Presentation on theme: "BLOOD AND TISSUE PROTOZOONS"— Presentation transcript:
1BLOOD AND TISSUE PROTOZOONS PLASMODIUMTRYPANASOMABABESIADoç.Dr.Hrisi BAHARDoç.Dr.Hrisi BAHAR
2PLASMODIUM SPECIES CAUSES The Malarias: PLASMODIUMS Plasmodium falciparum Plasmodium vivax Plasmodium malariae Plasmodium ovalePLASMODIUM SPECIES CAUSES“MALARIAS”IN HUMAN►Plasmodium falciparum►Plasmodium vivax►Plasmodium malariae►Plasmodium ovale
3PLASMODIUMS►The malaria parasite exhibits a complex life cycle involving an insect vector (mosquito) and a vertebrate host (human).► Four Plasmodium species infect humans.► All four species exhibit a similar life cycle with only minor variations.
4PLASMODIUMS1*The infection is initiated when sporozoites are injected with the saliva of a feeding mosquito.Sporozoites are carried by the circulatory system to the liver and invade hepatocytes2*The intracellular parasite undergoes an asexual replication known as exoerythrocytic schizogony within the hepatocyte
5PLASMODIUMS3*Exoerythrocytic schizogony activates the production of merozoites which are released into the bloodstream4*Merozoites invade erythrocytes and undergo a trophic period in which the parasite enlarges5*The early trophozoite is often referred to as 'ring form' because of its morphology.
6PLASMODIUM Ring form Ring form Plasmodium vivax Plasmodium malaria
7Scanning electron micrograph of Plasmodium-infected red blood cells Scanning electron micrograph of Plasmodium-infected red blood cells. One cell has burst open, releasing merozoites
8PLASMODIUM► Trophozoite enlargement is accompanied by an active metabolism including the ingestion of host cytoplasm and the proteolysis of hemoglobin into amino acids.► The end of the trophic period is manifested by multiple rounds of nuclear division without cytokinesis resulting a schizont
9PLASMODIUM ► A proportion of the liver-stage parasites from P. vivax and P. ovale go through a dormantperiod instead of immediately undergoingasexual replication► These hypnozoites will reactivate several weeks to months (or years) after the primary infection and are responsible for relapses.
10PLASMODIUM► The merozoites from the mature schizont are released following rupture of the infected erythrocyte.► Invasion of erythrocytes reinitiates another round of the blood-stage replicative cycle
12PLASMODIUM► The blood stage is responsible for the pathology associated with malaria► The intermittent fever paroxyms are due to the synchronous lysis of the infected erythrocytes
13PLASMODIUM► P.malariae exhibits a 72 hour periodicity, whereas the other three species exhibit 48 hour cycles for the fever.►P. falciparum often exhibits a continuous fever rather than the periodic paroxyms.P.falciparum also is responsible for more morbidity and mortality than the other species
14PLASMODIUM► This increase virulence is due in part to the higher levels of parasitemia associated withP. falciparum infections. In addition, more complications are associated with P. falciparum because of the sequestration of the trophozoite- and schizont-infected erythrocytes in the deep tissues
15PLASMODIUM► As an alternative to the asexual replicative cycle, the parasite can differentiate into sexual forms known as macro- or microgametocytes► The gametocytes are large parasites which fill upthe erythrocyte, but only contain one nucleus.► Ingestionof gametocytes by the mosquito vectorinduces gametogenesis and escape from the hostErythrocyte.
16PLASMODIUM ►Microgametes, formed by a process known as exflagellation , are flagellated formswhich will fertilize the macrogameteleading to a zygote .► The zygote develops into a motile ookinetewhich penetrates the gut epithelial cells anddevelops into an oocyst
17PLASMODIUM► The oocyst undergoes multiple rounds of asexual replication resulting in the production of sporozoites .► Rupture of the mature oocyst releases the sporozoites into the body cavity of the mosquito The sporozoites migrate to and invade the salivary glands, thus completing the life cycle.
19General Clinical Manifestation of “Malaria” ► Infection is characterized by acute febrile attacks (malaria paroxysms) due to blood stage (not liver stage or gametocytes)► Manifestations and severity of the infection depend on species and host status, immunity, general health,nutritional state, genetics.
20General Clinical Manifestation of “Malaria” ► Recrudescences or relapses can occur over months or years and can develop severe complications.(especially P. falciparum)
22PATHOGENESIS OF “MALARIA” Primary attack► Infected erythrocyte rupture products of schizont, stimulate the release of cytokines (TNF) paroxysm (shiver, fever, sweat)
23PATHOGENESIS OF “MALARIA Relapse► It is a recurrence that taken place after complete initial clearing of the erythrocytic infection and implies reinvation of the blood stream by merozoites from activated hypnozoites in liver.
24PATHOGENESIS OF “MALARIA Recrudescence► It is a recurrence of symptoms in a patient whose blood stream infection has previously been at such a low level as not to be clinically demonstrable or cause symptoms.
25Complications Of “MALARİA” ► AnemiaHemolysis of infected erythrocytesHypersplenismAutoimmunization of uninfected erythrocytesTNF-► Splenomegaly:► Malarious nephrosis► Cerebral malaria
26Diagnosis of “Malaria” ► 1.Parasite; Species; Density*Thin blood films (species identification)*Thick blood films
27Diagnosis of “Malaria” ► 2 Immuno-diagnosis*Specific antibody detection *Antigen detection*Specific DNA or RNA detection
28Treatment 1. Treatment by classes of antimalarial drugs ► 1) Blood schizonticides (quinine; chloroquine; artemisinin; mefloquine; sulfadoxin-pyrimethamine)-Effect on erythrocytic stage, use for acute attack.
29Treatment ► 2) Tissue schizonticides (Primaquine) -Effect on the stages in liver (including hypnozoite), use for prevent relapse (radical cure) of P.v or P.o malaria
30Choice of drugs1) Treatment of vivax, malariae, ovale and chloroquine-sensitive falciparum malaria: chloroquine2) Radical cure of vivax or ovale malaria: chloroquine + primaquine3) Treatment of chloriquine-resistant falciparum malaria: artemisinin or mefloquine or quinine
31Transmission and prevention ► Factors of transmissionSuitable species of anopheles (60 species are considered to be vectors of malaria, major vectors in China:A. sinensis, A. minimus)
32Transmission and prevention Breaking the human-mosquito-human cycle1) Control of the source of infection by chemotherapy2) Control of transmission route:residual insecticides, avoidance of infected mosquitoes
33Transmission and prevention 3) Chemoproplylaxis Taking suppressive drugs, beginning one week before travel to endemic area and continuing until 6 weeks after return4) Malaria vaccines
34TRYPANASOMA► Trypanosomes infect a variety of hosts and cause various diseases, including the fatal disease SLEEPING SICNESS in humans. These deadly parasites mostly live in the blood and tissue fluids but can also inhabit intracellular locations in the host's body as well.
36Life cycle► < Infection occurs when infected metacyclic trypomastigotes enter the body through wound openings or mucous membranes.► < The trypomatigotes enter various cells, differentiate into amastigotes and multiply intracellularly.
37Life cycle► < The amastigotes differentiate into trypomastigotes which are then released back into the bloodstream.► < The life cycle is continued when a reduviid bug feeds on an infected person and ingests trypomastigotes in the blood meal.
39TRYPANASOMA► Human African Trypanosomiasis, also known as sleeping sickness, is a vector-borne parasitic disease.► The parasites concerned are protozoa belonging to the Trypanosoma Genus.► They are transmitted to humans bytsetse fly (Glossina Genus) bites which have acquired their infection from human beings or from animals harbouring the human pathogenic parasites.
41TRYPANASOMA► Sleeping sickness occurs only in sub-SaharanAfrica in regions where there are tsetse flies thatcan transmit the disease.► For reasons that are so far unexplained, there are many regions where tsetse flies are found, but sleeping sickness is not.
42TRYPANASOMA► Sleeping sickness generally occurs in remote rural areas where health systems are weak or non-existent. The disease spreads in poor settings. Displacement of populations, war and poverty are important factors leading to increased transmission.► The disease develops in areas whose size can range from a village to an entire region. Within a given area, the intensity of the disease can vary from one village to the next
43TRYPANASOMAHuman African Trypanosomiasis takes two forms, depending on the parasite involved.1.form► Trypanosoma brucei gambiense (T.b.g.) is found in west and central Africa. This form represents more than 90% of reported cases of sleeping sickness and causes a chronic infection.► A person can be infected for months or even years without major signs or symptoms of the disease. When symptoms do emerge, the patient is often already in an advanced disease stage when the central nervous system is affected.
44TRYPANASOMA2.Form► Trypanosoma brucei rhodesiense (T.b.r.) is found in eastern and southern Africa. This form represents less than 10% of reported cases and causes an acute infection.First signs and symptoms are observed after a few months or weeks. The disease develops rapidly and invades the central nervous system.
45TRYPANASOMAAnother form of trypanosomiasis occurs in 15 Central and South American countries. It is known as :American Trypanosomiasis or “Chagas disease”. The causal organism is a different species from those causing the African form of the disease.
46Symptoms of “Sleeping Sicness” The disease is transmitted through the bite of an infected tsetse fly. At first the trypanosomes multiply in subcutaneous tissues, blood and lymph. In time, the parasites cross the blood-brain barrier to infect the central nervous system. The process can take years.
47Symptoms of “Sleeping Sicness” ► The first stage of the disease, known as a “haemolymphatic phase”, entails bouts of fever, headaches, joint pains and itching.► The second stage, known as the “neurological phase”, begins when the parasite crosses the blood-brain barrier and invades the central nervous system .
48Symptoms of “Sleeping Sicness ► In general this is when the signs and symptoms of the disease appear: confusion, sensory disturbances and poor coordination. Disturbance of the sleep cycle, which gives the disease its name, is an important feature of the second stage of the disease.► Without treatment, sleeping sickness is fatal.
49DiagnosisDiagnosis must be made as early as possible and before the neurological stage in order to avoid complicated, difficult and risky treatment procedures.Diagnosis follows a three-step pathway► Screening► Diagnostic confirmation,► Staging.
50Diagnosis► ► Diagnostic confirmation then relies on the finding of trypanosomes in the blood, lymph nodes, or cerebrospinal fluid (CSF). Unfortunately, it is estimated that 20 to 30% of patients are missed by the standard parasitological techniques
51Treatment First stage treatments Pentamidine: discovered in 1941, used for the treatment of the first stage of T.b. gambiense sleeping sickness.Suramin: discovered in 1921, used for the treatment of the first stage of T.b. rhodesiense.
52Treatment Second stage treatments Melarsoprol: discovered in 1949, it is used in both forms of infection.Eflornithine: this molecule, less toxic than melarsoprol, was registered in It is only effective against T.b. gambiense.
53BABESIA► Babesia is a protozoan parasite of the blood that causes a hemolytic disease known as Babesiosis.► Babesia microti and Babesia divergens are the two species to most frequently infect humans
54BABESIA SP ► There are >100 specicies of this intracellular parasite.► Babesia microti is the predominant human pathogen,endemic to the Midwest.► 10-20% of adults are seropositive in endemic areas► Natural parasite reservoir is rodents► Carried by the hard-bodied Ixodes Deer tick.► Also carries agents for Lyme Disease, andEhrlichoisis.► Can also be transferred transplacentally and throughblood transfusion.
55Babesia in erythrocyts Presence of 4 daughter merozoites in a tetrad .Never seen in malaria.
56Clinical presentation ► Ranges from asymptomatic infection to fatal illness (rare)► No direct correlation between parasitemia and severity.► More severe infection tends to occur in immunnocompromised, elderly, and the very young.
57Clinical presentation ► The extreme end of the spectrum is often described as a malaria-like infection; symptoms may include malaise, chills, mylagia, anemia, fatigue, and fever .Some cases also described emesis,night sweats, weight loss, and hematuria.
58Life cycle► The trophozoite is very similar to the ring form of the Plasmodium species► The organism (sporozoite) is transmitted by a tick and enters the red cell where it undergoes mitosis and the organisms (merozoite) are released to infect other red cells. Ticks acquire the organism during feeding on an infected individual. In the tick, the organism divides sexually in the gut and migrates into the salivary gland
60Special Case – Splenectomy ► Illness appears suddenly, with hemoglobinuria as the presenting symptom followed by jaundice due to severe hemolysis.► Parasitemia can reach 80% of RBCs► Can be a medical emergency.► In the most severe cases, patients develop a shock-like picture, with renal failure and pulmonary edema.► Chronic disease with many relapses over months to years may occur if not treated.
61Co-Infection► It is estimated from serologic surveys that as many as 13% of Lyme disease patients in babesia-endemic areas are coinfected with B. microti► The initial symptoms of both babesiosis and Lyme disease overlap significantly.► Like babesiosis, Lyme disease also presents with nonspecific symptoms of fever,fatigue, and other flu-like symptoms.► Patients coinfected with B. microti and B. burgdorferi experience more severe symptoms, but does not increase the duration of Babesia parisitemia.► Doxycycline will not kill Babesia.
62Diagnosis history of exposure. used . ► Diagnosis is based on clinical suspicion andhistory of exposure.► Thick and thin smears remain most clinicallyused .► Various PCR detection assays are availablefor detection of B microtic and other species.► Indirect fluorescent antibody test can also beused as a confirmatory test.► Can have false negatives (HIV) or false pos(autoimmune)
63Treatment► Current treatment is Quinine plus Clindamycin► 72% receiving quinine and clindamycin had side effects attributed to the drugs—diarrhea, tinnitus, or vertigo► 15% receiving atovaquone plus azithromycin experienced side effects (usually diarrhea or rash).► For severe cases (asplenic) with high levels of parasitemia, RBC exchange transfusions may also be necessary.