Thursday, May 28, 2009

Paludism

INTRODUCTION

Paludism (of Latin paludis, marsh [1]), also called malaria (of Italian badly' aria, bad air [2]), is a parasitosis due to a protozoon transmitted by the puncture of the female of a mosquito, the anophèle, causing intermittent fevers. With 300 to 500 1,5 and patient million to 2,7 million death per annum, paludism remains the tropical parasitosis most important. 80% of the cases are recorded in sub-Saharan Africa, where they mainly concern the children of less than five years and the women pregnant (WHO, 2005) (see the areas at the risks).
The cause of the disease was discovered on November 6, 1880 at the military hospital of Constantine (Algeria) by a doctor of the French Army, Alphonse Laveran, who accepted the Nobel Prize of medicine and physiology in 1907. It is into 1897 that the English doctor Ronald Ross (Nobel Prize 1902) proved that the mosquitos (Anopheles) were the vectors of the malaria. Previously, it was the bad emanating air of the marshes which was accused.
The parasites Plasmodium (especially P. falciparum - called in the past praecox -, P. vivax, more rarely P. oval and P. malariae) is transmitted by the puncture of the female of a mosquito called anophèle (Anopheles kind). The parasite prevails in an endemic state, infects the hepatic cells of the victim then circulates in blood, by colonizing red blood corpuscles (red globules) and by destroying Paludism gold malaria

Definition
Malaria is most frequent off the parasitic infections observed in the world.
The transmission off the parasite is gives by puncture off has mosquito, the female anophele. In year exceptional way, it edge Be gives by blood transfusion.
The serious clinical demonstrations observed in unquestionable boxes are related to the fast multiplication off Plasmodium falciparum in the capillaries (small blood vessels) off the brain with anoxia (major reduction in the oxygen contribution).
Causes and factors off risk
Responsible The infectious agent has parasite off the Plasmodium kind. Several species off Plasmodium repugnant edge the man:

* Plasmodium falciparum: re-press the most frequent species and especially more dangerous;
* Plasmodium oval: is found only in Black Africa;
* Plasmodium vivax: is not found in Black Africa;
* Plasmodium malariae: rarer than the preceding species.

The parasitizes is present in intertropical Al the hot and wet areas, with the exception off the French West Indies, off Tahiti, off the Meeting and New Caledonia. The anophèle put off urban centers South America and Southeast Asia have well have zones crossed by the tourist turns to the Far East.
Lastly, it was described boxes off paludisms known have “airports off” (mosquito transported in the baggage hold off has planes coming from has tropical country, box observed in countries with climate moderated in particular in France).

.Causes

Paludism is caused by parasitic offspecies Plasmodium, themselves transmitted by the mosquitos off the kind Anopheles.
Plasmodium, parasite off paludism

One sporozoïte Plasmodium cross-country race the cytoplasm off intestinal year epithelial concealment, seen by electronic micrography false colors.

Icon off detailDetailed article: Plasmodium.

Paludism is caused by one parasite protozoon kind Plasmodium (Phylum apicomplexa). At the human ones, paludism, primarily, is caused by P. falciparum (dominating in tropical areas), P. malariae, P. oval (the rarest species, except West Africa) and P. vivax (the least demanding species in temperature).

P. falciparum is the most common causes off the infections and person in load for approximately 80% off Al the boxes off paludism like 90% off the deaths[]. Plasmodium also the birds, the reptiles, the monkeys, the chimpanzees and the rodents repugnant (warm-blooded animal). One reported boxes off human simiesques infections with species off the paludism, off which P. knowlesi, P. inui, P. cynomolgi[44], P. simiovale, P. brazilianum, P. schwetzi and P. simium. However, except for P. knowlesi, thesis infections remain limited and off No importance in terms off public health. Avian paludism edge kill chickens and turkeys, goal this disease does not causes notable economic ramming with agriculture[45]. However, since it was introduced by the human ones, paludism decimated the species endemic birds offHawaii, which had evolved/moved, in its absence, without defense against this one. Plasmodium appears itself have one protozoon very small (1 to 2 µ according to the forms). Colouring with May-Grünwald-Giemsa show that it consists off one cytoplasm blade blue surrounding one vacuole nutritive clear and containing has red core and brown-gilded gold black pigment (hémozoïne).

The evolutionary cycle off Plasmodium is rather complex and requires two hosts, has final host: man and has primary education host: the female hematophagus off mosquito off the kind has Anopheles (off the Greek anôphelês meaning: useless). From has strictly biological off view, the true final host is the mosquito (the sexuée reproduction parasitizing itanophèle). Replicative The man would Be only one host intermediate in his cycles. Nevertheless, for let us reasons anthropocentric, it is considered that the vector is not the man goal the mosquito and consequently that this zoonose is off the standard zooanthroponose.
The anophèle, vector off paludism

One Anopheles albimanus nourishing blood one has human ARM

Icon off detailDetailed article: Anophèle.
Technique off hunting off the anophèle

Only the females are hematophagi. The males whose only activities are reproduction species and to steal die die to nourish juice off seedlings and nectar C not transmitted the disease.

The females anophèles nourish themselves preferably the night, and start to seek to their meal in the twilight, continuously during the night until they found it.

When the human ones gold the animals breathe, they produce CO2 and to their body releases constantly from heat and moisture (transpiration) like much off other gravitational substances likeacid lactic however it sebum. The mosquitos, have well have other insects stitchers, are whitebait to detect Al thesis emanations since long distances (± 20 m for CO2) and are immediately attracted by thesis sources. The mosquitos, have well, are also attracted by the alcohol vapors that by the dark colors and in particular the black. With this intention, they steal die die (maximum 2 km) by using to their sensors.

Confused Not to the various mosquitos vectors

Name off zoonose


Cause


Transmission


Vector

Chikungunya


Virus


The day


female Aedes

Dengue


Virus


The day


female Aedes

Japanese Encephalite


Virus


The night


female Culex

Yellow fever


Virus


The day


female Aedes

Paludism


Parasite


The night


female Anopheles
Cycle parasite At Anopheles

vector parasite off have its primary education host is the female one mosquito kind Anophèle. The Young mosquitos introduce the parasite for the first time when they nourish blood (necessary to this female for its production off eggs) off year infected human subject. The infected mosquito transport then them gamétocytes Plasmodium in theirs salivary nipples. Ounce swallowed, they not in blood while crossing itepithelium salivary to different Be in gamètes male and females which link themselves to form one zygote mobile called ookinète which penetrates the stomachic wall to become one oocyst spherical whose core will divide without end to form sporozoïtes. The duration off this maturation is narrowly depends one the outside temperature. For example for P. falciparum : No maturation in lower share off 18°C gold with the signal off 35°C, it is maximum towards 24°C. When the oocyst station-wagons, it slackens the sporozoïtes which migrate in the body off the mosquito to salivary nipples from where they edge, At the time off has new meal off blood, to repugnant A new human host, while crossing skin, with salivate also containing anticoagulants and off enzymes.
. Cycle parasite At the human one
- Hepatic Phase

Thin spindle off 12 µ /1 µ, it sporozoïte infectious injected with the man, At the time off this puncture by one female off anophèle infected, circulates quickly (less than one half hour) in blood to the liver in which it is sequestration in great adhesive share thanks to the let us reasons off protein majority off its envelope (protein circumsporozoïte gold CSP = Cysteine String Protein), for then infecting them hépatocytes. This hepatic pre-érythrocytaire crisis which will last 6 days for P. falciparum, 8 days for P. vivax, 9 days for P. oval and probably 12 days for P. malariae will Al the parasite to continues its cycle. The sporozoïtes which will not reach the liver will Be is eliminated by phagocytes, that is to say unable to continues to their evolution yew they reach others bodies.

With first transformation rounds this form “cryptozoïte” (off the Greek κρυπτός (kruptos) meaning “hidden”) in year element uninucléé (with only one core) called trophozoïte who is the occasion for the parasite to multiply directly (it is always thus for P. falciparum), by schizogony, during one week At fifteen days leading to enormous schizonte (name given to protozoon when it becomes activates after the phase off incubation) from 40 to 80 µ. This blue body (because consisted off one cytoplasm blade blue when it is coloured with May-Grünwald-Giemsa) bud, while losing its mobility, in manner to emitted blisters, containing the Young people mérozoïtes who will Be transferred in blood, thus initiating the training course érythrocytaire, i.e. the infection off the red globules.

However, nap mérozoïtes off P. oval however P. vivax edge remain hidden in the liver several years, even the whole life for P. malariae, before being reactivated in successive waves. This phase off the parasite is called “sleeping phase”: Plasmodium does not retort themselves goal sleeps, from where the names which are given to him At this time: “hypnozoïte” (off the Greek Ὕπνος which is Hypnos the ancient Greek god off the sleep).
Phase off transfer

The blisters are released in the hepatic sinusoids (vessels capillaries liver making the junction between this one and the blood network) to join blood circulation then and to spread has flood Young people there off mérozoïtes “pre-érythrocytaires” loans to repugnant them red globules. Each concealment off liver infected contains approximately 100.000 mérozoïtes (each schizonte is whitebait to produce 20.000 mérozoïtes). It has off true technical “ Trojan Horse ” which is used young stag to not from the hepatic concealments to blood. The imagery in vivo showed in 2005-2006 At rodents that the mérozoïtes were whitebait to manufacture dead concealments enabling them to leave the liver for blood circulation while thus escaping immune system). They At the same time seem to guide this “vehicle” and to hide there by masking the biochemical signals which alert them normally macrophages. There are perhaps there has new track for activates drugs gold one vaccinate anti-training course exo-érythrocytaire before the training course off the invasion off the red globules.
Blood phase

Long At the beginning off the blood phase] : the mérozoïtes are joined with red globules, invade them, develop to with it in trophozoïtes then divide there (schizontes). While being diffused, the mérozoïtes make burst them red globules (it is ithémolyse). Thesis brutal are and synchronous burstings which are At the origin off the accesses off fever. The time which master keys between the penetration off has parasite in one red globule and the bursting off this one rather constant and is reached in the human being 48 hours for P. vivax, P. oval and P. falciparum (third fevers) and 72 hours for P. malariae (quartan fever). The destruction off the red globules one causes weaken and, in the box off cerebral paludism (to see under one this subject), died intervenes following year obstruction off the blood vessels off brain by the infected red globules. This destruction off red globules is accompanied by the release byhémozoïne, which will disturb the operation offhypothalamus (production off cytokine like TNFα) and to causes the very strong ones fevers who edge go untilhyperpyrexie.

The bursting off the scraper schizontes gold “rivet washers” finishes the first schizogonic cycle érythrocytaire while releasing in blood, with waste off metabolism plasmodial (pigments and cellular linen remains off the red globule), has new generation off plasmodiums, them mérozoïtes “érythrocytaires” whitebait to reinfect other red globules.

With regular succession off similar cycles will follow, which will Be gradually replaced (them immunizing defenses organizing itself) by gamogonic sexuées cycles érythrocytaires preparing the forms. The trophozoïtes stop dividing and modify to their nucléo-plasmatic ratio. Thesis forms off trophozoïtes with one core bulky and one cytoplasm densified are gamétocytes males and females, which will remain one standby in blood.

The parasites At the time off this phase C not cuts any chances off survival in the human being: they remain alive A score off days then disappear. They will Be whitebait to continues to their evolution only in the mosquito. At this time yew one anophèle female pricks has sick person, it absorbs gamétocytes contained in blood, and has new cycle, sexué this time, begins in the mosquito. The sporozoïtes produced by this reproduction not in the salivated off the mosquito, which repugnant edge has new host, and so one…
Note

For P. Falciparum it is Al there it cycle life. With the others Plasmodium, nap pre-érythrocytaires mérozoïtes, C not profit blood directly, goal attack the new ones hépatocytes : it is the beginning off the secondary cycles exo-érythrocytaires which will maintain in the liver the parasitosis during two gold three years for P. Oval, 3 to 5 years gold more for P. Vivax and during the whole life for P. Malariae.
Animation and diagram off the parasitic cycle off Plasmodium [

* Animation Abode Flash Player

Diagram Animation and diagram of the parasitic cycle of Plasmodium [

* Animation Abode Flash Player

Schém Animation and diagram of the parasitic cycle of Plasmodium [

* Animation Abode Flash Player

* Diagram

* causes off Other transmission

The parasites edge also Be transmitted by placental way off the mother to foetus (congenital paludism), by division off has syringe soiled gold by blood transfusion, although this last rare transmission resource is rather].
Diagnosis
Symptoms

symptoms paludism include fever, off tremors intermittent, off arthralgies (articular breads), off nauseas and vomiting, offweaken caused byhémolyse, ithémoglobinurie, and off convulsions. Feelings off tinglings edge appear in the skin, particular when paludism is caused by P. falciparum. The most traditional symptom off paludism is the cyclic repetition off has sudden feeling off cold followed off shivers and off fever and sudations during furnace to six hours, occurring every two days during the infections due to P. vivax and P. oval, but every three days for those due to P. malariae]. P. falciparum edge involve fevers the every 36 to 48 hours gold has continuous and less marked fever. For let us reasons still little included/understood, goal being whitebait to Be related to intracranial presses, the children reached off paludism often cuts year abnormal posture, indicating severe cerebral ramming paludism edge involve cognitive delays, in particular in the children. It one causes weaken general for one period off fast cerebral development, have well have direct cerebral ramming. The neurological cerebral ramming results from the paludism to which the children vulnerable are more[54],[55].

Serious paludism is caused quasi exclusively by the infections off P. falciparum and generally occurs 6 to 14 days after the infection]. Standard This off paludism edge involve it coma and death yew it is not treated. The pregnant children and women vulnerable are particularly. Other symptoms include splénomégalie (enlargement off spleen), off cephalgias severe (headaches), itischaemia cerebral, ithepatomegaly (enlargement off the liver), ithypoglycemia, the hémoglobinurie have well have renal problems. Yew the kidneys cease functioning, has particular fever edge occur, when the haemoglobin off the red globules flees in the urine. Severe paludism edge progress extremely quickly and causes death in A few days even has few hours In the most serious boxes, the death misses edge exceed 20%, even with important care. In the endemic zones, the treatments total are often not very satisfactory and the death misses for Al the boxes off paludism edge reach one one ten]. Later one, off the problems off development were brought back for the children having suffered from periods off severe paludism

Chronic paludism edge Be caused by P. vivax and P. oval not by drank P. falciparum. In the box off chronic paludism, the disease edge reappear several months gold years after the exposure, because off the latent presence off parasitic in the liver. Thus, one boat say that has off subject is cured paludism simply by observing the disappearance the parasitic off blood flow. The longest incubation period brought back for P. vivax is 30 years. Approximately has box off paludism P. vivax one five in the moderate zones it implieshibernation with the hypnozoites (the relapses begin the year after the puncture off the mosquito.

Serious paludism is often diagnosed in Africa in the place off other diseases, preventing to their effective treatment. In the endemic zones, parasitemy does not Al to diagnosis the serious boxes off paludism, because this method edge diagnosis other parasitic diseases. Recent investigations suggest that retinopathy malariale edge Be better than the other methods to distinguish the coma paludic and non-paludic[ Prevention]

The methods used to prevent the disease from spreading itself, but to protect the inhabitants from the endemic zones, include disease prevention by the wrestling off drugs, eradication off the mosquitos and prevention off the punctures off mosquitos. For paludism edge exist continuously At has place, one needs has combination off factors: strong density off population, strong misses transmission off off human to the mosquitos and reciprocally. Yew one off thesis factors decreases, the parasite ends up disappearing, have in North America and Europe. Conversely, the parasite edge Be reintroduced in year area and to survives it yew thesis factors are joined together there.

There does not exist vaccinate present At against paludism, goal the search for A vaccinates has very activates sector.

Some researchers affirm that the effective prevention off paludism would Be more financially than its length-term treatment; the expenses to Be engaged for that important are too for poorest drank. The economist Jeffrey Sachs estimate have well have paludism could Be controlled with 3 billion US dollars per annum. So reaching them objectify the millenium for the off development, money currently Al with the fight against AIDS should Be reallocated with the prevention off paludism, which would profit more with the African economy.

Some countries like Brazil, Érythrée, India gold Vietnam succeeded in reducing the plague off paludism. The analysis off thesis programs shows that many factors had to Be joined together to successfully fight against the disease, that it is off the financings, the action off the State and ONG, gold off the concrete action off the social workers.
Means off fighting the mosquito gold off protecting themselves nap]

One edge fight the vector off paludism (the female anophèle) by several means off effective prevention, which edge prove to Be yew they are well implemented.

The true problem off this prevention is the very high cost off the treatments for the touched populations. Effective Indeed, it edge Be At the travellers, goal the countries in the process off development, which principal are the victims off this disease, bread to organize very effective actions. Give One edge for proof the example off the island off the Meeting where paludism prevailed off have in the other islands the area (Madagascar and Mauritius) in particular. The Meeting being has French territory off overseas, the problem off the too high cost did not exist and one could éradiquer the malaria off this island without difficulty.

Two modes off prevention are applied in the countries concerned. They aim one the one hand protecting the populations against the punctures from mosquitos and, one the other hand, At eliminating to lath by the installation from various means. Principal The goal off this disease prevention is to limit the population off mosquitos vectors disease and thus to try éradiquer this plague.

In the years 1960, the principal method used for éradiquer the female anophèles was the massive uses offinsecticides. More used was it DDT (Dichloro-Diphényl-Trichloréthane). This method boron its fruits in many areas where paludism was completely éradiqué. Unfortunately, the intensive uses off the DDT supported the selection off resistant mosquitos. This resistance was named KDR (Knock Down Resistance : resistance to the effect off shock). Moreover, it edge generate intoxications and diseases in the population have it was the box in India however it was used in year abusive way in agriculture. Although this product is completely interdict in Europe since 1972 and that, since 1992, it is classified byWHO POP like (persist organic pollutant), this same WHO seems to reconsider its position by preaching new recommendations relating to the uses this pesticide off (exclusive intended for the fight against paludism inside off the buildings uses)[85]. And yet, incontestably, the DDT is:

* persisting : its half-life is 15 years, i.e. yew one pulverizes 10 kg in A field, 15 years afterwards, there will remain 5 kg butt it, after 30 years 2,5 kg and so one natural When manufactures has complex molecule, it manufacture, into same time, the molecule off one enzyme who ranges it, it that it boat make for unknown molecules like the DDT. organic molecules introduced by the man thus violate this rule according to which for each molecule which is built, year enzyme destroyed. They thus generate, according to to their stability, them toxicity and to their persistence in the environment;
* dispersive : one found nap in snows offThe Arctic;
* bio cumulative : the animals which in absorb C not die butt it, goal C not manages to eliminate it. They it blind in to their greases and one finds great concentrations off them in the animals off the signal off the food chain. One the other hand, its toxicity is preaches to debate although year ingestion off 35 G edge lethal Be for has person off 70 kg.

To replaces the DDT, which proves to Be dangerous and less and less off effective, the alternate means possible are in order to fight the vector off paludism

* draining off the marshes (without upsetting the ecological system), drainage off stagnant toilets where the larvae develop off anophèles (year old abandoned car and filled off toilets by the rains is sufficient with the mosquito to lay there its eggs);
* anti-larval fight by vegetable oil gold oil spreading and uses off widespread soluble insecticides one the surface off stagnant toilets, to try to limit the births off anophèles gold to prevent larvae to like to breathe one the surface. Measurements very little advisable completely anti-ecological bus ;
* sowing off toilets with the predatory ones off the anophèles gold off to their larvae like some molluscs gold fish (tilapias, guppys, gambusies, aphanius)[87] ;
* reintroduction, and protection, off the varieties off chiroptères insectivorous where they disappeared (A beats edge swallow butt half off its weight in insects in one night)[88];
* targeted starting from the sequencing off genome mosquito[89]. This genome offers, amongst other things, has off catalogue the increase in constrained off detoxification and obstructed mutant which code proteins aimed by insecticidal aces well have variations off nucleotides individual, called SNPs (pronounce SNIPS) (individual nucleotide polymorphisms) which is in the genome:
o employment offinsects repellant and offinsecticides only targeted against the anophèle;
o dispersion off male anophèles deads in nature;
o genetic interventions one the species vectrices but, in one unspecified future, with vaccinate blocking the transmission in inducing antibodies preventing the maturation off the training courses sexués off parasite At the anophèle.

Effective thesis measurements are only one one limited territory. It is very difficult to apply them one has unintermitting scale such have Africa.

Each one, one has purely individual basis, edge avoid the punctures off anophèles by mechanical, physical and chemical measurements: let custom recall before very that the anophèle has has night activity, starting to prick with fallen the night, and resting the day in the dwellings.

* installation off mosquito Nets (meshs lower than 1,5 mm) impregnated off perméthrine however off derived from pyrethrinoid. Off more in more thesis mosquito Nets are provided At very democratic prices (maximum 1,70 $) even free with the populations off the zones off endémie. Effective thesis mosquito Nets are during 3 to 5 years according to the model and them conditions off uses;
* installation off netting mosquito Net to the Windows;
* use off insecticidal one has small scale: pulverization insecticides intradomicilaires (pyrethrinoid, DDT,…) in dwellings (rooms to Be slept);
* installation off air conditioning in the dwellings to make to lower the temperature and to brew the air (the mosquito cuts horror off air volume displacements which disturb it in its displacements and in its sensory faculty to find its target);
* after laying down it sun: wearing off full, long clothing and off clear color and alcohol abstinence (the anophèles have well attracted by the sunk colors, in particular the black, than by alcohol vapors);
* application off repulsive cream one the skin gold clothing have to lay off down sun. Off Al the repulsive ones off synthesis, those which contain DEET (NR, N-diethyl-m-toluamide) efficient are most. The DEET does not kill the insects goal its vapors discourage from them being posed gold climbing one the person.

Generally, the products concentrated between 25 and effective 30% off DEET are most over the longest period (± 8 H against the crawling insects and from 3 to 5 a.m. against the anophèles). They are also regarded have inoffensive for adult people gold children off more than 2 years yew the concentration does not exceed 10% for to lath. To proscribe in the pregnant woman and the infant off less than 3 months. The products concentrated with more than 30% are not approved any more.

The marketed products are to Be applied to same the skin gold to clothing gold the mosquito Nets. Attention however so that they deteriorate the plastics, some synthetic fabrics like nylon, rubber, leather and painted gold varnished surfaces. Direct To also take attention with the eyes and the inhalation with the products out off spray like with ingestion. The applicators provided with has ball will thus Be preferred.

Transcutanée The resorption is 50% into 6 H and elimination will Be urinary. The not eliminated share (30%) will Be stored in the skin and greases.