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Canada: 40 Regal Road, Guelph, Ontario N1K 1B5Canada: 1287 St. Clair Avenue West, Toronto, Ontario M6E 1B8New Zealand: 206 Papanui Road, Christchurch 5U.S.A.: 1623 Military Road, #279, Niagara Falls, NY 14304-1745E-mail: How to Protect Yourself Against Malaria
Sunset — the hunt for human blood begins. From dusk to dawn the female Now that the burglar has entered your premises she is waiting in a dark corner for the Anopheles, the malaria-carrying mosquito, searches for a host to supply her with right moment to rob you of your blood. The insidious Anopheles, attracted by the blood. Blood is an absolute necessity for her because it provides the protein needed warmth of your body and the carbon dioxide you exhale, approaches silently. She for the development of her eggs, which she later deposits in her breeding place. does not hum or hover as other mosquitoes do.
She has a tiny, elegant body, measuring from 8 mm to 1 cm. She has dark spots In a moment she will land on an exposed part of your body and pull out from her on her wings, three pairs of long, slender legs and a prominent tubular proboscis proboscis her armament, consisting of six stylets. First, two needle-pointed stylets will stab your skin, then two blades bearing very fine teeth will lacerate the skin The Anopheles enters your room at night. You may recognize her by the way she like a microscopic saw, searching for a small vein. Soon she pierces the vessel with rests on the wall — she stands on her head with the tail-end of her body tilted a flexible tube, the “food canal” through which blood is conveyed into her mouth.
upwards, protruding into the air like a rocket on a launching pad. She is unlike the During the feeding, she will introduce into the wound her sixth weapon, a hollow common pests of our temperate climates, the Culicines (Culex, Aedes, etc.), which stylet containing a duct which is connected to the salivary glands. Through this duct assume a position parallel to the surface.
she injects a few drops of her saliva to act as a local anaesthetic so that you do notfeel her bite.
Simultaneously with her saliva she will introduce into your bloodstream hundreds of motile sporozoites (Gr.: sporá=sowing, seed; zõon=animal). These malariaorganisms have been multiplying in her intestine for two weeks, the result of havingbitten a person infected with malaria.
Soon she will fly away, loaded to twice her unfed weight with blood, to conceal herself in a dark corner of your room. During the forty-eight hours it takes to digestthe blood she has taken, her ovaries will completely develop and she will be readyto lay her eggs.
At sundown she will leave your room for her breeding place nearby. She can breed almost anywhere water collects — a footprint, a puddle, a tire track, even a coconutshell or a man-made container. After laying her eggs, her ovarian cycle starts again,and she may return to see you the same night. During her three-month life span shemay lay up to three thousand eggs.
This shuttling between blood source and breeding place makes malaria a “focus” disease; that is to say, its area of infective activity is localized and dependent upon the She is your enemy, because only she can harbor the human malaria parasite and radius of the flight range of the Anopheles, usually from a few hundred yards to a mile. carry it from an infected person to a new victim. In fact in East Africa the same word, The most dangerous species of Anopheles attack human victims between midnight umbu, means both malaria and mosquito. In tropical Africa alone, where half the pop- and dawn. This means you are a prime target when you are most vulnerable — asleep.
ulation is infected with malaria, she kills two million people each year, mostly children.
The unprotected international traveller pays her a heavy toll — she is responsible THE THREE LIVES OF THE MALARIA PARASITE
for infecting thousands with malaria every year. Her bite is the direct cause of death The malaria organism is a protozoan (Gr.: proto=primitive; zõon=animal), that is to for many who contract the disease in their travels. (Male mosquitoes do not bite.) say a microscopic, single-celled animal, not to be confused with a bacterium, which The twenty-six hundred species of mosquitoes are grouped into the family of belongs to the plant kingdom. The parasite has a complex life-cycle, reproducing Culicidae, of which the genera Aedes, Anopheles and Culex are the most wide- first in the liver, then in the red blood cells and finally in the mosquito. During these spread. Throughout the world, each species of Anopheles is peculiar to a localized three cycles the parasite transforms itself and emerges each time with new physical area. Of the four hundred Anopheles species, about sixty are proven carriers of the The Liver: Hiding Place of the Parasite
Mosquitoes prey on a variety of hosts — humans, monkeys, lizards, birds — The malaria organisms (sporozoites) injected into the body by the bite of the infected carrying different species of malaria parasites which in turn infect only specific hosts.
mosquito remain in the bloodstream for only a short period — see the illustration Of the approximately fifty different species of malaria parasites sharing the genetic of the Life-Cycle of the Malaria Parasite (1) — usually less than one hour. They name Plasmodium, only four infect humans: Plasmodium falciparum, the killer; the disappear from the circulation and establish themselves in the cells of the liver (2a), benign Plasmodium vivax; and the less common Plasmodium malariae and where they commence cycles of reproduction, a process lasting from six to twelve Plasmodium ovale, both benign.
days, depending on the species. This stage corresponds to the incubation period Malaria parasites are older than humankind. They have accompanied the evolution of the disease. During this time, each sporozoite grows through repeated divisions of primates throughout the geological ages from their earliest ancestors up to the of the nucleus into one large cell named schizont (Gr.: schizein=to divide; on emergence of humans. The parasites too underwent adaptive changes, and it is ontos=being), now containing thousands of tiny new parasites (2b).
believed that the Plasmodium falciparum, which causes the fatal form of human malaria, The increased pressure causes the schizont to burst and release these newly is the latest evolved species of the parasite, which the benign Plasmodium malariae, formed parasites, called merozoites (Gr.: meros=part, zõon=animal) (2c), which leave the oldest on the scale of evolution, may have been the first to invade humans.
the liver and enter the red blood cells where they initiate cycles of reproduction.
It is now well established that on entering the liver, all sporozoites of Plasmodium that of DDT) and short residual action period (two weeks only). Furthermore, some falciparum, the most dangerous of malaria parasites, and of Plasmodium malariae, Anopheles are already showing resistance to these new compounds. Because of one of the benign forms, immediately enter into a reproductive phase which exhausts these new “super Anopheles”, malaria is now making a comeback in areas previously itself after one generation. If you are harbouring an infection caused by these considered conquered. This situation puts a renewed emphasis on the mechanical parasites, suppressive medication will eliminate the parasites from the red blood cells, and because no new invasions from the liver can occur, you will be completelycured of the infection. (2a, 2b, 2c) MECHANICAL PROTECTION
However, Plasmodium vivax and Plasmodium ovale, the other two benign forms Mechanical forms of protection are still the most effective means of preventing the of parasites, enter the liver cell as two different forms of sporozoites: one strain immediately enters into a phase of reproduction (2a, 2b, 2c); and one, calledhypnozoite (Gr.: hypno=sleep, zõon=animal), lies dormant in the liver cell (2d red Window and Door Screens
cell). The hypnozoites enter into reproductive phases at different times (2e, 2f), even Ensure that the window and door screens of your room fit tightly and are free of after months or years, depending upon the species, and are therefore responsible holes. At the same time check the screens to be sure the mesh is small enough for the well-known relapses of Plasmodium vivax and Plasmodium ovale. These to prohibit the entrance of any mosquitoes.
relapses may persist for months or years, even though an antimalarial regimen hasbeen meticulously followed. The Mosquito Bed Net
In malarious areas, unscreened bedrooms require mosquito bed nets except in
The Red Cell: Life at the Expense of the Red Corpuscle
buildings with sealed windows and central air conditioning. If possible, bed nets From the liver, the merozoites enter the bloodstream and penetrate the red blood should be rectangular rather than cone-shaped to prevent skin contact with the cells (3g), where they multiply in cycles. Each merozoite, feeding at the expense netting allowing the Anopheles to bite through. Netting should be of stiff cotton or of the red cell, grows into a ring-shaped parasite called trophozoite (Gr.: synthetic thread to allow the movement of air. The net must be white to allow trophé=nourishment; zõon=animal) (3h). Upon reaching its full size (about .016 mm), mosquitoes to be seen against the background, and should have a wide, tightly each trophozoite, through repeated divisions of the nucleus, forms a schizont, a cluster woven border to be tucked under the mattress.
containing sixteen to twenty-four new oval-shaped parasites, again called merozoites A netting with twenty-six holes per square inch will prevent even the smallest (3l). When the infected red blood cells burst, the merozoites flood the circulation Anopheles from penetrating. (This figure is obtained by adding the number of holes and invade fresh red blood cells to start new cycles of reproduction (3m, n, o, p).
along the bottom line of a square inch of net and the number of holes along the These cycles repeat themselves every two to three days depending on the species.
diagonal.) Not one single tear should be permitted, since mosquitoes will spend The rhythmic release into the circulation of so many parasites — estimated at a quarter of a billion — coincides with the characteristic clinical picture of malaria: There are several good reasons for using bed nets in addition to preventive periodic high fever, preceded by shivering and followed by profuse sweating. medication.
• Because the bed net gives protection when the Anopheles is most active, chances The Mosquito: The Sexual Life of the Parasite
of infection are reduced. Some malariologists estimate that with proper use of Some merozoites are distinguished from others in that they grow in the red blood bed nets malaria cases could be reduced by two-thirds.
cell without dividing. They transform themselves into sexual cells, the male and • The bed net offers protection from other diseases transmitted by mosquitoes, such female gametocytes (Gr.: gameté=wife, gamétes=husband; kútos=cell) which are as filariasis, known for massive swelling of the limbs.
necessary for the perpetuation of the parasite (3q). However, they can mature only • Bed nets also protect against ticks, beetles, flies, bed-bugs and other insects which outside the human body, and because they cannot leave the bloodstream on their own, they need outside help — the Anopheles mosquito. During evolution an affinity To accommodate a real need for a practical bed net, IAMAT has designed La has developed between the malaria parasite and the Anopheles: the Anopheles Mosquette,TM a light-weight, portable free-standing aluminum frame and a rectan- requires blood for the protein she needs to lay her eggs, and the parasite requires a gular bed net. It is available at cost of U.S. $110.00 (CAN. $145.00) plus postage.
When the Anopheles bites an infected person, the merozoites drawn from the bloodstream are digested in the stomach of the mosquito, while the gametocytes(4q) develop in the intestine into mature cells called gametes, the female ovule andthe male spermatozoon (4r). The fertilized eggs, ookinete (Gr.: õon=egg;kinesis=motion) (4t), moves to the outside wall of the mosquito gut where, by secretinga cyst wall around itself, it develops into an oocyst (4u, v), which will give rise to a myriad of new parasites, the sporozoites. As soon as these sporozoites (4z) arereleased from the oocyst they migrate to the salivary glands of the Anopheles, waitingto be injected into the next victim. The endless cycle starts all over again.
The World of Anopheles
To visualize the mechanism of malaria transmission in a given area, one must take
into consideration the behavior of the local species of Anopheles. The knowledge of
her habits will give you a better chance to protect yourself against her bite.
Like humans, anopheline mosquitoes are concerned with food, shelter and If you are contemplating a long residency in a high risk malarious area, you might reproduction. Will she feed on humans or on domestic animals? Will she enter human like to soak your bed net in an insect repellent solution, which will impregnate the dwellings to bite or will she feed outdoors? Does she prefer to bite soon after dusk, net for up to six months. (Brand names: Coulston’s Permethrin Arthropod Repellent; late at night or at dawn? Will she use houses as a daytime resting place or will she Duranon permethrin clothing repellent; Permanone Tick Repellent). These products seek shelter in dense vegetation? Will she breed in peridomestic waters such as are available through pharmacies and out-door equipment stores). These solutions small ponds, footprints or artificial containers, or far away in large bodies of water? have proven to be very effective binding itself tightly to the fabric and remaining Different preferences characterize each species. Take for instance Anopheles effective through several washings. Outer clothing (vests, jackets, hats) may also be gambiae, the mosquito responsible for so many deaths in Africa south of the Sahara.
She chooses her breeding place a few yards from your habitation. She may even be travelling with you by car, plane or boat. In fact she once crossed the Atlantic FOUR STEPS TO MOSQUITO PROTECTION
by boat and spread misery and death along the northeastern coast of Brazil. On The following precautions require self-discipline, and should be taken every day the other hand, the main vector of malaria in the Philippines, the Anopheles minimus beginning at sunset by everyone visiting the tropics.
flavirostris, has different habits. She prefers to breed along the margins of foothillstreams and lakes, and her presence is confined to rural areas. That is why, although Step one: protective clothing
there is no malaria in large cities like Manila, there is malaria transmission in African Beginning at sunset, wear long-sleeved shirts and long trousers in light colors such as beige or yellow. Dark clothing attracts mosquitoes, as does the scent of perfume Two factors influence the reproduction of Anopheles: rainfall and temperature. The rainy season, bringing an increase in the anopheline population, will determine Step two: mosquito repellent
the annual high-risk period of malaria transmission. Lower temperatures will Apply mosquito repellent, available in sprays, lotions and towelettes, to all exposed decrease the Anopheles population and, more important, will arrest the development areas of skin, as well as thin clothes, avoiding eyes and mouth. The active ingredient of parasites in the mosquito gut. Since temperature lowers with increased altitude, keeps mosquitoes away but does not kill them. Since repellent gradually evaporates transmission of the disease is not possible over a certain height above sea level.
and some will be lost through perspiration, swimming and active exercise, re-apply (See IAMAT’s publication WORLD MALARIA RISK CHART.) every few hours accordingly to the manufacturer’s directions for continuous protec-tion. (Caution: repellent may damage plastic items such as eye-glass frames, watch The Super Anopheles
With the knowledge of the habits of the Anopheles, humans learned to fight her Step three: pyrethrin insecticides (brand name: Raid)
by poisoning her resting places with DDT. A single indoor spraying, leaving a layer Pyrethrin insecticides (active ingredient pyrethrin, extracted from the pyrethrum flower, of microscopic crystals, made surfaces lethal to mosquitoes for months. But, although a member of the chrysanthemum family) kills mosquitoes instantly by acting on the this residual insecticide reversed the odds in the struggle, within a few years the central nervous system. Frequent spraying is necessary since pyrethrin dissipates Anopheles had developed a resistance to these chemicals. Other pesticides followed, when exposed to air. Spray bed net and under the bed, as well as walls, baseboards, always with the same inglorious result. Today, forty-five species of Anopheles have corners, furniture, behind pictures and inside closets in the bedroom, and under the been reported resistant to traditional insecticides. The more recent insecticides, sink in the bathroom. Cover any food and cooking utensils. Do not open windows the carbamate compounds, are not suitable because of their high cost (ten times while spraying, and allow vapor to settle before returning to the room.
Step four: preparing your bed for the night
• Since an adequate concentration of the drug in the blood is reached a few hours During the day, the bed net should be left hanging in a knot from the ceiling. Before after ingestion, you may start the medication on the day of your departure. However, retiring lower the net and search carefully for mosquitoes hidden inside. Mend any it is advisable to start your regimen one to two weeks before leaving — while still holes or tears with adhesive tape or thread. Tuck the edge of the bed net under the at home you will acquire confidence with the drug and you can seek the advice mattress, making sure there are no openings.
of your family physician in case of any adverse reaction.
If you are camping, avoid campsites near native villages or any kind of habitation, • It would be ideal to take a complete supply of medication with you to avoid any even when empty. Before camping check surrounding area for possible Anopheles confusion which might arise in the new country.
In offering guidance on the choice of antimalarial drugs the main
concern is to provide protection against Plasmodium falciparúm
The most widely used antimalarial drugs will suppress the clinical symptoms of malaria malaria, the most dangerous and often fatal form of the disease.
but will not prevent the establishment of malaria infection. If anti-malarial drugs were The appearance of chloroquine-resistant and multi-drug-resistant
true prophylactics (Gr.: prophylasso=to guard before) they would prevent malariainfection by killing the parasites (sporozoites) the moment they are introduced into your Plasmodium falciparum in many malarious areas makes the choice of
bloodstream by the bite of the Anopheles. Instead, they act by eliminating the parasites suppressive drugs problematic as none of the medications currently
during their multiplication phase in the red blood cells (red cell cycle). Suppressive used is 100% effective. Regardless of which medication is being used
medication will eliminate the infection caused by P. falciparum and P. malariae, but for malaria prophylaxis, it is of utmost importance for travellers and
will not always prevent a delayed first attack or relapses caused by P. vivax and their physicians to consider fever and flu like symptoms appearing
P. ovale, which may appear months or years after discontinuing the suppressive drug.
seven days to 3 months after leaving a malarious area as a malaria
It is mandatory that you take the medicine at regular intervals throughout your stay in a breakthrough. Early diagnosis is essential for successful treatment of
malarious region, and you should continue to do so for 4-6 weeks after leaving the area. such an infection.
• Taking the full course of suppressants is essential even for a short stay.
Reliable information on malarious areas and a sound knowledge of Remember, one single bite is sufficient to infect you.
geography of the area to be visited, including knowledge of the feeding • If you are on a weekly regimen, always take your suppressant the same day and and breeding habits of the local anopheles mosquitoes, will help you to take at the same hour soon after your meal. Establish this as a habit so you will notforget. Take the suppressant with plenty of liquids to reduce stomach discomfort the appropriate antimalarial measures. (See IAMAT’s publication WORLD THE LIFE-CYCLE OF THE MALARIA PARASITE
Mefloquine hydrochloride is very effective for the prevention of chloroquine-resistant and multi-drug-resistant Plasmodium falciparum malaria. However, it may not always prevent a delayed first attack Travellers to areas with chloroquine-sensitive P. falciparum malaria should follow the following regimen: or relapses caused by Plasmodium vivax.
USE CHLOROQUINE (ARALEN) IN WEEKLY DOSES OF 500mg (300mg base). START ONE WEEK CAUTION: Lariam is generally well tolerated. Mild side effects include nausea, headache, dizziness. BEFORE ENTERING MALARIOUS AREA, CONTINUE WEEKLY DURING YOUR STAY AND Serious side effects such as skin rashes, seizures, psychosis, and diarrhea have been rarely reported CONTINUE FOR FOUR WEEKS AFTER LEAVING. TAKE IT AFTER A MEAL TO AVOID STOMACH when Lariam is taken for prophylaxis. CONTRAINDICATIONS: Persons suffering from coronary heart diseases, liver and kidney diseases, CHLOROQUINE (Chloroquine diphosphate (brand names: ARALEN by Winthrop, AVLOCLOR by
epilepsy or psychiatric disorders such as severe depression, should not use this drug. Lariam may ICI, RESOCHIN by Bayer); Chloroquine sulfate (brand name: NIVAQUINE by Société Spécia)
interact with beta blockers, digoxin, calcium channel blockers, metaclopramide, etc. Lariam should Chloroquine is the antimalarial drug used most commonly around the world for the suppression of not be taken concurrently with chloroquine, quinine or quinidine. If treatment of severe malaria was falciparum malaria in areas where the parasites are still sensitive to it. In case of infection, chloroquine initiated with these drugs, Lariam should not be started before an interval of 12 hours and only under will completely cure malaria caused by sensitive strains of P. falciparum. For chloroquine-sensitive close medical supervision. Lariam is contraindicated for pregnant women and children under 30 lbs.
malarious areas see IAMAT’s publication WORLD MALARIA RISK CHART.
(15 kg) in weight. If Lariam has been used for prophylaxis and a malaria breakthrough occurs, Lariam Chloroquine is also the drug of choice for the suppression of malaria caused by P. vivax, P. ovale should not be used for treatment. If Lariam is taken for longterm prophylaxis periodic liver function and P. malariae, the benign forms of the disease. Travellers should be aware that chloroquine will not tests and ophthalmic examinations should be performed.
always prevent delayed first attacks or relapses of malaria months to years after departure from Lariam is available by prescription in Canada and the U.S.A.
malarious areas even when the chloroquine regimen has been followed meticulously. Depending on ATOVAQUONE+PROGUANIL (brand name: MALARONE by GLAXO)
the strain (subspecies) of the parasite these delayed attacks develop in 30 to 70% of persons.
Atovaquone 250mg+proguanil hydrochloride 100mg is effective for the prevention of chloroquine- Inconveniences: The bitter taste makes the drug unpalatable. Minor stomach upsets, itching skin, resistant and multi-drug resistant P. falciparum malaria. It is less effective against vivax malaria, and nausea and diarrhea may occur; it may also cause blurring of vision and a transitory headache.
a malaria breakthrough with P. vivax may occur.
CAUTION: Since chloroquine is deposited in high concentration in the liver and white blood cells, it CAUTION: MALARONE may cause mild side-effects when used for prophylaxis such as stomach should be used with caution by persons with a liver condition, alcoholism or blood disorder. Patients upsets, vomiting, headaches, nausea. MALARONE should be taken with food or milk.
on phenylbutazone should discontinue this drug while taking chloroquine since it may enhance the CONTRAINDICATION: Persons suffering from renal (kidney) disorders or with known allergies to chances of dermatitis. It may also aggravate the condition of persons suffering from porphyria and atovaquone or proguanil should not use this drug. The safety of this drug in pregnancy, nursing psoriasis. Due to the adverse effect of chloroquine on the optic nerve, persons with diseases of the mothers and children weighing less than 11kg (24 lbs) has not been established.
retina and optic nerve (diabetic retinopathy, optic neuritis, etc.) should not use this drug. Persons con- MALARONE is available by prescription for prophylaxis and treatment in the U.S. In Canada it is templating a prolonged course with chloroquine should have an eye examination at least once a year available for treatment; the application for use as prophylaxis is pending.
to detect any changes in the retina. Persons with a history of epilepsy should not take chloroquine. DOXYCYCLINE (brand name: VIBRAMYCIN)
Doxycycline belongs to the tetracycline group of antibiotics and has proven effective in preventing RESISTANT P. FALCIPARUM (CRPF) MALARIA IS PRESENT BUT
malaria in multi-drug resistant areas. It is also used in combination with quinine for the treatment ofsevere and multi-drug resistant malaria.
CAUTION: Doxycycline may cause photosensitive skin reactions (avoid exposure to direct sunlight (Afghanistan, Bolivia, Tajikstan — see IAMAT’s Malaria Risk Chart) and use sun-screen with high protection against UVA (long range ultraviolet radiation) to minimize In areas with chloroquine-resistant Plasmodium falciparum (CRPF) malaria accounting for risk of photosensitive reaction). It may also cause vaginal yeast infections in women, and produce less than 20% of total malaria cases, a first-choice prophylactic regimen of chloroquine should be antibiotic-resistant pathogenic bacteria. Antibiotic associated colitis, a severe form of diarrhea, can followed. It is the drug of choice for benign forms of malaria, and it will lessen the severity of a break- also follow a prolonged use of this drug class.
through with resistant P. falciparum strains and thus prevent fatal malaria.
CONTRAINDICATIONS: Doxycycline should not be used by persons with known photosensitive skin However, in case of flu-like symptoms — general malaise, fever, headache, nausea — appearing reactions. It is contraindicated for pregnant and lactating women and children under 8 years of age.
about 7 days or later after entering the malarious area, immediate medical attention should be sought Tetracyclines permanently stain the teeth of unborn fetuses, infants and children up to eight years of age.
as these symptoms may signify a malaria breakthrough.
In case medical attention cannot be reached within 24 hours, adult individuals with no history SUPPRESSIVE MEDICATION IN AREAS WITH HIGHLY CHLOR-
of sulfonamide intolerance should take one treatment dose of three tablets of Fansidar (sulfadoxine+ pyrimethamine) carried from home as a self-treatment for the presumptive diagnosis of a malaria OQUINE FANSIDAR AND LARIAM RESISTANT P. FALCIPARUM
breakthrough. Medical attention should be sought as soon as possible. MALARIA (Border areas of Thailand–Cambodia, Thailand–Myanmar)
Persons travelling to multi-drug-resistant P. falciparum malaria areas should follow a MALARONE or TAKE CHLOROQUINE (ARALEN) IN WEEKLY DOSES OF 500mg (300mg base). START ONE DOXYCYCLINE antimalarial regimen as described above. Persons who cannot follow one of these WEEK BEFORE ENTERING MALARIOUS AREA, CONTINUE WEEKLY DURING YOUR STAY AND regimens or contemplate a long term visit to these areas should seek advice from a specialist in trop- CONTINUE FOR FOUR WEEKS AFTER LEAVING.
ical diseases for a possible alternative drug regimen. Contact IAMAT for referrals to specialists.
CARRY WITH YOU A TREATMENT DOSE OF THREE TABLETS OF SULFADOXINE- Treatment of a breakthrough of multi-drug-resistant malaria should be given under medical supervi- PYRIMETHAMINE (FANSIDAR) TO BE TAKEN IN A SINGLE DOSE OR 4 TABLETS AS A SINGLE
sion and may include a variety of drugs in different combinations. Fast medical attention is imperative DOSE DAILY FOR THREE DAYS OF MALARONE FOR THE SELF-TREATMENT OF A PRESUMED
CHLOROQUINE — see description above.
Fansidar is a very effective drug for the treatment of chloroquine-resistant Plasmodium falciparum AMODIAQUINE
malaria. At this time, it is not recommended for weekly prophylaxis because of potential serious side Amodiaquine dihydrochloride (brand names: CAMOQUINE, FLAVOQUINE)
effects which may develop after multiple doses.
Belonging to the same chemical family as chloroquine (4-Amino-quinolines) this drug offers protection Caution: Persons with known allergies or intolerance to sulfonamides should not take this drug. The similar to chloroquine, but unfortunately experience has shown that it causes serious side effects intolerance, which affects five percent of the population, becomes apparent with a skin rash, sometimes such as hepatitis and agranulocytosis. It should not be used for malaria prophylaxis.
due to photosensitivity after prolonged exposure to sunlight. Fever may develop, accompanied by itchi- ARTEMISININ, ARTEMETHER and ARTESUNATE
ness, nausea and general malaise. These symptoms will disappear when the drug is discontinued. These drugs are derivatives from the Chinese plant Qinghaosu, and are used for the treatment of Seek medical attention as soon as possible even when you have taken the stand-by treatment regimens.
multi-drug resistant P. falciparum malaria. It should not be used for prophylaxis. They are not available MALARONE — see description below.
This combination drug eliminates the difficulty of taking chloroquine on a weekly basis and proguanilon a daily basis. However, the usefulness of this drug is compromised by the high resistance of P. fal- AMINE-RESISTANT P. FALCIPARUM MALARIA
ciparum malaria to both drugs. This drug is not available in Canada or the United States.
Travellers to areas with a high incidence of chloroquine-resistant and sulfadoxine-pyrimethamine- DAPSONE-PYRIMETHAMINE (brand name: MALOPRIM)
resistant P. falciparum malaria should follow ONE of the following regimens:
An alternative to Fansidar, this drug is not available in Canada or the United States.
HALOFANTRINE (brand name: HALFAN by SmithKline Beecham)
LARIAM 250mg (adult dosage) ONCE A WEEK. START ONE TO TWO WEEKS BEFORE ENTER- Halofantrine is effective for the treatment of chloroquine-resistant and sulfodoxine-pyrimethamine- ING THE MALARIOUS AREA, CONTINUE WEEKLY DURING YOUR STAY AND CONTINUE FOR resistant Plasmodium falciparum and Plasmodium vivax malaria. It is less effective for the treatment FOUR WEEKS AFTER LEAVING. (See below for description of drug.) of mefloquine-hydrochloride-resistant P. falciparum malaria.
CONTRAINDICATIONS: Halfan should not be used for prophylaxis but only for the treatment of multi- 2) FOLLOW A MALARONE (ATOVAQUONE+PROGUANIL) REGIMEN: TAKE ONE TABLET OF
drug-resistant malaria. It is contraindicated for pregnant and nursing women and children under 3 MALARONE DAILY (atovaquone 250mg+proguanil 100mg adult dosage). START ONE TO TWO months of age. Halfan is contraindicated for persons with cardiac condition defects (congenital or pre- DAYS BEFORE ENTERING THE MALARIOUS AREA, CONTINUE DAILY DURING YOUR STAY AND existing Q-T wave prolongation on an electrocardiogram or persons on medications known to prolong CONTINUE FOR 7 DAYS AFTER LEAVING. (See below for description of drug.) Q-T wave intervals), persons taking beta-blockers, dioxin, calcium-channel blockers, or on quinidine; or persons suffering from thiamine deficiency or severe electrolyte imbalance. Halfan should not be 3) FOLLOW A DOXYCYCLINE REGIMEN: TAKE ONE TABLET OF DOXYCYCLINE DAILY (100mg
taken concomitantly with mefloquine hydrochloride, quinine or tetracyclines.
adult dosage). START ONE DAY BEFORE ENTERING MALARIOUS AREA, CONTINUE DAILY NOTE: Halfan must be taken on an empty stomach (1 hour before or 2 hours after a meal). It should be DURING YOUR STAY AND CONTINUE FOR FOUR WEEKS AFTER LEAVING. (See below for administered under medical supervision and monitored by ECG’s before and 4 hours after treatment.
This drug is used for the eradication of liverstage malaria parasites of P. vivax and P. malariae to pre- 4) FOLLOW A CHLOROQUINE REGIMEN:
vent future malaria attacks. Primaquine is also used for prophylaxis for persons living for extended Persons for whom the above medications are contraindicated should follow a CHLOROQUINE periods in highly malaria endemic areas. It is contraindicated for persons suffering from glucose-6- REGIMEN: TAKE CHLOROQUINE (ARALEN) in weekly doses of 500mg (300mg base). START phosphate dehydrogenase deficiency (G6PD), and patients must be screened before this drug is pre- ONE WEEK BEFORE ENTERING THE MALARIOUS AREA, CONTINUE WEEKLY DURING YOUR STAY, AND CONTINUE FOR FOUR WEEKS AFTER LEAVING. IT IS IMPERATIVE THAT PROGUANIL (brand name PALUDRINE by Ayerst)
YOU USE A MOSQUITO BED NET TO AVOID THE BITE OF THE NOCTURNAL ANOPHELES Although proguanil hydrochloride is the oldest and safest of malaria suppressants, Plasmodium fal- MOSQUITO. USE REPELLENTS AND INSECTICIDES AS DESCRIBED ABOVE UNDER ciparum has become so highly resistant to it that its usefulness is now seriously compromised in all SECTION “MECHANICAL PROTECTION”.
malarious areas. Recent studies have shown that proguanil is less effective against the benign forms IN COUNTRIES WITH HIGHLY CHLOROQUINE-RESISTANT P. FALCIPARUM MALARIA, A of malaria (P. vivax, P. ovale and P. malariae) than chloroquine. In areas with a high incidence of multi- REGIMEN OF PALUDRINE (PROGUANIL HYDROCHLORIDE) 200mg DAILY (ADULT DOSE) drug-resistant P. falciparum, proguanil may be added to a chloroquine regimen in daily doses of SHOULD BE ADDED TO THE WEEKLY CHLOROQUINE REGIMEN.
200mg (adult dosage). It should not be used alone as a malaria suppressant. Caution: Mouth ulcers PERSONS FOLLOWING A CHLOROQUINE OR A CHLOROQUINE PLUS PROGUANIL HYDRO- CHLORIDE REGIMEN MUST BE AWARE THAT THESE DRUGS ARE LESS EFFECTIVE THAN Proguanil is not available in the U.S.A.
Quinine is used in combination with other antimalarial drugs (such as primaquine, tetracycline andothers) for the treatment of relapsing Plasmodium vivax malaria and multi-drug-resistant Plasmodium Persons travelling to or working in remote areas where medical attention cannot be sought within 24 falciparum malaria. It cannot be used for prophylaxis, and it should be administered under close med- hours should consult with a specialist before leaving their home country for advice on a possible self- ical supervision because of potential serious side effects. A 7-day course (8mg base/kg orally 3 times treatment regimen in case of a malaria breakthrough attack.
daily) of quinine may be prescribed as a stand-by treatment for chloroquine-resistant P. falciparum CHLOROQUINE — see description above.
malaria for travellers who spend prolonged periods of time in remote areas.
1889, Rome
Chloroquine is the best antimalarial drug for children. The liquid form, not available in Canada or the Three years later, Ettore Marchiafava differentiated a third species of human malaria parasites, United States, may be purchased in some countries in Europe and malarious regions (Nivaquine by Plasmodium falciparum, named for the crescent shape of the sexual form of the parasite (L.: falx=sickle;parere=to bring forth). However the mechanism of transmission of the disease was still a mystery.
Société Spécia, Paris, France). Parents are warned to keep chloroquine out of the reach of childrensince misuse has resulted in some fatalities. Breast-fed infants are not protected by their mother’s 1894, London: Patrick Manson, the grey eminence behind malaria research
prophylactic regimen, but must be given their own dosages according to their weight and/or age.
Patrick Manson, an eminent English physician, had discovered that mosquitoes could suck up the Children should always sleep under a bed net. Special care should be taken with the application of microscopic threadlike worms from the blood of patients infected with a disease called filariasis. He anti-mosquito lotion, especially on infants, overuse may produce neurological symptoms. Infants and believed that mosquitoes might also draw out the malaria parasites from human blood, and that small children should not travel to areas with chloroquine and multi-drug-resistant P. falciparum malaria.
transmission would occur by ingestion of water contaminated by infected mosquitoes.
Fansidar (sulfadoxine + pyrimethamine) and Halfan (halofantrine) are contraindicated for children July 4, 1898, Calcutta: Ronald Ross, “It is the bite”
under 3 months of age. Lariam (mefloquine hydrochloride) is contraindicated for children under 30 lbs.
Manson, realizing he could never experiment enough in England to prove his theory, convinced (15 kg) in weight. Vibramycin (doxycycline) is contraindicated for children under eight years of age.
Ronald Ross, a British army surgeon who visited him in 1894, to carry on this research. Together they Malarone (atovaquone+proguanil) is contraindicated for children weighing less than 11 kg (24 lbs).
planned a series of experiments which Ross was to carry out upon his return to India. Ross began Schoolage children are very vulnerable to malaria, as proven by the high incidence of the disease by raising Culex and Aedes larvae, and let the adult mosquitoes feed on patients with malaria. Thenhe let these mosquitoes bite volunteers, but with no result — since he wasn’t an entomologist he among this group. Children on holiday visits to parents working in the tropics should be watched to wasn’t aware that he was using the wrong species of mosquito. After several unsuccessful ensure that they continue the suppressive treatment for 4-6 weeks after their return to school. Their experiments, in April 1897, while working in Ootacamund near Madras, he saw for the first time the guardians must be warned that fever and flu-like symptoms appearing 7 days to several months after dapple-winged Anopheles, and started to experiment with this species. On August 20, 1897, looking their return may signify a malaria breakthrough and early diagnosis are imperative for successful treatment.
through his microscope at the gut of mosquitoes which had fed on a patient with malignant malaria, ANTIMALARIAL REGIMEN DURING PREGNANCY
he saw for the first time the human malaria parasite growing in the gut of Anopheles. Since all drugs taken by a pregnant woman reach her unborn child, it is never advisable to take Unwillingly he had to interrupt his investigations, and when moved to his new post in Calcutta he medication during pregnancy. However, if travel to malarious regions cannot be avoided, the risk of started working with the avian malaria parasites, which are transmitted by a Culex species. He provedthat the spindle-shaped malaria organisms (sporozoites), freed by the rupturing of the fertilized eggs, miscarriage or premature delivery as a result of contracting malaria far outweighs the risk of possible migrate from the gut of the mosquito to its salivary glands, to be injected into the victim when the side effects from antimalarial drugs. Chloroquine and proguanil are considered safe during pregnancy insect bites. To Ross goes the credit for the discovery that malaria is transmitted by mosquito bite.
in doses used for malaria prophylaxis. Pregnant women should not travel to chloroquine-resistant andmulti-drug-resistant areas. If travel cannot be avoided, mechanical anti-mosquito measures should be 1898, Baltimore
followed meticulously to minimize the possibility of infection. Sulfadoxine + pyrimethamine (Fansidar), Later in the same year William George McCallum, a Canadian pathologist also working with birds, was ableto interpret and describe the fertilization process of the parasite taking place in the gut of the mosquito.
mefloquine (Lariam), Malarone (atovaquone+proguanil), halofantrine (Halfan), quinine and tetracyclines(doxycycline) are contraindicated in pregnancy. If you have taken Lariam, Fansidar or Halfan for pro- 1886-1899, Rome: the magnificent four
phylaxis avoid becoming pregnant for 3 months, after a doxycycline regimen wait for about a week.
Simultaneously, a group of Italians were working to solve the puzzle of the transmission of malaria inhumans. During the decade 1886 to 1896, G. Bastianelli, A. Bignami, A. Celli and G.B. Grassi had WHEN YOU RETURN…
been actively investigating the life-cycle of the human malaria parasites and making accurate Back home from the tropics you may feel a general malaise, headache and some fever, all symptoms descriptions of the lesions produced by the parasites in the different organs of the body. A break- usually associated with flu. But you should be aware that falciparum malaria, the malignant form of through came with the observations of Giovanni Battista Grassi, a physician with a keen interest in this disease, may simulate flu, and that you may be having a breakthrough of malaria due to laxity zoology, particularly mosquitoes. He noticed that when malaria was present there was always a large during your antimalarial regimen or the appearance of strains of P. falciparum resistant to your population of Anopheles, while in areas of large Culex populations there was no malaria.
medication. Remember to tell your doctor where you have been even if the fever develops months From the Campagna Romana near Rome he collected Anopheles mosquitoes, which his colleague, after your return, since such an episode could be a delayed first attack or a relapse of vivax malaria.
Amico Bignami, allowed to feed on a volunteer patient from the Santo Spirito Hospital, a few steps For the same reason blood is not accepted from donors who have taken malaria suppressant away from St. Peter’s Basilica. On November 1, 1898, the patient, Abele Sola, developed the classic medication within the preceding two years.
symptoms of falciparum malaria. Together with Giuseppe Bastianelli and Angelo Celli, they were ableto reproduce malaria infections in other volunteers and prove that only the Anopheles mosquito, and THE SEARCH FOR THE KILLER
no other species, transmits malaria in humans.
November 6, 1880, Constantine, Algeria: the end of a superstition
1936, Rome: Giulio Raffaele discovers the liver cycle
It was soon discovered that a link was missing in the knowledge of the life-cycle of the malaria
Thousands of years of superstition attributing malaria (L.: mala aria=bad air) to some kind of parasite. Still unexplained was the time elapsed between the introduction of the parasites through the air-borne poison is overthrown by a French army surgeon. Charles Louis Alphonse Laveran. He iden- bite of the mosquito and the appearance of the symptoms of malaria. Raffaele discovered while tified the malaria parasite for the first time while examining with the aid of a microscope the fresh working with birds that malaria parasites entering the host first undergo a cycle of transformation blood of a patient infected with falciparum malaria. But Laveran’s times were under the spell of the within the blood-forming cells of the liver.
genius Louis Pasteur, and the bold idea that malaria was caused by the presence of millions of minuteanimal parasites in the blood, and not by bacteria, was difficult to accept. It took six years for the 1948, London: the final touch
Now the road was open for British researchers Colonel H.E. Shortt and P.C.C. Garnham to demonstrate
skeptical medical profession to recognize the importance of his discovery.
the liver cycle of the malaria parasite in humans. Following a period of extensive trials on monkeys, 1886, Pavia, Italy
in 1948 a human volunteer — a Mr. Howard — was bitten during three days by nearly eight hundred Camillo Golgi definitively identified two human malaria parasites: Plasmodium vivax and Plasmodium Anopheles infected with Plasmodium falciparum. On the fifth day, a surgeon removed a small piece malariae. He described the asexual multiplication of the parasite in the red corpuscle of the blood and of tissue from his liver which, examined under the microscope, demonstrated the growth of the par- demonstrated its relationship to the periodic appearance of the fever characteristic of malaria.
asites in the liver cells. The last mystery of the life-cycle of the malaria parasite was finally unraveled.
★ See text for details; take after a meal, with at least 240 ml / 8 oz. of water.
★ ★ Other formulations are available.
★ ★ ★ ★ Proguanil should not be taken alone as a malaria suppressant. See text.
If a malaria breakthrough occurs, medical attention should be sought immediately. The following treatment dosages are recommended when medical attention cannot be reached within 24 hours.
* See text for details; take after a meal, with at least 240 ml / 8 oz. of water.
■ 1 teaspoon (tsp.) = 5 ml = 25 mg of chloroquine base; 1 tablespoon (tbsp.) = 3 tsp.
■ ■ Your pharmacist will be able to crush tablets and prepare children’s dosages in gelatine capsules as needed.
These dosages are to be used as a guide only. Check with your pediatrician before leaving the country.
The recommendations outlined in this document are intended as guidelines only. For a prophylactic malaria regimen tailored to your needs, seekfurther advice from your physician or travel clinic.


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