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The "six" kingdom taxonomic scheme. Image from Purves et al.

, Life: The Science of Biology, 4th Edition, by Sinauer Associates (www.sinauer.com) and WH Freeman (www.whfreeman.com),

PROTOZOA (Animal-like Protists)


Kingdom: Protista Phylum: Sarcomastigophora Subphylum: Mastigophora
mastigo = whip = flagellates

Genera: Trypanosoma, Leishmania, Giardia, Trichomonas

(Sarcodina (amoebae)

Entamoeba, Naegleria, Acanthamoeba


Plasmodium, Toxoplasma, Cryptosporidium, Isospora Balantidium

Apicomplexa

Ciliophora

Klasifikasi
Kingdom :Protista Phylum :Apicomplexa Class :Aconoidasida Order :Haemosporida Family :Plasmodiidae Genus :Plasmodium Species :.
Stephens 1922

MALARIA

Ecological Niches in the Human Body:

Skin Eye Mouth

: Leishmania : Acanthamoeba : Amoebae and flagellates (usually nonpathogenic) Gut : Giardia, Entamoeba (and invasion to liver), Cryptosporidium, Isospora, Balantidium G.U. tract : Trichomonas Bloodstream: Plasmodium, Trypanosoma Spleen : Leishmania Liver : Leishmania, Entamoeba Muscle : Trypanosoma cruzi CNS : Trypanosoma, Naegleria, Toxoplasma, Plasmodium

What is malaria?
Malaria is a serious and sometimes fatal disease caused by a parasite. Patients with malaria typically are very sick with high fevers, shaking chills, and flu-like illness. Four kinds of malaria parasites can infect humans: Plasmodium falciparum, P. vivax, P. ovale, and P. malariae.

Infection with any of the malaria species can make a person feel very ill; infection with P. falciparum, if not promptly treated, may be fatal. Although malaria can be a fatal disease, illness and death from malaria are largely preventable.

Nama, Penyebab dan Sejarah Malaria

Kata "malaria" berasal dari bahasa Itali "Mal" yang artinya buruk dan "Aria" yang artinya udara, sehingga "malaria" berarti udara buruk (bad air). Hal ini disebabkan oleh karena malaria terjadi secara musiman di daerah yang kotor dan banyak tumpukan air. Malaria disebabkan oleh parasit yang ditularkan oleh nyamuk Anopeles betina. Pada tahun 1938 malaria telah diatasi dengan memberikan getah chincona (kina) kepada penderita malaria Pada tahun 1950an, dilakukan program pengendalian malaria menggunakan residu pestisida. Program ini sukses melenyapkan malaria di benua Eropa dan Amerika Malaria di Indonesia: Prevalensi Malaria di Indonesia adalah 50 per 1000 penduduk (2004) dan ditargetkan turun hingga 5 per 1000 penduduk tahun 2010 (Indonesia Sehat 2010) Daerah endemik malaria (tingkat tinggi): NTB, NTT, Papua, Manado, Palu, Kaltim dan Samarinda (2001)

Is malaria a common disease?


Yes. The World Health Organization estimates that each year 300-500 million cases of malaria occur and more than 1 million people die of malaria.

MALARIA
40% of the worlds population lives in endemic areas 3-500 million clinical cases per year 1.5-2.7 million deaths (90% Africa) increasing problem (re-emerging disease)
resurgence in some areas drug resistance ( mortality)

causative agent = Plasmodium species


protozoan parasite member of Apicomplexa 4 species infecting humans

P. falciparum P. vivax P. malariae P. ovale

transmitted by anopholine mosquitoes

Is malaria a serious disease?


Yes. Malaria is a leading cause of death and disease worldwide, especially in developing countries. Most deaths occur in young children. For example, in Africa, a child dies from malaria every 30 seconds.

Biological characteristics
Sporozoa (without conspicuous locomotory organelles) Complicated life cycle: 1) Two types of hosts 2) Multiple stages 3) Human infection is caused by bite of an infected female mosquito.

Structure

In Human body
1 Exoerythrocytic stage - schizogony ) (in liver) 2 Erythrocytic stage - schizogony (in blood) 3 Formation of gametocytes

In mosquito
1 Completion of gametogony 2 Sporogony

Life cycle

The malaria parasite life cycle involves two hosts. During a blood meal, a malariainfected female Anopheles mosquito -inoculates sporozoites into the human host

Sporozoites - infect liver cells and mature into schizonts, which rupture and release merozoites

Merozoites - infect red blood cells . The ring stage trophozoites mature into schizonts, which rupture releasing merozoites

Some parasites differentiate into sexual erythrocytic stages (gametocytes)

Blood stage parasites are responsible for the clinical manifestations of the disease.

In mosquito

The gametocytes, male (microgametocytes) and female (macrogametocytes), are ingested by an Anopheles mosquito during a blood meal

The parasites multiplication in the mosquito is known as the sporogony.


In the mosquitos stomach, the microgametes - penetrate the macrogametes - generating zygotes

The zygotes in turn become motile and elongated (ookinetes) which invade the midgut wall of the mosquito where they develop into oocysts

The oocysts grow, rupture, and release sporozoites, which make their way to the mosquitos salivary glands

Inoculation of the sporozoites into a new human host perpetuates the malaria life cycle .

SIKLUS HIDUP

FASE ASEKSUAL (SKIZOGONI) FASE SEKSUAL (SPOROGONI)

Life Cycle
sporozoites injected during mosquito feeding invade liver cells exoerythrocytic schizogony (merozoites) merozoites invade RBCs repeated erythrocytic schizogony cycles gametocytes infective for mosquito fusion of gametes in gut sporogony on gut wall in hemocoel sporozoites invade salivary glands

Sporogony
occurs in mosquito (9-21 d) fusion of micro- and macrogametes zygote ookinete (~24 hr) ookinete transverses gut epithelium ('trans-invasion')

Life Cycle

1* The sporozoite is infective stage.

2* There are two kinds of sporozoites, tachysporozoite and brady-sporozoite 3* When the brady-sporozoites get into the liver cells , they undergo dormancy and called hypnozoites

Exflagellation

The process of male gametocyte to form male gamete.

Morphology

Malarial parasite trophozoites are generally ring shaped, 1-2 microns in size, although other forms (ameboid and band) may also exist. The sexual forms of the parasite (gametocytes) are much larger and 7-14 microns in size. P. falciparum is the largest and is banana shaped, while others are smaller and round.

Morphology
Ring form: (Plasmodium vivax ) a ring of bluish cytoplasm with a dot-like nucleus

Trophzoite of Plasmodium vivax

irregular cytoplasm and enlarged nucleus with malarial pigment ( hemozoin)

Gametocytes

Male gametocyte

Female gametocyte

Note: compact cytoplasm and absence of nuclear division.

Ring form of P. falciparum

Ring with double nuclei

Multiple infections

Gametocyte of P. falciparum

banana shaped gametocyte ( P. falciparum)

Trophozoites of P.malariae

band-like or elliptic

In peripheral blood, every erythrocytic stages can be found in P. vivax and P. malariae infections. Only ring forms and gametocytes can be found in P. falciparum infection. Other stages of P. falciparum do not appear in the blood. (they hide in deep tissues)

Pathogenesis
Paroxysm Cold stage
Fever (39- 41degrees C ) Profuse perspiration and the temperature begins to drop. Within a few hours the patient feels exhausted but symptom-less and remains symptomatic until the next paroxysm

Malaria Paroxysm
paroxysms associated with synchrony of merozoite release between paroxysms temperature is normal and patient feels well falciparum may not exhibit classic paroxysms (continuous fever) tertian malaria quartan malaria

2 Typical symptoms Chilly stage (30min 1 hr, cold and shivering) hot stage (1-4 hr, intense heat and delirium

sweating and crisis stage (1-2 hr)copious perspiration Three successive stages Fever is associated with severe headache, nausea (vomiting) and convulsions

3 The mechanism of the paroxysm


Rupture of R B Cs (schizonts)

merozoites, metabolic substances, hemozoin engulfed by white cells and monocytes

to produce

pyrogens

temperature regulating center(hypothalamus)

Fever

Bila ada infeksi atau zat asing masuk ke tubuh akan merangsang sistem pertahanan tubuh dengan dilepaskannya pirogen. Pirogen adalah zat penyebab demam, ada dua -- berasal dari dalam tubuh (pirogen endogen) dan luar tubuh (pirogen eksogen) yang bisa berasal dari infeksi oleh mikrooganisme atau merupakan reaksi imunologik terhadap benda asing (noninfeksi). Pirogen selanjutnya membawa pesan melalui alat penerima (reseptor) yang terdapat pada tubuh untuk disampaikan ke pusat pengatur panas dihipotalamus. Dalam hipotalamus pirogen ini akan dirangsang pelepasan asam arakidonat serta mengakibatkan peningkatan produksi prostaglandin (PGE2). Ini akan menimbulkan reaksi menaikkan suhu tubuh dengan cara menyempitkan pembuluh darah tepi dan menghambat sekresi kelenjar keringat. Pengeluaran panas menurun, terjadilah ketidakseimbangan pembentukan dan pengeluaran panas.

4 Relapse Some patients relapse back in to disease weeks, months even years after the apparent cure. (The cause of relapse is hypnozoite activation) 5 Recrudenscence The paroxysm appears in some patients after inadequate or incomplete treatment. ( The cause is the remained erythrocytic stage multiplication )

What are the signs and symptoms of malaria? Symptoms of malaria include fever and flu-like illness, including shaking chills, headache, muscle aches, and tiredness. Nausea, vomiting, and diarrhea may also occur. Malaria may cause anemia and jaundice (yellow coloring of the skin and eyes) because of the loss of red blood cells. Infection with one type of malaria, Plasmodium falciparum, if not promptly treated, may cause kidney failure, seizures, mental confusion, coma, and death.

Incubation Period

Following the infective bite by the Anopheles mosquito a period of time (the "incubation period") goes by before the first symptoms appear. The incubation period in most cases varies from 7 to 30 days. The shorter periods are observed most frequently with P. falciparum and the longer ones with P. malariae.

Uncomplicated Malaria

The classical (but rarely observed) malaria attack lasts 6-10 hours. It consists of a cold stage (sensation of cold, shivering) ; a hot stage (fever, headaches, vomiting; seizures in young children) and finally a sweating stage (sweats, return to normal temperature, tiredness)

Classically (but infrequently observed) the attacks occur every second day with the "tertian" parasites (P. falciparum, P. vivax, and P. ovale) and every third day with the "quartan" parasite (P. malariae).

beberapa bentuk manifestasi


= Penghancuran sel-sel darah merah mengakibatkan penderita menjadi anemis, hati dan limpa membesar, sumbatan-sumbatan pada pembuluh kapiler darah dapat menyebabkan kerusakan pada organ yang sangat sensitif terhadap kekurangan suplai darah, seperti otak dan sebagainya Ada beberapa bentuk peyakit malaria, antara lain : Malaria tertiana, disebabkan oleh Plasmodium vivax, demam muncul setiap hari ketiga. Malaria quartana, disebabkan oleh Plasmodium malariae, demam setiap hari keempat. Malaria serebral, disebabkan oleh Plasmodium falciparum, demam tidak teratur, disertai gejala terkenanya otak, koma dan kematian yang mendadak. Malaria pernisiosa, disebabkan oleh Plasmodium vivax, gejala dapat timbul sangat mendadak, mirip stroke, koma disertai gejala malaria yang berat

More commonly, the patient presents with a combination of the following symptoms: Fever Chills Sweats Headaches Nausea and vomiting Body aches General discomfort

Severe Malaria

Severe malaria occurs when P. falciparum infections are complicated by serious organ failures or abnormalities in the patient's blood or metabolism

Cerebral malaria, with abnormal behavior, impairment of consciousness, seizures, coma, or other neurologic abnormalities Severe anemia due to hemolysis (destruction of the red blood cells) Hemoglobinuria (hemoglobin in the urine) due to hemolysis Pulmonary edema (fluid buildup in the lungs) or acute respiratory distress syndrome (ARDS), which may occur even after the parasite counts have decreased in response to treatment Abnormalities in blood coagulation and thrombocytopenia (decrease in blood platelets) Cardiovascular collapse and shock

Other manifestations
Acute kidney failure

Hyperparasitemia, where more than 5% of the red blood cells are infected by malaria parasites
Metabolic acidosis (excessive acidity in the blood and tissue fluids), often in association with hypoglycemia Hypoglycemia (low blood glucose). Hypoglycemia may also occur in pregnant women with uncomplicated malaria, or after treatment with quinine.

Malaria Relapses

In P. vivax and P. ovale infections, patients having recovered from the first episode of illness may suffer several additional attacks ("relapses") after months or even years without symptoms. Relapses occur because P. vivax and P. ovale have dormant liver stage parasites (hypnozoites)that may reactivate.

Malaria during pregnancy(especially P. falciparum) may cause severe disease in the mother, and may lead to premature delivery or delivery of a low-birth-weight baby.

Clinical manifestations
1 Anemia 2 Splenomegaly 3 Cerebral malaria 4 Malaria nephropathy (nephrosis) 5 Congenital malaria usually fatal 6 black water fever

Malaria Vaccines
1 Anti-sporozoite vaccines 2 Anti-asexual blood stage vaccines 3 Transmission-blocking vaccines Vaccines are being developed and tried but none is available yet for routine use .

Diagnosis

Diagnosis is based on symptoms and detection of parasite in Giemsa stained blood smears. There are also antibody tests (left).

Control and treatment


Treatment: 1 Cloroquine, Qinghaosu, etc. (blood cycle) 2 Primaquine, Pyrimethamine,etc.(liver stage) 3 Primaquine.(Gametocytes) Mosquito control Malaria supervision

Pencegahan Malaria

Ada 3 cara untuk mencegah malaria 1. Mencegah dari gigitan nyamuk, dengan cara: a. Tidur dengan menggunakan kelambu (biasa/insektisida) b. Tutup jendela ketika tidur c. Oleskan cairan pencegah gigitan nyamuk

2. Kontrol Perkembangan Nyamuk a. 3M b. Memelihara binatang (Ikan) untuk membunuh larva nyamuk c. Taburkan insektisida khusus untuk membunuh larva nyamuk 3. Bunuh nyamuk dewasa a. Semprot ruangan dengan insektisida sebelum tidur b. Berpartisipasi dalam kegiatan penyemprotan yang diberikan oleh tenaga kesehatan 4. Khusus wanita hamil : selama kehamilan berjalan harus mengkonsumsi obat anti malaria