General Introduction: Parasitology

Apurba S Sastry; Sandhya  Bhat

SECTION 1

1INTRODUCTION

Section Outline

General Introduction: Parasitology 32

General Introduction: ParasitologyCHAPTER 1

CHAPTER OUTLINE

■ Taxonomy of parasites
■ Parasite
■ Host
■ Host-parasite relationship
■ Transmission of parasites
■ Life cycle of the parasites
■ Pathogenesis of parasitic diseases
■ Immunology of parasitic diseases
■ Laboratory diagnosis of parasitic diseases
■ Treatment of parasitic diseases

Medical Parasitology deals with the study of animal parasites, which infect and produce diseases in human beings.

TAXONOMY OF PARASITES

According to the binomial nomenclature as suggested by Linnaeus, each parasite has two names—a genus and a species name.

These names are either derived from: names of their discoverers, Greek or Latin words of the geographical area where they are found, habitat of the parasite, or hosts in which parasites are found and its size and shape.

All parasites are classified under the following taxonomic units—the kingdom, subkingdom, phylum, subphylum, superclass, class, subclass, order, suborder, superfamily, family, genus and species.

The generic name of the parasite always begins with an initial capital letter and species name with an initial small letter, e.g. Entamoeba histolytica.

PARASITE

Parasite is a living organism, which lives in or upon another organism (host) and derives nutrients directly from it, without giving any benefit to the host.

Protozoa and helminths (animal parasites) are studied in Medical Parasitology.

Parasites may be classified as:

Ectoparasite: They inhabit the surface of the body of the host without penetrating into the tissues. They are important vectors transmitting the pathogenic microbes. The infection by these parasites is called as infestation, e.g. Sarcoptes scabiei causing scabies
Endoparasite : They live within the body of the host (e.g. Leishmania). Invasion by the endoparasite is called as infection.

The endoparasites are of following types:

Obligate parasite: They cannot exist without a parasitic life in the host (e.g. Plasmodium species)
Facultative parasite: They can live a parasitic life or free-living life, when the opportunity arises (e.g. Acanthamoeba)
Accidental parasite: They infect an unusual host (e.g. Echinococcus granulosus infect humans accidentally)
Aberrant parasite or wandering parasite: They infect a host where they cannot live or develop further (e.g. Toxocara in humans).

HOST

Host is defined as an organism, which harbors the parasite and provides nourishment and shelter.

Hosts may be of the following types:

Definitive host: The host in which the adult parasites replicate sexually (e.g. Anopheles species), is called as definitive host. The definitive hosts may be human or nonhuman living things
Intermediate host: The host in which the parasite undergoes asexual multiplication is called as intermediate host. (e.g. in malaria parasite life cycle, humans are the intermediate hosts)
- Intermediate hosts are essential for the completion of the life cycle for some parasites
- Some parasites require two intermediate hosts to complete their different larval stages. These are known as the first and second intermediate hosts 4respectively (e.g. Amphibian snails are the first intermediate host and aquatic plants are the second intermediate host for Fasciola hepatica).

Hosts can also be:

Reservoir host: It is a host, which harbors the parasites and serves as an important source of infection to other susceptible hosts. (e.g. dog is the reservoir host for echinococcosis)
Paratenic host: It is the host, in which the parasite lives but it cannot develop further and not essential for its life cycle (e.g. fresh water prawn and crab for Angiostrongylus cantonensis, big suitable fish for plerocercoid larva of Diphyllobothrium latum and freshwater fishes for Gnathostoma spinigerum). It functions as a transport or carrier host
Amplifier host: It is the host, in which the parasite lives and multiplies exponentially.

HOST-PARASITE RELATIONSHIP

The relationship between the parasite and the host, may be divided into the following types:

Symbiosis: It is the close association between the host and the parasite. Both are interdependent upon each other that one cannot live without the help of the other. None of them suffer any harm from each other
Commensalism: It is an association in which the parasite only derives the benefit without causing any injury to the host. A commensal is capable of living an independent life
Parasitism: It is an association in which the parasite derives benefit from the host and always causes some injury to the host. The host gets no benefit in return.

Disease: The disease is the clinical manifestation of the infection, which shows the active presence, and replication of the parasite causing damage to the host. It may be mild, severe and fulminant and in some cases may even cause death of the host.

Carrier: The person who is infected with the parasite without any clinical or subclinical disease is referred to as a carrier. He can transmit the parasites to others.

TRANSMISSION OF PARASITES

It depends upon:

Source or reservoir of infection
Mode of transmission.

Sources of Infection

Man: Man is the source or reservoir for a majority of parasitic infections (e.g. amoebiasis, enterobiasis, etc.) The infection transmitted from one infected man to another man is called as anthroponoses
Animal: The infection which is transmitted from infected animals to humans is called as zoonoses. The infection can be transmitted to humans either directly or indirectly via vectors. (e.g. echinococcosis from dogs and toxoplasmosis from cats)
Vectors: Vector is an agent, usually an arthropod that transmits the infection from one infected human being to another. Vector can be biological or mechanical. An infected blood sucking insect can transmit the parasite directly into the blood during its blood meal.

Note: Vectors have been dealt in detail in Chapter 16 (Medical Entomology)
Contaminated soil and water: Soil polluted with human excreta containing eggs of the parasites can act as an important source of infection, e.g. hookworm, Ascaris species, Strongyloides species and Trichuris species.

Water contaminated with human excreta containing cysts of E. histolytica or Giardia lamblia, can act as source of infection
Raw or under cooked meat: Raw beef containing the larvae of Cysticercus bovis and pork containing Cysticercus cellulosae are some of the examples where undercooked meat acts as source of infection
Other sources of infection: Fish, crab or aquatic plants, etc.

Modes of Transmission

The infective stages of various parasites may be transmitted from one host to another in the following ways:

Oral or feco-oral route: It is the most common mode of transmission of the parasites. Infection is transmitted orally by ingestion of food, water or vegetables contaminated with feces containing the infective stages of the parasite. (e.g. cysts of E. histolytica, and ova of Ascaris lumbricoides)
Penetration of the skin and mucous membranes: Infection is transmitted by the penetration of the larval forms of the parasite through unbroken skin (e.g. filariform larva of Strongyloides stercoralis and hookworm can penetrate through the skin of an individual walking bare-footed over fecally contaminated soil), or by introduction of the parasites through blood-sucking insect vectors. (e.g. Plasmodium species, Leishmania species and Wuchereria bancrofti)
Sexual contact: Trichomonas vaginalis is the most frequent parasite to be transmitted by sexual contact. However, Entamoeba, Giardia and Enterobius are also transmitted rarely by sexual contact among homosexuals
Bite of vectors: Many parasitic diseases are transmitted by insect bite (Table 16.2 in Chapter 16) such as—malaria 5(female Anopheles mosquito), filariasis (Culex), leishmaniasis (sandfly), Chagas’ disease (reduviid bug) and African sleeping sickness (tsetse fly)
Vertical transmission: Mother to fetus transmission is important for few parasitic infections like Toxoplasma gondii, Plasmodium species and Trypanosoma cruzi
Blood transfusion: Certain parasites like Plasmodium species, Babesia species, Toxoplasma species, Leishmania species and Trypanosoma species can be transmitted through transfusion of blood or blood products
Autoinfection: Few intestinal parasites may be transmitted to the same person by contaminated hand (external autoinfection) or by reverse peristalsis (internal autoinfection). It is observed in Cryptosporidium parvum, Taenia solium, Enterobius vermicularis, Strongyloides stercoralis and Hymenolepis nana.

LIFE CYCLE OF THE PARASITES

The life cycle of the parasite may be direct (simple) or indirect (complex).

Direct/simple life cycle: When a parasite requires only one host to complete its development, it is referred as direct/simple life cycle (Table 1.1)
Indirect/complex life cycle: When a parasite requires two hosts (one definitive host and another intermediate host) to complete its development, it is referred as indirect/complex life cycle (Table 1.2). Some of the helminths require three hosts (one definitive host and two intermediate hosts) (Table 1.3).

PATHOGENESIS OF PARASITIC DISEASES

The parasites can cause damage to humans in various ways.

Mechanical trauma:

Eggs: Trematode eggs being large in size, can be deposited inside the intestinal mucosa (Schistosoma mansoni), bladder (Schistosoma haematobium), lungs (Paragonimus), liver (Fasciola hepatica) and can cause mechanical irritation

Larvae: Migration of several helminthic larvae (hookworms, Strongyloides or Ascaris) in the lungs produce traumatic damage of the pulmonary capillaries leading to pneumonitis

Table 1.1 Direct/simple life cycle—parasites that need only one host (man)

Protozoa	Helminths
Entamoeba histolytica Giardia lamblia Trichomonas vaginalis Balantidium coli Cryptosporidium parvum Cyclospora cayetanensis Cystoisospora belli Microsporidia	Cestodes Hymenolepis nana Nematodes Ascaris lumbricoides Hookworm Enterobius species Trichuris trichiura Strongyloides species

Table 1.2 Indirect/complex life cycle—parasites requiring one definitive host and one intermediate host

Man acts as definitive host
Parasites	Definitive host (man)	Intermediate host
Leishmania species*	Man	Sandfly
Trypanosoma cruzi*	Man	Reduviid bugs
Trypanosoma brucei*	Man	Tsetse fly
Taenia solium (intestinal taeniasis)	Man	Pig
Taenia saginata	Man	Cattle
Hymenolepis diminuta	Man	Rat flea
Schistosoma species	Man	Snail
Trichinella spiralis	Man	Pig
Filarial worms	Man	Mosquito (Culex, Aedes, Anopheles) and flies (blackflies and deerflies)
Dracunculus medinensis	Man	Cyclops
Man acts as intermediate host
Parasites	Definitive host	Intermediate host
Plasmodium species	Female Anopheles mosquito	Man
Babesia species	Tick	Man
Sarcocystis lindemanni	Cat and dog	Man
Toxoplasma gondii	Cat	Man
Echinococcus granulosus	Dog	Man
Taenia solium (Cysticercosis)	Man	Man
*Note: In Leishmania and Trypanosoma, the definitive and intermediate host terminologies are not applicable as there is no sexual cycle. The better terminologies used are vertebrate host (man) and the invertebrate host (insect vectors)

Table 1.3 Indirect/complex life cycle—parasites requiring one definitive host and two intermediate hosts

Parasites	Definitive host	First intermediate host	Second intermediate host
Diphyllobothrium species	Man	Cyclops	Fish
Fasciola hepatica	Man	Snail	Aquatic plant
Fasciolopsis buski	Man	Snail	Aquatic plant
Paragonimus species	Man	Snail	Crab and fish
Clonorchis species	Man	Snail	Fish
Opisthorchis species	Man	Snail	Fish
Gnathostoma spinigerum	Cat, dog and man	Cyclops	Fish

Adult worms: Adult worms of hookworm, Strongyloides, Ascaris or Taenia get adhere to the intestinal wall and cause mechanical trauma.

Space-occupying lesions: Certain parasites produce characteristic cystic lesion that may compress the surrounding tissues or organs, e.g. hydatid cysts and neurocysticercosis
Inflammatory reactions: Most of the parasites induce cellular proliferation and infiltration at the site of their multiplication, e.g. E. histolytica provokes inflammation of the large intestine leading to the formation of amoebic granuloma. Adult worm of W. bancrofti causes mechanical blockage and chronic inflammation of the lymphatics and lymph vessels. Trematode eggs can induce inflammatory changes (granuloma formation) surrounding the area of egg deposition
Enzyme production and lytic necrosis: Obligate intracellular parasites of man (Plasmodium, Leishmania and Trypanosoma), produce several enzymes, which cause digestion and necrosis of host cells. E. histolytica produces various enzymes like cysteine proteinases, hydrolytic enzymes and amoebic pore forming protein that lead to destruction of the target tissue
Toxins: Some of the parasites produce toxins, which may be responsible for pathogenesis of the disease, e.g. E. histolytica. However, in contrast to bacterial toxin, parasitic toxins have minimal role in pathogenesis
Allergic manifestations: Many metabolic and excretory products of the parasites get absorbed in the circulation and produce a variety of allergic manifestations in the sensitized hosts.

Examples include schistosomes causing cercarial dermatitis, rupture of hydatid cyst producing anaphylactic reactions and occult filariasis (tropical pulmonary eosinophilia)
Neoplasia: Some of the parasitic infections can contribute to the development of neoplasia (e.g. S. haematobium causes bladder carcinoma, Clonorchis and Opisthorchis cause cholangiocarcinoma)
Secondary bacterial infections: Seen in some helminthic diseases (schistosomiasis and strongyloidiasis).

IMMUNOLOGY OF PARASITIC DISEASES

The immune response against the parasitic infections depends on two factors:

Host factors: Immune status, age, underlying disease, nutritional status, genetic constitution and various defense mechanisms of the host
Parasitic factors: Size, route of entry, frequency of infection, parasitic load and various immune evasion mechanisms of the parasites.

Broadly, the host immunity against the parasitic diseases may be of two types:

Protective immune response
1. Innate immunity
2. Adaptive/acquired immunity.
Unwanted or harmful immune response (hypersensitive reactions).

Protective Immune Response

Both innate and acquired immunity play an important role in protecting the hosts against parasites. Some of the parasitic infections can be eliminated completely by the host immune responses (complete immunity) while few are difficult to eliminate. In some infections, the immune defense of the host is sufficient to resist further infection but insufficient to destroy the parasite. Immunity lasts till the original infection remains active and prevents further infection. This is called as infection immunity or premunition or concomitant immunity or incomplete immunity. This is observed in malaria, schistosomiasis, trichinellosis, toxoplasmosis and Chagas’ disease.

(i) Innate Immunity

Innate immunity is the resistance which an individual possesses by birth, due to genetic and constitutional makeup.

Factors influencing innate immunity

Age of the host: Both the extremes of age are more vulnerable to parasitic infections. Certain diseases are common in children like giardiasis and enterobiasis while certain infections occur more commonly in adults like hookworm infection. Congenital infection occurs commonly with Toxoplasma gondii; whereas newborns are protected from falciparum malaria because of high concentration of fetal hemoglobin
Sex: Certain diseases are more common in males like amoebiasis, whereas females are more vulnerable to develop anemia due to hookworm infection
Nutritional status: Both humoral and cellular mediated immunity are lowered and neutrophil activity is reduced in malnutrition
Genetic constitution of the individuals: People with hemoglobin S (sickle cell disease), fetal hemoglobin and thalassemia hemoglobin are resistant to falciparum malaria, whereas Duffy blood group negative red blood cells (RBCs) are resistant to vivax malaria.

Components of innate immunity

Anatomic barriers (skin and mucosa): Skin is an important barrier for the parasites that enter by cutaneous routes like schistosomes, hookworm and Strongyloides7
Physiologic barriers: It includes temperature, pH, and various soluble molecules like lysozyme, interferon and complement. Gastric acidity acts as a physiologic barrier to Giardia and Dracunculus
Phagocytosis: Phagocytes like macrophages and microphages (neutrophils, basophils and eosinophils) act as first line of defense against the parasites
Complements: They play an important role for killing the extracellular parasites by forming membrane attack complexes; which leads to the formation of holes in the parasite membrane
Natural killer cells: Natural killer (NK) cells are another important mediator of innate immunity. They play a central role in killing few of the helminthic parasites.

(ii) Acquired/Adaptive Immunity

This is the resistance acquired by an individual during life following exposure to an agent. It is mediated by antibody produced by B lymphocytes (humoral immune response) or by T cells (cell mediated immune response).

Cell mediated immune response

When a parasite enters, the parasitic antigens are processed by the antigen presenting cells, (e.g. macrophages) which present the antigenic peptides to T helper (T_H) cells. The antigen presenting cells also secrete interleukin-1 (IL-1) that activates the resting T_H cells. Activated T helper cells differentiate into T_H1 and T_H2 cells
T_H 1 secrete interleukin-2 (IL-2) and interferon gamma.
- Interleukin-2 activates the cytotoxic T cells (T_C) and NKs, which are cytotoxic to the target parasitic cells. They produce perforin and granzyme that form pores and lyse the target cells
- IFN-γ activates the resting macrophages which in turn become more phagocytic and release free radicals like reactive oxygen intermediate (ROI) and nitric oxide (NO) that kill the intracellular parasites.
T_H 2 release IL-4, IL-5, IL-6 and IL-10 which are involved in activation of B cells to produce antibodies [immunoglobin E (IgE) by IL-4]. IL-5 also acts as chemoattractant for the eosinophils. Eosinophilia is common finding in various helminthic infections.

Humoral immune response

T_H 2 response activates the B cells to produce antibodies which in turn have various roles against the parasitic infections. They are:

Neutralization of parasitic toxins (mediated by IgA and IgG)
Preventing attachment to the gastrointestinal tract (GIT) mucosa (mediated by secretory IgA)
Agglutinating the parasitic antigens thus preventing invasion (mediated by IgM)
Complement activation (by IgM and IgG): Complements bind to the Fc portion of the antibody coated to the parasitic cells. Activation of the complements leads to membrane damage and cell lysis
Antibody dependent cell-mediated cytotoxicity (ADCC) is important for killing of the helminths. NK cells bind to the Fc portion of the IgG antibody coated to the helminths. Activation of NKs leads to release of perforin and granzyme that in turn cause membrane damage and cell lysis
Mast cell degranulation: IgE antibodies coated on mast cells when get bound to parasitic antigens, the mast cells become activated and release a number of mediators like serotonin and histamine.

The Unwanted or Harmful Immune Responses

Sometimes immune responses may be exaggerated or inappropriate in the sensitized individuals on re-exposure to the same antigen. Such type of immunopathologic reactions are called as hypersensitivity reactions that may be harmful to the hosts causing tissue damage. These are of four types (Table 1.4).

Parasitic Factors that Evade the Host Immune Response

Sometimes, the hosts find it difficult to contain the parasitic infections mainly because of the following reasons:

Large size of the parasites
Complicated life cycles
Antigenic complexity.

There are a number of mechanisms by which the parasites evade the host immune responses (Table 1.5).

LABORATORY DIAGNOSIS OF PARASITIC DISEASES

It plays an important role in establishing the specific diagnosis of various parasitic infections. Following techniques are used in diagnosis of parasitic infections (discussed in detail in Chapter 15):

Parasitic diagnosis—either microscopically or macroscopically
Culture methods
Immunodiagnostic methods (antigen and antibody detection)
Intradermal skin tests
Molecular methods
Xenodiagnostic techniques
Animal inoculation
Imaging techniques.8

Table 1.4 Hypersensitivity reactions seen in parasitic diseases

Hypersensitive reactions	Parasitic diseases
Type I hypersensitivity reactions These are allergic or anaphylactic reactions, occurring within minutes of exposure to parasitic antigens due to IgE mediated degranulation of mast cells	Cercarial dermatitis (Swimmer's Itch) in schistosomiasis Loeffler's syndrome in ascariasis Ground itch (Hookworm infection) Anaphylaxis due to leakage of hydatid fluid (Echinococcus granulosus) Casoni's test (hydatid disease) Tropical pulmonary eosinophilia (occult filariasis)
Type II hypersensitivity reactions These are mediated by IgG or rarely IgM antibodies produced against the antigens on surfaces of the parasitic cells causing antibody mediated destruction of the cells by i) the complement activation or ii) by the NK cell activation (ADCC -antibody dependent cell mediated cytotoxicity)	Anemia in malaria Black water fever in malaria following quinine therapy Myocarditis in Chagas’ disease Killing of the helminths by NK cells
Type III hypersensitivity reactions Immune complexes are formed by the combination of parasitic antigens with the circulating antibodies (IgG) which get deposited in various tissues	Nephrotic syndrome in Plasmodium malariae Katayama fever in schistosomiasis African trypanosomiasis Onchocerciasis
Type IV hypersensitivity reactions This is T-cell mediated delayed type of hypersensitivity reaction. Previously sensitized T helper cells secrete a variety of cytokines, on subsequent exposure to the parasitic antigens. Usually, the pathogen is cleared rapidly with little tissue damage. However, in some cases, it may be destructive to the host resulting in granulomatous reaction	Elephantiasis (in filariasis) Granulomatous disease in schistosomiasis and other helminthic infections Leishmaniasis
Abbreviations: IgE, immunoglobulin E; IgG, immunoglobulin G; IgM, immunoglobulin M; NKs, natural killer cells.

Table 1.5 Immune evasion mechanisms of the parasites

Immune evasion mechanisms	Parasites involved
By intracellular location	Plasmodium species, Babesia species, Trypanosoma species, Toxoplasma species, Leishmania species and Microsporidia
Enters an immunologically protected site soon after infection	Plasmodium species entering into hepatocytes
Leave the site where the immune response is already established	Ascaris undergoes intestinal phase and migratory lung phase during its life cycle
Survives in macrophages by preventing phagolysosome fusion	Leishmania, Trypanosoma and Toxoplasma
Antigenic shedding (capping): Surface membrane antigens of the parasites bound to the antibodies undergo redistribution so that the parasite is covered by a folded membrane that later extrude as a cap containing most of the antibodies that were originally bound to the membrane	Entamoeba histolytica, Trypanosoma brucei and Ancylostoma caninum
Antigenic variation: By change of antigenic composition, the parasites can be protected from the antibodies which are formed against the original antigens	P. falciparum (pf-EMP protein), Giardia and Trypanosoma brucei
Antigenic mimicry: The adult flukes of Schistosoma get coated with the host red cell antigens and histocompatibility antigens, so that they are not recognized as foreign and live free from host attack	Schistosoma species
Inhibit antibody binding	Schistosoma mansoni
Lymphocyte suppression	Schistosoma mansoni
Polyclonal stimulation of lymphocytes	P. falciparum, Trypanosoma brucei, Babesia, Trichinella and E. histolytica
Suppression of immune system	Trypanosoma, Plasmodium and Leishmania

TREATMENT OF PARASITIC DISEASES

Treatment of parasitic disease is primarily based on chemotherapy and in some cases by surgery.

Antiparasitic Drugs

Various chemotherapeutic agents are used for the treatment and prophylaxis of parasitic infections (Table 1.6).

Surgical Management

For management of parasitic diseases like echinococcosis (or hydatid disease) and neurocysticercosis surgery is indicated. Semi-conservetive surgery is followed wherever possible; for example, PAIR (percutaneous aspiration, injection and reaspiration) is done for treatment of hydatid disease.

Table 1.6 Common antiparasitic drugs, their mechanism of action and clinical indications

Drugs for amoebiasis	Mechanism of action	Clinical indications
Metronidazole, tinidazole and ornidazole	Bioactivated to form reduced cytotoxic products which damage DNA	DOC for the amoebic colitis, amoebic liver abscess, and other extraintestinal amoebiasis
Dehydroemetine	Inhibits protein synthesis	Parenterally used for severe hepatic amoebiasis
Chloroquine	Probably by concentrating in parasite food vacuoles	Used for extraintestinal amoebiasis
Paromomycin (Aminoglycoside)	Inhibits protein synthesis by binding to 16S ribosomal RNA	Effective luminal agent
Diloxanide furoate (Acetanilide compound)	Unknown; it is thought to interfere with protein synthesis	Effective luminal agent
Iodoquinol (8-hydroxyquinoline compound)	Unknown	Luminal agent
Amphotericin B	Complex and multifaceted	DOC for Naegleria fowleri
Drugs for flagellates	Mechanism of action	Clinical indications
Intestinal/Genital Flagellates
Giardiasis
Metronidazole and tinidazole	Bioactivated to form reduced cytotoxic products which damage DNA	DOC for giardiasis
Nitazoxanide	Interference with the PFOR enzyme dependent electron transfer reaction which is essential for anaerobic energy metabolism
Furazolidone	Cross linking of DNA	Given to children
Paromomycin	Protein synthesis inhibitor in nonresistant cells by binding to 16S ribosomal RNA	Can be given in pregnancy
Trichomoniasis
Metronidazole or tinidazole	Bioactivated to form reduced cytotoxic products having nitro groups which damage DNA	DOC for trichomoniasis, given to both the partners
Drugs for hemoflagellates
Chagas’ disease (American trypanosomiasis)
Nifurtimox	Forms nitro-anion radical metabolite, which reacts with the nucleic acids of the parasite, causing a significant breakage in the DNA	Chagas’ disease
Benznidazole	Production of free radicals, to which Trypanosoma cruzi is particularly sensitive	Effective in the treatment of reactivated T. cruzi infections caused by immunosuppression (AIDS patients or patients of organ transplants)
Sleeping sickness (African trypanosomiasis)
Pentamidine	Accumulates to micromolar concentrations within the parasite to kill it by inhibiting enzymes and interacting with DNA	DOC for East African sleeping sickness
Suramin	Trypanocidal activity; inhibits enzymes involved with the oxidation of reduced NADH	DOC for West African sleeping sickness10
Leishmaniasis	Mechanism of action	Clinical indications
Sodium stibogluconate Meglumine antimoniate	Inhibition of the parasite's glycolytic and fatty acid oxidative activity resulting in decreased reducing equivalents for antioxidant defense and decreased synthesis of ATP	Leishmaniasis
Amphotericin B	Bind to ergosterol and disrupts cell membranes	Leishmaniasis
Paromomycin	Discussed earlier under giardiasis	Leishmaniasis
Miltefosine	Can trigger programmed cell death (apoptosis)	Leishmaniasis
Drugs for malaria	Mechanism of action	Clinical indications
Chloroquine	Probably, concentrating in parasite food vacuoles, preventing the polymerization of the hemoglobin into the toxic product hemozoin	DOC for uncomplicated benign malaria
Artemisinin derivative (Artemisinin or artemether or arte-ether)	Generate highly active free radicals that damage parasite membrane	DOC for complicated or falciparum malaria
Quinine	Probably similar to chloroquine; still not clear	DOC for complicated or falciparum malaria
Mefloquine	Same as chloroquine	DOC for complicated or falciparum malaria
Primaquine	Generating reactive oxygen species	DOC for relapse of vivax and ovale malaria
Sulfadoxine-pyrimethamine	Inhibits the production of enzymes involved in the synthesis of folic acid within the parasites	DOC for complicated or falciparum malaria
Lumefantrine	Accumulation of heme and free radicals	Complicated or falciparum malaria
Drugs for babesiosis	Mechanism of action	Clinical indication
Clindamycin plus quinine	Clindamycin: inhibits protein synthesis Quinine: discussed earlier	DOC for severe babesiosis
Atovaquone plus azithromycin	Azithromycin: inhibits protein synthesis Atovaquone: inhibits mitochondrial transport in protozoa by targeting the cytochrome bc₁ complex	DOC for mild babesiosis
Drugs for toxoplasmosis	Mechanism of action	Clinical indications
Cotrimoxazole (Trimethoprim-sulfamethoxazole)	Inhibiting folate synthesis from PABA (para-aminobenzoic acid), thus inhibiting purine metabolism	DOC for prophylaxis in HIV-infected people
Spiramycin	Inhibition of protein synthesis in the cell during translocation	DOC in pregnancy
Drugs for Cryptosporidium	Mechanism of action	Clinical indications
Nitazoxanide	Interferes with the PFOR enzyme-dependent electron-transfer reaction, which is essential to anaerobic metabolism in protozoan and bacterial species	DOC for Cryptosporidium infection
Drugs for Cystoisospora and Cyclospora	Mechanism of action	Clinical indications
Cotrimoxazole (Trimethoprim-sulfamethoxazole)	Inhibiting folate synthesis from PABA (Para aminobenzoic acid), thus inhibiting purine metabolism	DOC for Cystoisospora and Cyclospora infection
Drugs for cestodes	Mechanism of action	Clinical indication
Praziquantel	Increases the permeability of the membranes of parasite cells toward calcium ions which induces contraction of the parasites, resulting in paralysis in the contracted state	DOC for all cestode infections
Niclosamide	Niclosamide uncouples oxidative phosphorylation	Alternative drug for cestode infections
Albendazole	Causes loss of the cytoplasmic microtubules leading to impaired uptake of glucose by the larval and adult stages of the susceptible parasites, and depleting their glycogen stores	Given for cysticercosis and hydatid disease
Drugs for trematodes	Mechanism of action	Clinical indication
Praziquantel	Discussed earlier under cestodes	DOC for most of the trematode infections
Triclabendazole	Binds to beta-tubulin and prevent the polymerization of the microtubules	DOC for Fasciola hepatica and F. gigantica11
Intestinal nematodes
Mebendazole or albendazole	Discussed earlier under cestodes	DOC for most of the intestinal nematodes
Pyrantel pamoate	Acts as a depolarizing neuromuscular blocking agent, thereby causing sudden contraction, followed by spastic paralysis of the helminths	Alternative drug for intestinal nematodes
Ivermectin	Kills by interfering with nervous system and muscle function, in particular by enhancing inhibitory neurotransmission resulting in flaccid paralysis	DOC for strongyloidiasis. Alternative drug for Trichuris infections
Filarial nematodes
Diethylcarbamazine (DEC)	An inhibitor of arachidonic acid metabolism in microfilaria. This makes the microfilaria more susceptible to phagocytosis	DOC for lymphatic filariasis, Loa loa and Mansonella infections
Albendazole	Discussed earlier under cestodes	Alternative drug for lymphatic filariasis, Loa loa and Mansonella infections
Ivermectin	Discussed earlier under intestinal nematodes	Used for lymphatic filariasis in Africa DOC for onchocerciasis Alternative drug for Loa loa and Mansonella infections
Doxycycline	Targets the intracellular Wolbachia present inside the Microfilaria	Alternative drug for lymphatic filariasis
Abbreviations: DNA, deoxyribonucleic acid; DOC, drug of choice; RNA, ribonucleic acid; PFOR, pyruvate ferredoxin oxidoreductase enzyme; ATP, adenosine triphosphate; NADH, nicotinamide adenine dinucleotide.

EXPECTED QUESTIONS

Write short notes on:
1. Paratenic host.
2. Reservoir host.
3. Indirect/complex life cycle.
4. Immune evasion mechanisms of the parasites.
5. Antiparasitic drugs.
Differentiate between:
1. Definitive host and intermediate host.
2. Direct and indirect life cycle.
Multiple choice questions (MCQs):

1. A host harboring adult or sexual stage of a parasite is called:

Definitive host
Intermediate host
Reservoir host
None of the above

2. Parasite which may be transmitted by sexual contact is :

Trypanosoma cruzi
Trichomonas vaginalis
Trypanosoma brucei
Ascaris

3. Cholangiocarcinoma is associated with chronic infection of :

Paragonimus westermani
Fasciola hepatica
Clonorchis sinensis
Schistosoma haematobium

4. Which of the following parasite is transmitted by dog :

Taenia saginata
Hymenolepis nana
Echinococcus granulosus
Diphyllobothrium latum

5. Blood-sucking vector may transmit:

Ascaris lumbricoides
Ancylostoma duodenale
Strongyloides stercoralis
Plasmodium

Answers

1. a

2. b

3. c

4. c

5. d

Chapter Notes

General Introduction: ParasitologyCHAPTER 1