Parasites and Parasitology in this SARS-CoV-2, COVID-19 World: An American Society of Parasitologists Presidential Address

For science and the scientific community, 2020 has been a year like no other. With the emergence of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)/novel coronavirus disease 2019 (COVID-19) pandemic, most U.S. universities and their international counterparts shuttered their doors in March (Gewin, 2020; Mervosh and Swales, 2020). In the ensuing months, universities and their laboratories have gradually reopened with strict safety measures and restricted occupancy, and most student instruction has moved online (Burki, 2020; Subbaraman, 2020b; Witze, 2020). This has required that institutions invest in new infrastructure, and that faculty learn and adopt new pedagogical methods. As a result, progress in scientific research laboratories has slowed, and much energy has been put forth toward ensuring effective mentoring and teaching. Scientists that spent years preparing for field seasons that were ultimately cancelled have perhaps been the most affected, as have been graduate students and postdoctoral researchers in time-limited positions who have been locked out of laboratories, and young professionals whose reduction in productivity has been compounded by increased family workloads (Ahmed et al., 2020; Fikrig, 2020; Viglione, 2020a). Minorities have been disproportionately affected by tragedy, and women are experiencing a larger increase in family responsibilities (Collins, 2020; Subbaraman, 2020a).

The effects of COVID-19 on the scientific community extend beyond the closure and partial reopening of universities. As a result of the pandemic, museums and their collections also closed their doors, and many scientific societies were forced to cancel their 2020 scientific meetings, therefore limiting the sharing of ideas between scientists and collaborators (Viglione, 2020c). As we enter autumn, some scientific societies have moved their meetings online, and new Zoom-based seminar series have been created (Achakulvisut et al., 2020; Viglione, 2020b). Although the reach of some scientists has increased because online seminars are now accessible to a truly global audience, the cancellation of in-person meetings has all but eliminated the happenstance, in-person encounters that often result in new collaborations, support networks, and friendships. This was felt by the membership of the American Society of Parasitologists (ASP) after the cancellation of our society's 2020 annual meeting (Hillyer, 2020).

However, the effect that the COVID-19 pandemic has had on colleges, universities, museums, and scientific societies pales in comparison with the horrific toll it has taken on society as a whole. As of this writing, there have been over 34 million reported cases of COVID-19 and over 1 million deaths worldwide (Johns Hopkins Coronavirus Resource Center, 2020). In the United States, there have been over 7 million cases and over 200,000 deaths. In addition to the morbidity and mortality associated with SARS-CoV-2, the COVID-19 pandemic has caused great financial hardship to many, slowed the education and social development of children and young adults, increased the rate of domestic violence, and negatively impacted the mental health of many. Drastic measures to limit transmission have been taken, but in the United States, the lack of coordination among federal, state, and local governments, together with an abundance of misinformation, has led to a failure to contain the virus (Ball and Maxmen, 2020; Haffajee and Mello, 2020).

The core of the COVID-19 pandemic is the rapid transmissibility of this virus, its morbidity and mortality, and the presence of infectious asymptomatic carriers (Cyranoski, 2020). Even when misinformation campaigns have, to the detriment of our community, touted that SARS-CoV-2 is less deadly than seasonal influenza, the fact that an average of 35,000 Americans die of seasonal influenza every year whereas over 200,000 persons have died of COVID-19 in less than 9 mo has mobilized the scientific community to join the effort to contain the virus. As a result, the genome of SARS-CoV-2 was quickly sequenced, the evolution of the virus continues to be scrutinized, novel therapies are being developed, and in a period of just a few months, several vaccine trials are already under way (Coronaviridae Study Group of the International Committee on Taxonomy of Viruses, 2020; Ledford, 2020). This call for discovery and vaccine development has been amplified by the alarming pathogenicity associated with 2 other coronaviruses that emerged in human populations over the past 20 yr: severe acute respiratory syndrome (SARS) in 2002 and Middle East respiratory syndrome (MERS) in 2012. The SARS (SARS-CoV) and MERS (MERS-CoV) epidemics, although deadly, did not spread on a global scale, and this was in part because their transmissibility is much lower than SARS-CoV-2 (Ledford, 2020; Scudellari, 2020).

As we consider SARS-CoV-2 and the COVID-19 pandemic, it is essential that scientists, governments, the media, and the general population also come to grips with the everyday cost of parasitic diseases. These diseases are not new, but they take a tremendous toll on local communities. Yet, because most of these diseases are no longer endemic to high-income countries, governments and private companies are not funding their research and intervention at levels that are proportional to their global morbidity and mortality.

Consider malaria, a disease that in humans is caused by 5 species of protozoan parasites: Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale, and Plasmodium knowlesi (Phillips et al., 2017). Plasmodium infection results in a febrile illness that can devolve into severe anemia, respiratory distress, organ failure, a condition of the brain called cerebral malaria, and death. The World Health Organization estimates that there were 228 million cases of human malaria in 2018, which led to 405,000 deaths (World Health Organization, 2019). An astounding 67% of deaths were children under the age of 5, and greater than 90% of infections and deaths were in Africa. Controlling and preventing malaria relies on killing the mosquito vector, reducing human-mosquito contact, and treating infected persons. These approaches are hampered by insecticide resistance of the vectors, and drug resistance of the parasites. Currently, the most effective medical treatment used against malaria is an artemisinin-based therapy that combines an artemisinin derivative with 1 or more complementary compounds (Phillips et al., 2017; World Health Organization, 2019). Artemisinin was first isolated in 1971, and from a chemotherapy perspective, it remains our strongest line of defense, yet drug resistance in the parasite has been spreading since at least 2007, and there is no effective vaccine (Phillips et al., 2017; Talman et al., 2019; Tse et al., 2019). Although various initiatives have over the years reduced the incidence of malaria, this reduction has reached a plateau, and therefore, it is surprising that more drugs are not in the developmental pipeline, given that 13 million persons died from malaria between 2000 and 2018 (World Health Organization, 2010b, 2019).

Humans acquire malaria via the bite of an infectious anopheline mosquito, making it a vector-borne disease. If we define a vector as a hematophagous arthropod (more specifically, an insect or a tick) or gastropod (a snail) that transmits a pathogen, 17% of all infectious diseases of humans are transmitted by vectors (Fig. 1) (World Health Organization, 2017). The major nematodes that mosquitoes transmit to humans are Wuchereria bancrofti, Brugia malayi, and Brugia timori, which are the causative agents of lymphatic filariasis, also known as elephantiasis (Taylor et al., 2010). In the most severe form, lymphatic filariasis is a chronic disease that impairs the flow of lymph, resulting in the abnormal enlargement of the legs, arms, and genitalia. This hardens the skin and decreases immune function, and, devastatingly, the physical deformities associated with lymphatic filariasis often lead to social stigma, psychological problems, and financial hardship because of the inability to work. In 2015, over 38 million persons had lymphatic filariasis (GBD Disease and Injury Incidence and Prevalence Collaborators, 2016). Disease control and prevention rely on killing the vector, preventing vector-human contact, and chemotherapy. The primary drugs used to treat infected persons are ivermectin, albendazole, and diethylcarbamazine, given alone or in combination (Taylor et al., 2010). These drugs, all discovered more than 40 yr ago, kill the microfilarial offspring of the adult worms but not the adults themselves, which poses challenges for disease control because the adults live for several years. Although strategic mass drug administrations have reduced prevalence worldwide, no new treatments, except perhaps the repurposed antibiotic doxycycline, have been developed this century.

Other filarial worms that are transmitted by insects are Onchocerca volvulus, which causes a disease called river blindness and is transmitted by black flies, and Loa loa, which causes a disease called loiasis and is transmitted by deer flies (Kelly-Hope et al., 2017; World Health Organization, 2017). In 2015, there were an estimated 15 million persons infected with onchocerciasis, with over 12 million exhibiting the cutaneous manifestations of the disease and more than 1 million having gone blind (GBD Disease and Injury Incidence and Prevalence Collaborators, 2016). Onchocerciasis is treated with ivermectin (Taylor et al., 2010), which was derived from avermectin, a compound for which the nematocidal activity was discovered by former ASP President Dr. William Campbell and his collaborator, Dr. Satoshi Ōmura. This discovery, together with the discovery of artemisinin by Dr. Tu Youyou, was recognized with the 2015 Nobel Prize in Physiology or Medicine (Campbell, 2016; Esch, 2016). Loa loa, known as the African eye worm, is estimated to infect 10 million persons, and it causes cerebral, cardiac, pulmonary, and renal complications, alongside neurological and psychiatric disorders (Metzger and Mordmuller, 2014). Loiasis is treated with albendazole, which much like what occurs when lymphatic filariasis and onchocerciasis are treated, reduces microfilaria burden without killing the adult worms.

Other notable parasitic diseases transmitted by insects are the kinetoplasts that cause leishmaniasis, African sleeping sickness (African trypanosomiasis), and Chagas disease (American trypanosomiasis) (World Health Organization, 2017). These are transmitted by sand flies, tsetse flies, and triatomine bugs, respectively. Leishmaniasis is caused by over 20 species or subspecies of protozoan parasites of the genus Leishmania, and close to 4 million infections are estimated to take place every year (World Health Organization, 2010a, 2017; GBD Disease and Injury Incidence and Prevalence Collaborators, 2016). Depending on the infecting species, the clinical manifestation of the disease can be either cutaneous or visceral, and treatment usually relies on toxic, pentavalent antimonials (World Health Organization, 2010a). African sleeping sickness is caused by Trypanosoma brucei brucei and Trypanosoma brucei rhodesiense (Büscher et al., 2017). If left untreated, the disease is fatal, but in recent years, the implementation of land management practices and the success of vector-control programs have reduced the number of annual confirmed infections to around 10,000 (GBD Disease and Injury Incidence and Prevalence Collaborators, 2016; World Health Organization, 2017). Treatment of infected persons is suboptimal and usually involves a complex regimen of drugs with strong side effects (Büscher et al., 2017). Although nifurtimox (introduced in 2009) and fexinidazole (introduced in 2019) were approved relatively recently to treat Trypanosoma brucei brucei, no new drugs that treat infection with Trypanosoma brucei rhodesiense have been developed over the past 30 yr (Dickie et al., 2020). Chagas disease is caused by Trypanosoma cruzi, and between 5 and 7 million persons are infected with this protozoan (GBD Disease and Injury Incidence and Prevalence Collaborators, 2016; World Health Organization, 2017). Disease progression can lead to cardiomyopathy (including heart failure), megacolon, megaesophagus, and stroke, and drug treatment has secondary complications and is most effective only during the early stages of infection (Perez-Molina and Molina, 2018). The incidence of both Chagas disease and African trypanosomiasis is in the decline, but not too much comfort can be taken with this trend because previous declines have been followed by significant resurgences (Schofield and Kabayo, 2008). In addition to the parasites noted above, insects also transmit a multitude of viruses and bacteria. Mosquitoes, for example, transmit dengue, yellow fever, Zika, West Nile, and Chikungunya viruses, fleas transmit plague, lice transmit typhus, and ticks transmit Lyme disease and relapsing fever (World Health Organization, 2017).

Snails are vectors for several trematodes of great concern to human health. Human schistosomiasis, for example, is mainly caused by Schistosoma mansoni, Schistosoma haematobium, and Schistosoma japonicum (Colley et al., 2014; McManus et al., 2018). It is estimated that greater than 250 million persons harbor human schistosomiasis, with symptoms varying depending on the infecting species. Intestinal schistosomiasis causes intermittent abdominal pain and bloody diarrhea and may devolve into hepatosplenomegaly. Urogenital schistosomiasis can result in hematuria and pelvic discomfort. In addition, eggs of S. japonicum travel to the brain, where they cause granulomas that can lead to epileptic seizures and both visual and motor impairment, and chronic infection with S. haematobium—a group-1 carcinogen—increases the probability of bladder cancer (Vennervald and Polman, 2009; Colley et al., 2014; McManus et al., 2018). Schistosomiasis is treated by administering praziquantel, which is a tetrahydroisoquinoline that was discovered in the 1970s and approved for human use in the 1980s, and its mechanism of action is not fully understood (Park and Marchant, 2020). Other trematodes transmitted to humans by snails include Fasciola hepatica, Paragonimus westermani, Clonorchis sinensis, and Opisthorchis viverrini; the latter 2 species are also classified as group-1 carcinogens because of their propensity to induce cholangiocarcinoma (Keiser and Utzinger, 2009; Vennervald and Polman, 2009). Depending on the species, these trematode infections are treated with praziquantel or triclabendazole.

Protozoan parasites such as Giardia duodenalis and Entamoeba histolytica cause intestinal distress and dysentery (Fig. 2) (Einarsson et al., 2016; Carrero et al., 2020). They are acquired by ingesting cysts in contaminated water, and infections with this flagellate and ameba are treated with metronidazole, a drug that was discovered in the 1950s and is also used to treat Trichomonas vaginalis (Freeman et al., 1997). Cryptosporidium parvum, Cyclospora cayetanensis, and Toxoplasma gondii are apicomplexan protozoans that are also acquired by ingestion, and for which there is no standard curative drug regimen (Montoya and Liesenfeld, 2004; Dorny et al., 2009; Siddiqui, 2017). Nevertheless, these parasites can be devastating when they infect immunocompromised persons, and transplacental transmission of Toxoplasma parasites is a major cause of congenital birth defects and still births.

Various tapeworms infect humans, including Diphyllobothrium latum, Diphyllobothrium dendriticum, Taenia solium, Taenia saginata, Echinococcus granulosus, and Echinococcus multilocularis (Dorny et al., 2009). Taenia solium, also known as the pork tapeworm, causes disease in around 2 million persons (GBD Disease and Injury Incidence and Prevalence Collaborators, 2016). The most serious clinical manifestation of T. solium infection is called neurocysticercosis, whereby the larval stage of the parasite migrates to the brain and causes pressure necrosis and epilepsy (Garcia et al., 2014). Infected persons are treated with praziquantel or niclosamide, but when neurocysticercosis occurs, specialized treatment regimens are required because killing the cysticerci in the brain can result in a damaging inflammatory response. Echinococcus granulosus, Echinococcus multilocularis, and related species cause cystic and alveolar echinococcosis in more than 1 million persons (GBD Disease and Injury Incidence and Prevalence Collaborators, 2016). Symptoms depend on the location where the cysts develop; for example, cysts in the lungs can cause chronic cough, chest pain, and shortness of breath, which can be fatal. Treatment requires surgery, which is often accompanied by albendazole treatment (Wen et al., 2019).

Soil-transmitted nematodes infect an astounding 24% of the world's population (World Health Organization, 2020). Approximately 428 million persons are infected with hookworms (Necator americanus and Ancylostoma duodenale), 762 million are infected with roundworms (Ascaris lumbricoides), 464 million are infected with whipworms (Trichuris trichiura), and 370 million are infected with Strongyloides stercoralis (Bisoffi et al., 2013; GBD Disease and Injury Incidence and Prevalence Collaborators, 2016). Infection results in intestinal blood loss, malabsorption of nutrients, loss of appetite, and in some cases, the reduced cognitive and physical development of children (Loukas et al., 2016; Else et al., 2020). Infection with hookworm also leads to iron deficiency anemia and poor birth outcomes, and Strongyloides hyperinfection syndrome is life threatening in immunocompromised hosts (Bisoffi et al., 2013; Loukas et al., 2016; Vasquez-Rios et al., 2019). Infection is treated with albendazole and mebendazole, except Strongyloides stercoralis, which is treated with ivermectin (Bisoffi et al., 2013; Loukas et al., 2016; Else et al., 2020). Other nematodes also cause disease in humans. In the United States, for example, toxocariasis causes blindness, Angyostrongilus cantonensis causes neural disorders, and the pinworm, Enterobius vermicularis, is widespread among daycare centers (Woodhall et al., 2014; Stockdale-Walden et al., 2015). Despite the worldwide toll of nematode infections, a success story has been the control and near eradication of the Guinea worm, Dracunculus medinensis. Although no drug is available to treat the disease, behavioral modification and land management practices have reduced the number of human infections from an estimated 3.5 million persons in 1986 to only 30 in 2017 (Hopkins et al., 2018). Unfortunately, eradication efforts are now complicated by the emergence of Guinea worm infection in what is now a reservoir host: the domestic dog (Roberts, 2019).

Some of the primary reasons that SARS-CoV-2 has received so much attention in so little time include the novelty of the virus and disease, the severe pathogenesis, and its global spread. However, a characteristic embedded in this global spread is the fact that many of the most affected countries have vast economic resources. As of this writing, the United States has suffered more than 200,000 fatalities due to COVID-19, and more than 140,000 persons have died between the United Kingdom, Italy, France, and Spain (Johns Hopkins Coronavirus Resource Center, 2020). To put it in another perspective, the United States, with 4% of the world's population, has suffered more than 20% of deaths.

However, if we consider parasitic diseases, today's world is not too dissimilar from Norman Stoll's “This wormy world.” In his 1946 presidential address to the ASP, Stoll estimated that in 1946 there were 457 million persons infected with hookworm, 644 million with Ascaris, 355 million with Trichuris, and 144 million with schistosomes (Stoll, 1947). Those numbers are not dissimilar from those of today, although, for honest perspective, the world's population has just about tripled since Stoll's address (Fig. 3) (GBD Disease and Injury Incidence and Prevalence Collaborators, 2016; United Nations Department of Economic and Social Affairs Population Division, 2019). Nevertheless, one certain change since Stoll's seminal address is the near disappearance of these parasites from industrialized nations. Today, for example, hookworms disproportionately impact poor regions of the world and cause immense economic and health burdens there (Bartsch et al., 2016; GBD Disease and Injury Incidence and Prevalence Collaborators, 2016; Loukas et al., 2016). Hookworms were endemic in the United States less than a century ago, and the work of the Rockefeller Sanitary Commission—with one of its scientific leaders being ASP President Charles Wardell Stiles—together with economic growth, rural depopulation, and other factors, forged the near eradication of these parasites from U.S. soil (Elman et al., 2014; Hawdon, 2019). The near eradication of hookworm disease in the American South is credited with substantial gains in income and schooling (Bleakley, 2007), which once again ties the burden of parasitic diseases to the rate of economic growth.

Consider malaria as a parallel example. Plasmodium parasites infect more than 200 million persons every year, resulting in greater than 400,000 deaths (GBD Disease and Injury Incidence and Prevalence Collaborators, 2016). Of the 6 countries most affected by malaria—Nigeria, the Democratic Republic of the Congo, Uganda, Ivory Coast, Mozambique, and Niger—4 are classified by the United Nations as “least developed countries,” which is not surprising because malarial burden is associated with slower economic growth (United Nations, 2018; Sarma et al., 2019; World Health Organization, 2019). In contrast, less than a century ago, there was endemic transmission of malaria in the United States and Europe, yet the United States was declared free of malaria in 1951, and Europe was free of endemic transmission in the 1970s (Linscott, 2011; Carter, 2014; Piperaki and Daikos, 2016). Since then, traveler-associated malaria is occasionally detected in the United States, and temporary incursions leading to endemic transmission have occurred in southern and western Europe. Regardless, coordinated resolve and innovative public health measures in countries with prospering economies have virtually eliminated all endemic transmission within their borders. In the United States, the action of the U.S. Public Health Service and the Tennessee Valley Authority's malaria control program (among others), together with improvement in regional living standards, led to the eradication of malaria (Carter, 2014). Similar trends can be seen for other locations and parasites, including the elimination of schistosomiasis from Puerto Rico (Hillyer, 2005).

It is precisely because parasitic diseases devastate the poor that the global investment in their control and prevention has been subpar. A look at the primary drugs used to treat these diseases shows that most were developed decades ago (Table I). Drug resistance continues to be a problem for the treatment of malaria (Talman et al., 2019; Tse et al., 2019), and it is becoming more of a problem for leishmaniasis, trypanosomiasis, and giardiasis (Leitsch, 2015; Capela et al., 2019). On the bright side, praziquantel and ivermectin remain highly effective against trematodes and nematodes that infect humans, in part because the long generation times of these metazoan parasites result in chronologically slower selection for drug resistance. Through the generosity of governments and pharmaceutical companies, praziquantel and ivermectin (among other drugs) have been leveraged in mass drug administration campaigns. These campaigns currently offer preventative chemotherapy or drug treatment for a variety of helminth parasites to more than 700 million persons every year (Webster et al., 2014; Hotez et al., 2019). Eric Loker, in his 2013 ASP presidential address titled “This de-wormed world?,” argued that the success of mass drug administration campaigns and other health measures gives us hope that significant reductions in the burden of disease are on the horizon, and Bruce Christensen and David Bruce Conn reminded us in their 2004 and 2010 ASP presidential addresses that further research is necessary, especially given the likely emergence or reemergence of novel diseases (Christensen, 2004; Conn, 2009; Loker, 2013). A fulminating epidemic or pandemic with a novel protozoan or metazoan is most likely not imminent, but the devastating reemergence of Zika—a mosquito-borne virus that causes congenital brain abnormalities and is a trigger of Guillain-Barré syndrome—tells us that complacency is not an option (Krauer et al., 2017; World Health Organization, 2017).

SARS-CoV-2 and the COVID-19 pandemic emerged less than a year ago, yet combating this virus has complicated the prevention and treatment of parasitic diseases. Early evidence suggests that the COVID-19 pandemic has had a limited impact on malaria transmission (Roberts, 2020), but 2 recent independent analyses predicted that COVID-19-associated disruption of antimalarial drug treatment and insecticide-treated net distribution may lead to a doubling of malaria mortality in Africa (Sherrard-Smith et al., 2020; Weiss et al., 2020). Therefore, it is essential that malaria control programs are maintained throughout the COVID-19 pandemic and beyond, including vector-control efforts (Nature Editors., 2020; Seelig et al., 2020).

COVID-19 has also suspended some annual mass drug administration programs. This, for example, has allowed a schistosomiasis outbreak to expand unchecked in Malawi (Kayuni et al., 2020), a scenario that is likely common in other places and for other neglected tropical diseases. COVID-19-related roadblocks will require that existing programs for the control of parasitic diseases adapt to a new normal (Jesudason, 2020; Molyneux et al., 2020), and, in doing so, it will be important to consider that co-infection with SARS-CoV-2 and parasites may shift the age pattern of severe COVID-19 to younger persons, leading to worse overall outcomes (Gutman et al., 2020).

SARS-CoV-2 and the COVID-19 pandemic have altered the narrative, and for good reason. However, as we consider how COVID-19 has altered the narrative, it is important to remember that the public health crisis that we are experiencing today, with its burden of disease, shares many similarities with the public health crises that many countries have faced for decades because of the devastating toll of acute and chronic parasitic diseases. These infections kill upwards of a million people every year, and many more are incapacitated. So, yes, let's devote our energy toward combating SARS-CoV-2 and COVID-19, but while doing so and beyond, let's also steadfastly resolve to understand and combat the parasitic diseases that for centuries have haunted humankind.

I thank the members of the American Society of Parasitologists for entrusting me to be their president and lead our society. I also thank Bruce Christensen for the kind introduction and for his support during my academic career, first as my Ph.D. advisor and later as a career mentor (Christensen, 2011, 2015, 2020; Hillyer, 2011, 2015). Although ASP has one president at any given time, running the society is a team effort. I especially thank Secretary/Treasurer Lee Couch for efficiently managing the daily operation of our society, and the 2 ASP presidents that preceded me—Susan Perkins and John Hawdon—for their support and advice. For the health and safety of our members, ASP was forced to cancel the 2020 annual meeting, which was to be held in Kansas City, Missouri. Nevertheless, significant work went toward planning this meeting. I thank the local organizing committee (LOC), including Kirsten Jensen, Janine Caira, Joanna Cielocha, Kaylee Herzog, Rich Clopton, and Deb Clopton, for working through the logistics and having everything in place, and Dennis Kyle, Lyric Bartholomay, and Patrick Hanington for graciously agreeing to present in a presidential symposium that ended up never taking place. Finally, I thank Don Duszynski, Steven Nadler, Eric Loker, Kelly Weinersmith, Vasyl Tkatch, the LOC, and the other members of ASP's Council for their advice and work toward the cancellation of the annual meeting, and the membership as a whole for their support in this process. Although COVID-19 has caused serious setbacks to ASP, by working together, we will emerge from this pandemic as a stronger and more vibrant society. (Figures 1 and 2 were created using Biorender.)