting coronavirus infection. This author is

unaware of any competing hypothesis offered as an alternative explanation for the evidence that

patients in more well-developed countries are more than one hundred times more likely to acquire

and die from a coronavirus infection than those of less well-developed countries. This fact

demands explanation.

A few have noted, at least peripherally, the association between low prevalence of

coronavirus infection and the presence of malaria. Usually this has been loosely associated with

the use of hydroxychloroquine. However, hydroxychloroquine is less commonly used for malaria

prophylaxis. So, the anti-coronavirus action of may be common to other antimalarials and not

limited to just hydroxychloroquine. At least one study has considered that an antimalarial agent,

again hydroxychloroquine, may have prophylactic benefit.

This study made no association with

the low death rates in Africa or the use of antimalarials in African travelers. This writer specifically

suggests that the prophylactic benefit in the prevention of the transmission of coronavirus may

extend beyond hydroxychloroquine to other antimalarial agents commonly used for malaria

prophylaxis. To this writer’s knowledge, the specific association between the widespread use of

prophylactic antimalarial agents in arriving travelers and the remarkably low rate of coronavirus

and death in malaria-endemic sub-Saharan Africa has never been described in the medical

literature.

This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3586954

Conclusion

The data analyzed here demonstrates that those living in sub-Saharan African countries

have a 99% less chance of dying from coronavirus compared to the U.S. and the high risk Western

European countries. This low death rate is backward and counterintuitive. It occurs despite the

relative poverty and limited access to health care in these countries. These countries, so successful

at combating or avoiding coronavirus, are distinguishable by their high endemic rates of malaria

and the associated use of antimalarial drugs as prophylaxis by visitors to their respective counties.

It is thus hypothesized that the low incidence of COVID-19 in these countries is because

antimalarial drugs have some protective or prophylactic effect against coronavirus as well as

malaria. Because hydroxychloroquine is not widely used as prophylaxis against malaria, it is not

responsible for the effect seen here. Hydroxychloroquine may or may not be the best drug. Other,

newer antimalarial agents should be studied for safety and efficacy.

The hundred-fold disparity in coronavirus infection and fatality rate seen here in the data

although counterintuitive, is not insignificant. This data should not be ignored. No one can

guarantee that the numbers presented here will not reverse, and a catastrophic COVID-19

pandemic engulf the African continent. Unless and until that occurs, there is evidence that

antimalarials may prevent or in some other way mitigate the COVID-19 pandemic. The data

should not be ignored because one thinks the data might change. Even if the numbers do reverse,

and the COVID-19 pandemic were to accelerate in South Asia and sub-Saharan Africa, the

question would remain, why the delay in the progression of the pandemic in Africa? This

unexpected, hundred-fold, inverse disparity in fatality rates should not be ignored.

Recommendations for Further Study

It is hypothesized antimalarial agents may play a role in the prevention of transmission or

seeding by incoming travelers to sub-Saharan Africa. This writer is unaware of any other

compelling alternative explanation having been proposed to satisfactorily explain the relatively

low coronavirus death rates in malaria-endemic countries.

In addition to our mitigation efforts and our hope for a vaccine, we should aggressively

pursue the discovery of an active and early treatment strategy for coronavirus infection. The

hypothesis that antimalarial agents are effective in the prophylaxis and treatment of novel

coronavirus known as SARS-CoV-2 or COVID-19 should be studied aggressively and

collaboratively. Different, newer, antimalarial agents should be studied as well in hopes of

identifying any mechanisms whereby the broader class of antimalarial agents may exhibit some

therapeutic and prophylactic effect against coronavirus.

Finally, we should not ignore the data before us because we think the data might change.

If we can identify an oral agent which can be used earlier to treat or at least mitigate coronavirus

infection, such a drug will also prove invaluable to Africa as well as the rest of the world if and

when Africa experiences an increase in coronavirus infection. We should study this disparity in

fatality rates in the hope that African experience with antimalarials will lead to a coronavirus cure.

Funding: There was no funding for this paper.

Competing interests: The authors declare that they have no competing interests.

This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3586954

Author details: Geoff Mitchell, MD, JD

Department of Emergency Medicine

The University of Toledo

gmitch@columbus.rr.com

Sadik Khuder, PhD

Professor of Biostatistics and Epidemiology

Department of Medicine

The University of Toledo

This preprint research paper has not been peer reviewed. Electronic copy available at: https://ssrn.com/abstract=3586954

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