INTRODUCTION
Medical parasitology deals with the parasites, which cause human infections and the diseases they produce.
- It is broadly divided into two parts:
- Protozoology
- Helminthology.
- The pioneer Dutch microscopist, Antonie van Leeuwenhoek of Holland in 1681, first introduced single lens microscope and observed Giardia in his own stools.
- Louis Pastuer in 1870, first published scientific study on a protozoal disease leading to its control and prevention during investigation of an epidemic silk worm disease in South Europe.
- A seminal discovery was made in 1878 by Patrick Manson about the role of mosquitoes in filariasis. This was the first evidence of vector transmission.
- Afterwards, Laveran in Algeria discovered the malarial parasite (1880), and Ronald Ross in Secunderabad and Calcutta in India, showed its transmission by mosquitoes (1897). A large number of vector-borne disease have since then been identified.
- By mid 20th century, with dramatic advances in antibiotics and chemotherapy, insecticides and antiparasitic drugs, and improved lifestyles, all infectious diseases seemed amenable to control.
PARASITES
Parasites are living organisms, which depend on a living host for their nourishment and survival. They multiply or undergo development in the host.
- The term “parasite” is usually applied to Protozoa (unicellular organisms) and Helminths (multicellular organisms) (Flow chart 1).
- Parasites can also be classified as:
- Ectoparasite: Ectoparasites inhabit only the body surface of the host without penetrating the tissue. Lice, ticks and mites are examples of ectoparasites. The term infestation is often employed for parasitization with ectoparasites.
- Endoparasite: A parasite, which lives within the body of the host and is said to cause an infection is called an endoparasite. Most of the protozoan and helminthic parasites causing human disease are endoparasites.
- Free-living parasite: It refers to nonparasitic stages of active existence, which live independent of the host, e.g. cystic stage of Naegleria fowleri.
- Endoparasites can further be classified as:
- Obligate parasite: The parasite, which cannot exist without a host, e.g. Toxoplasma gondii and Plasmodium.
- Facultative parasite: Organism which may either live as parasitic form or as free-living form, e.g. Naegleria fowleri.
- Accidental parasites: Parasites, which infect an unusual host are known as accidental parasites. Echinococcus granulosus infects man accidentally, giving rise to hydatid cysts.
- Aberrant parasites: Parasites, which infect a host where they cannot develop further are known as aberrant or wandering parasites, e.g. Toxocara canis (dog roundworm) infecting humans.
HOST
Host is defined as an organism, which harbors the parasite and provides nourishment and shelter to latter and is relatively larger than the parasite.
- The host may be of the following types:
- Definitive host: The host, in which the adult parasite lives and undergoes sexual reproduction is called the definitive host, e.g. mosquito acts as definitive host in malaria.
- Intermediate host: The host, in which the larval stage of the parasite lives or asexual multiplication takes place is called the intermediate host. In some parasites, two different intermediate hosts may be required to complete different larval stages. These are known as first and second intermediate hosts, respectively (Box 1).
- Paratenic host: A host, in which larval stage of the parasite remains viable without further development is referred as a paratenic host. Such host transmits the infection to another host, e.g. fish for plerocercoid larva of D. latum.
- Reservoir host: In an endemic area, a parasitic infection is continuously kept up by the presence of a host, which harbors the parasite and acts as an important source of infection to other susceptible hosts, e.g. dog is the reservoir host of hydatid disease.
- Accidental host: The host, in which the parasite is not usually found, e.g. man is an accidental host for cystic echinococcosis.
ZOONOSIS
The word zoonosis was introduced by Rudolf Virchow in 1880 to include the diseases shared in nature by man and animals.
- Later, in 1959, the World Health Organization (WHO) defined zoonosis as those diseases and infections, which are naturally transmitted between vertebrate animals and man.
- It is of following types:
- Protozoal zoonoses, e.g. toxoplasmosis, leishmaniasis, balantidiasis and cryptosporidiosis.
- Helminthic zoonoses, e.g. hydatid disease, taeniasis.
- Anthropozoonoses: Infections transmitted to man from lower vertebrate animals, e.g. cystic echinococcosis.
- Zooanthroponoses: Infections transmitted from man to lower vertebrate animals, e.g. human tuberculosis to cattle.
HOST-PARASITE RELATIONSHIPS
Host-parasite relationships are of following types (Flow chart 2):
- Symbiosis
- Commensalism
LIFE CYCLE OF PARASITES
- Direct life cycle: When a parasite requires only single host to complete its development, it is called as direct life cycle, e.g. Entamoeba histolytica requires only a human host to complete its life cycle (Table 1).
SOURCES OF INFECTION
- Contaminated soil and water:
- Soil polluted with embryonated eggs (roundworm, whipworm) may be ingested or infected larvae in soil, may penetrate exposed skin (hookworm).
- Infective forms of parasites present in water may be ingested (cyst of ameba and Giardia).
- Water containing the intermediate host may be swallowed (cyclops containing guinea worm larva).
- Infected larvae in water may enter by penetrating exposed skin (cercariae of schisotosomes).
- Free-living parasites in water may directly enter through vulnerable sites (Naegleria may enter through nasopharynx).
- Food:
- Ingestion of contaminated food or vegetables containing infective stage of parasite (amebic cysts, Toxoplasma oocysts, Echinococcus eggs).
- Ingestion of raw or undercooked meat harboring infective larvae (measly pork containing cysticercus cellulosae, the larval stage of Taenia solium).
- Vectors: A vector is an agent, usually an arthropod that transmits an infection from man to man or from other animals to man, e.g. female Anopheles is the vector of malarial parasite.Vectors can be:
- Biological vectors: The term biological vector refers to a vector, which not only assists in the transfer of parasites but the parasites undergo development or multiplication in their body as well. They are also called as true vectors. Example of true vectors are:
- Mosquito: Malaria, filariasis
- Sandflies: Kala-azar
- Tsetse flies: Sleeping sickness
- Reduviid bugs: Chagas disease
- Ticks: Babesiosis.
- Mechanical vectors: The term mechanical vector refers to a vector, which assists in the transfer of parasitic form between hosts but is not essential in the life cycle of the parasite. Example of mechanical vectors is:
- Housefly: Amebiasis
In biological vectors, a certain period has to elapse after the parasite enters the vector, before it becomes infective. This is necessary because the vector can transmit the infection only after the parasite multiplies to a certain level or undergoes a developmental process in its body. This interval between the entry of the parasite into the vector and the time it takes to become capable of transmitting the infection is called the extrinsic incubation period.
- Animals:
- Domestic:
-
Table 2 Parasites having indirect life cycle requiring one intermediate host and one definitive host ParasiteDefinitive hostIntermediate hostProtozoaPlasmodium spp.Female Anopheles mosquitoManBabesiaTickManLeishmaniaMan, dogSandflyTrypanosoma bruceiManTsetse flyTrypanosoma cruziManTriatomine bugToxoplasma gondiiCatManCestodesTaenia soliumManPigTaenia saginataManCattleEchinococcus granulosusDogManTrematodesFasciola hepaticaManSnailFasciolopsis buskiMan, pigSnailSchistosoma spp.ManSnailNematodesTrichinella spiralisManPigWuchereria bancroftiManMosquitoBrugia malayiManMosquitoDracunculus medinensisManCyclopsTable 3 Parasites having indirect life cycle requiring two intermediate host and one definitive host ParasiteIntermediate hostsDefinitive hostFasciola spp.Snail, plantManClonorchis sinensisSnail, fishManDiphyllobothrium latumCyclops, fishManParagonimus westermaniSnail, crustaceanMan - Pig, e.g. T. solium, Trichinella spiralis
- Dog, e.g. Echinococcus granulosus
- Cat, e.g. Toxoplasma, Opisthorchis.
-
- Wild:
- Wild game animals, e.g. trypanosomiasis
- Wild felines, e.g. Paragonimus westermani
- Fish, e.g. fish tapeworm
- Molluscs, e.g. liver flukes
- Copepods, e.g. guinea worm.
- Carrier: A person who is infected with parasite without any clinical or subclinical disease is known as carrier. He can transmit parasite to others. For example, all anthroponotic infections, vertical transmission of congenital infections.
- Self (autoinfection) (Box 2):
- Finger-to-mouth transmission, e.g. pinworm
- Internal reinfection, e.g. Strongyloides.
MODES OF INFECTION
- Oral transmission: The most common method of transmission is through oral route by contaminated food, water, soiled fingers, or fomites. Many intestinal parasites enter the body in this manner, the infective stages being cysts, embryonated eggs, or larval forms. Infection with E. histolytica and other intestinal protozoa occurs when the infective cysts are swallowed.
- Skin transmission: Entry through skin is another important mode of transmission. Hookworm infection is acquired, when the larvae enter the skin of persons walking barefooted on contaminated soil. Schistosomiasis is acquired when the cercarial larvae in water penetrate the skin.
- Vector transmission: Many parasitic diseases are transmitted by insect bite, e.g. malaria is transmitted by bite of female Anopheles mosquito, filariasis is transmitted by bite of Culex mosquito. A vector could be a biological vector or a mechanical vector.
- Direct transmission: Parasitic infection may be transmitted by person-to-person contact in some cases, e.g. by kissing in the case of gingival amebae and by sexual intercourse in trichomoniasis.
- Vertical transmission: Mother to fetus transmission may take place in malaria and toxoplasmosis.
- Iatrogenic transmission: It is seen in case of transfusion malaria and toxoplasmosis after organ transplantation.
PATHOGENESIS
Parasitic infections may remain inapparent or give rise to clinical disease. A few organisms, such as E. histolytica may live as surface commensals, without invading the tissue.
- Clinical infection produced by parasite may take many forms: acute, subacute, chronic, latent, or recurrent.
- Pathogenic mechanisms, which can occur in parasitic infections are:
- Trauma: Attachment of hookworms on jejunal mucosa leads to traumatic damage of villi and bleeding at the site of attachment.
- Allergic manifestations: Clinical illness may be caused by host immune response to parasitic infection, e.g. eosinophilic pneumonia in Ascaris infection and anaphylactic shock in rupture of hydatid cyst.
- Physical obstruction: Masses of roundworm cause intestinal obstruction. Plasmodium falciparum malaria may produce blockage of brain capillaries in cerebral malaria.
- Inflammatory reaction: Clinical illness may be caused by inflammatory changes and consequent fibrosis, e.g. lymphadenitis in filariasis and urinary bladder granuloma in Schistosoma haematobium infection.
- Neoplasia: A few parasitic infection have been shown to lead to malignancy. The liver fluke, Clonorchis may induce bile duct carcinoma, and S. haematobium may cause urinary bladder cancer.
- Space occupying lesions: Some parasites produce cystic lesion that may compress the surrounding tissue or organ, e.g. hydatid cyst.
IMMUNITY IN PARASITIC INFECTION
Like other infectious agents, parasites also elicit immunoresponses in the host, both humoral as well as cellular (Fig. 1). But immunological protection against parasitic infections is much less efficient, than it is against bacterial or viral infections. Several factors may contribute to this:
- Compared to bacteria and viruses, parasites are enormously larger or more complex structurally and antigenically, so that immune system may not be able to focus attack on the protective antigens.
- Many protozoan parasites are intracellular in location, and this protects them from immunological attack. Several protozoa and helminths live inside body cavities. This location limits the efficiency of immunological attack.
- Once the parasitic infection is completely eliminated, the host becomes again susceptible to reinfection. This type of immunity to reinfection is dependent on the continued presence of residual parasite population and is known as “premunition”.
- Antibodies belonging to different immunoglobulin classes are produced in response to parasitic infections. Selective tests for immunoglobulin M (IgM) are helpful in differentiating current infections from old infections.
- Excessive IgE response occurs in helminthiasis. A characteristic cellular response in helminth parasite is eosinophilia both local and systemic (Fig. 1).
- Parasites have evolved to be closely adapted to the host and most parasitic infections are chronic and show a degree of host specificity. For example, malarial parasites of human, bird and rodents are confined to their own particular species.
- Parasites like trypanosomes exhibit antigenic variation within the host. This genetic switch protects them from antibodies. Similar mechanism may be operative in the recrudescences in human malaria (Box 3).
- Some parasites adopt antigenic disguise. Their surface antigens are so closely similar to host components that they are not recognized as foreign by the immune system.
- Some infections may produce immunodeficiency due to extensive damage to the reticuloendothelial system, as in case of visceral leishmaniasis.
The fact that immunity normally plays an important role in the containment of parasitic infections is illustrated by the florid manifestations caused by opportunistic parasites such as Pneumocystis jirovecii and T. gondii, when the immune response is inadequate as in acquired immunodeficiency syndrome (AIDS) and other immunodeficiencies.
IMMUNE EVASION
All animal pathogens, including parasitic protozoa and worms have evolved effective mechanism to avoid elimination by the host defense system as described in Table 4.
VACCINATION
No effective vaccine for humans has so far been developed against parasites due to their complex life cycles, adaptive responses and antigenic variation, great progress has been made in identifying protective antigens in malaria and some other infections, with a view to eventual development of prophylactic vaccines.6
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LABORATORY DIAGNOSIS
Most of the parasitic infection cannot be conclusively diagnosed. On the basis of clinical features and physical examination laboratory diagnosis depends upon:
- Microscopy
- Culture
- Serological test
- Skin test
- Molecular method
- Animal inoculation
- Xenodiagnosis
- Imaging
- Hematology.
Microscopy
An appropriate clinical specimen should be collected for definitive diagnosis of parasitic infections.
- Following specimens are usually examined to establish a diagnosis:
- Stool
- Blood
- Urine
- Sputum
- Cerebrospinal fluid (CSF)
- Tissue and aspirates
- Genital specimens.
Stool Examination
Examination of stool is very important for the detection of intestinal infections like Giardia, Entamoeba, Ascaris, Ancylostoma, etc.
Cysts and trophozoites of E. histolytica, G. lamblia can be demonstrated in feces. Eggs of roundworm and tapeworm are also found in stool. The larvae are found in the feces in S. stercoralis infection (Table 5).
For further details, refer to Chapter 23.
Blood Examination
Examination of blood is of vital importance for demonstrating parasites which circulate in blood vessels (Table 6). Malarial parasite is confirmed by demonstration of its morphological stages in the blood.
Urine Examination
The characteristic lateral-spined eggs of S. haematobium and trophozoites of T. vaginalis can be detected in urine. Microfilaria of W. bancrofti are often demonstrated in the chylous urine (Box 4).
Sputum Examination
The eggs of P. westermani are commonly demonstrated in the sputum specimen. Occasionally, larval stages of S. stercoralis and A. lumbricoides may also be found in sputum.
Cerebrospinal Fluid Examination
Some protozoa like T. brucei, Naegleria, Acanthamoeba, Balamuthia and Angiostrongylus can be demonstrated in the CSF.
Tissue and Aspirates Examination
The larvae of Trichinella and eggs of Schistosoma can be demonstrated in the muscle biopsy specimens. By histopathological examination of brain, Naegleria and Acanthamoeba can be detected. In kala-azar, Leishman-Donovan (LD) bodies can be demonstrated in spleen and bone marrow aspirate. Trophozoites of Giardia can be demonstrated in intestinal aspirates. Trophozoites of E. histolytica can be detected in liver pus in cases of amebic liver abscess.
Genital Specimen Examination
Trophozoites of T. vaginalis are found in the vaginal and urethral discharge. Eggs of E. vermicularis are found in anal swabs.7
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Culture
Some parasites like Leishmania, Entamoeba and Trypanosoma can be cultured in the laboratory in various axenic and polyxenic media.
Serological Tests
Serological tests are helpful for the detection and surveillance of many protozoal and helminthic infections. These tests are basically of two types:
- Tests for antigen detection
- Tests for antibody detection.
Antigen Detection
Malaria antigen like P. falciparum lactate dehydrogenase (pLDH) and histidine-rich protein 2 (HRP-2) are detected by rapid immunochromatographic test. Filarial antigens are detected in current infection by enzyme-linked immunosorbent assay (ELISA) (Table 7).
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Antibody Detection
The following antibody detection procedures are useful in detecting various parasitic infections like amebiasis, echinococcosis and leishmaniasis in man:
- Complement fixation test (CFT)
- Indirect hemagglutination (IHA)
- Indirect immunofluorescent antibody (IFA) test
- Rapid immunochromatographic test (ICT)
- Enzyme-linked immunosorbent assay test (ELISA).
Skin Test
Skin tests are performed by injecting parasitic antigen intradermally and observing the reaction. In immediate hypersensitivity reaction, wheal and flare response is seen within 30 minutes of infection, whereas erythema and induration seen after 48 hours of injection is called as delayed hypersensitivity reaction (Box 5).8
Molecular Diagnosis
Molecular methods most frequently used to diagnose human parasitic infection are deoxyribonucleic acid (DNA) probes, polymerase chain reaction (PCR) and microarray technique. These tests are very sensitive and specific.
Animal Inoculation
It is useful for the detection of Toxoplasma, Trypanosoma and Babesia from the blood and other specimens.
Xenodiagnosis
Some parasitic infection like Chagas disease caused by T. cruzi can be diagnosed by feeding the larvae of reduviid bugs with patient's blood and then detection of amastigotes of T. cruzi in their feces.
Imaging
Imaging procedures like X-ray, ultrasonography (USG), computed tomography (CT) scan and magnetic resonance imaging (MRI) are now being extensively used for diagnosing various parasitic infections like neurocysticercosis and hydatid cyst disease.
Hematology
Anemia is frequently seen in hookworm infection and malaria. Eosinophilia is frequently present in helminthic infections. Hypergammaglobulinemia occurs in visceral leishmaniasis. Leukocytosis is seen in amebic liver abscess.
REVIEW QUESTIONS
1. Write short notes on:
- Parasites
- Host
- Host-parasite relationship
- Zoonoses
- Immune evasion mechanism of the parasites.
2. Discuss briefly the laboratory diagnosis of parasites.
3. Describe immunity in parasitic infections.
4. Differentiate between:
- Direct and indirect life cycle
- Definitive host and intermediate hosts
1. Definitive host is one
- In which sexual multiplication takes place and harbors adult form
- In which asexual multiplication takes place and harbors adult form
- In which sexual multiplication takes place and harbors larval form
- In which asexual multiplication takes place and harbors adult form
2. Autoinfection is seen in all except
3. Antigenic variation is exhibited by
- Entamoeba
- Schistosoma
- Trypanosoma
- Leishmania
4. Which parasite enters, the body by piercing the skin
- Trichuris trichiura
- Ascaris
- Necator americanus
- Plasmodium
5. Which parasitic infection leads to malignancy
- Babesiosis
- Clonorchis sinensis
- Trypanosoma cruzi
- Schistosoma haematobium
6. Xenodiagnosis is useful in
- Wuchereria bancrofti
- Trypanosoma cruzi
- Trichinella spiralis
- All of the above
7. The following are zoonotic disease except
- Leishmaniasis
- Balantidiasis
- Scabies
- Taeniasis
8. Two hosts are required in
- Taenia solium
- Entamoeba histolytica
- Trichuris trichiura
- Giardia
9. Which of the following parasite passes its life cycle through three hosts
- Fasciola hepatica
- Fasciola buski
- Schistosoma haematobium
- Clonorchis sinensis
10. Man is the intermediate host for
- Strongyloides stercoralis
- Plasmodium vivax
- Entamoeba histolytica
- Enterobius vermicularis
1. a
2. d
3. c
4. c
5. b
6. d
7. c
8. a
9. d
10. b