Medical Parasitology - Sporozoans PDF

Medical Parasitology- Sporozoans DR JONATHAN ASANTE DEPARTMENT OF PHARMACEUTICAL MICROBIOLOGY UCC  Protozoa sarcomastigophora Sporozoans Mastigophora Sarcodina...

Medical Parasitology- Sporozoans DR JONATHAN ASANTE DEPARTMENT OF PHARMACEUTICAL MICROBIOLOGY UCC  Protozoa sarcomastigophora Sporozoans Mastigophora Sarcodina Apicomplexa (sporozoans) Intestinal (Amoeba) Blood Ciliophora Plasmodium Giardia Intestinal Tissue Intestinal Genital Entamoeba Toxoplasma Balantidium coli Trichomonas Others Intestinal Blood & Tissue Coccidians Trypanosoma Naegleria Leishmania Acanthamoeba  Characteristics: Nonmotile, Intracellular parasites Complex life cycles, undergo sexual/asexual reproduction (alternation of generations) Genus Plasmodium E.g. Plasmodium falciparum (malaria) Sporozoans transmitted by female anopheles mosquito Genus Cryptosporidium E.g. C. parvum (diarrhoea; AIDS related) Genus Toxoplasma e.g. T. gondii (toxoplasmosis; AIDS related)  Plasmodium- characteristics The life cycle of malaria is passed in two hosts (alternation of hosts) Has sexual and asexual stage (alternation of generations). Vertebrate host - man (intermediate host), where the asexual cycle takes place. The parasite multiplies by schizogony and there is formation of male and female gametocytes (gametogony).  Plasmodium- characteristics Invertebrate host - mosquito (definitive host) where the sexual cycle takes place. Union of male and female gametes ends in the formation of sporozoites (sporogony). Plasmodium-Malaria (Introduction) Caused by blood parasites of the genus Plasmodium Transmitted by the ‘bite’ of an infective female Anopheles mosquito. Other means of transmission include: Blood transfusion Organ transplant. Congenital Introduction Four species of normally infect humans: Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae. These species utilize humans as a natural intermediate host Malaria P. knowlesi, a simian malaria parasite-reported in humans Considered a zoonotic malaria (NIH-macaque monkeys) Globally, 229 million cases of malaria were reported in 2019, 409,000 people died, mostly children in Africa. Major features of species P. falciparum The most important species as it is responsible for 50% of all malaria cases worldwide and nearly all morbidity and mortality from severe malaria. Found in the tropics & sub-tropics (dominant species in West Africa). Major features of species P. vivax The malaria parasite with the widest geographical distribution. Seen in tropical and sub-tropical areas but rare in Africa. Estimated to cause 43% of all malaria cases in the world. Major features of species P. ovale This species is relatively rarely encountered. Primarily seen in tropical Africa, especially, the west coast, but has been reported in South America and Asia. P. malariae Responsible for only 7% of malaria cases. Occurs mainly in sub-tropical climates. Major features of species Two kinds of malaria, P. vivax and P. ovale, can occur again (relapsing malaria). In these species, some parasites can remain dormant in the liver for several months up to about 4 years after a person is bitten by an infected mosquito. When these parasites come out of hibernation and begin invading red blood cells (“relapse”), the person will become sick. Introduction Malaria constitutes a serious public health issue, especially in warm climates and in developing countries Leading cause of morbidity and mortality among children under five, pregnant women and non-immune travellers/immigrants. Factors affecting mosquito ecology are key determinants of malaria transmission Such as temperature and rainfall Introduction- features Malaria: 300-500 mill people worldwide are infected each year Two hosts: Mosquito Definitive host: harbors sexually reproducing stage Human Intermediate host: harbors asexually reproducing stage Destruction of red blood cells (anemia) Release of toxins (fever/chill cycles) Alteration of RBC shape can clog tissue capillaries (kidney, liver, brain damage) Introduction - features The female mosquito bites during dusk and dawn and needs a blood meal to feed her eggs. Anopheles mosquitoes breed in water. Incubation period varies from 7 to 30 days. Shorter periods are observed most frequently with P. falciparum and the longer ones with P. malariae. Life Cycle Life Cycle During a blood meal, the malaria- infected female Anopheles mosquito injects sporozoites into human host. Hepatic, tissue or exo-erythrocytic phase: Sporozoites infect liver cells and develop into schizonts. Life Cycle Schizonts rupture to release merozoites. Dormant stage in P. vivax and P. ovale [hypnozoites] Persistent in liver-invade blood-weeks/years later-relapse Multiplication of parasite in human host-schizogony Exo-erythrocytic schizogony (initial replication in liver) Erythrocytic schizogony (asexual multiplication in the erythrocytes) Life Cycle Exo-erythocytic phase: Merozoites P. falciparum: All P. vivax and P. ovale: are liberated on merozoites invade some merozoites rupture of schizonts RBC’s without re- invade RBC’s and about 7th – 9th day invading liver cells. some re-invade liver of the ‘bites’ and cells initiating enter into the blood further Exo- stream. erythrocytic schizogony, responsible for relapses. Life cycle Erythrocytic phase: Merozoites infect red blood cells. The red cells lyse and this causes bouts of fever and the other symptoms of the disease. This cycle repeats as merozoites invade other red cells. Blood stage parasites-clinical manifestations of the disease. Sexual phase: Some parasites differentiate into sexual erythrocytic stages (gametocytes) Gametocytes are ingested during a blood meal by an anopheles mosquito. These develop into sporozoites in the gut of the insect host and travel to its salivary glands. Then the cycle starts again Life cycle In P. vivax, P. ovale and P. falciparum erythrocytic schizogony is completed in 48 hours; and 72 hrs in P. malariae. Erythrocytic merozoites do not reinvade the liver cells Multiplication of the parasite in the mosquito-sporogonic cycle. Takes 8-12 days depending on temperature Life cycle A low parasitaemia in falciparum malaria does not exclude a serious infection, WHY?  https://www.youtube.com/watch?v=Xaxjg9JOxug Host factors determine the outcome of exposure to malaria Naturally-acquired immunity: constant exposure promotes immunity Disease most severe in the non-immune Genetic factors that protect against malaria ▪ Duffy blood group: P. vivax requires the Duffy blood receptor to enter red blood cells ▪ Most Africans are Duffy blood group negative ▪ Persons with the haemoglobin genotype HbAS are protected against severe falciparum malaria. ▪ Parasitaemia is lower because HbAS cells sickle in the circulation and are removed by the spleen before the parasites can develop into schizonts. ▪ Sickle cell anaemia (HbSS) is not protective and can cause fatalities in young children with falciparum malaria. ▪ HbF Epidemiology and geographic distribution About 40% of the world’s population is at risk of malaria. It is endemic in 91 countries Epidemiology and Geographic distribution  Epidemiology and Geographic distribution Endemic in tropical and subtropical areas. P. falciparum: predominant species in the world. P. knowlesi is found in southeast Asia.  Clinical Presentation 3 possible outcomes following a bite by an infected mosquito: Asymptomatic parasitaemia Acute, uncomplicated malaria Severe malaria P. falciparum has the shortest incubation period-7 to 10 days  Asymptomatic parasitaemia Seen in people with acquired natural immunity- Clinical Presentation in areas with high malaria endemicity Important reservoirs for disease transmission Clinical presentation Simple, uncomplicated malaria The affected person manifests symptoms of illness-not life-threatening disease. Common symptoms-fever Fever may occur in paroxysms (caused by the release of merozoites upon RBC lysis resulting in fever, chills and rigors). Vomiting Diarrhoea Convulsions Pallor Jaundice Clinical presentation Typically, victims experience symptoms 10-28 days after infection. Chills and fever occur in periodic attacks They last 4-10 hours, consists of: First stage of fever & chills and a stage of fever & severe headache And finally a stage of profuse sweating during which temperature drops back to normal Clinical Presentation ▪ The classic attack cycles, A victim may be infected with recurring at intervals of 48 h different species at the same (tertian malaria) or 72 h time or may have different generations of the same species (quartan malaria) coincide at the same time being released with the synchronised out of synchrony release of each new Results in more frequent generation of merozoites paroxysms into bloodstream Clinical Presentation Other symptoms include: Anorexia Cough Headache Malaise Muscle aches Splenomegaly Tender hepatomegaly Clinical Presentation-Severe (complicated malaria) Cerebral malaria –P. falciparum-infected erythrocytes, adhere to the vascular endothelium of venular blood vessel walls and do not freely circulate in the blood. Clinical Presentation-Severe(complicated malaria) When this sequestration of infected erythrocytes occurs in the vessels of the brain it is believed to be a factor in causing the severe disease syndrome known as cerebral malaria, which is associated with high mortality. Abnormal behaviour, seizures, coma, impairment of consciousness or other neurologic abnormalities.  Kidney damage, resulting in an illness called “black water” fever (malarial haemoglobinuria): Rapid destruction of RBCs results in high haemoglobinuria which leads to acute renal failure and tubular necrosis. Can lead to death. Liver involvement is characterized by abdominal pain, vomiting of bile, hepatosplenomegaly, severe diarrhoea, and rapid dehydration. Clinical presentation-severe (complicated malaria) Symptoms of blackwater fever include: Rapid pulse High fever and chills Extreme prostration A rapidly developing anaemia Passage of urine that is black or dark red in colour Clinical Presentation-Severe (complicated malaria) Nearly all severe disease and the estimated >1 million deaths from malaria are due to P. falciparum. Frequently a fatal disease Important manifestations of severe malaria include: Cerebral malaria Severe malaria anaemia Hypoglycaemia Clinical Presentation-Severe (complicated malaria) Metabolic Acute renal Pulmonary acidosis failure oedema Circulatory Haemoglobinuria collapse, shock or due to “algid malaria” haemolysis Diagnosis Exclude other possible Blood film examination causes of fever (e.g. signs of viral and bacterial Thick blood film (larger volume infections) of blood is examined) Allows detection of even low levels of parasitaemia Determines parasite density Diagnosis ▪ Diagnosis of malaria based on clinical symptoms alone is not reliable. ▪ It can result in unnecessary expenditure and inappropriate use of antimalarial drugs and a delay in establishing the correct diagnosis and treatment of a patient. ▪ Laboratory support is needed to diagnose malaria, especially: ▪ in children (1–5 y) and pregnant women in areas of stable malaria (intense malaria) transmission. ▪ in all age groups in areas of unstable transmission where serious epidemics may occur and diagnosis can be difficult during times of low malaria transmission.  Diagnosis Thin blood film Gives more information about the parasite morphology Used to identify the particular infecting species of Plasmodium  Diagnosis Ring forms or trophozoites; many red cells Gametocytes (sexual stages); After a infected – some with more than one blood meal, these forms will develop in parasite(thin BF) the mosquito gut (thin BF) Rings of P. falciparum in a thick blood smear. Diagnosis Antigen capture kits: Uses a dipstick and a finger prick blood sample. Rapid test - results are available in 10-15 minutes. Expensive and sensitivity drops with decreasing parasitaemia. Molecular diagnosis: Detects DNA or mRNA sequences specific to Plasmodium. Sensitivity and specificity high but test is expensive, takes several hours and requires technical expertise. Diagnosis Fluorescent techniques: Relatively low specificity and sensitivity. Cannot identify the parasite species. Expensive and requires skilled personnel. Serologic tests: Based on immunofluorescence detection of antibodies against Plasmodium species. Useful for epidemiologic and not diagnostic purposes.  Malaria in Pregnancy May cause severe disease in the mother Premature delivery or delivery of a low-birth-weight baby. Stillbirth Maternal anaemia Cerebral malaria, pulmonary oedema, and hypoglycaemia frequently occur. Intermittent preventive treatment (IPT) recommended by WHO E.g. sulphadoxine-pyrimethamine during antenatal care Shown to substantially reduce the risk of maternal anaemia in the mother and low birth weight in the newborn. Treatment Depends on: Severity of disease Species of malaria parasite involved Pregnancy status COMBINATION therapies Artesunate + Amodiaquine Artemether + Lumefantrine Dihydroartemisinin + Piperaquine pyrimethamine – sulphadoxine Treatment Chloroquine Doxycycline Primaquine-prevent relapse from latent liver stages Mefloquine Halofantrine Primaquine Atovaquone Proguanil Treatment Complicated malaria Artesunate/Artemet her, IM or IV Quinine, IM, IV VACCINE  Toxoplasma gondii – Definitive host- causative agent domestic cat and Toxoplasma for other felines. toxoplasmosis. gondii (Toxoplasmosis) Intermediate Parasite-usually hosts-Humans acquired by and other ingestion mammals Toxoplasma gondii (Toxoplasmosis) Apart from Transplacental transplacental transmission from an transmission, human– infected mother to the to–human transmission foetus can occur. does not occur.  Parasite infects the intestinal epithelium and spreads to other organs, notably the brain, lungs, liver, and eyes. Toxoplasma gondii In immunocompetent adults most primary infections are asymptomatic Toxoplasma gondii The life cycle of this parasite involves domestic cats. The trophozoites, called tachyzoites, reproduce sexually and asexually in an infected cat Oocysts, each containing eight sporozoites, are excreted with faeces.  If the oocysts are ingested by humans or other animals, the sporozoites emerge as trophozoites, which can reproduce in the tissues of the new host T. gondii is dangerous to pregnant Toxoplasma women, because it can cause congenital gondii infections in utero. Tissue examination and observation of T. gondii are used for diagnosis. Life cycle  Life cycle Unsporulated oocysts are shed in the cat’s feces (1) IH in nature (including birds and rodents) become infected after ingesting soil, water or plant material contaminated with oocysts (2). Oocysts transform into tachyzoites shortly after ingestion. Tachyzoites localize in neural and muscle tissue and develop into tissue cyst bradyzoites (3).  Life cycle Cats become infected after consuming intermediate hosts harbouring tissue cysts or by directly ingesting sporulated oocysts (4). Other animals like livestock and wild game may also become infected with tissue cysts after ingestion of sporulated oocysts in the environment (5)  Human infection by any of these routes: Ingesting undercooked meat of animals harboring tissue cysts (6). Life cycle Consumption of food or water contaminated with cat faeces or by contaminated environmental samples (such as fecal- contaminated soil or changing the litter box of a pet cat) (7). Blood transfusion or organ transplantation (8). Transplacentally from mother to fetus (9). Life cycle Although tissue cysts Diagnosis: may be observed in Congenital infections usually by can be diagnosed by stained biopsy serology using PCR to detect T. specimens (10) gondii DNA in amniotic fluid (11). Epidemiology and Geographic Distribution Leading cause of death attributed to foodborne illness in the United States. A high prevalence of infection in countries where preference for eating raw or undercooked meat is rampant. Central America-stray cats Clinical presentation 10% to 20% of patients with acute infection may develop cervical lymphadenopathy and/or a flu-like illness. Benign and self-limited. Symptoms usually resolve within a few weeks to months. In cases of ocular infection with visual loss can occur. Clinical Presentation Immunocompromised patients-(CNS) disease may result. In AIDS patients-toxoplasmic encephalitis Those taking immunosuppressive drugs May be due to either newly acquired or reactivated latent infection Laboratory Diagnosis Serologic testing Molecular detection (PCR) Microscopy Antibody Detection Toxoplasma gondii tachyzoites, stained with Giemsa, from a smear of peritoneal fluid obtained from a laboratory-inoculated mouse  Treatment Targets tachyzoite stage of the parasite and does not eradicate encysted parasites in the tissues. Drugs Pyrimethamine (co-administered with folinic acid) Sulfadiazine Clindamycin (in case of hypersensitivity to sulpha drugs) Trimethoprim with sulfamethoxazole. Atovaquone and pyrimethamine Further reading Babesia microti Cryptosporidium