Bagaimana dengan amebiasis? Pernahkah kawan mendengarnya? Amebiasis dapat diartikan sebagai penyakit infeksi di usus besar yang disebabkan oleh parasit intestinal, Entamoeba histolytica. Penularannya secara fecal-oral baik secara langsung atau tidak langsung. Langsung berarti melalui tangan yang telah menyentuh feses atau tidak langsung melalui makanan atau minuman yang telah tercemar oleh E. histolytica. Amebiasis ini nantinya dapat berkembang menjadi liver abses.
Baik malaria dan amebiasis ini sering terjadi di negara-negara tropis. Oleh karena itu, ada baiknya kita mengetahui sedikit tentang pengobatan penyakit ini. Berikut adalah sedikit obat-obatan sehubungan dengan malaria dan amebiasis. Silahkan dibaca... ^^
CHAPTER II
CONTENT
2.1 Malaria
Malaria is characterized by periodically fever, anemia, and splenomegay.2 The incubation of Plasmodium depends on the types of Plasmodium. The incubation period of Plasmodium falciparum is between 9 until 14 days, Plasmodium vivax is between 12 until 17 days, Plasmodium ovale is between 16 – 18 days, and Plasmodium malariae is between 18 until 40 days. The prodormal signs usually appear before the fever, such as malaise, headache, anorexia, stomachache, and chill.
The classic sign of malaria is called Trias Malaria. There are chill, fever, and sweat. In chill period, the patient usually wrap himself then it is followed by increasing of temperature (fever period). In fever period, the patient has high temperature for hours with red face and tachicardia. In sweat period, the temperature reduce with sweat and the patient feels healthy.
Anemia and splenomegaly are usual sign in malaria. Anemia is caused by erythrolysis caused by parasites, temporary obstacle of erythropoiesis, hemolysis caused by complement mediated immune complex, erythrophagocytosis, obstacle in expendituring reticulocyte, and effect of cytokines.2 The splenomegaly occurs on the third day after infection with pain and hyperemia.
The diagnose of malaria need an acurate anamnesis, if the patient came from endemic region of malaria, or history of travelling to endemic region of malaria, or the medicine history of the patient. From the physical examination, it is found the trias malaria with the clinical manifestation that has been explained above. However, fever is the most sign of malaria that can be found in other viral or bacterial infection. The supportive examinations are giemsa-stained thick and thin smears, antigen detection, and serology testing. Giemsa-stained need to be applied arround 3 times. Once the result giemsa-stained says negative, it does not mean malaria can be excluded from diagnosis. If 3 times giemsa-stained said it was negative, the malaria could be excluded from diagnosis.2
According to Buku Ajar Ilmu Penyakit Dalam, there are four principles to treat patient with malaria. First, the degree of severity. Patient with uncomplicated malaria (there is no complication) can be treated with oral drugs. Patient with severe malaria is treated with parenteral drugs. Second, patient with malaria have to be get an effective treatment, no failure in treatment, and prevent the transmission by using Artemisinin base Combination Therapy (ACT). Third, ACT treatment have to be based on possitive result of malaria examination and follow up treatment. The last, non-ACT drugs are used to treat patient with malaria based on clinical manifestation or without further examination.
The drugs of malaria generally can be divided into two groups, Artemisinin base Combination Therapy (ACT) and non-ACT drugs.
1. Artemisinin base Combination Therapy (ACT)
The artemisinin group of drugs was discovered in China. A crude extract of the wormwood plant Artemisia annua (qinghao) was first used as an antipyretic 2000 years ago, and its specific effect on the fever of malaria was reported in the 16th century.3 Artemisinin derivate active against asexsual form of four types Plasmodium that infect human. Antiparasitic
effects on the younger ring-form parasites lead to their clearance and prevent development to the more mature pathogenic forms that induce the parasitized erythrocytes to adhere to uninfected cells (rosetting) or to vascular endothelium (cytoadherence).4 First, heme iron within the parasite catalyzes cleavage of the endoperoxide bridge. This is followed by rearrangement to produce a carbon-centered radical that alkylates and
damages macromolecules in the parasite. This group also active against gametosit form of plasmodium but it does not affect either the primary or latent liver stage.
When used alone, the artemisinins are associated with a high level of parasite recrudescence; the reason for this is not clear but may be related to their rapid metabolism or perhaps to a postantibiotic-like effect on the parasite.5 Artemisinins should not be used for prophylaxis because of their short half-life, incompletely characterized safety in healthy subjects, and unreliability when used alone.
The routes of artemisinins and derivates can be oral for artemisinin, dihydroartemisinin, artesunate, and artemether, intramuscular for artesunate and artemether, intravenous for artesunate, and rectal for artemisinin, dihydroartemisinin, and artesunate. For the combination, artemisinin and derivates can be divided into 2, there are fixed dose and non fixed dose. The example of fixed dose is Co-Artem, combination between artemether 20 mg and lumefantrine 120 mg, 4 tablets twice a day for 3 days.2 The examples of non fixed dose are combination between artesunat and mefloquine, artesunat and amodiaquine, artesunat and chlorowuine. From many combinations, in Indonesia there is artesunate and amodiaquine combination that is called artesumoon. The dose for adult is artesunate (50 mg / tablet) 200 mg on the first until the third day (4 tablets) and amodiaquine (200 mg / tablets) 3 tablets on the first and second day and 1,5 tablets on the third day.2
2. Non-ACT drugs
There are some non ACT drugs, for example chloroquine, quinine, mefloquine, primaquine, and pyrimethamine. The detail will be explained below.
1. Chloroquine
The drug is effective against all four types of malaria with the exception of chloroquine-resistant P. falciparum. Chloroquine appears to work by intercalation with DNA, inhibition of heme polymerase or by interaction with Ca++ calmodulin mediated mechanisms. It also accumulates in the parasite’s food vacuoles, where it inhibits peptide formation and phospholipases, leading to parasite death. The absorption of chloroquine from the gastrointestinal tract is rapid and complete. Chloroquine also can be used prophylactically in areas where resistance does not exist. The dose for adult is 4 tablets on first and second day and 2 tablets on the third day.2 Chloroquine can cause gastrointestinal irritation, skin rash, and headache at low dose, but at high dose it can cause severe skin lession, peripheral neurophaties, myocardial depression, retinal damage, auditory impairment, and toxic psychosis.
2. Quinine
Quinine is used to treat patient with Plasmodium falciparum infections that resistant to chloroquine. It blocks DNA proliferation and transcription to RNA. It usually combined with doxycycline to shorten the duration of therapy and limit toxicity. Quinine is rapidly absorbed following oral ingestion and metabolized before renal excretion. In severe malaria, the isomer of quinine, quinidine, is given intravenously. It should not use for prophylaxis to delay the resistant of this drug. Cinchonism describes the toxic state induced by excessive plasma levels of free quinine. Symptoms include sweating, ringing in the ears, impaired hearing, blurred vision, nausea, vomiting, and diarrhea.
3. Mefloquine
Mefloquine is used both prophylactically and acutely against resistant Plamodium falciparum malaria. It is ineffective against the liver stage of Plasmodium vivax malaria. The mechanism is still unknown. It can be given orally. It can cause gastrointestinal distress, skin rash, headache, and dizziness. In high dose it can cause neurologic symptoms and seizures.
4. Primaquine
Primaquine is an important antimalarial because it is essentially the only drug effective against the liver (exoerythrocytic) forms of the malarial parasite. The drug also kills the gametocytes in all four species of human malaria. Primaquine is relatively ineffective against the asexual erythrocyte forms. It work by which 8-aminoquinolines exert their antimalarial effects is thought to be through a quinoline–quinone metabolite that inhibits the coenzyme Q–mediated respiratory chain of the exoerythrocytic parasite. Primaquine is given orally and readily absorbed from the gastrointestinal tract. For patient with P. Falciparum it is given in single dose 45 mg (3 tablets) and for patient with P. Vivax it is given 15 mg / day for 14 days.2 In individuals with a genetically determined glucose 6-phosphate dehydrogenase deficiency, primaquine can cause lethal hemolysis of red cells. In high dose or prolonged use, it can cause gastrointestinal distress, nausea, headache, pruritus, and leukopenia.
5. Sulfadoxine-Pyrimethamine
Sulfadoxine-pyrimethamine is used to treat patient with P. Falciparum infections. It is not effective against P. Vivax infections. The pyrimethamine inhibit the parasite’s ability to synthesize folic acid. Parasites cannot use preformed folic acid and therefore must synthesize p-aminobenzoic acid (PABA), pteridine, and glutamic acid. The sulfadoxine inhibit the initial step whereby PABA and the pteridine moiety combine to form dihydropteroic acid. The combination has antimalarial effect through the sequential blockade of two steps in folic acid synthesis. It is given orally 3 tablets single dose for adults.2 It can cause skin rashes, gastrointestinal distress, hemolysis, kidney damage, and in high dose cause folic acid deficiency.
Beside drug therapy, the pastient should get follow up treatment to see if there is drug resistant or not. The important one is to do the prevention. There are A, B, C, and D strategies to prevent malaria.6
1. Awarness of risk
Knowing the types of Plasmodium that are live the most in an area and knowing the area where has the highest cases. Prepare the preventive medicine when go to endemic area.
2. Bite avoidance
Bite avoidance can be perform by cover the doors and windows with gauze. Using air conditioner is also good. Spray the room with an insecticide before entering to kill any mosquitoes that have got inside during the day. Mosqito net should be used around the bed, impregnated with an insecticide such as pyrethrum or permethrine.
3. Chemoprophylaxis
Some drugs can be used for prophylaxis, for examples are choloroquine, mefloquine, and pyrimethamine. Chloroquine is used for prophylaxis in area that is still not resistant to this drug. Quinine should not be used as prophylaxis to delay the resistant.
4. Diagnosis is made promptly with early treatment
The prompt diagnosis is important to prevent the severe case of malaria and reduce the mortality caused by malaria.
2.2 Amebiasis
Amoebiasis can be classified into some groups, there are carrier, mild amoebiasis, moderate amoebiasis, severe amoeba dysentery, and chronic amoeba dysentery. In carrier, there is no symptom because amoeba is in the lumen of colon and does not invaded to the intestinal wall.2 In mild amoebiasis, it is found flatulence and pain on stomach, mild diarrhea about 4 – 5 times a day, feces with blood and mucus, pain on sigmoid area, sometimes with mild fever and mild hepatomegaly. In moderate amoebiasis, the symptoms are more severe and there are fever and hepatomegaly. In severe amoeba dysentery, the patient get diarrhea with a lot of blood and mucus more than 15 times a day, high fever (40 – 40,5 degrees Celcius), nausea, and anemia. In chronic amoeba dysentery, the symptoms are the same as mild amoebiasis, usually the patient show neurasthenia.
The diagnosis is made by clinical manifestation and laboratory examination. Some laboratory examination that can be applied are feces examination, colon rontgen, sigmoidoscopy, colonoscopy, and serology test. In feces examintion of patient without diarrhea, it is found cyst of E. histolytica. In microscopic feces examination, it is found trophozoit. The feces examination is conducted 3 times in a week before the patient get the treatment. The feces of amoebiasis patient does not contain much leucosites. Colon rontgen is not helpfull because the ulcers usually are not seen.2 Sigmoidoscopy and colonoscopy help to diagnose patient with disentery symptoms when there is not found amoeba in the feces. Serology test to help diagnose amoeba liver abscess.
The amoeba in amoebiasis can be found in many area of colon, such as lumen of colon, in the intestinal wall, or outside the intestinal wall. The single therapy can not effectively work in all side of those areas, therefore it is needed combination therapy. The treatmen depends on the invasiveness of the amoeba. Therapy for invasive infection differs from therapy for noninvasive infection. Noninvasive infections may be treated with paromomycin, while nitroimidazoles, particularly metronidazole, are the mainstay of therapy for invasive amebiasis.7 The treatment is diferentiated by the condition of the patient :
1. Asymptomatic or carrier
Carrier patient should be treated by luminal agents. Oral drugs that are effective against luminal infection include diloxanide furoate (available only through the Centers for Disease Control and Prevention; causes frequent gastrointestinal disturbances and rare diplopia), paromomycin (rarely causes ototoxicity and nephrotoxicity but frequently causes gastrointestinal disturbances), and iodoquinol (rarely causes optic neuritis and atrophy with prolonged use).8
· Diloxanide furoate
Diloxanide furoate is an amebicide that is effective against trophozoites in the intestinal tract. It is coverted in the gut to the diloxanide freebase form, which is the active amebicide. The drug is administered only orally and is rapidly absorbed from the gastrointestinal tract and excreted in the urine. It is remarkably free of side effects, but occasionally flatulence, abdominal distention, anorexia, nausea, vomiting, diarrhea, pruritus, and urticaria occur.
· Paromomycin
Paromomycin is an aminoglycoside of the neomycin/kanamycin family that is used as an oral agent to treat E. histolytica infection.5 It is work by binding to the 30S ribosomal subunit as the second line drug. It is given orally. The adult dose is 500 mg 3 times a day for 10 days. Adverse gastrointestinal effects are common, beside that, it can cause headache, dizziness, rashes, and arthralgia.
· Iodoquinol
Iodoquinol is a halogenated 8-hydroxyquinoline derivate that is orally active luminal amebicide. Iodoquinol is absorbed from the gastrointestinal tract and is excreted in the urine as glucuronide and sulfate conjugates. For adults, the recommended dose of iodoquinol is 650 mg orally three times daily for 20 days, whereas children receive 10 mg/kg of body weight orally three times a day (not to exceed 2 g/ day) for 20 days.5 The adverse gastrointestinal effects are common but usually mild. In high dose, it can cause thyroid enlargement and neurotoxic effects.
2. Mild until severe amebiasis
Drug of choice for mild until severe amebiasis is metronidazole. Preparations of metronidazole are available for oral, intravenous, intravaginal, and topical administration, but the drug usually is absorbed completely and promptly after oral intake.5 It undergoes a reductive bioactivation of its nitro group by ferredoxin to form reactive cytotoxic products. The adult dose is 750 mg three times a day for 5 – 10 days. Therapy with metronidazole should be followed with a luminal agent, since patients are otherwise at risk of relapsing from residual infection in the intestine.8 Adverse effect of metronidazole include gastrointestinal irritation, headache, and dark color of urine.
The resistant amoeba or contraindicated metronidazole can be treated with diloxanide furoate (plus doxycycline), paromycin, or chloroquine. Chloroquine is directly toxic to E. histolytica trophozoites and is highly concentrated within the liver, making it an effective therapy for amebic liver abscess, however, it is not as effective as metronidazole.5 Chloroquine is not effective against intestinal amebiasis because it is absorbed in the small bowel and attains low concentrations in the colonic lumen and wall.
3. Amoeba liver abscess
Drug of choice of amoeba liver abscess is the same as intestinal amebiasis. Metronidazole is given orally 750 mg 3 times a day for 5 – 10 days plus diloxanide furoate and followed by chloroquine.
The resistant amoeba or contraindicated metronidazole can be treated by emetines that is followed by chloroquine plus diloxanide furoate. Emetines inhibit protein synthesis by blocjing ribosomal movement along messenger RNA. It is given parenterally. It can cause gastrointestinal distress, muscle weakness, and cardiovascular dysfunction.
The preventive action is related to individual hygiene and enviromental sanitation. Because cysts are resistant to low doses of chlorine or iodine, in developing countries water must be boiled before it is safe to drink, and raw vegetables must be washed with soap and then soaked in vinegar for 15 min before they can be eaten.8 Patient with carrier state should be treated and should not take a job as food handler. Chemoprophylaxis for traveller is not recommended. Until now, there is no specific vaccine for amebiasis.
Semoga sedikit pengetahuan ini berguna untuk kawan-kawan. Mari lawan penyakit dengan mencegahnya!!
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