Animals can be hazardous to human health. When asked to name the most dangerous animal, many people will give the wrong answer. Sharks have captured the attention of the public, and other animals that kill people may come to mind, such as black widow spiders, rabid dogs, and venomous snakes. And don’t forget the human animal: gun control is a hot topic. When humans murder other humans with guns, it gets a lot of press. We are subject to the availability heuristic: if we can think of examples or have recently read a news story about it, we tend to overestimate its prevalence. An article on BBC’s Science Focus magazine website reports the actual number of people killed by the top ten animals that kill people, either directly or indirectly by transmitting disease (“Top 10” n.d.). Sharks didn’t even make the list. The actual number of deaths recorded for each deadly animal around the world may surprise you. Here they are (the number represents number of humans killed each year):

10. Lions: 200

9. Hippos: 500

8. Elephants: 600

7. Crocodiles: 1,000

6. Scorpions: 3,300

5. Assassin bugs (by transmitting Chagas disease): 10,000

Note: Chagas disease occurs only in the Americas. It is particularly icky. The so-called “kissing bug” poops while feeding. The poop gets rubbed into wounds and mucous membranes, and the disease can damage the heart muscle, leading to death decades later. It has been suggested that Chagas disease contracted during the voyage of the Beagle might have contributed to Charles Darwin’s lifelong ill health and his death.

4. Dogs (especially those that carry rabies): 59,000

3. Snakes: 138,000

2. Other humans (only counting homicides): 400,000

1. Mosquitos: 725,000

Other animals can also be done in by mosquitos; your pet dog may succumb to the deadly heartworm disease, where masses of worms up to a foot long accumulate inside the heart. Heartworm disease is transmitted only by mosquitos. It can be treated, but it sometimes kills even with treatment. It’s better to prevent it. Protect your puppy from those deadly mosquitos!

Mosquitos can transmit several viral and parasitic diseases to humans. Aedes mosquitos transmit Chikungunya, dengue, lymphatic filariasis, Rift Valley fever, yellow fever, and Zika. Culex mosquitos transmit Japanese encephalitis, lymphatic filariasis, and West Nile fever. Anopheles mosquitos transmit lymphatic filariasis and malaria.

Dogs bite people. Although we talk of mosquito “bites,” that’s inaccurate. Mosquitos don’t exactly bite—at least not in the way that dogs do. Dogs have teeth; mosquitos don’t. The male mosquito is harmless. The female mosquito inserts her proboscis through the skin and uses it to suck up blood and inject saliva. The itchy bump that annoys us is our body’s reaction to her saliva. Some people are more attractive to mosquitos than others. I used to come home from family camping trips with dozens of itchy bumps, while other family members had only a few or none at all. You might say I was a sucker for bloodsuckers; I just thought “That sucks.” I didn’t appreciate being “in good taste.”

Malaria

The most serious disease transmitted by mosquitos is malaria, but it’s not automatic. To get malaria from an encounter with the deadly mosquito,

• The mosquito must be female;
• She must belong to the genus Culex and Aedes species do not transmit malaria, although they transmit several other diseases;
• She must be one of the thirty to forty species of Anopheles mosquitos (out of a total of 340) capable of transmitting the disease;
• She must have previously sucked blood from an infected human or animal; and
• She must inject viable malaria organisms through her proboscis.

The Center for Disease Control and Prevention (CDC) has a handy map showing areas of the world where malaria is endemic (Centers for Disease Control and Prevention 2020). If there is no malaria in the area, there is no risk.

Malaria is one of the world’s most serious public health problems. The World Health Organization (WHO) tells us 409,000 people died of malaria in 2019, 67 percent of them children under the age of five (World Health Organization 2021). Most cases and deaths (94 percent) were in Africa. Babies and pregnant women are particularly susceptible. During World War II, 500,000 American troops were infected in the South Pacific, and 60,000 died.

Malaria parasites are protozoa belonging to the Plasmodium genus. At least four species are known to infect humans: P. falciparum, P. vivax, P. ovale, and P. malariae. The parasite’s life cycle is complicated and requires two hosts. The terminology can be confusing. When a mosquito takes a blood meal from an infected host, it ingests male and female gametocytes. These mate in the mosquito’s gut, producing sporozoites. After ten to eighteen days, the sporozoites migrate to the mosquito’s salivary glands and can be transferred to a human host. In the human, the sporozoites mature and multiply in the liver, producing schizonts. When schizonts rupture, they produce merozoites, which then infect red blood cells. There they develop into ring-stage trophozoites, which develop into schizonts, in turn rupturing and releasing merozoites.

After an incubation period of a week to a month, the infected human develops symptoms such as fever, chills, sweats, headache, nausea and vomiting, body aches, and general malaise. Attacks of fever can be tertian (recurring every third day) or quartan (recurring every fourth day). Or the parasite may enter a dormant stage, unexpectedly relapsing many years later. In severe cases, every part of human physiology may be affected. Cerebral malaria can cause abnormal behavior, impairment of consciousness, seizures, coma, and neurologic abnormalities. Destruction of red blood cells can cause serious anemia. The lungs, kidneys, blood pressure, and coagulation system can be affected. The patient may develop jaundice. In rare cases, the spleen can rupture. There may be long-term consequences, especially in children, including deafness, blindness, and palsies.

History

Periodic fevers have been recognized throughout recorded history, and the parasites that cause malaria have been detected in fossils millions of years old. The name “malaria” comes from the Italian words for “bad air.” In the prescientific era before germ theory, malaria was believed to be caused by fumes emanating from swamps. It came from the swamps all right, but it was brought by mosquitos that lived there, not by fumes. Malaria may have contributed to the fall of the Roman Empire.

Tertian and quartan fevers were recognized long before their cause was known. Spanish Jesuit missionaries in South America learned of an effective treatment—cinchona bark—from the Quechuas and introduced it to Europe in the early 1600s. It worked for malarial fevers because it contained the effective anti-malarial drug quinine. Fevers were indistinguishable from each other in the prescientific era before the discovery of microorganisms and the germ theory of disease, so quinine was used to treat all fevers. Sometimes it seemed to work.

An Interesting Evolutionary Dilemma

An inherited enzyme deficiency, G6PD deficiency, affects 600,000 people worldwide. It can be asymptomatic or can cause anemia and death. It killed 33,000 people in 2015. Hemolytic crises are triggered by several factors, including illnesses and certain medications such as antimalarial drugs. A common trigger is eating fava beans, which are a common dietary component in some areas of the world and can cause favism. Favism can be triggered by just walking through a field where the plant is in flower (Editors n.d.a). Because G6PD deficiency tends to impair survival, one might wonder why evolution hasn’t been able to eliminate it. The answer: it offers a survival advantage by reducing the risk of malaria and sickle cell disease.

Anti-Malaria Drugs

Quinine was the first successful use of a chemical compound to treat an infectious disease (Editors n.d.b). Up until World War II, quinine was the only effective drug for malaria, but it did not prevent relapses and could not be synthesized in commercial quantities. Synthetic derivatives were developed. Chloroquine was more effective than quinine but did not prevent relapses. Primaquine produced complete cures without relapses. As resistance to newer anti-malarial drugs developed, quinine resurfaced in some parts of the world as the drug of choice, despite its risk of toxic side effects, which can include hearing loss and visual disturbances.

Malaria itself was used as a treatment for tertiary syphilis in the early twentieth century before the germ theory of disease was universally accepted and before antibiotics were available. Patients were intentionally infected with malaria; the resulting fever killed the heat-sensitive spirochetes, and then quinine could be used to cure the malaria. Unfortunately, malariotherapy killed 15 percent of those treated with it. More recently, Henry Heimlich advocated malariotherapy as a cure for AIDS. Some small studies in China found that it reduced HIV viral loads, but it can’t be recommended.

A Chinese scientist, Youyou Tu, won a Nobel Prize in 2015 for her work on artemisin, a derivative of wormwood. It proved very effective against malaria, but resistance to the drug has developed, and it doesn’t prevent relapses. It is therefore commonly combined with other drugs.

Prevention

It’s always preferable to prevent a disease in the first place than to play catch-up by treating it after it develops. Persons traveling to areas where malaria is endemic are advised to take a prophylactic drug before, during, and after travel. The specific drugs recommended vary by country. Drugs are not 100 percent effective and must be combined with personal protective measures, such as long sleeves, insect repellants, and bed nets. For people living in endemic areas, mosquito control measures can reduce the risk. Indoor spraying, eliminating standing water that harbors mosquito larvae, and housing modifications can be helpful. Insecticide-impregnated bed nets are estimated to have saved the lives of 250,000 infants in sub-Saharan Africa between 2000 and 2008. Bed nets are inexpensive ($5 each) and are provided free by several organizations. Unfortunately, they have only reached a minority of those at risk (32.8 percent of African households owned at least one bed net in 2008 [Institute for Health Metrics and Evaluation 2010]).

A small phase 1 trial of a monoclonal antibody was promising, apparently preventing malaria in a few subjects who were exposed to a controlled infection after subcutaneous or intravenous treatment with the antibodies (Gaudinski et al. 2021). It’s too early to know how effective it will be; further studies will be needed.

Vaccines

A vaccine for malaria has finally been developed after a decades-long effort. The RTS,S vaccine (trade name Mosquirix) was recommended for children in sub-Saharan Africa by the World Health Organization (WHO) in October 2021. A real breakthrough, it is the first vaccine ever for a parasitic disease. Unfortunately, it is only modestly effective, cutting the risk of infection by 40 percent and the risk of severe infection by 30 percent. And getting it to those who most need it will be problematic; it requires a series of four injections for infants who live in an area with poor access to medical care.

Counterintuitively, the most deadly animal is the smallest: mosquitos that transmit malaria. Despite their bad press, sharks kill only ten people per year. Those annoying little mosquitos do far more damage to humans than big scary sharks.

References

Centers for Disease Control and Prevention. 2020. Where malaria occurs. Available online at https://www.cdc.gov/malaria/about/distribution.html.

Editors, The. N.d.a. Favism. The Encyclopaedia Britannica. Available online at https://www.britannica.com/science/favism.

———. N.d.b. Quinine. The Encyclopaedia Britannica. Available online at https://www.britannica.com/science/quinine.

Gaudinski, Martin R., Nina M. Berkowitz, Azza H. Idris, et al. 2021. A monoclonal antibody for malaria prevention. New England Journal of Medicine 385: 803–814. Available online at https://www.nejm.org/doi/full/10.1056/NEJMoa2034031.

Institute for Health Metrics and Evaluation, The.  2010. African countries rapidly distribute bed nets to fight malaria (August 17). Available online at https://www.healthdata.org/news-release/african-countries-rapidly-distribute-bed-nets-fight-malaria.

Top 10: World’s most dangerous animals. N.d. Science Focus. Available online at https://www.sciencefocus.com/nature/what-animals-kills-the-most-people/.

World Health Organization. 2021. Malaria (fact sheet). Available online at https://www.who.int/news-room/fact-sheets/detail/malaria.