Introductory Chapter: Roundworms from Past to Present

1. Introduction

More than 30,000 members of the phylum Nematoda, also known as roundworms, live in different habitats. This number increases even more with phylogenetic studies [1, 2].

Some of these are free-living organisms in terrestrial and aquatic environments. A significant number are parasitic on animals and plants. Their bodies are bilaterally symmetrical, without segments, covered with a cuticle layer. They are separate sexes, but there are rare hermaphrodite species. The first nematode identified in humans was Ascaris, described by Linneaus in 1758. Classification studies started in 1808 when Rudolphin used the name “Nematoidea.” Various types of phylogenetic research on nematode systematics are carried out by continuously changing molecular techniques. These studies have added many new species to the nematode group [1, 2, 3].

Phylum Nematoda: based on evolutionary relationships, developmental and morphological features and recent molecular evidence, a new classification model was created in 2019. Accordingly, Nematodas consist of three classes, eight subclasses, 12 superorders, 32 orders, 53 suborders, 101 superfamilies, 276 families, 511 subfamilies, 3030 genera and 28,537 species [1].

Nematode diseases are one of the oldest diseases of civilization, having been recited as far back as ancient Greece and Rome. The many of hookworms, whipworms or flamentous worms are also called soilborn worms. The many of hookworms, whipworms or flamentous worms are also called soilborn worms. They are more common in children and women and cause intestinal disorders, growth and development disorders, cognitive impairment and death [4].

It is estimated that a quarter of the world’s population is infected with soil-transmitted nematodes such as hookworms, Ascaris, Trichuris and Schistosoma. Their presence is still a major cause of morbidity and mortality in developing countries, especially in Africa. According to WHO data, the burden of nematode diseases is greater than that of the world’s most common major tropical diseases, such as trypanosomiasis, dengue fever and leprosy [5]. It is estimated that 75% of children in endemic areas are infected and require treatment [5, 6].

Some nematodes are vector-borne and cause different pathologies in the eye, subcutaneous connective tissue and lymphatic system, called filarial nematode infections. Eight important species of filarial nematodes live in the blood and lymph system and cause elephantiasis in humans. Filarial nematodes need a second intermediate host, defined as a vector, to complete their evolution. Their spread worldwide depends on the regions where these intermediate hosts are located. Today, it is known that more than 120 thousand people in tropical countries are infected with filarial nematodes. Symptoms of filarial nematode disease include overgrowth of connective tissues due to obstruction of the lymphatic system and consequent overgrowth of the legs, arms, scrotum, vulva and mammary tissues [5, 6, 7, 8].

Onchocerciasis, another filarial nematode disease that causes blindness in humans, occurs in the Arabian peninsula, Africa and parts of South and Central America. Transmitted by river flies, Onchocerca and Loa loa cause blindness in more than 37,000 people in endemic areas. Dirofilaria immitis (canine heartworm), a zoonotic agent in various countries of the world, especially in the USA, is another common filarial nematode. Dracunculus medinensis, which is transmitted through freshwater crustaceans in some parts of Africa where thirst is common, is one of the longest filamentous nematodes common in the world. They are localized in subcutaneous connective tissue [5, 6, 8, 9].

The larval stages of nematodes, whose adult forms live in the intestines of some animals in our immediate environment, cause “larval migrans” diseases in humans. It is especially widespread in children who have intensive contact with animals and soil, and in those who come into contact with infected animals. Since the symptoms can be recognized with many other diseases, it is estimated that there are many more cases than known. Although larval nematodes cannot develop into adult form in humans, they can cause severe damage such as hepatosplenomegaly, blindness and death in addition to allergic symptoms. Toxocariasis is one of the zoonotic helminth infections with the highest prevalence globally, especially in tropical and rural areas [6, 10, 11, 12].

While some nematodes can directly infect and parasitize humans, others may have one or more hosts in their evolution. However, one of their common life traits is that they all go through four different larval stages before they develop into adults. They are usually hermaphroditic and reproduce by eggs. The eggs laid by their hosts in the external environment are found in the soil until they reach a certain maturity, and the temperature and humidity of the soil are essential in their geographical spread. Nematodes with the soil-borne transmission have almost no chance of transmission in regions where the temperature drops below 10°C. However, there are also free-living species in Arctic regions and thermal waters. Approximately 30% of the more than 28,000 species identified to date are known to parasitize marine and freshwater vertebrates [6, 7, 10].

Today, improved sanitation, hygiene education and the widespread use of anthelmintics reduce the disease burden of nematodes. However, both intestinal and vector-borne nematodes remain prevalent in developing countries [5, 6, 10].

In addition to their negative effects on living organisms, nematodes have many significant benefits, such as transforming the ecosystem, directing genetic and toxicity studies, playing an active role in biological warfare, taking part in the food chain and being used in the fight against autoimmune diseases [13].

2. History

Parasites recovered from human remains and mummified human bodies at archeological excavations make an important contribution to the analysis of past lives. For example, Enterobius eggs and lizard parasites, isolated from human bodies dating back to 100,000 BC, indicate that they were feeding on lizards and were in close contact with other primates [14].

Ascaris eggs have been found in organic remains dating back 30,000 years. Another prehistoric study showed that Ascaris were widespread among both South and North American Indians. Archeologists suggest that they spread here after migrations from the old world. Nematodes such as hookworms and Tirichuris date back 9000 years. Paleoparasitological studies have also shown that soil-borne nematodes, which are common in Africa and Europe, arrived in the Americas much later [3, 4, 14].

Historians have learned from genome studies of coprological materials that parasitic infections accompanied the evolution of humans. In this way, much has been revealed about the origin of man. From this information, we learn that the first humans emerged as Homo sapiens about 150 thousand years ago in East Africa and spread around the world in waves. During their migrations, they brought some parasites with them and collected some of them from the roads and spread across the globe with their parasites. In this spread, contact with soil during agricultural practices and contact with animals have also been factors that facilitate transmission. The formation of cities and increased human density were other factors that facilitated transmission. In the 1500s, with the opening of the slave trade and other trade routes to the world, endemic species spread to other continents [14, 15, 16, 17].

In paleoparasitological studies, hookworms were identified in Africa around 7000 BC. As with other helminths, they are estimated to have spread to the Americas in the following years through the slave trade. During these investigations, examining naturally or artificially fossilized coprolites and tissue samples helps us define the history of parasites and human evolution [14, 18].

The first written records date back to Egyptian papyrus between 3000 and 400 BC. Later, parasites were described in the works of the ancient Greek physician Hippocrates. Diseases caused by parasites were mentioned in Chinese medicine between 3000 and 300 BC, in India in 2500–200, in Rome in 700 BC and 400 AD and by Arab physicians in 850–953 AD. This was a period when medieval Europe was inadequate in science due to religion and superstition, but with the renaissance, great discoveries began in the nineteenth century with Pastor, Koch, Roux and Manson [12, 16].

Ascaris was the first nematode to be identified in mummies. One of the best-documented parasitic diseases known from the earliest times was Dracunculus medinensis, a parasite up to 80 cm in length living in subcutaneous connective tissue. It was mentioned in the Eber papyrus in 1500 BC. It has been shown on Egyptian mummies. It was described as a febrile snake disease that enveloped the Red Sea. It is also mentioned in the Bible and the book was written by Arab physicians in the seventh century BC [4, 14, 17].

Nematodes are among the oldest known parasitic diseases of mankind. Ascaris was mentioned by physicians in ancient Greece and Rome. Since the late nineteenth century, they have been the subject of important scientific studies. For example, meiosis and gametogenesis, the basis of chromosome studies, were carried out on Ascaris species. They are expected to form the basis of future molecular and genomic studies of biological processes [4, 18, 19].

Filarial worms were described by Manson in 1877. Historically, lymphatic filariasis was widespread along the Nile River, as evidenced by the swollen limbs of a statue dating from 2000 BC. In the sixteenth century, the disease was described as the curse of St. Thomas. However, it was not until after the microscope’s discovery that the disease’s larval stage was elucidated [3, 4].

Hookworms were described in general terms by Tyson in 1683. In 1836, the dermal transmission of hookworm larvae was described after a laboratory accident [20].

In Utah, North America, Enterobius vermicularis eggs have been isolated from caves inhabited by settlers 10,000 years ago. This represents the oldest human parasite isolated from coprolites in 7837 BC. In Asia, E. vermicularis eggs were found in a 7000-year-old female skeleton in Iran, representing the presence of the infection on this continent [14, 16, 17].

After the 2000s, the rates of Ascaris and Trichuris, the most common intestinal nematodes worldwide, have decreased by 10% with various measures and preventive medication. However, the numbers are still high. Almost all nematode infections are diseases of poverty. All living things, especially humans, are at risk in places where there is no clean food and water and where sanitation is inadequate [21, 22, 23].

3. Diagnosis

Hundreds of millions of people worldwide, especially in developing countries, live with intestinal and tissue nematodes. In recent years, the spread of nematodes from endemic areas to different countries has increased due to wars, migration and tourist travel. Despite the various technological possibilities in developed countries, there are difficulties in diagnosis due to problems in diagnosis. Parasitologic diagnosis is often difficult to obtain, while serologic diagnosis is less reliable due to cross-reactions between helminth species. Molecular tests are not ubiquitous and still need optimization [22, 23, 24].

Laboratory diagnosis depends on the location of the nematode in the body. Methods for demonstrating the causative agent are always the gold standard in diagnosis. While the criteria for diagnosis and classification are based on the morphological and morphometric characteristics of the nematode, serological and molecular methods are also used today. Serologic methods can sometimes lead to misdiagnosis due to the common cuticle antigen of nematodes. Molecular methods are very successful in species identification and phylogenetic studies, but they can only be applied in certain research centres and are time-consuming. MALDI-TOF, a new identification method, is based on detecting particles released after ionization of samples with a laser [22]. Studying the protein profiles of pathogenic nematodes with this method can help decipher host-pathogen interactions [5, 6, 18, 22, 24, 25, 26].

4. Results

WHO recommends microscopic examination using the Kato-Katz method to diagnose soil-transmitted nematodes. The sedimentation technique has been found to be more successful in preparing stool samples. Intestinal obstructions require urgent surgery. In endemic areas, nutritional and vitamin supplements for children alleviate the damage of nematodes. Single-dose chemotherapy, recommended by WHO since 2001, is one of the measures to protect school-age children. Although anthelmintic drugs are available, they do not provide long-term protection against reinfection.

Since 2000, the World Health Organization has launched the Global Program to “Eliminate Lymphatic Filariasis,” which affects 863 million people in 47 countries. According to 2018 data, there has been a 74% decrease in the disease rate since the start of the program. Key targets for surveillance and treatment were decided to be maintained beyond 2020.

Despite the measures taken in low-income countries, nematodes still remain the most critical public health problem. Drug resistance emerging in endemic areas reduces success rates in treatment. There is a need to take new steps in the fight against nematodes by reviewing recently developed genetic studies.