Intestinal Parasites from Past to Present: Taxonomy, Paleoparasitology, Geographic Distribution, Prevention and Control Strategies

Abstract

Intestinal parasites are among the oldest human infectious agents. Throughout history, many parasite species have continued to evolve with humans during migrations, hunting, and domestication. Intestinal parasites are still a major cause of morbidity and mortality in the world, especially among children in underdeveloped countries. In developing countries, helminth infections such as hookworms, Ascaris, whipworms and amoebiasis caused by Entamoeba histolytica are parasitic agents that cause significant mortality and growth retardation. Soil-transmitted helminths and intestinal parasites of zoonotic origin cause significant mental and physical developmental disorders in poor people in endemic areas. It is an important public health problem affecting a quarter of the world’s population, increasing the global health burden and impairing quality of life. Intestinal protozoa are among the leading causes of diarrhea in developed and developing countries. In order to achieve success in prevention and control programs, it is necessary to identify people with parasites through community-based epidemiological studies and to carry out treatment and post-treatment controls. Although epidemiologic studies on intestinal parasites are mostly related to children, infants, pregnant women, and immunocompromised populations are at significant risk. Today, microscopy is still the gold standard for diagnosis, but serologic and molecular techniques have also been successfully applied.

1. Introduction

Intestinal parasites are the leading infectious agents among the causes of death in the world, especially in children. Diseases caused by Ascaris lumbricoides, Ancylostoma duodenale, Necator americanus, Schistosoma species, Enterobius vermicularis, Giardia lamblia and Entamoeba histolytica are intestinal parasites that cause significant morbidity and mortality in developing countries [1, 2, 3, 4, 5, 6].

Although intestinal parasites do not have obvious clinical symptoms, abdominal pain, sleep disorders, nervous symptoms, growth and development disorders due to malabsorption are the most prominent symptoms, especially during childhood. The most important factor in the spread of intestinal parasites is people with parasites. Epidemiologic surveys with intermittent controls in societies can identify and treat many people infected with parasites. In this way, societies provide the necessary measures to prevent an important disease that will cause destruction in individuals and to prevent social destruction. From past to present, microscopic examination of stool samples taken on consecutive days for the presence of parasites (cysts, trophozoites, eggs and larvae) is an easy, cheap and gold standard method in diagnosis. It can be applied wherever a microscope is available, but requires experience [1, 2, 3, 4, 5, 6, 7].

Intestinal parasites are most common in tropical climates and in regions where the necessary infrastructure and sanitation conditions are not provided, and clean drinking water is not available. The best preventative measurements in a community are the provision of infrastructure and safe water supplies, as well as the identification and treatment of people with parasites. With regard to infectious diseases, people can be infected with a parasite throughout their lives without showing any symptoms. A slight change in the system host-parasite-environment relationship can shift the balance, and diseases can develop [4, 5, 8, 9, 10].

Gastrointestinal parasites have been described as the “infectious disease of poverty”. Protozoa and helminths living in the human gastrointestinal tract are estimated to infect one-sixth of the global population. Children in sub-Saharan countries have the highest prevalence, followed by rural areas in Asia, Latin America and the Caribbean. It is estimated that 250 million people in sub-Saharan countries, mostly children, are infected with at least one type of intestinal parasite. Although developed donor countries and local communities are taking various initiatives, economic crisis, poor personal and environmental conditions for hygiene, lack of education, population growth, wars and migration as well as inadequate treatment facilities in these regions are causing the increase of new cases [1, 4, 8, 9, 10]. According to WHO reports, although safe and effective drugs have now been developed for the treatment of intestinal parasites, their availability in mass treatment programs and for individual treatment worldwide may be limited by economic resources, existing production and distribution networks and national regulations. Increasing population density, environmental pollution and global migration patterns will continue to encourage the transmission of human intestinal parasites in the future.

In the twenty-first century, malabsorption, diarrhea, blood loss, impaired work capacity and reduced growth rate due to intestinal parasitic infections continue to pose significant health and social problems in many countries. The success of prevention and control strategies depends on safe and effective treatments, improved diagnostic procedures and the availability of general health services. For successful control, it is necessary to know the history of parasites, their migration routes, old and new methods used in diagnosis, treatment protocols and most importantly prevention and control strategies. In this review article, the place of intestinal parasites in classification, history, epidemiology, diagnosis, treatment and prevention methods are discussed in a historical perspective from past to present.

2. Classification of intestinal parasites

Although common names are often used to describe parasitic organisms, these names may represent different parasites in different parts of the world. To avoid these problems, a binomial nomenclature system is used, where the scientific name consists of genus and species. As with all living things, intestinal parasites are classified according to certain rules. Today, this classification can be moved to different places and changed from time to time with the discovery of some biochemical and physiological features depending on phylogenetic studies. Based on phylogenetic classification, living organisms are divided into Prokaryotes and Eukaryotes according to the presence of a nuclear membrane. All parasites are in the Eukaryotes group and in the Animalia kingdom (Figure 1) [11, 12].

Figure 1.

Taxonomy and classification of human parasitic protozoa and helminths.

In addition to unicellular protozoan parasites, many species of parasites called helminths can be found in the human gastrointestinal tract. Intestinal parasites are among the most common gastrointestinal infections worldwide, especially in developing countries. They are also among the leading causes of child mortality in developing countries, especially in the tropics and subtropics [1, 4, 6, 8]. Intestinal parasites, which are still an important source of morbidity and mortality in the world, are divided into two important groups [11, 12].

2.1 Intestinal protozoa

Sarcomastigophora (Amoebae): Entamoeba histolytica, Entamoeba dispar, Entamoeba hartmanni, Entamoeba coli, Entamoeba polecki, Entamoeba moshkovskii, Entamoeba gingivalis, Endolimax nana Iodamoeba bütschlii and Blastocystis hominis. The place of some of these (Blastocystis sp etc.) in the classification and their pathogenicity are still controversial.

Mastigophora (flagellates): Giardia lamblia, Chilomastix mesnili, Dientamoeba fragilis, Pentatrichomonas hominis, Trichomonas hominis, Enteromonas hominis and Retortomonas intestinalis.

Coccidia: Cryptosporidium spp. Cyclospora cayetanensis, Isospora (Cystoisospora) belli, Sarcocystis hominis, Sarcocystis suihominis and Sarcocystis bovihominis.

Ciliata (cilia): Balantidium coli.

Microsporidia: Enterocytozoon bieneusi and Encephalitozoon (Septata) intestinalis.

2.2 Intestinal helminths

Nematodes: Ascaris lumbricoides, Ascaris suum, Enterobius vermicularis, Ancylostoma duodenale, Necator americanus, Strongyloides stercoralis, Strongyloides fuelleborni, Trichostrongylus spp. Trichuris trichiura, Capillaria philippinensis, Oesophagostomum spp. and Ternidens deminutus.

Cestodes: Diphyllobothrium latum (broad, fish tapeworm), Dipylidium caninum (dog tapeworm), Hymenolepis (Rodentolepis) nana (dwarf tapeworm), Hymenolepis diminuta (rat tapeworm), Taenia solium (pork tapeworm), Taenia saginata (beef tapeworm) and Taenia asiatica (Taiwanese variant of T. saginata).

Trematodes: Fasciolopsis buski (giant intestinal fluke), Echinostoma ilocanum, Eurytrema pancreaticum, Heterophyes heterophyes, Metagonimus yokogawai and Alaria spp.

In addition to these, species of the Annelida and Acanthacephala, which are less common in the world, can also parasitize. These are not normally human-specific parasites and are known as “unusual parasites” that can be found in sporadic cases. The evolution of a small number of species of Acanthocephala has been elucidated, as they have a complex evolutionary history, changing many hosts during their evolution. The three most common species implicated in human disease, M. hirudinaceus, M. ingens and M. moniliformis, use pigs, raccoons and rodents, respectively, as their primary definitive hosts, but other carnivores can also function as definitive hosts. Acanthocephaliasis may be an ancient disease of humans. Analysis of fossilized feces from prehistoric humans in Utah revealed Moniliformis sp. eggs, but it is not known whether this represents real or spurious infections. Of the few cases described today, most have been identified in diapers of children under 2 years of age. It is thought to be caused by infants ingesting a cockchafer (Melolontha melolontha) in their environment. The larvae cause mild to severe reactions in the gastrointestinal tract and are usually diagnosed incidentally [11, 12].

3. Intestinal parasites in historical process and paleoparasitology

In the 1990s, standard scientific analyses of parasitology were carried out from the perspective of a new discipline, anthropology of knowledge. With this period, studies on the historical and sociocultural development, limitations, relations with other disciplines and social needs were initiated within the science of parasitology. There are certain periods in parasitological history that are characteristic of all emerging disciplines of the natural sciences. The first systematic description of natural phenomena and their interpretation began in the sixteenth century and continued until the mid-eighteenth century. During these periods, many of the correct facts were not adequately explained and were based on different natural phenomena and religious rituals, many of which were not accepted by Western scholars. Natural sciences gained momentum in the late eighteenth century, and most of the parasites were systematized in this period. Population growth, intensified urbanization, wars and the rapid increase in infectious diseases among humans played an important role in these developments. In the nineteenth century Europe, different theorems due to scientific competition in different countries continued until World War I. Parasitology emerged as a separate discipline in this period. Due to wars and many tropical diseases such as malaria that emerged in colonized countries, European settlers established tropical institutes in various regions. Not satisfied with this, sub-disciplines of Parasitology were established and financially supported by European and American supporters in colonial and developing countries. After the Second World War, parasitology departments were established in universities in many places. Many specialists were trained and specialized diagnostic and treatment stations for parasitic diseases, and their vectors were established in both developed and developing countries [13, 14, 15].

The concept of Paleoparasitology has been formed by bringing together studies in different disciplines that have been carried out for 30 years. Paleoparasitology, which is also interpreted as the study of the presence of parasites in the remains of ancient times, is a field of parasitology that has developed as a research field combining archaeology, anthropology, biology and health sciences. Paleoparasitology aims to detect traces of parasites in prehistoric times and to study the evolution of parasitism over time and space and is the study of parasites in archeological remains of humans and animals [13, 14, 15, 16, 17].

It has long been hypothesized that the ancient ancestors of humans hosted various species of parasites, especially large worms, but until recently, there has been no direct evidence to support such an assumption. However, studies of archeological artifacts, such as the presence of helminth eggs or protozoan cysts in coprolites and preserved bodies, are now providing researchers with information about parasitic diseases of the past [17, 18, 19, 20].

Throughout history, humans have encountered and been infected with more than 400 parasite species through the evolution process and migrations. Most of these were acquired from animals they came into contact with in their immediate environment or through nutrition. However, they were most exposed to parasites in the process of domesticating various animals in their immediate environment. Most of the domestication process took place in Asia. It can also be said that examples of this are still going on in nomadic communities to this day [15, 16].

Humans first appeared on the African continent, and when they started to migrate, they carried their dietary habits and parasites with them to the new areas they explored. According to previous knowledge, most researchers blame the Portuguese and Spanish sailors and their slave trade in the tenth and eleventh centuries for the spread of parasites around the world, but paleoparasitological studies reveal that the situation was different [14, 15, 16].

Luiz Fernando Ferreira from the Oswaldo Cruz Institute in Brazil was one of the first to pioneer paleoparasitological studies. The studies that started with the identification of Schistosoma eggs in the kidney tissue of Egyptian mummies were followed by two bodies found in a swamp in Prussia: Ascaris lumbricoides, Trichuris trichiura and Diphyllobothrium latum in two bodies found in a swamp in Prussia. In the following years, paleoparasitological studies have continued, and many data on the relationship between humans and parasites and their evolution have been obtained. Today, with the use of molecular tests in paleoparasitology, protozoan parasites can be identified in coprolites. In 2009, the Journal of Parasitology published a large special issue under the title “Paleoparasitology” [15, 16].

Paleoparasitological research began with Schistosoma haematobium eggs identified in the kidney tissues of Egyptian mummies, followed by Professor Szidat’s publication of notes on three different helminth eggs identified in two corpses from the fifth century in a swamp in East Prussia. Around this time, Taylor described helminth eggs in Roman remains in England. During this period, the first paleoparasitological publications in the New World were made by Professor Pizzi from the University of Chile, who reported Trichirus trichiura eggs together with Entamoeba coli cysts in an Inca mummy [21]. This study was the first detection of protozoa in coprolites and paved the way for the forthcoming assumptions on the identification of different protozoan species in the future. Prof. Camerun also identified Diphyllobothrium sp. eggs in coprolites from the prehistoric inhabitants of Huaca Prieta on the Peruvian coast [15, 16, 19, 22].

Parasite eggs and cysts found in coprolites, mummies and other human remains tell us little about parasitic infections and diseases of the past, which is why most historians prefer to rely more on written records. The first such records belong to a period of Egyptian medicine between 3000 and 400 BC, notably the Ebers papyrus of about 1500 BC, which mentions worms clearly identifiable as roundworms (Ascaris lumbricoides), threadworms (Enterobius vermicularis) and Guinea worms (Dracunculus medinensis). Of all the diseases caused by parasitic worms, the best documented since ancient times is dracunculiasis caused by the Guinea worm D. medinensis [19, 20, 22, 23].

Few parasitic infections cause specific and clear signs and symptoms, but references to some of them, notably dracunculiasis, hookworm disease, elephantiasis, schistosomiasis, malaria and amoebiasis, often appear in early literature.

The concept of parasitism consists of three subsystems:

1. Parasite

2. Host

3. Environment.

With the emergence of life on the Earth, parasites began to evolve along with their hosts and the environment. Their diversity, which may have been minimal at the beginning, is constantly changing due to biodiversity and climatic factors. Population density, people’s constant mobility, new technologies, agriculture, migrations, domestication of animals and climatic changes have led to a rapid expansion of their global distribution. When early humans lived among small groups of hunter-gatherers on the African savannah, only some parasite species were able to infect these nomadic hosts without establishing themselves in a permanent habitat. Two parasite species can be used here as examples: Nematodes, Enterobius vermicularis, and Arthropods, the head louse, Pediculus humanus. Closely related species of these parasites are found in hosts closely related to humans, such as chimpanzees and gorillas, indicating that they have a common host ancestor. The direct transmission and migratory dispersal of these two parasites is due to the fact that they did not evolve in the soil. They are not affected by environmental changes and can migrate anywhere with humans [19, 20, 22, 23].

Paleoparasitological studies also define the geography of distribution of helminths and protozoa. For example, it has been easy to identify and protect helminth eggs from external conditions due to their 30–160 micron-sized structures and multi-layered eggs that are highly resistant to external conditions. However, protozoan cysts cannot withstand environmental conditions for a long time due to their 4–40 micron-sized cyst forms and delicate structures, and the possibilities of identification by standard diagnostic methods are limited. For these reasons, protozoa have only been identified by immunologic molecular methods in the last 10 years. While the first identified helminth egg was Schistosoma haematobium seen in the kidneys of an Egyptian mummy at the beginning of the twentieth century, recently the presence of Entamoeba histolytica was identified in coprolites from a cave in the USA by radiocarbon and ELISA tests. The selection of the appropriate material and method is of particular importance in identification. Extraction of helminth eggs requires three consecutive steps: rehydration, homogenization and filtration/sieving. Antigen research can be performed on samples prepared following the standard method described previously. However, the use of additional solutions (e.g., formalin) for sample preservation and storage can be problematic. For this reason, the identification of protozoan parasites due to the use of the wrong method in the early years of paleoparasitological diagnosis has only now been possible [14, 15, 16, 17, 18, 19, 20, 22, 23].

Coproparasitological examinations are carried out through various extraction stages according to the residue material examined. Coprolite, sediment or textile-like samples are usually taken for microscopic examination after rehydration, homogenization and sieving/filtering. The amount of residues is very important for parasitological investigations. Recently, parasites identified in coprolites have provided information about the migration routes and climatic conditions of humans in prehistoric times. Some parasites require special environmental conditions to complete their life cycle. For example, hookworms and Trichuris trichiura are two intestinal parasites that probably originated from African human ancestors. They are transmitted from one host to another after maturing in soil under limited climatic conditions. Eggs or larvae passed in host feces need pH, moisture and a temperature close to 22°C in the soil to reach the infective stage and infect another individual. In this way, the journey that started from the African continent has shown that especially geo-helminths cannot withstand cold climatic conditions and cannot reach the Americas [14, 17, 18, 22, 24, 25].

Recent discoveries have shown that parasites were also prevalent in the Americas in prehistoric times. However, the fact that the number of eggs found was lower than in Africa is an indication that the prevalence was lower in these regions. In addition, the fact that there were more hunter-gatherer nomadic groups during these periods is also a significant factor. When European colonizers set foot on the continent, they came with various diseases, built villages and enslaved the indigenous people. Later, they brought slaves from Africa and spread new diseases to Americas. The global spread of parasites is indisputably linked to human activity. Migration, in all its different forms, played an important role in introducing parasites into new areas. In ancient times, mass migrations were the main causes of the spread of parasites, while in the recent past and today, migration, immigration, relocation, internal and external migration and labor migration are the causes of the spread of parasites. With the advent of offshore vessels, long-distance trade has become another important route for the spread of parasites. This article summarizes the spread of parasites using remarkable examples. Different hypotheses explaining the arrival of Plasmodium vivax and soil-transmitted helminths in pre-Columbian America are also discussed [15, 16, 17, 22, 23, 26].

According to phylogeographic studies, a new field, the distribution of human parasites can be categorized into three groups.

1. Out-of-Africa

2. Domestication

3. Globalization

According to these three main hypotheses, new zoonotic parasites were added to the parasites that migrated with African people, domesticated in new places and during the transition to sedentary life, or during nutrition. These numbers have reached approximately 400 species. The species, which spread to other regions and continents with the first human migration, have reached a global scale due to human activities such as trade, migration, wars and travel. Since domestication took place mostly in Asia, paleoparasitological and phylogenetic studies show the highest species diversity in the Middle East and Asia [22, 23, 27, 28, 29].

In studies on the Asian continent, seven species of intestinal parasites have been identified in evidence from Neolithic Qing Dynasty mummies, ancient toilets and soil from the pelvic region of bodies in tombs. These are Ascaris lumbricoides, Trichuris trichiura, Chinese liver fluke, Schistosoma sp., Enterobius vermicularis, Taenia sp. and Fasciolopsis buski. In the past, the roundworm, whipworm and Chinese liver fluke were much more common than other species. While the roundworm and whipworm remained widespread until the late twentieth century, a marked decline in the incidence of the Chinese liver fluke has been reported over time [16, 21, 30, 31, 32].

The Silk Road may have played an important role in the distribution of ancient diseases. On this route, Fasciolopsis buski, which is found in endemic areas of China, was reported to have been carried 1500 km by traders following this route [33].

Today, with the addition of various sub-disciplines to the research, paleoparasitology studies continue with more than 50 scientists and more than 500 scientific publications.

Parasite cysts and eggs identified in paleoparasitological studies provide information on the evolutionary dimensions of the human-parasite relationship, as well as the hygiene and health habits of prehistoric human communities. Paleoparasitology is advancing by interpreting the findings and drawing inferences about the impact of parasitic diseases among prehistoric populations. Hunter-gatherers were found to be less infected by helminths, while agricultural groups had a relatively higher prevalence of intestinal parasites at archeological sites in the United States [23, 26, 31, 34, 35, 36].

Although parasitism can occur in all living organisms, paleoparasitology has focused more on species living in the intestines of humans and animals. These studies have yielded information on diet and lifestyle, habits, culture, organic waste and hygiene habits. For example, as intestinal parasites are ingested orally, parasite biodiversity has undergone many variations over the centuries. For example, fish parasites in coprolites indicate that people were fishing and feeding on fish in the 3400 s BC; later, a variety of animal helminths were identified in the Old World and New World due to their diet of land creatures; and during the migration of humans from Siberia to the Americas, soil-borne helminth infections disappeared due to cold climatic conditions. For this reason, helminth infections were not found in those who migrated to the North American continent, while helminths were found in those who reached North and South America by different routes. Paleoparasitological studies have also facilitated the study of the transmission cycles of different species infecting humans and animals [36, 37, 38, 39, 40].

In medieval Europe during this period, coprolites and mummies were full of intestinal worms, and geo-helminth infections took over large parts of the population due to poor sanitation and overcrowding. However, due to strict religious beliefs during this period, written records are almost non-existent. Epidemiologic information from a large-scale survey of intestinal helminths in medieval Europe was obtained by analyzing 589 samples of grave remains from seven different regions in Europe between 680 and 1700 AD. The most common helminths found in the soil samples were Ascaris lumbricoides, Trichuris trichiura, Diphylobothrium latum and Taenia sp. These studies show that especially soil-transmitted helminths were very common in medieval Europe [41, 42, 43, 44, 45].

The coastal city of Acre in present-day Israel dates back to 3000 BC. Under the control of the Ottoman Empire between 1516 and 1517, and the city was a commercial port city that controlled a large part of Southeastern Europe, the Near East and the North African coast. During this period, the diversity of parasites in the region increased due to the large number of livestock products being shipped. Since the majority of the people were Muslims and Jews, it is estimated that parasites of animal origin such as liver fluke, tapeworms, whipworms and protozoa such as Giardia and entamoeba, which had not been seen in the region before, entered the region through ship trade. This research shows how cultural and dietary habits of societies influence transmission [46].

The nineteenth century can be considered the golden age of parasitology because it was during this century that most of the life cycles of parasites were elucidated and the various discoveries of previous centuries were brought together into coherent stories. It was also a period dominated by some of the biggest names in parasitology, all of whom made many contributions, often in different fields [47].

The twentieth century was not only a period of adding the finishing touches to what was known but also of defining the cause-and-effects of the blood and tissue parasites now called Chagas disease. In the early years and towards the end of the century, a number of opportunistic parasitic infections in immunocompromised patients, particularly those with AIDS, came to the fore [31, 47, 48, 49, 50, 51, 52, 53]. During this period, efforts were focused on control and eradication of many parasites due to the elucidation of their evolution. As a result of the elimination of copepod intermediate hosts from water sources, the Guinea worm is now almost completely eradicated, and Onchocerciasis continues to be eradicated through measures against housefly larvae, together with the availability of cheap and effective drugs [51, 52, 53].

Scientific debate on the mechanisms and migratory pathways that facilitate the spread of the major helminth species infecting human populations in the western hemisphere will continue into the twenty first century. From the 1990s to the present day, paleoparasitology has benefited from the creativity and productivity of its researchers. The accumulated results from decades of analyses of thousands of specimens have provided a database for framing research questions addressing the transmission and distribution of parasites as a function of epidemiological and evolutionary processes. Increased communication through the Internet has created more opportunities for collaboration and standardization of methods among researchers worldwide. This in turn has led to greater interest in paleoparasitology, as reflected in the number of publications submitted by researchers to various journals and the establishment of laboratories and postgraduate training programs identified with the sub-discipline [8, 17, 26, 47, 48, 51, 52, 53].

With the advent of ships sailing on the high seas, long-distance trade became an important route for the spread of parasites. The presence of parasites is the result of different lifestyles, habits or behaviors. Paleoparasitology provides information about ancient populations, cultures and environments. Funeral practices, cultural changes, organic waste management and hygiene are potential topics of such studies. In the case of intestinal parasites, since the route of contamination is mainly oral, some conclusions can be drawn about some aspects of ancient nutrition. For example, whipworms, tapeworms, giant kidney worms and liver flukes have been identified in the remains of human communities living by lakes between 3900 and 2900 BC in the northern Alpine region. The changing diversity of the parasites identified here over the years has been attributed to dietary, cultural and climatic changes. When parasite biodiversity is sufficient, it is possible to hypothesize about the biological origin of these specimens and/or the function of certain archeological structures by associating or considering parasites with a specific host spectrum [49, 52, 53].

Paleoparasitological studies have been carried out for many years and continue to make many contributions to science on evolution-migration and host-parasite relationships. Today, with the contribution of technological progress, microscopic and molecular methods can open new horizons and make new contributions. However, studies are still limited to certain regions. For example, paleoparasitological studies in West and Southern Africa, Eastern and Central Europe and Asia, which are very important in terms of early human density, will provide comprehensive information in understanding the global history and evolution of gastrointestinal parasites.

4. Intestinal parasites in evolution and geographic studies

Throughout history, people have been infected with various parasites due to cultural and behavioral changes. Domestication of animals, wildlife and climate change have increased the chance of contracting zoonotic and foodborne parasites. In fact, there is no organism that can resist parasites.

4.1 Intestinal nematodes

4.1.1 Trematoda (flukes)

The first trematode identified in paleoparasitological studies was Schistosoma from Egyptian mummies. Molecular data show that, unlike other parasites, they did not originate from the African continent, but were parasites of other mammals (monkeys) in Asia, and spread first to Egypt and then to West-Central and South Africa via their definitive and intermediate hosts (snails) via the slave trade with ships. Among these, it can be said that Schistosoma mansoni was brought to Latin America with enslaved Africans in the post-Columbian period. To give an example from recent history; during the establishment of the State of Israel in 1948, in a town built by the river by 500 thousand migrants from endemic areas, about 10% of school children swimming in the river were infected with Schistosomas. An example of parasite introduction by migrant workers is the spread of S. mansoni in the Wonji Sugar Estate in the upper Awash valley of Ethiopia. Initially, every effort was made to ensure that migrant workers were not infected, but by 1964, 10 years after the sugar factory was established, S. mansoni infection among workers exceeded 20%. In the 1980s, S. mansoni rates of 80% were reported in children playing on the sugar platform [15, 17, 19, 23, 27, 30, 37, 54].

A recent example is the outbreak of Schistosoma haematobium that infected more than 120 people swimming in the river Chavu on the island of Corsica in 2013. Another trematode that spreads through migration is Opisthorchis viverrini. In the 1950s, this parasite was found only in the north of Thailand, where almost the entire population was infected, but it has now spread throughout Thailand, with infected people moving to other parts of the country through labor migration. Liver parasites (fasciolids) are parasites of herbivores, but can also cause disease in humans. Molecular phylogenetic analysis shows that fasciolids spread from elephants in Africa to herbivores in Asia. The most common liver fluke, Fasciola hepatica, originated in Eurasia, where it spread to other continents through the ship trade of livestock. It was also taken to South America by Spanish sailors [54, 55].

4.1.2 Cestodes (tapeworms)

Data on tapeworm eggs from past periods are very rare. Cysticercus was found in Egyptian mummies dating back to 200–100 years BC. Julius Caesar, who lived between 100 and 400 BC, is thought to have died of neurocysticercus. Although not fully elucidated by paleoparasitological studies, phylogenetic analyses show that Taenia solium and Taenia saginata were present before the domestication of pigs and cattle. An interesting example of its geographical distribution is the pig tapeworm T. solium. In 1973–1976, indigenous people living in the highlands of New Guinea were repeatedly admitted to hospital with burns. After long investigations, it was revealed that the burns were caused by people falling asleep at night and falling into the fire, and that this was due to “neurocysticercus” caused by the larvae of the pork tapeworm T. solium settling in the brain. It was found that there were no pigs in the area before, and that the disease had spread from infected pigs sent to suppress the rebellion on the island a few years earlier [19, 23, 26, 56].

4.1.3 Nematodes (roundworms)

Nematode eggs isolated from archeological remains or from coprolites in mummies are the most important documents of the dietary habits of humans in the past. Dating back 10 thousand years, lizard parasites in human coprolites are the most obvious example of the use of lizards as a source of protein. Among nematodes, Ascaris lumbricoides, hookworms and Trichuris trichura are nematodes originating from the African human ancestors of Homo sapiens, dating back 30 thousand years. However, geohelminths such as these did not reach other continents during the first human migrations, as they had to spend a period in warm and moist soil. However, it is thought that the geohelminths detected in the Americas and Europe during molecular research may have been brought to the continent by immigrants reaching the continent through different migration routes in later periods. On the other hand, directly transmitted nematodes such as Enterobius vermicularis are known to have reached other continents with the first migrations [13, 15, 16, 17, 21, 23, 24, 27, 30, 35, 36].

Soil-transmitted hookworm infections were thought to have been taken first to India and then to other continents by coastal migration in the 12th century BC. Even in recent history, hookworms have been recognized as an industrial occupational hazard thanks to migration and nomadic workers. Brought to the Americas by slaves brought from Africa during the Columbian era, hookworms spread to large areas as a miner’s disease in many parts of Europe in the 1870s, causing significant morbidity and mortality [22, 23, 27].

New findings require a reassessment of old ones. For example, while hookworms, a geohelminth, were known to have entered the Americas with African slaves brought over during the Columbian era, the identification of hookworms in a Peruvian mummy showed that the parasite had been present here before [27, 35, 48].

Other nematodes brought to the Americas with infected African slaves during the Columbian era include Onchocerca volvulus, Wuchereria bancrofti, Mansonella perstans and Loa loa, known as “filarial nematodes”. These vector-borne nematode diseases have found suitable vectors in the Americas, but have remained sporadic in certain regions. In fact, lymphatic filariasis, such as Wuchereria banchrofti, was reported to have originated in Asia 50,000 years ago, from where it spread to Madagascar and Africa 1500 years ago. The largest epidemiologic spread of this parasite was in hemp field workers in the Philippines between 1903 and 1937. Large numbers of people were infected due to stagnant water suitable for the development of vectors. Dracunculus medinensis, known as the guinea worm, is another nematode that came to the Americas with African slaves. However, this nematode could not spread here because it requires special conditions and intermediate hosts [23, 27, 30, 54]. In addition to a 10,000-year-old Enterobius vermicularis egg found in a coprolite sample, several trematode eggs are the oldest remains identified in coprolites [25].

4.1.4 Intestinal protozoa

Due to their sensitive nature, the history of protozoa has been limited to recent times, that is, to the period when molecular and immunologic methods were used. They collected historical data on amoebic dysentery and estimated that Entamoeba histolytica has been present in Western Europe since the Neolithic Age and spread to other countries with the crusades. In the data from the New World, molecular analyses have shown that it was present in the Caribbean and the Americas in the pre-Columbian period. Before paleoparasitological research, the history of amoebiasis caused by Entamoeba histolytica begins in 1859 when they saw amoebae in the feces of a patient with dysentery, but 10 years before that, a doctor named Lösh, who injected a fecal sample taken from a patient who died of dysentery in Russia into dogs and named the amoeba that caused ulcers in them “Amoeba coli”. The parasite was shown to cause lysis by Shaudin in 1903. In 1913, the first experimental human studies were conducted on 20 volunteer prisoners. Diamond performed in vitro axenic culture of trophozoites in 1978. Diagnostic methods, pathogenesis and vaccine studies on amoeba have been carried out for the last 30 years. However, there are still some parts of the pathogenesis that remain to be understood [25, 26, 39, 48, 57].

Amoebiasis, of which many mechanisms have been elucidated today, is a parasitic disease caused by Entamoeba histolytica, an extracellular enteric protozoan. This infection mainly affects people in developing countries with limited hygiene conditions, where it is endemic. The parasite has different mechanisms of pathogenicity, adhering to the intestinal epithelium and degrading extracellular matrix proteins, producing tissue lesions, particularly in the large intestine, which progress to abscesses and an acute inflammatory response of the host. The World Health Organization (WHO) has reported that 500 million people worldwide may be infected with Entamoeba sp.; 10% of these individuals are likely to be infected with E. histolytica and the rest with other non-pathogenic species. Amoebiasis causes 40,000–100,000 deaths annually and is the fourth leading cause of death due to protozoan infection. Blastocystis sp. is an anaerobic intestinal parasite of humans and animals In numerous epidemiological studies conducted in different countries, Blastocystis sp. is the most common eukaryotic parasite reported in human fecal samples, but its pathogenicity is still controversial [8, 57, 58, 59].

More than 100 years have passed since Tyzzer described his first observations of the genus Cryptosporidium in 1907. Until the 80s, the parasite was considered an insignificant organism that occasionally caused disease in the intestines of vertebrates. With HIV, it has been named as an opportunistic parasitic infection with high morbidity and mortality and has been the subject of numerous studies. It causes waterborne outbreaks in developed and developing countries and has more than 40 species [60, 61, 62].

4.2 Geographical studies

The disease burden associated with intestinal parasites is considerable, threatening approximately 4.5 billion people worldwide. According to WHO data, 300 million people are affected by intestinal parasites. Regarding soil-borne helminths; 800–1000 million Ascaris lumbricoides, 700–900 million hookworm, 500 million Trichuris trichiura, 200 million Giardia lamblia, 500 million Entamoeba histolytica/dispar cases are reported. It is also estimated that around 39 million disabilities and life years are lost due to these infections. An important disadvantage is that 90% of cases are asymptomatic and therefore the spread of parasites continues [9].

Intestinal parasites are more prevalent in developing countries, especially in the tropics and subtropics. In these countries, their infectivity becomes more dominant with the effect of climate and socioeconomic conditions. It is generally believed that helminths are more prevalent in developing countries while protozoan intestinal parasites are more common in developed countries. Soil-borne helminths are endemic in countries with poor sanitation conditions and insufficient clean water. It is estimated that Ascaris lumbricoides still infects 1 billion people, Trichuris trichiura 800 million and hookworms 750 thousand. The weight of the parasite load, inadequate food and water supply, physical and mental developmental delays, as well as additional chronic diseases, make losses inevitable [50, 51, 52, 53, 63, 64].

In addition to helminths, diarrhea caused by protozoa such as Giardia lamblia, Entamoeba histolytica, Cryptosporidium and Cyclospora is the third leading cause of death in these regions, especially in children. WHO reported that 50 million people are infected with invasive amobiasis each year and 40–100 thousand of them are fatal. Giardia and cryptosporidium and microsporidia are among the most important causes of diarrhea in developed countries. Intestinal parasites are particularly prevalent in developing countries and in growing children. The most important factor is the lack of clean water and inadequate personal and environmental hygiene conditions. However, there are some special groups in which the prevalence of intestinal parasites is higher than in the normal population. Among these, individuals with intellectual disabilities with low capacity for learning and understanding are at significant risk. In studies conducted in 10 different provinces of Iran in mentally disabled individuals, intestinal parasites were found to be considerably higher than in the normal population [8, 50, 51, 52, 53, 63, 64].

Antiparasitic drugs, taken once or twice a year in endemic areas, are a low-cost solution. In this way, by preventing the treatment and spread of parasites in children, it will support their school success and healthy and productive living in the future. These studies are currently being carried out in certain areas, albeit limited [65, 66].

Intestinal parasites have also been suggested to play a potential role in or predispose to various metabolic diseases, for example, diabetes mellitus. There is also a large number of studies suggesting that intestinal parasites may coexist with different infectious diseases. Tuberculosis (TB) and intestinal parasites are two important infections affecting mostly poor people and are important risk factors for one another. In a meta-analysis study conducted in Ethiopia, where both infectious agents are common, 414 articles on the subject were reviewed from scientific databases, and in 11 articles involving a total of 3158 TB patients, one third of the patients were found to be infected with intestinal parasites, and the most common intestinal parasites were; Ascaris lumbricoides 10.5% (95% CI: 6.0, 17.5), hookworm 9.5% (95% CI: 6.10, 14.4), Giardia lamblia 5.7% (95% CI: 2.90, 10.9) and Strongyloides sterocoralis 5.6% (95% CI: 3.3, 9.5). In the study, there was no significant difference between protozoa and TB compared to the normal population, while the association of helminth infections and TB was higher than in the normal population [67].

Intestinal parasites continue to be a public health problem among patients with HIV. Rapid and effective antiretroviral therapy is needed to reduce parasite density [68].

Nomadic and pastoral communities have become geographical areas where many parasitic diseases of zoonotic origin are more intense. The most important risk factors are close contact with animals, inadequate hygiene conditions, lack of access to drinking water and food. Global health efforts are also insufficient in these groups [69]. In nomadic communities in the mountainous areas of Asia and in the highlands of Ecuador, where heat and poverty prevail, about 90% of children are reported to be infected with one or more intestinal parasites [70].

Zoonotic enteric parasites (ZEP), which can infect animals and humans, are transmitted through contact, contaminated water and food. Multicellular ZEPs, commonly called worms, are members of three taxonomic groups belonging to the Helminths group (Cestodes (tapeworms), Nematodes (Ascaris sp., Strongyloides spp., Toxocara sp. and Trichinella sp.) and Trematodes (Fasciola spp., Clonorchissp. and Pentastomida sp.). Most intestinal protozoa are human-specific and are usually transmitted through water and food. In nomadic communities, where ZEPs are most common, the major risk factors for transmission include contact with animals, nutritional habits, difficulties in obtaining clean water and inappropriate living conditions. Unfortunately, ZEPs are still not prevented today due to lack of education and low socio-economic status [69, 70].

Zoonotic enteric parasites that use humans or animals as hosts, like other enteric parasites, are transmitted through contaminated soil, water and food. Cystic echinococcosis, the larval stage of the canine cestode, Fasciola sp., the ruminant liver fluke, Clonorchis and Pentastomids are important helminths. However, zoonotic protozoa are a more common group that can occur anywhere in the world. They are microscopic and occasionally cause water and foodborne epidemics. Cryptosporidium sp. Babesia sp. and Microsporidia sp. are among the most common species. Enteric protozoa are easily transmitted through food products, contact with infected meat and meat products, and exposure to contaminated water [63, 70, 71].

Intestinal parasites, like many enteric pathogens, are also spread through people working in the food industry, as they cause foodborne infections. There are numerous papers showing that protozoa, especially protozoa such as amoeba, giardia, cryptosporidium species, as well as some soil-evolved helminths, tapeworms, Enterobius vermicularis are transmitted in this way [69, 70, 72].

According to the global disease burden concept first defined in 1993, the global burden of soil nematodes such as Ascaris, trichuris and hookworms has not fallen below 10%. Entamoeba, Toxoplasma, Cyclospora, Giardia and Cryptosporidium are among the major contributors to the global intestinal parasitic disease burden. The fact that intestinal parasites are generally not fatal and that they persist more frequently in developing countries and are not under control is largely due to the inattention of developed countries. Especially prevention and control strategies and treatment protocols are unfortunately inadequate in countries struggling with economic problems. Intestinal parasites are a major cause of morbidity and mortality, especially in sub-Saharan Africa, India and some Asian countries where access to food is difficult. They bring different co-infections with them. With the effect of heat and poor sanitation conditions, excreted cysts and eggs maintain their viability and infectivity in the environment for a long time. Considering that about half of the intestinal parasites are transmitted by fecal oral route, the prevalence increases with the effect of factors such as poor sanitation, suitable climatic conditions and lack of education. Studies have shown that the rates can be halved by hand washing, use of footwear, washing and cooking of food. Parasites not only take up certain vitamins in humans but also cause changes in the immune system due to the metabolites they produce [60, 65, 67, 68, 69, 73].

5. Diagnostic methods in intestinal parasites from past to present

Intestinal parasites continue to have a devastating impact from past to present. In recent years, they have been considered as an infectious agent only seen in developing countries, but nowadays, due to increased migration, international travel, wars and global warming, they have started to increase their effectiveness all over the world. One of the most important problems in this context has been the delay in diagnosis and treatment because intestinal parasites are not recognized outside endemic areas. Sometimes this leads to fatal outcomes in organ or blood transplants. Even today, when there are still major problems in antiparasitic treatment, the most effective method is the development of accurate and rapid diagnostic methods. Since the discovery of the microscope, microscopy has been the gold standard for parasitological diagnosis, especially for protozoan parasites. It is low-cost and is still successfully used in routine diagnosis, especially in epidemiologic studies, especially in countries with high parasite load. However, it is time-consuming and requires experienced personnel in large-scale epidemiologic studies. In addition, due to the fact that parasites are not always present in feces, diagnostic errors may occur. Today, various serologic and molecular methods are being developed for large-scale epidemiologic studies and more descriptive diagnosis. This enables faster and more accurate diagnosis. The microscopic examination method, which is inadequate to distinguish between amoebic dysentery and other amoebas and to prevent unnecessary treatment, can be prevented by serologic and molecular diagnostics used in diagnosis today. Again, it is almost impossible to distinguish helminths from each other by microscopic examination, especially in their larval stages. Today, with the use of serological and molecular techniques, a significant progress has been made in paleoparasitological diagnosis [7, 74, 75, 76].

Since 1908, qualitative research has been carried out in the parasitological diagnosis of stool samples. Initially applied to increase the chances of visualization, methods for removing residues and concentrating parasite cysts and eggs have continued with the identification of suitable solutions and dyes. Samples prepared by enrichment methods with the use of various equipment are examined by microscopic examination. However, Sporozoa group parasites such as Microsporidium spp. (1–2.5 microns), Cryptosporidium spp. (4–6 microns), Cyclospora spp. (6–8 microns), Cystoisospora spp. (20–30 microns), which are frequently encountered in immunocompromised patients today, cannot be seen under the microscope with routine parasitological examinations. They need to be examined with special staining methods and immersion objective. In the 1940s, Ritchie and Teleman offered new alternatives to parasitological examinations, and in 1970, they introduced the technique of sedimentation with the addition of ethyl-ether to break down stool artifacts. In the 1980s, the semi-automated commercial paratest method was used in fecal examinations. Today, sedimentation, flotation and Kato-Katz methods are still successfully used in routine diagnosis to increase the detection rate of cysts and eggs in stool, the only disadvantage being the need for experienced personnel/specialists. Baerman and Harada-Mori methods are used for identification of nematode larvae. Today, the search for fast, easy, inexpensive and accurate diagnostics for large-scale and routine research continues [74, 75, 76, 77].

5.1 Microscopic diagnosis

The use of microscopy in biological specimens is a simple, inexpensive and often gold standard method of morphologic diagnosis of the parasitic agent. It requires a good microscope and an experienced microscopist. With this method, the appropriate sample (blood, urine, stool, vaginal swab, abscess material, duodenal aspirate and tissue biopsy) is examined under a light or fluorescence microscope using appropriate solutions (saline, lugol, various parasite dyes, calcoflour, etc.) using various lenses of the microscope. All protozoan parasites can be diagnosed by this method. For Cryptosporidium sp, Cyclospora and Isospora, microscopic examination is also performed with fluorescent stains as well as Ziehl-Nelsen and Kinyon stains. Microscopic diagnosis can also be used to identify the eggs or larvae of helminths. Microscopic examination has always been the gold standard in parasitologic diagnosis, but it requires a high level of parasitologic experience. It is labor-intensive and time-consuming and occasionally leads to inaccuracies in cases of poor excretion of parasites. In addition, it is microscopically almost impossible to differentiate pathogen from apathogen, especially for amoeba species. The diagnosis requires a high parasite load of protozoa or helminths in stool [7, 74, 75, 76].

5.2 Serologic tests

Unfortunately, the few serologic tests used in parasitologic diagnosis can only be used for the routine diagnosis of a limited number of blood and tissue parasites. There are no serologic tests routinely used for gastrointestinal parasites. Specificity and sensitivity are low compared to molecular tests. Cross-reactions can be seen due to the common antigenic structure of helminths [74, 75, 76, 77, 78].

5.3 Immunochromatographic tests

Based on the simple principle of reading the markings on the membrane of specific biomarkers in the material under study. They are commercial tests. The infrastructure conditions in the laboratory must be appropriate. Widely used in the diagnosis of blood and tissue parasites. It is used in the diagnosis of intestinal protozoa. It is easily used in large-scale serologic investigations as it does not require experience and time. However, special equipment and proper sample handling are required [74, 75, 76].

5.4 Multiplex PCR

As in many infectious diseases, molecular testing has ushered in a new era in parasitologic diagnosis. This method allows simultaneous analysis of multiple pathogens and resistance genes. It is easy to identify the parasite and its strains, to follow the treatment and control process, as well as in large-scale epidemiological and surveillance studies. Compared to microscopic examination, the detection rate of parasite infections is considerably higher when targets are included in multiplex PCR. Detection and quantification of parasite-specific DNA in stool is highly sensitive and specific. Numerous studies using various nucleic acid-based techniques have contributed to the genetic diversity, epidemiology and clinical significance of intestinal parasites. For evident reasons, in a routine setting, standardization and harmonization of protocols are essential for the cost-effective implementation of these new techniques. Gastrointestinal Multiplex molecular panels, unlike conventional tests, allow the identification of multiple pathogens in a single material (stool). They also contribute to diagnosis and treatment by determining the intensity of infection and demographic characteristics of the infection. They require appropriate laboratory equipment and are costly [77, 78].

Serologic and molecular tests are costly tests and unfortunately cannot be applied in poor communities where the burden of parasitic infections is high. Although the process of developing appropriate and rapid diagnostic methods against common infections in the world continues rapidly, unfortunately, there is not much progress on tests for parasitic diseases, which are seen as a problem in developed countries. However, it is limited to large-scale epidemiological studies of developed countries. Updates for these tests are ongoing. Gastrointestinal parasite panels are still limited to a small number of species. Diagnosis is difficult due to the nature of helminths. In addition to new specific markers, there is a need to improve specificity and sensitivity, to measure parasite load and to meet affordability requirements [74, 75, 76, 77, 78].

Delays in the accurate diagnosis of parasitic diseases lead to delays in treatment and control strategies, facilitating the spread of causative pathogens. Provided by developed countries, the use of affordable and reliable tests in endemic regions; training of specialists to work in these regions, as well as hygiene education of the public and provision of clean water, are important factors for the future of undeveloped countries regarding prevention of the spread of parasitic diseases.

5.5 Parasite cultivation

Although not all parasites can be cultivated, it is possible to produce a limited number of protozoa and larval stages of some helminths in cultivation. These are planned not only for diagnostic purposes but also for studies on parasite evolution, biochemistry, physiology and various invitro studies. Intestinal parasites can be grown in xenic, monoxenic and axenic cultivation, but are demanding due to contamination [76].

6. Prevention and control strategies

Intestinal parasites place an additional burden on people in poor and developing countries where they are endemic. Developed countries have been able to eradicate many soil-borne nematodes through clean water supply, education, sanitation and treatment of infected people. In these regions, protozoan outbreaks of protozoa from vegetables and fruits eaten raw or zoonotic origin can be seen occasionally. The most successful methods in the fight against intestinal parasites are as follows:

6.1 Hand hygiene

The most important method for all fecal-oral infections. The habit of washing hands with soap and similar products after toilet and before meals destroys the effect of eggs and cysts. The importance of hand hygiene in the prevention of infectious diseases has been proven in many epidemiologic studies.

6.2 Food and water

The most important source of intestinal parasites is contaminated food and water.

In developing countries, inadequate sewerage and the spread of human feces in the environment and food cause both the formation of endemic areas and the outbreaks of gastroenteritis in countries that trade with these countries. Areas where wastewater is used in agriculture are the most important factor in the spread of many helminths and protozoa. They are resistant to washing as well as cooking. In this way, imported fruits and vegetables cause outbreaks in developed countries. Street vendors are also among the most important sources of foodborne transmission. The main cause of large-scale epidemics in endemic areas is contaminated food and water. Lack of drinking and utiliary water also affects hand hygiene [1, 4, 5, 8, 58, 60, 64, 66, 69].

6.3 Chemotherapy

Treating infected people is one of the most important control strategies. This will break the chain of transmission. In developed countries, antihelminthic treatment has been effective in the elimination of soil-borne helminths for many years. In recent years, in project supported studies, it has been reported that the rate of parasites in patients and soil has decreased by more than half with antiparasitic treatment given 1 or 2 times a year in endemic areas. The biggest problem in these studies is the increasing resistance to antiparasitic drugs, which are already in short supply. The most successful study example came from South Korea. Between 1969 and 1995, the rate of intestinal parasites was reduced from 84 to 3% with antiparasitic treatment administered to primary school children. Chemotherapy as a fast-acting intervention is a good strategy to immediately improve the lives of poor populations in developing countries. However, such a practice is currently not possible in nomadic communities in poor countries. Chemotherapy is very important in reducing the prevalence of intestinal parasites. Chemotherapeutics developed for protozoa and helminths were originally intended for veterinary use, but were later developed and used in humans. In the late 1970s, they began to be given to children and adults with symptoms of parasites, especially helminth infections, all over the world. In the 1980s, Bundy and Stephenson led studies in children in which antiparasitic treatment was given to all children and a significant reduction in parasite load was observed in endemic areas.

The identification and treatment of infected people through epidemiologic studies is one of the most important factors in reducing the incidence. Reduction or termination of excretion, especially helminth infections, with treatment will prevent soil and water contamination. Antihelminthic chemoterpine has an important role in the fact that soil helminths are no longer seen in many parts of the world. In the southern Curry, a chemotherapy program in primary school children from 1969 to 1995 reduced the incidence of helminths from 90–3%. Economic progress, education and environmental regulation have all contributed to this. Chemotherapy alone cannot be successful where the necessary regulations are not in place [79, 80].

In 2001, Resolution 54.19 of the World Health Assembly (WHA) encouraged all member states endemic for schistosomiasis and nematodiasis to achieve “a minimum target of regular chemotherapy for at least 75% and up to 100% of all school-age children at risk of disease by 2010”. Praziquantel has assumed important roles in anthelmintic treatment and control programs. Similar concerns have been shown for other therapeutic drugs commonly used to control hookworm infections, such as mebendazole and pyrantel. Various drug stewardship strategies (cyclical use of drugs) have been proposed to address these issues; however, if drug resistance trends continue, global efforts to control parasitic diseases using drugs may come to an end, a well-known phenomenon in the use of antibiotic/antiviral drugs [8, 58, 59, 79, 80].

Benzimidazole group of drugs used as antihelmintics are also used in cancer treatment. The mechanism of action of these drugs is to cause cell death by blocking the microtubule systems of parasite and mammalian cells. They also cause ovicidal, vermicidal, larvicidal and cell death of the parasite. Albendazole, ornidazole and mebandazole are used not only in the treatment of intestinal helminths and protozoon, but also in the treatment of tissue and reticuloendothelial nematodes. Ivermectin in combination with diethylcarbamazine is also used in the treatment of lymphatic filarial nematodes. Although these drugs are safe, liver toxicity and various side effects as well as resistance problems may develop [79].

7. Recent developments and future directions

Although more than 160 years have passed since the first identification of intestinal parasites, they are still an important cause of morbidity and mortality in developing countries, especially in children. In various immunosuppressive diseases that have been on the rise in the last 20 years, many chronic protozoa have emerged as important causes of mortality.

Today, amoebiasis caused by Entamoeba histolytica continues to be an important problem, especially in endemic areas. One of the most important problems of the parasite is the large number of asymptomatic infected people in the communities. Another problem is that traveling people returning home from endemic regions are often undiagnosed, leading to deaths and economic losses. The fecal-oral parasite causes no symptoms in some people, but sometimes causes tumor-like formations, especially in the colon mucosa, and fatal amoebiasis that can reach the brain. Today, epidemiologic diagnostic problems persist in many geographical areas and adequate and effective treatment cannot be provided due to economic problems. Although intestinal parasites, which have weakened and exhausted people’s strength since prehistoric times, have become uncommon with education and treatment in some countries, they have increased again with the effect of growing migration, urban slum systems, poverty and global warming. It is one of the leading causes of child mortality and physical and mental retardation in developing countries. Due to increased migration from endemic areas, there are problems in the population control of countries and consequently, adequate health services cannot be provided. The lack of clean drinking water and sanitation in newly established urban slums causes the parasite to move from endemic areas to different regions. Conducting large-scale epidemiologic studies in areas of migration is one of the most important control strategies. The development of new and appropriate treatments to make treatment cheaper and widespread, and supporting R&D studies to develop appropriate vaccines for endemic areas will be the most effective methods to reduce the global parasite load. For sustainable and effective prevention, it is essential to develop global strategies rather than isolated or country-specific approaches. Mass hygiene education should be provided all over the world with appropriate funders. Countries should improve private and public health conditions and continue campaigns to combat parasitic diseases. In this way, the fight against other infectious agents will also be realized.