Human Parasitology (人体寄生虫学) Liwei Li Department of Medical Microbiology and Parasitology College of Medicine, Zhejiang University lilw2@zju.edu.cn Introduction to Parasitology • F. E. G. Cox. History of Human Parasitology. Clin Microbiol Rev. 2002 October; 15 (4): 595– 612 http://www.pubmedcentral.nih.gov/articlerender.f cgi?artid=126866 • Olson & Guselle. Are pig parasite a human health risk? http://www.banffpork.ca/proc/2000pdf/Chap13Olson.pdf You need to know in the course of human parasitology • • • • • What is parasitology? What are parasitism, parasite and host ? What is the life cycle of a parasite? How is the host-parasite interplay ? How do we diagnose the infections with parasites? • What do we need to understand in the epidemiology of parasitic infections? • What are principles of control of parasitic diseases? Pathogens microbes bacteria viruses fungi parasites protozoa helminthes arthropods Mosquito Pathogens Infectious or communicable diseases! Definition of Parasitology Parasitology is a discipline dealing with the biology of animal parasites, ecology of parasitism with emphasis on parasite--host and parasite--environmental interactions. Human parasitology or Medical parasitology is restricted in studying those parasites that are of importance in medicine Protozoology, helminthology and entomology Parasitology is usually in the scope of preventive medicine and the foundation of clinical parasitic diseases Subject outline In this course we will concentrate on 3 major groups of parasites: 1. Medical protozoa - flagellates, amoebae, malarial organisms 2. Medical Helminthes - parasitic worms such as the flukes, tapeworms, and roundworms 3. Medical Arthropods - insects and arachnids that are ectoparasites and carriers (vectors) of diseases Why do we study parasitology? 1. Parasites provide unique examples of biological phenomena not found in freeliving organisms 2. _ • Medical importance • Veterinary importance • Economic importance Medical Importance of Parasites • Humans are hosts to over 100 species of parasites. • Many of these parasites are causative agents of major public health problems of the world. Medical Importance of Parasites Ten major tropical diseases (UNDP/World bank/TDR, 2000) • Malaria(疟疾) • Shistosomaiasis(血吸虫病) • Filariasis (丝虫病,Lymphatic filariasis and Onchocerciasis) • Leishmaniasis(利什曼病) • Trypanosomiasis (锥虫病,African trypanosomiasis and chagas disease ) • Leprosy(麻风病) • Tuberculosis (结核病) • Dengue fever (登革热) Major human parasites • Estimated World Prevalence of the Major Parasitic Infection of Human: – – – – – – – – – – – Malaria Schistosomiasis Lymphatic filariasis Onchocerciasis Leishmaniasis Trypanosoma cruzi (South America) Ascaris infection Hookworm infection Amoebiasis Trichuriasis Gardiasis 300-500 million 200 million 120 million 85 million 12 million 18 million 1300 million 1300 million 60 million 900 million 200 million (WHO,1999) Examples of Medical Importance in the World Medical Importance in China • Five major parasitic diseases • • • • • Malaria Schistosomiasis Kala-azar (黑热病) Filariasis Hookworm disease Medical Importance in China Medical Importance in China Parasite infection Estimated number of cases(2004) Malaria (P.v & P.f infection) 60.2 thousand (2006) Ascariasis (large roundworm infection) 85.9 million Trichuriasis (whipworm infection) 29.1million Hookworm disease(A. d and N. a infection) 39.3 million Clonorchiasis (oriental liver fluke infection) 12.5 million Fasciolopiasis (intestinal fluke infection) 2 million Paragonimiasis(lung fluke infection) 2.95 million Taeniasis (pork and beef tapeworm infection) 1.5 million Schistosomiasis (blood fluke infection) 843 thousand (2003) China’s parasite infection based on the nationwide parasite survey Medical Importance in China Food-borne parasitic disease is still a big problem. Prevalence of pet-borne parasitic disease has increased. Prevalence of opportunistic parasitic disease has increased. Material exchange and population migration has widened the geographical scope of parasitic disease. Medical professionals generally lack the knowledge of parasitology. WHAT TYPES OF LIVING ORGANISMS ARE PARASITIC? Parasites occur in two of the five kingdoms of living organisms. What are the 5 kingdoms? KINGDOM PROTISTA - contains the single-celled protozoans. KINGDOM ANIMALIA contains 32 phyla. Parasites of importance are concentrated in 3 phyla. • PHYLUM PLATYHELMINTHES – Class Trematoda; Cestoda • PHYLUM NEMATODA – Class Nematoda • PHYLUM ARTHROPODA – Class Insecta…… What are parasitism, parasite and host? Evolution of parasitism: Understanding start with basic concept of symbiosis • Symbiosis was first coined by the German de Bary in 1879 - to mean “living together”. It was originally coined to refer to all cases where dissimilar organisms or species (e.g., heterogenetic associations) live together in an intimate association Interactions of Symbionts In order to facilitate our understanding of symbiosis, 3 subordinate categories of symbiotic relationships are indicated. They are: commensalism (including phoresis), mutualism, and parasitism Symbiosis (cont.) 1. Mutualism(互利共生) • This occurs when each member of the association benefits the other • The mutuals are metabolically dependent on one another. Sometimes, one cannot survive in the absence of the other • eg. the flagellate cannot survive outside the termite Sea anemones and anemonefish Symbiosis (cont.) 2. Commensalism(偏利共生,共栖) • • Commensalism means “eating at the same table” and in many commensalistic relationships one organism (the commensal) is feeding on food that was not consumed by the host Commensalism occurs when one member of the associating pair, usually the smaller, receives all the benefit and the other member is neither benefited nor harmed • • To carry -- phoresis Example: Remora fish associated with sharks feeds on leftover food Symbiosis (cont.) 3. Parasitism(寄生) • A parasitos (para: beside; sitos: grain or food): Original meaning from the Greek is a relationship in which "one eats at another's table or lives at another's expense." • Parasitism is a relationship in which one of the participants, the parasite, either harms its host (the part that got harmed) or in some sense lives at the expense of the host. Debate: The amoeba Entamoeba invadens is harmless in turtles but causes 100% mortality in snakes. Is it then a commensal (when it’s in turtles) or is it a parasite (when it’s in snakes)? The true nature of parasitism involves an ecological relationship between the parasite and its host. A parasite is metabolically dependent on its host. Symbiosis (sum.) •The categories of symbiosis are man-made constructs introduced primarily for convenience (they allow us to categorize natural symbiosis associations). There can in fact be overlap between various categories. Commensalism and Phoresis Mutualism Parasitism Overlap between the major categories of symbiosis Parasite — In the relationship known as parasitism, the partner lives in or on another from which it gains benefit, always smaller, is the parasite which to some degree injures its partner. — Parasites (animal parasites) are invertebrates that can not live independently and should depend upon others to maintain their lives (live at the expense of others). —Parasites may be classified according to different ways: residing site---endoparasite / ectoparasite ecology---obligatory/facultative; accidental or opportunistic duration of parasitism---permanent/intermittent Kinds of Parasites • An organism that does not absolutely depend on the parasitic way of life, but is capable of adapting to it if placed in such a relationship is known as a facultative parasite • If an organism is completely dependent on the host during a segment or all of its life cycle the parasite is known as an obligatory parasite • Parasites that live within the body of their host (intestinal tract, liver, etc.) are called endoparasites • Parasites that are attached to the outer surfaces of their hosts are called ectoparasites Host — Definition: In the parasitism, the partners which provide the food and shelter for parasites, and to some degree are injured by this association, are scientifically called as hosts. larger, more complex and better regulated bodies Types of the host • A definitive host(终宿主) is the host in which the parasite become sexually mature (where the adult worm harbor or undergoing sexual reproduction). • An intermediate host(中间宿主) is host in which the parasite undergoes larval development but does not reach sexual maturity, parasites often can undergo asexual reproduction in this type of host. Definitions of Hosts (cont.) Reservoir host( 保 虫 宿 主 ) is referred to those animals that harbor an infection that can be transmitted to humans. Even if the animal is the normal host of the parasite, it is the reservoir for the zoonotic infection of people . Thus , the reservoir host shares the same stage of the parasite with humans. Zoonosis( 人 兽 共 患 病 ): a disease of animals that may be transmitted to humans under natural conditions. Definitions of Hosts (cont.) A transport/paratenic/transfer host ( 转 续 宿 主 ) : When parasite enters the body of an abnormal host and not undergoes any development but continues to stay alive and be infective to the normal host.The host is called the transport host. not necessary for the completion of the parasite’s life cycle Definitions of Hosts (cont.) • Immune compromised hosts are persons who are considered to have reduced resistance to illness include: infants, hospital patients, pregnant women, frail, elderly people, malnourished individuals, people with controlled physical or metabolic disorders (e.g., diabetes or high blood pressure), people with AIDS. Definitions of Hosts (cont.) • Opportunistic parasitic infection: Any infection caused by a parasite that does not normally cause disease in humans; occurs in persons with abnormally functioning immune systems (as AIDS patients or transplant patients receiving immunosuppressive drugs). – For example: Toxoplasma gondii, Crypsosporidium (Pneumocystis jeroveci (carinii) ----- Pneumocystis pneumonia, PCP) Definitions of Hosts (cont.) Vector parasite infections may be carried from one host to another by means of arthropod vectors. A vector may also be a host if development of the parasite takes place with its body.(If the arthropod is simply an instrument of passive transfer, we refer to it as a mechanical vector) What is the Life Cycle Life cycle described the ontogenesis, development and reproduction of the parasite, tracking it through the various phases of its life history which will encompass both parasitic and non-parasitic stages. The key to understanding the transmission of a parasite species and parasitic disease is its life-cycle Generalized stages of a parasite’s life cycle Stage in human host (linking to pathogenesis) Stage to discharge (diagnostic stage) Stage developing outside human host ( in external environment, intermediate host or insect host)--- (linking to transmission) Stage infecting men (infective stage) Parasite Life Cycle—A generalized mode Invading Oral Skin Vector contact Human residing stage Infective Pathogenesis Site No. Stage to discharge stage (soil, water, animal host, insect) Epidemiology Extra-Human development Via: feces Urine Sputum Vector blood Diagnosis The types of life cycle of parasites Direct type: one host (definitive host) ---geo-helminth Indirect type: more one hosts(intermediate host(s) and definitive host) ---bio-helminth Life cycle (cont.) • Simple or Direct Life Cycle (monoxenous) is one in which there is only one host where the parasite often spends most of its life, usually as an adult, and where it reproduces. Life cycle (cont.) • Many parasites have more complex cycles which include 2 or more hosts and are classified as having indirect life cycles. host-parasite interactions Adaptations to parasitism Profound morphological adaptation to their way of life Organs not necessary to a parasitic existence are frequently lost or degenerated Reproductive system is very highly developed in association with increased reproductive capacity Specialized attachment organs in the form of suckers and hooks have been developed Physiological and biochemical adaptations Immune evasion host-parasite interactions The harmful effects on the host • Depriving for nutrition • Mechanical damage • Toxic effects • Immune-pathological consequences Ascaris in small intestine Hookworm and anemia Complete blockage of intestine caused by Ascaris Allergy caused by mosquito bites schistosomiasis host-parasite interactions Effects of the host to the parasite • Genetic constitution of the host may profoundly influence the host-parasite relationship (racial variations in resistance to certain strains of Plasmodium vivax; sickle cell trait increased resistance to infection with P. falciparum ) host-parasite interactions Effects of the host to the parasite •Anti-parasitic immune responses Natural immunity– mucocutaneous barrier, blood brain barrier, phagocyte, complement, defensins… Acquired immunity Sterilizing immunity (cutaneous leishmaniasis) Non-sterilizing immunity– premunition ( 带 虫 免 疫 ), concomitant immunity (伴随免疫) host-parasite interactions • Colonized (“infected”), asymptomatic – Differences in host susceptibility • Many people are asymptomatically infected with Toxoplasma gondii. – Capable of spreading microbe • Amoeba carrier • Colonized, infected, symptomatic • Infected, host death Characteristics of parasitic disease (infection) • Chronic infection, carrier • Suppressive infection(隐性感染) • Polyparasitism • Eosinophilia(嗜酸性粒细胞增多) • IgE ↑ • Larva migrans(幼虫移行症) • Ectopic parasitism(异位寄生) Diagnosis Diagnostic techniques • Etiological techniques • Immunodiagnostic techniques • Other molecular diagnostics Epidemiology & principles of control • Basic and essential links for parasitic diseases: – Source of infection: patients, carriers, reservoir hosts – Route of infection – Susceptible population Epidemiology & principles of control(cont.) • Endemic factors – Natural factors • One won’t get parasitic diseases in the polar area – Social factors • Eating habits, hygienic habit… • Sexual transmitted diseases… Epidemiology & principles of control(cont.) • Principal of disease control – Control the source of infection – Cut off the route of transmission – Massive protection, esp. for the susceptible population • no successful vaccine Epidemiology & principles of control(cont.) • Health Education Round Worms Introduction • Among the commonest of all parasites and responsible for diseases of major importance in humans • Non-segmented roundworms belonging to the Phylum Nemathelminthes, Class Nematoda • The sexes are usually separate (Dioecious), the male which is smaller than the female commonly has a curved posterior end Morphology • • • • • Cylindrical and slender Bilaterally symmetrical Sex-differentiated Celomic cavity: protocoele The supporting body wall consists of cuticle layer, syncytial layer (subcutical layer) and longitudinal muscular layer • The alimentary tract is a simple tube extending from the mouth to the anus Morphology • No circulatory system • The reproductive system is in tubular form with dioecious (sexdifferentiation): – Male: testis, vas deferens, seminal vesicle, and ejaculatory duct, also cloaca and spicule – Female: ovary, oviduct, seminal receptacle, uterus, ovejector and vagina Digestive system male reproductive system female reproductive system Physiology • The methods of obtaining food may be classified as – – – – Sucking with ingestion of blood (Ancylostoma) Ingestion of lysed tissues and blood (Trichuris) Feeding on the intestinal contents (Ascaris) Ingestion of nourishment from the body fluids (filarial worms) • Metabolism: mainly aerobic metabolism, and most species need free-living periods for larvae, which are capable of withstanding a wide range of environmental condition • During larval development, nematodes pass through several molts or ecdysis, both inside and outside the host Life cycle • Geo-helminths – Only one host: the larvae pass from host to host directly or after a free-living existence – Transmission to a new host depends upon • the ingestion of the mature infectious eggs with larvae (Ascaris, Pinworm) • the penetration of the skin or mucous membranes by the larvae (Hookworm) • Bio-helminths – Have an intermediate host – Transmission to a new definitive host is intermediated by the arthropod--- (filarial worm) Common medical nematodes species • Intestinal lumen residing nematodes: – Ascaris, Hookworm, Whip worm, Pinworm---the adult parasite inhabit in human intestinal tract • Blood and tissue residing nematodes: – Filaria, Thichinella----the location of the adult parasite is blood or tissue Ascaris lumbricoides (似蚓蛔线虫,蛔虫) General Introduction • Common saying “round worm of man” • The largest of the intestinal nematodes parasitizing humans • The most common worm found in human • It is worldwide in distribution and most prevalent through out the tropics, sub-tropics and more prevalent in the countryside than in the city Morphology • Adult: – Cylindrical in shape – Creamy-white or pinkish in color – The female averages 20-35cm in length, the largest 49cm – The male is smaller, averaging 15-31cm in length, has a typical curled tail with a pair sickle like copulatory spines – On the tip of the head there are three lips, arranged as a Chinese word “ 品 ” – Male has a single reproductive tubule – The female has two reproductive tubules and the vulva is ventrally located at the posterior part of the anterior 1/3 of the body Adult worm of A. lumbricoides The lips of A. lumbricoides The three lips are seen at the anterior end. The margin of each lip is lined with minute teeth which are not visible at this magnification Morphology Egg • There are three kinds of the eggs – fertilized eggs – unfertilized eggs – decorticated eggs • We usually describe an egg in 5 aspects – size, color, shape, shell and content Morphology • Fertilized egg: – – – – – an average size 60×45µm broad oval in shape brown in color The shell is thick Albuminous coat is thick and stained brown by bile – The content is a fertilized ovum – There is a new-moon(crescent) shaped clear space at each end inside the shell Morphology • Unfertilized egg Longer and slender than fertilized egg – The shell and albuminous coat are thinner than those of the fertilized egg – The content is made of many refractable granules various in size – • Decorticated egg: – Both fertilized and unfertilized eggs sometimes may lack their outer albuminous coats and are colorless Life Cycle Life Cycle • • • • Site of inhabitation: small intestine Infective stage: embryonated eggs Route of infection: by mouth Blood-lung migration: intestine--blood stream --- right side of the heart -- lung --- respiratory tree --- coughed up and swallowed --- small intestine Life Cycle • No intermediate and reservoir hosts • The time from the ingestion of embryonated eggs to oviposition by the females is about 60-75 days • Life span of the adult: about 1 year • Female may produce approximately 240,000 eggs per day, which are passed in feces Pathogenesis 1. The blood-lung migration phase of the larvae: During the migration through the lungs, the larvae may cause a pneumonia (temporary). – The symptoms of the pneumonia are low fever, cough, blood-tinged sputum, asthma – The clinical manifestation is also called Loeffler’s syndrome Pathogenesis 2. The intestinal phase of the adults • No symptoms to vague abdominal pains or intermittent colic, especially in children • A heavy worm burden can result in malnutrition • Wandering adults may block the appendical lumen or the common bile duct and even perforate the intestinal wall which cause complications of ascariasis: • • • • • intestinal obstruction Appendicitis biliary ascariasis (the most common one) perforation of the intestine cholecystitis, pancreatitis and peritonitis Diagnosis • The symptoms and signs are for reference only • Intestinal ascariasis: feces are examined for the ascaris eggs – Direct fecal film: it is simple and effective and is the first choice – brine-floatation method: – recovery of adult worms: when adults or adolescents are found in feces or vomit and tissues • Ascaris pneumonitis: examination of sputum for Ascaris larvae is sometimes Epidemiology • Worldwide distribution, very common in China, especially in the countryside. Infection rate: rural >urban; children > adults • Factors favoring the spread of the transmission: – Simple life cycle – Enormous egg production ( 240,000 eggs/ day/ female ) – Eggs are highly resistant to ordinary disinfectants ( due to the ascroside) which may remain viable for several years – Social customs and living habits. – Disposal of feces is unsuitable Prevention • Treatment to ascariasis: Mebendazole(甲苯咪唑) Albendazole(阿苯达唑) • Sanitary disposal of feces. • Hygienic habits such as cleaning of hands before meals. • Health education. Hookworms (钩虫) Two major species of hookworms can infect human Necator americanus (美洲板口线虫) Ancylostoma duodenale (十二指肠钩口线虫) General Introduction • • • • • • Human intestinal nematode of smaller size, inhabits the small intestine World-wide distribution, about 900 million infections in the world A. duodenale is prevalent in Southern Europe, North Africa, Northern Asia (North China), and the more pathogenic one N. americanus is the predominant species in the Western hemisphere and equatorial Africa (South China) Many areas are endemic for both species Heavy infection may evoke anemia known as "Yellow Laziness" Morphology: Adults Ancylostoma duodenale • Female is 10-13 mm in length by 0.6 mm in diameter • Males are 8-11 mm by 0.4 mm • Posterior end has an umbrella-shaped bursa with riblike rays • Two pairs of curved teeth on the ventral wall of its buccal capsule Morphology: Adults Necator americanus • Females are 9-11 mm in length by 0.4 mm in diameter • Males are 7-9 mm by 0.3 mm • Smaller than A. duodenale • A pair of semilunar cutting plates on the ventral wall of the buccal capsule Buccal capsule Ancylostoma duodenale Necator americanus Morphology: Egg oval or can-shaped with a thin, hyaline shell, measured 6075 by 36-40 µm. Life cycle Life cycle • • • • No intermediate host is necessary Larva takes a free living mode The filariform larva is the infective stage Infection routes: skin penetration(mainly); orally swallow; maternal-child • Residing in human upper small intestine: duodenum, jejunum • Blood-Lung migration: skin --- lymphatic system --right side of the heart --- lung --- respiratory tree --coughed up and swallowed --- small intestine • Persisting migrans( 迁 延 移 行 ): Ancylostoma duodenale Pathogenesis 1. Hookworm larvae dermatitis: Penetration of the skin by the filariform larvae may be asymptomatic in previously uninfected individuals. However, those experiencing repeated infections develop itching, known as "ground itch" or "dew itch". Pathogenesis 2. Migration of pre-adult cause temporary pulmonary inflammation: In heavily infected individuals (i.e., 500-1000 worms), there can be symptoms of pneumonia during the migratory phase in the developmental cycle of these worms Pathogenesis 3. Abdominal pains, diarrhea, loss of appetite… 4. Anemia – Especially in young children – Hypoproteinemic because of some loss of serum proteins – Iron-deficiency – Why the small worms can cause anemia? • The pump-like action when worms suck blood • The worms secrete an anticoagulant, which facilitates bleeding • The worms usually change the sites when suck blood 5. Allotriophagy (Geophagy): due to the irondeficiency 6. Ancylostomiasis in infant Allotriophagy Laboratory diagnosis • Brine floatation is the method of first choice • Hookworm larvae cultivation is used for species identification • Hookworm larvae in sputum Epidemiology • • Most prevalent in the tropical and subtropical zones In China, mostly mixed infected, while A.duodenale is somewhat northward distributed and N. americanus in southward Epidemiology • Moist, shady, sandy, or loamy soil favors persistence of these worms • Larvae can survive for up to 6 weeks • Do not live long in clay, dry, hard packed soils, or where temperatures are freezing, or are higher than 45C Principles of Control 1. Chemotherapy: Albendazole; Mebendazole 2. Sanitary disposal of human feces is the most effective control measure in preventing the spread of infection with the hookworms 3. Protection of the susceptible population