THE CONCEPT OF INFECTION, REGULATED BY THE INTERNATIONAL HEALTH nREGULATIONS. PLAGUE. YELLOW FEVER. HEMORAGHIC FEVER OF LASS, MARBURG, EBOLA.

TETANUS. ERYSIPELAS. ANTHRAX. FOOT AND MOUTH DISEASE.

 

Quarantine and nespecially dangerous infections

 

http://intranet.tdmu.edu.ua/data/books/And-INF.pdf

Protective measures against import of and spreading of ninfectious diseases from other countries were specified by the World Health nOrganization in 1969 and 1973. Each country must have special system of nmeasures aimed at prevention of import of infectious diseases from abroad, and nif an infection is taken into a country, measures should be taken to prevent nits spreading. Quarantines should be organized in cases of plague, cholera, nyellow fever. (Smallpox has been completely eradicated in the world by 1982).

Quarantines nmeasures should be taken in international sea and river ports, airports, and at nposts of international highways, on the border posts on highways. The following nmeasures are necessary at border intersection points:

(1) nmedical examination of persons who arrive into or depart from a given country, ntheir vehicles and belongings;

(2) navailability of special medical documentation (international certificate of nvaccination, certificate of deratization, and the like) must be checked;

(3) nrevealing and isolation of persons with infectious diseases, and isolation of npersons who require medical observation;

(4) ndisinfection, deratization, disinsection of means of transporta­tion, of cargo nand luggage (for special indications).

Special measures should nbe taken to protect import and spreading of infectious diseases such as plague, ncholera and yellow fever. Preventive measures should also be taken against nhaemorrhagic fever, louse-bome and recurrent fever, malaria, anthrax, nbrucellosis, foot-and-mouth disease, glanders, myeloidosis, rabies, and npsitacco-sis, that can be imported from other countries.

Quarantine

The term quarantine nmeans: to separate and isolate to prevent the spread of disease. This includes nbacterial infections, viruses, funguses, and parasites (both internal and nexternal). http://ratguide.com/health/basics/

Quarantining nat a separate mouse/rat free location and maintaining a persistent quarantine nenvironment is possibly the most efficient way to prevent illness and /or death nfrom contagious disease in a colony. During the quarantine period strict nattention is necessary to determine any signs of illness. It is advisable to nfamiliarize yourself with signs of illness, basic diseases of the rat, and to nfind a veterinarian that treats rats in the event that you see illness during nquarantine.

Those involved with rats nuse levels of quarantine ranging from none, to very lax, to stringent. The type nof quarantine used will depend on the needs associated with the colony, and the npreferences of the person that maintains the colony. Unfortunately, if the nlevel of quarantine is not high enough for the particular scenario it puts the nrats at risk.

Note: nMice and other rodents can also carry disease of the rat. Tack care to factor nthem, as well as wild rats, in quarantine scenarios. Incoming supplies or nequipment can also act as a potential source of disease transmission.

Quarantine Time Frames

New & Returning Rats- Quarantine Time nFrame

The absolute minimum quarantining for nbringing rats in is 14 days. This covers the acquisition of new rats or the nreturn of resident rats to the colony after exposure to other rats (shows, nco-breeding, returned placements, etc.). When acquiring a new rat from a show, npet store, breeders, or rescue facilities, check it over for signs of illness nfirst. This will help reduce the risk of exposure to your other rats.

This will be enough time nto detect certain dangerous viruses (such as SDA and Sendai), obvious bacterial ninfections, ectoparasites (such as mites, fleas, and lice), and possibly ninternal parasites.

Generally the quarantine time for nexternal parasite infections is 3 weeks. Quarantine begins on the first day of ntreatment. Treatment must include the environment as well as the rat.

Igeneral, a two-week quarantine will not alert one to asymptomatic viral ninfections such as parvo virus (including Kilham rat virus) or to persistent nfestering diseases such as CAR bacillus (Cilia Associated Respiratory).

If any nhealth issues arise while in quarantine seek immediate treatment from a nqualified veterinarian. The quarantine will start again after the rat nhas recovered and is off any medications that may mask signs of illness. If any nrats are introduced into the group it also necessitates starting quarantine nover.

Signs nof illness may include but are not limited to any of the following:

·        nPorphyrisecretions from eyes or nose

·        nSneezing

·        nWheezing

·        nRough coat

·        nLabored breathing n

·        nLethargy

·        nHunched posture

·        nSwelling oeck nor body

·        nAbscesses

·        nScabs or itching

·        nDiarrhea

·        nConstipation

·        nLack of appetite

·        nEye ulcerations, nbleeding, or swelling

·        nVisual nidentification of parasites including lice nits

·        nAbnormal odor nfrom the rat

·        nAbnormal smelling nfeces or urine

·        nRespiratory ndistress

·        nHead tilt or nabnormal gait

·        nThinness

Note: nQuarantine concerns may not be the same in different areas/countries depending non the prevalence and/or virulence of particular pathogens.

Outbreak and Post Infection-Quarantine Time nFrame

During an active ninfectioo rats must enter or leave the colony. All breeding must be stopped nto prevent perpetuation of the illness. After a colony has been exposed to a ncontagious disease it is essential to quarantine them so as not to spread the nillness to others. The length of quarantine depends on the pathogen involved, nthe size of the colony, and whether or not there has been breeding. It will ntake longer to be sure that the illness has passed in a larger group.

Outbreaks in a colony noften tend to be viral iature. Although viruses cannot be treated it is nimportant to aggressively treat the secondary infections that inevitably accompany nthem. Viral outbreaks can be reported to the Viral Tracking Database.

Note: Immuno-compromised nrats in the colony can stay persistently infected with certain diseases.

A post-infection quarantine is performed ithe rats home colony and begins only after the following criteria has been met:

·        nAll of the rats nhave recovered

·        nAll rats off nmedications that may mask signs of illness

·        nAll breeding is nceased

·        nAny rats born or nconceived during exposure are weaned

Post Infection for Specific Pathogens (for nmore detail use the highlighted links):

·        nSDA– The accepted minimal quarantine is n30 days (after all babies are weaned, all rats are recovered, and all rats have ncompleted their full course of treatment) even though the virus is not usually nshed for that long. In a large or breeding colony it is not unusual to see a ntwo-month quarantine just to be sure that the virus is no longer present.

·        nKilham Rat nVirus– Minimum nquarantine is 60-90 days and involves draconian methods of sanitization. Other nfactors can affect post infection time frame such as persistent infection iprenatal or postnatal rats.

·        nSendai– The accepted minimal quarantine is n30 days (after all babies are weaned, all rats are recovered, and all rats have ncompleted their full course of treatment) even though the virus is not usually nshed for that long. In a large or breeding colony it is not unusual to see a ntwo-month quarantine just to be sure that the virus is no longer present.

·        nCAR Bacillus– Persistent contagious infectiothat will not be resolved through quarantine.

·        nMycoplasma nPulmonis– Persistent ncontagious infection that will not be resolved through quarantine.

Methods of nQuarantine

In Home Quarantine

Often rat owners will nquarantine by putting any new rat(s) in a separate room. This method, along nwith stringent hand washing, can be useful for preventing the spread of certaibacteria or parasites. It is not effective for containing airborne viruses such nas SDA, Sendai or Parvo Virus.

Using a garage, separate nroom, basement, or porch connected to the colonies living area is not nconsidered a safe alternative. Such locations may reduce the risk of contagion, nbut as you pass from such areas into the main part of the colonies living area, nyou will be allowing air that may be contaminated with airborne pathogens to nenter with you. This puts the resident rats at risk for infection.

In-home nquarantine is not recommended as an advisable method, particularly if one is nbringing in rats from high-risk scenarios or if breeding.

Separate Location Quarantine

As the nname implies this method of quarantine involves isolating in a rat free nenvironment at either a separate location from the colony or in an area where nthere is a totally separate air supply. This is the safest method of quarantine nfor a fancier or non-laboratory colony.

Some npossible locations are, a friend’s home, the home of a family member, a nneighbor, a climate controlled out building, or at your job.
nIt is advisable to have someone else care for the quarantined rats rather tharisk bringing diseases home that can be carried on your person, or clothing. If nthere is no alternative, upon returning to your home, shed your clothes outside nand immediately shower.

Persistent Quarantine

Once a colony is ndetermined to be in good health a persistent quarantine scenario can help keep nit that way. In addition to the stand new rat quarantine there are additional nrecommendations that you can follow:

·        nAvoid pet stores nthat sell rats.

·        nDo not handle nrats at pet stores or shelters.

·        nHave fellow rat nfanciers wash up before visiting.

·        nIf you are nexposed to outside rats, clean up as soon as you return home or wait awhile nbefore going into your home. SDA and Sendai will only remain contagious wheaway from the host for approximately 3 hours.

·        nAvoid housing nrats in areas where wild rats have access.

·        nAvoid taking your nrats to rat inclusive events.

·        nAvoid constantly nadding to your colony. It is safer to get rats less often and quarantine them nwell.

·        nIf showing rats nquarantine them at a separate location before returning them to the colony.

Isolator Maintained & Full Barrier nQuarantine

This nis the method most often used where rats are being bred and/or kept for the npurpose of research. Certain diseases can be catastrophic to research projects. nRats are quarantined using methods such as airflow units, and isolator units. nSterilization of supplies and equipment, and periodic testing for pathogens are nrequired to prevent research results from being contaminated. In some cases, nSPF quarantined colonies are stared by harvesting embryos and transferring them nto a pathogen free or defined flora recipient mother. Not all rats in laboratories and nresearch colonies are free of pathogens. Some are only SPF (Specific PathogeFree), DFD (Defined Flora Derivations), and others are specifically infected nwith certain diseases so that researchers may learn more about the disease nand/or determine its impact on research.

Links

The following links ncontain additional information:

·        nRMCA Viral Tracking Database

·        nEctoparasites- nRat Guide Entry

·        nSDA virus n(Sialodacryoadenitis)-Rat Guide Entry

·        nKRV (Kilham Rat nvirus)-Rat Guide Entry

·        nCAR bacillus-Rat nGuide Entry

·        nMycoplasma-Rat nGuide Entry

·        nSigns of Illness-Rat nGuide Entry

 

PLAGUE

Plague is nan acute infectious disease caused by Yersinia pestis with an severe nintoxication, fever, affection of lymphatic system and lungs. It belongs to the ngroup of the extremely dangerous infections (quarantines).

Historic nreference

Apparently, nthe word “plague” comes from the ancient Arabic word “jumma” which means n“bean”.

During the last 2000 years, Y. pestis has caused social and neconomic devastation on a scale unmatched by other infectious diseases or by narmed conflicts. It is generally considered that there have been three world npandemics of plague and credible estimates indicate that together these nresulted in 200 million deaths. During these pandemics, the disease occurred iboth the bubonic and pneumonic forms.

 The first, nthe Justinian plague, occurred during the period AD 542 to AD 750. This npandemic is thought to have originated in Central Africa and then spread nthroughout the Mediterranean basin. The second pandemic started on the Eurasiaborder in the mid-14th century’. It is this pandemic which resulted in 25 nmillion deaths in Europe and which is often referred to as the “black death”. nThis pandemic lasted for several centuries, culminating; in the Great Plague of nLondon in 1665. The third pandemic started in China in the mid-19th century, nspread East and West, in 87 ports, in almost all continents.

Eight epidemic nbreakouts of plague have been registered in Odessa. The biggest epidemic took nplace at 1812, when about 3000 people fell ill and more than 2000 people died. nProfessor Stefansky V. K. – the first head of the chair of infectious diseases nin Odessa medical institute was one of the pioneers of using serum for the ntreatment of sick people.

World Health Organization (WHO) nindicated plague, cholera, hemorrhagic  fevers and small pox as internationally quarantinable ninfectious disease (most dangerous). nAs a class 1 notifiable disease, all suspected cases must be reported to, and ninvestigated by, public health authorities and confirmed cases must be reported nto the WHO in Geneva, Switzerland. During the period 1967-1993, the average worldwide incidence of nplague was 1,666 cases. Although the incidence trend was downwards until 1981, nthere has been an apparent increase in the incidence of disease over the last ndecade, possibly because of more efficient diagnosis and reporting of cases. nEven today, many cases of plague are not diagnosed and it is likely that the ntrue incidence of disease is several times the WHO figures.

The Indiaoutbreak of plague in 1994. Despite the high incidence of plague in India during the first half of this century, the number of cases had declined since 1950, nand the last recorded case occurred in 1966. However, between August and nOctober 1994 two outbreaks of suspected plague occurred. One of bubonic plague nin the Beed District of Maharashtra State, and the other of pneumonic plague ithe city of Surat in Gujarat State. The Surat epidemic caused panic throughout India, resulting in a mass exodus of up to half a million people from the city, and nattracted international media attention.

At the peak of the epidemic, over n6300 suspected cases were recorded. However, official figures released later nindicated that only 876 presumptive cases of plague were identified (by nserological testing for antibodies to Fl antigen of Y.pestis) and there nwere 54 fatalities. The cases were confined to six states in central and nwestern India; none of the suspected cases in other states, such as Bihar, nPunjab, Rajasthan and West Bengal, had positive serological markers for npresumptive plague.

Etiology

Yersinia pestis (bacillus pestis) Fig.1, the etiological agent nof plague was first described by A. Yersen in 1894 in Hong-Hong, the International committee of systematization of bacteria (1982) referred it to Yersinia ngenus together with bacillus pseudotuberculosis and yersiniosis.

Fig.1. Yersinia npestis (bacillus pestis)

 

It is a short, noval bacillus with rounded ends occurring singly and in pairs. In the tissues a ntypical capsule may be observed, in cultures grown at 37 °C material can be demonstrated by means of India ink preparations, but it no well-defined.

The organism is Gram-negative, and when stained with a weak stai(methylene blue) shows characteristic bipolar staining which is an important nfeature in identification.

In culture the nplague bacillus is less typical. Longer forms are frequent and polar nstaining is less obvious. Pleomorphism is marked especially in old cultures, and ninvolution or degeneration forms are particularly noticeable. These are nmarkedlly enlarged, stain faintly and include globular, pear-shaped, elongated nor irregular forms. In fact the microscopic picture of an old culture oftesuggested that of a yeast or mould. Involution in culture can be hastened by nthe presence of 3% sodium chloride and this has sometimes been utilized iidentifying the organism.

In fluid nculture the bacilli tend to be arranged in chains. The organism is non-motile nand non-sporing.

Rodents are nnatural reservoir for plague infection. Yersen was the first who noticed the nconnection between a rats plague epizootic and a human epidemic. Bacillus npestis carriage was proved for black and gray rats and for such steppe nrodents as gophers, marmots, sandworts, small mousekind rodents and others. nThere are almost 300 species and subspecies of basic sources and keepers of nplague infection. Besides, during an epizootic among rodents, there can be nfound other mammals contaminated with plague – polecats, shrews, foxes, monkeys n(makaky genus), domestic cats, one- and two-humped camels. Epizootics among nrodents are kept by different species of fleas – carriers of plague infection.

It is now known that plague is not communicable from animal to animal by nsimple contact, but is readily communicated by fleas (Fig.2), which bite man, ndogs and other animals. Conglomerate of Y. pestis block esophagus and npre-stomach of the flea. During the bite and sucking of blood bacilli nregurgitate into the wound of object.

Fig.2. Flea

Especially nconvincing are the experiments of the Indian Plague Commission, which clearly nshowed that, if fleas are excluded, healthy rats will not contract the disease, neven if kept in intimate association with plague-infected rats. Young rats may neven be suckled by their plague-stricken mothers and remain healthy. It nsuffices to transfer fleas from a plague-infected to a healthy animal, or to nplace the latter in a room in which plague rats had died recently and had beesubsequently removed. The fleas that have left the body of the dead rats, try nto found another host for living.

In ordinary ncircumstances the rat-flea completes its developmental cycle in from 14 days to n3 weeks, but in warm damp weather this may be shortened to 10 days. It requires nideal tropical conditions for propagation. The average life of a flea, nseparated from its host, is about ten days, but it is capable of remaining nalive without food for two months, should the temperature of the air be low.

Humainfection, however, is not always transmitted by fleas. In a small percentage nof the bubonic cases, infection occurs after direct contact of skin with Bacillus npestis. Instances of such infection have occurred in barefooted individuals nwith small wounds of the feet from walking on floors or stepping on material ninfected with plague bacilli, or through abrasions on the hands of those who nhave performed autopsies on or handled the bodies of those who have died of nplague, or who have shot and skinned rodents infected with plague.

Infection iprimary human septicemic plague is usually acquired through the mucous nmembranes, particularly of the mouth and throat and the conjunctivae. Particles nof infected sputum which have been accidentally coughed into the eye have nproduced human septicemic plague. Animals such as monkeys may be given primary nsepticemic plague by instilling a few drops of a culture of Bacillus pestis ithe eye, or by rubbing a small amount of the culture on the mucous membranes of nthe gums without producing visible erosions. Infection of the mucous membranes nof the mouth may occur also in man through the hands conveying infection, as nmight occur in individuals who have shot or skinned infected rodents.

Clinical nmanifestations

Incubation period of human plague varies usually from 2 to 10 days, but nis generally from 3 to 4 days. In primary pneumonic plague it may not be over 2 nor 3 days.

In bubonic nplague premonitory symptoms are not usually observed, though occasionally nthere may be 1 or 2 days of malaise and headache. The onset, except in mild ncases, is usually abrupt, with fever commonly accompanied by a moderate rigor nor repeated shivering. The temperature rises rapidly to 39,4 °C or 40 ˚C. sometimes even reaching 41,7 °C. The pulse becomes rapid and the respirations increased. There is headache which is usually nsevere and mental dullness, and this condition is generally followed by mental nanxiety or excitement. The patient may become maniacal. The skin is hot and ndry, the face bloated, the eyes injected, and the hearing dulled. The tongue is nusually swollen and coated with a creamv fur, or later with a brown or black nlayer. The symptoms usually complained of within the first 24 hours are very nsevere headache and backache. Burning in the throat or stomach, and nausea and nvomiting may occur. Constipation is present as a rule. The pulse is either very nsmall and thread-like or full and bounding. At times there may be acute delirium; nat others, lethargy and coma. In children, convulsions usually occur. The urine nis scanty and generally does not contain more than a trace of albumin and no ncasts. Later in the disease the albumin may increase somewhat, The high febrile nstage lasts from 2 to 5 days or longer. The decline in temperature may be nsudden or gradual. Cases that do well usually show a gradual fall of ntemperature, and after 14 days the temperature may be subnormal. Buboes, ninflammatory enlargements of the lymph glands are sometimes the first sign to nattract attention by their pain. They more often make their appearance from the nsecond to the fifth day after the onset of the fever. The temperature nfrequently shows a decline when they appear.

 The affected gland is often hard and painful to the touch. In fatal ncases, it may retain these characteristics; in others it suppurates. The naverage size of the bubo is from a walnut to an egg.  Generally the plague bubo nat the onset is hard to the touch and very painful. Often at the time of onset nof the bubo, pain in it is the symptom of all others of the disease most ncomplained of. In rare instances, however, the pain may not be marked. Usually nif the bubo is in the groin the pain is sufficient so that the patient lies ibed with the thigh flexed and the leg drawn up to relieve any pressure on the ninflamed glands while if the bubo is in me axillary region the affected arm is nheld away from the side. The bubo may terminate by resolution, suppuration, or ninduration (Fig.3).

Fig.3. nRuptured plague bubo

 

If the bubo suppurates, the gland becomes at first more swollen and the noverlying skin gradually more inflamed and tense during the first week. Later nthe gland begins to soften and necrosis then occurs more quickly. Frequently nthe whole center of the gland breaks down into an abscess cavity and nperforation then occurs, revealing a cavity with dark scarlet or bright red nwalls. Later the walls become reddish yellow in appearance and emit nwhitish-yellow pus. On microscopical examination of the pus normal and ndegenerating plague bacilli are found and many polymorphonuclear leucocytes and ndegenerating endothelial cells. The bacilli are often seen engulfed iphagocytic cells. In the later stages the buboes often become secondarily ninfected with other microorganisms, particularly the pus cocci. Rarely the bubo ndoes not perforate for several weeks. Sometimes its suppuration is accompanied nby much sloughing of the skin in the vicinity when fairly large ulcers result nwith indurated infiltrated margins. In some instances the lesions may heal ifrom a week to ten days, but with larger buboes sometimes complete ncicatrization does not occur for a month or two. In many other cases the bubo nterminates by resolution. The tenderness, and periglandular infiltration thegradually decrease, the overlying and adjacent skin becomes softer, and the nglands may eventually return almost to their normal size with but moderate ninduration about them. In other instances an enlarged cicatricial node remains nat the site of the bubo.

Buboes nappear in 75 % of the cases. In the cases in which buboes are present, they noccur in the inguinal glands in approximately 65 to 70 %,  in the axillary. 15 to 20 %, and the cervical, 5 to 10 %. Carbuncles appear in about 2 %, in which there are reddened indurated patches of skin, nwhich subsequently necrose. The spleen is frequently moderately enlarged, but noften cannot be palpated. Hemorrhages from the stomach and intestine are not nuncommon, and when the disease is complicated with the pneumonic form they may noccur from the lung. Epistaxis is also not infrequent. The blood usually shows na leucocytosis of forty thousand or more the increase being in the npolymorphonuclear leucocytes. The plague organism can be isolated front the nblood in about forty-five per cent of the bubonic cases.

The attack of high fever lasts generally three to five days or longer, nbut the patient may die earlier. If however, he lives for five days there is ngreater chance of recovery. If the bubo suppurates recovery may be delayed from ntwo or three weeks to a month.

 The onset nof pneumonic plague is usually somewhat abrupt; nprodromal symptoms are rare. The disease usually begins with chilly sensations, nbut a distinct rigor is unusual. Epistaxis is also rare. There is headache, nloss of appetite, an increase in the pulse rate, and fever. Within from ntwenty-four to thirty-six hour after the onset, the temperature usually has nreached 39,4 °C or 40 °C, and the pulse 110 to 130 or more beats per minute. Cough and dyspnoe appear within twenty-four nhours after the onset of the first symptoms. The cough is usually not painful. nThe expectoration is at first scanty, but soon becomes more abundant. The nsputum at first consists of mucus which shortly becomes blood-tinged. Later the nsputum becomes much thinner and of a bright red color; it then contains nenormous numbers of plague bacilli in almost pure culture. The typical rusty nsputum of croupous pneumonia was not observed. The conjunctiva become injected, nand the tongue coated with either a white or brownish layer. The expression is nusually anxious, and the face frequently assumes a dusky hue. Labial herpes is nvery uncommon. The patients sometimes complain of pain in the chest, but nusually this is not severe. Apart from the disturbances due to the dyspnoe and ntheir anxiety for their condition, they usually appear to suffer but little and nusually do not complain of pain. In the later stages of the disease, the nrespirations become greatly increased and the dyspnoe usually very marked, the npatients frequently gasping for air for several hours before death. Cyanosis is nthen common.

The signs of ncardiac involvement are always marked in the advanced cases, the pulse becoming ngradually more rapid, feeble, and running; finally it caot be felt.

Septicemic plague occur during the course of bubonic nplague, always occurs in pneumonic plague, and may occur as a form of primary ninfection. When primary septicemic plague results, the infection has usually noccurred through the mucous membrane of the mouth and throat, death resulting nfrom septicemia before macroscopic lesions are visible in the lymphatic glands nor lungs. Nevertheless, at autopsy, at least some of the lymphatics are usually nfound to be enlarged, congested, and even hemorrhagic, and in a few instances nearly buboes may develop shortly before death.

In this form, nthe nervous and cerebral symptoms often develop with great rapidity and nintensity, and the course of the disease is very rapid, the bacilli appearing nin the blood almost at the onset of severe symptoms. The attack usually begins nwith trembling and rigors, intense headache, vomiting, and high fever. The ncountenance usually depicts intense anxiety. Extreme nervous prostration, nrestlessness, rapid shallow respirations, and delirium are common symptoms. Isome cases the cardiac symptoms are the most prominent. The patients soon pass ninto a comatose condition, and die sometimes within 24 hours of the onset of nthe attack, but sometimes not until the third day.

Cases of primary septicemic plague are always fatal. Hemorrhages from the nintestine sometimes occur in this form of plague as well as in bubonic plague. nThere is no distinct evidence that such cases are of primary intestinal origin. nHemorrhages from the nose and kidneys are also not uncommon.

The plague nbacillus produces a powerful endotoxin which often causes a dilatation of the narteries, lowering of the blood pressure, and alterations in the functional nactivity of the heart, as well as degenerative changes in the heart muscle. It nalso acts particularly upon the endothelial cells of the blood vessels and nlymphatics, the inflammatory reaction frequently causing circulatory nobstruction. One of the most characteristic features of the pathology of plague nis the tendency to produce general dilatation and engorgement of the vessels, nwith cutaneous, subserous, submucous, parenchymatous, and interstitial nhemorrhages. In patients who have died of plague, the most common of the latter nare in the epicardium, the pleura, peritoneal surfaces, the stomach and nintestines, and the mucosa of the stomach and small intestine. Sometimes nextensive hemorrhages are found in the peritoneal, mediastinal or pleura ncavities. In the kidneys there are frequently subcapsular and renal nhemorrhages, and blood extravasation into the pelves of the kidneys and nureters, as well as in the bladder and generative organs.

Sometimes there are considerable nextravasations of blood into the substance of the brain. In bubonic plague, nnumerous hemorrhages are almost always present in the bubo. The tissues are ncharacterized by vascular dilatation and engorgement. followed by edematous ninfiltration, the effect of the toxin being evident on the vessel walls. The nendothelial cells become swollen, proliferated, and degenerated. Later hyaline ndegeneration of the walls may occur.

During the nclinical course of the disease, hemorrhages are frequent. The bleeding may take nplace from the nose, mouth, lungs, stomach, or kidney, and sometimes from the nuterus and bladder. These hemorrhages generally occur in severe cases of the ndisease. On examining the skin small punctifonn hemorrhages from about 1 to 2 millimeters in diameter are sometimes observed scattered over the skin in greater or less nprofusion. The petechie may occur on the face, neck. chest, abdomen or nextremities. Sometimes larger patches of ecchymosis, in the neighborhood of 1 centimeter in diameter, are observed in the skin. Larger cutaneous effusions of blood are rarely nseen, except at autopsy. The purpuric hemorrhages in bubonic plague usually do nnot appear before the third day of the disease. However, in septicemic plague nthey may be seen earlier.

At autopsy, nthe right side of the heart and the great veins are usually distended with nfluid or only partially coagulated blood. During the disease, the patient nfrequently experiences a feeling of oppression over the precardial region. The nheart sounds at first are clear, and the second pulmonic sound may be naccentuated, but as the disease progresses they become feebler, or nembryocardiac, in character and die first sound may be no longer heard. nSometimes heart failure may occur without any other sign of collapse. It may noccur following exertion. such as sitting up. but it sometimes takes place nwhile the patient is lying in bed. In primary septicemic plague, the course of nwhich is very rapid, the cardiac symptoms are frequently the most prominent nones. In pneumonic plague, the limits of dullness of the heart are sometimes nincreased to the right of the sternum. At onset, the second pulmonic may be naccentuated, but it soon becomes indistinct. As the disease progresses, gallop nrhythm may occur. Death takes place usually from cardiac paralysis and nexhaustion.

Diagnosis

After penetration into the organism plague bacillus fill up the lymphatic nnodes, blood and sputum. Their presence in the urine is very inconstant, but ntheir detection during the bacteriological examination is very valuable for ndiagnostic. All the materials from the patients are to be received before the nantibiotic treatment.

The materials for the bacteriological diagnostics are taken from the ninflamed lymphatic node or bubo with the help of the sterile syringe. After the nskin. which is over it, is cleansed, the node is fixed by the left hand and the nneedle attached to the syringe is slicked into it. It is better to take the npunctate from the peripheral dense part of the bubo. With the slight movement nof the needle several times up and down in the node the aspiration is made. The nreceived liquid is poured into a small test-tube and when with all the required nprecautions it is to be send to the special laboratory, where one drop is used nfor the inoculation into of ligue agar, and another one for the smears, and the nrest is injected under the skin of the guinea-pig.

Treatment

Patients, who suffer from plague necessarily, hospitalize in appropriate nhospitals where they are transported by ambulance.

Treatment should be started already on place of revealing of the patient. nEarly prescription of antibiotics (during the beginning of disease), as a rule, nsalvages it life. Efficiency of therapy by antibiotics in later terms is nconsiderably lowest.

The most effective is nStreptomycinum. At the bubonic form immediately infuse 1 gm of preparation into muscle, and then in hospital indicate 0.5-1.0 gm 3 times per day during one week. At a pulmonary and septic plague a dose of Streptomycinum nenlarge to 5-6 gm. Antibiotics of tetracyclines (oxytetracycline, nchlortetracycline), 0.25-1.0 gm 4-6 times are recommended. From other nantibiotics it is possible to indicate monomicin, morphocyclin, ampicilin. nAfter clinical indications it will be carried out pathogenic and symptomatic ntreatment.

After normalization of a body temperature and reception of negative datas nof bacteriological researching from nasopharynx, sputum, punctate  of bubones- npatients leave hospital after 4-6 week.

 

HEMORRHAGIC FEVERS

(FEBRES HAEMORRHAGICAE)

http://emedicine.medscape.com/article/830594-overview

http://emedicine.medscape.com/article/969877-overview

Group of acute natural foci diseases ncharacterized by a general intoxication, fever, systemic lesion of small-sized nveins with development of a hemorrhagic syndrome.

There are hemorrhagic fevers with a renal nset of symptoms hemorrhagic fever with renal syndrome, Lassa, Ebоlа and Маrburg nfevers, Yellow fever, caused by viruses of miscellaneous sets and labors.

Etiology

The diseases are caused by RNA-containing nviruses of Bunyaviridae family: from Hantaan kind (HFRS), Togaviridae n- Flavivirus (Yellow fever), Filoviridae – (Ebola fever, Marburg fever), Arenaviridae (Lassa fever). They are inactivated at the temperature nof 50 °C during the 30 minutes, at 0-4 °C they preserve stability till 12 hours.

Epidemiology

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http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/vhf.htm

 Source of hemorrhagic fever with a renal nsyndrome are mice-like (about 16 kinds), which are excreting the virus with nurine, stool and saliva. Among the gnawers the transmissible way of causative nagent is possible. The contamination of the person descends by air – dust, nnutritional and contact pathes (routes). The transplacental transmission of a nvirus from the pregnant woman is possible. The probability transmission from nthe ill person is not fixed.

In the natural foci the source of an infection – nmultipapillary rat, and ill in the main (basic) visitants. For Ebola fever and nМarburg the source of contamination in the nature is not known yet, probably, nit is primacy. The relevant feature contagious hemorrhagic fever Lass, Ebola nand Мarburg – capability of transmission of a virus from the person. It results nin originating intrahospital flashes, including among employees of hospitals nand secondary diseases in monogynopaediums. The transfer (transmission) of the nhospital causative agent from the person descends by an aerogenic way, and also nat common use by subjects of household activities, at sexual contacts, is more noften – at maintenance for ill, usage of not sterile medical instruments. The ncontamination is possible both in height of illness and in the period of a nreconvalescence.

There are two forms of a yellow fever: a yellow fever of njungle (natural foci – monkey, hedgehogs) and urban yellow fever (source – ill nperson). Both are diffused by mosquitoes Haemagogus and Aedes n(Fig.4). The contamination those at a puncture of the ill person are possible nat the end of an incubation interval or per the maiden 3 days of illness. A nsensibility of the people overall.

 

Fig.4. Yellow fever mosquitoes

Contagious hemorrhagic fevers Lassa, Ebola and Маrburg are nusual for definite terrains of Africa. The cases of their delivery in countries nof America and Europe by ill primacy and people are described, which one have ncaught and were in an incubation interval of illness. Yellow fever Peru is recorded in countries of Africa, and also in Bolivia, Brazil, and Columbiums. She falls into nto conventional illnesses, the strife with which one is regulated by (with) ninternational medico sanitary rules.

As the majority of causative agents hemorrhagic fever can be ndiffused with the help of the air drop, they are also potential agents of nbiological weapons.

Pathogenesis

 After inoculation of organism of the nperson through an injured skin and mucous of respiratory tract or digestive ntract the virus propagates lymphatic system, falls in a blood with the nsubsequent virusemia. The antipathy, histic destruction, and responses of aorganism by the way immunopathologic processes, changes of a curtailing system nof a blood, endocrine disturbance, development of acute renal failure develops. nThe virus causes a serious capillary toxicosis, multiple hemorrhages, nhemorrhagic eruption, rising of a permeability of capillary tubes with aoutput for limits of a vascular bed of a fluid part of a blood, severe edema of ntissues, violation of microcirculation, and dystrophic changes of internal norgans of an internals.

Clinic

http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/Fact_Sheets/Viral_Hemorrhagic_Fevers_Fact_Sheet.pdf

Hemorrhagic fever with a nrenal syndrome. An incubation interval on the average 10-15 day (duratiofrom 8 about 35 day).

The illness starts is acute with extremely nstrong chills. Temperature of a body is increased till 39-40 °С. nThe visual disturbances, decrease of visual acuity, “mist” before eyes) ncomplain on a sharp headache, backache, muscles of extremities, photophobia. nArise nausea and vomiting. At inspection ill mark paleness nasolabial triangle, nhyperemia of a face, necks, upper half of trunk. The palpebral fissures are nnarrowed down, scleratis. A mucosa of an oral cavity and pharynx are bright red nwith haemorrhages. The Kerning’s signs, Brudzinsky sign can be determined and nstiff neck. Fever 7-9 days is prolonged. Ill at first is provoked, theflaccid, apathetic, sometimes delirium.

On 3-5th day of illness on a neck, lateral nareas of a thoracic cell, in axillaries fossas, above clavicles occurs npetechial eruption. It is sporadic the members small-sized, have the shape of nsprockets and are assorted by the way of red or violet strias the eruptiopresent during all feverish season (Fig.4). Then there are nasal, intestinal, npulmonary bleedings.

Fig.5. Petechial eruption

Cardiac sounds are dull; the initial ntachycardia is replaced by a bradycardia, hypotonia. The phenomena of nbronchitis are possible. Almost for all ill the signs of a lesion of the nalimentary canal are watched: dryness of tongue, nausea, vomiting, inflatioand abdominal pain without definite localization. For 25 % of patients enlarged na liver and spleen and the icterus are possible.

Leading is the renal syndrome patient nshows the sharp back pain, positive sign Pasternatsky from both sides, ndevelopment of an oliguria, and in sever cases – anuria and uremia. In height nof illness find a proteinuria reaching 40 gm/l and higher, hematuria, hyaline nand fibrinous barrels, augmentation of number of cells of a renal epithelium. nIn a blood is sharply raised the level of a filtrate nitrogen, urea, ncreatinine. In a hemogram: the moderate hypochromia anemia, leukocytosis with a nneutrocytosis, thrombocytopenia, increased ESR.

Flow of illness is predominantly severe, nlethality up to 6-8 %. There are also moderate, mild and deleted forms .

Congo-Crimean hemorrhagic nfever. The incubation interval lasts 3-7 day. The illness starts with nchills, hyperthermia till 39-40 °С. There are pains in a head, njoints and muscles, extremities and spin, gaste, repeated vomiting. Vessels of nscleras and conjunctivas injected are provoked, their face, and neck, top of a nchest hyperemic (Fig.5, 6). The mucosa of an oral cavity bloodshots with npunctulate exanthema, the soft palate is hydropic.

The fever stays 7-8 days, for the majority nan ill temperature curve double-peak, the decrease of temperature of a body nwith occurrence (appearance) of a hemorrhagic set of symptoms is ncharacteristic.

 

Fig. 6. Skleritis

Fig.7. Conjunctivitis

On 2-4th the day of illness on a skin of a lateral area of a ntrunk, inguinal and axillary areas, on a gaste and extremities petechias and neruption occurs. The eruptions are of the round or oval shape with legible ncontours of dark – cherry colour, peter on 5-8th day. Simultaneously with aeruption there are odontorrhagias, nose, mild, alimentary canal, and icterus. nThe condition ill is sharply degraded. The hyperemia of a face is replaced by npaleness and одутловатостью. It is marked sleepiness, adynamia, sometimes stiff nneck, and Kernig’s sign. The liver enlarged, the icterus is possible n(probable). The Pasternatsky sign is positive. Develop an oliguria, microhematuria, nand proteinuria. In a peripheral blood: a leukopenia with a neutrocytosis, nthrombocytopenia, augmentation ESR, on 2nd week of illness – relative nlymphocytosis.

The illness can be mild, moderate and sever degree. The nlethality reaches 40 %, predominantly owing to an infectious-toxic shock, nmassive bleedings, and hepatonephric failure.

http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/cchf.htm

Lassa fever. Incubatioperiod lasts 3-17 day. The disease starts with a minor fever, malaise, muscle naches, and conjunctivitis. Step-by-step temperature reaches 39-40 °С nand develops representative pharingitis, more often ulcerative-necrotic. The nulcers have yellowish center with bright erythematic borders, are localized oa soft palate, tonsils and mucosa of a pharynx. In height of illness the nmeningeal signs is marked a strong headache, giddiness, sleepiness, at a normal nstructure of liquor, violation (disturbance) of consciousness. Are watched nnausea, a vomiting, diarrhea, deaquation, abdominal pain and chests, tussis, nthe dysuric phenomena generalized lymphadenopathy, specially enlarged cervical nlymphonoduses. It are marked a relative bradycardia, sometimes dicrotism of nsphygmus. The liver enlarged. In the analysis of a blood – leukopenia with nshift of the formula to the left, the thrombocytopenia, ESR is step-by-step nincreased till 40-80 mm/hour. In moderate and severe cases – moderate bleedings nof miscellaneous localization and petechias an eruption on a skin and mucosa, nless often – roseola, papule, and spot. In very sever cases develops an edema nof a face and neck, exudates (pleural, pericardial, peritoneal). Considerably ncomplicate flow of illness pneumonia, fluid lungs, uremia, and infectious-toxic nshock. Lethality is up to 30-67 of %. In the period of a reconvalescence the npalindromias, deterioration of hearing, baldness are seen an asthenia, nsometimes.

http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/lassaf.htm

Incubation period of Ebola fever n7-14 day,  Marburg fever – 4-9 days a beginning is acute, precursory nsymptoms serve conjunctivitis and exanthemas. Per the maiden days of illness nthere are a strong pain of a head, chills, fever till 39-40 °С, ndorsodynias, muscles, joints, the nausea, vomiting, often watery chair, that ncan result in a considerable deaquation of an organism. The маculo-papular neruption distributing to a neck and a face, upper extremities, breech is nrepresentative, further there is an eruption on palms and base surfaces. Is nwatched enantema on a mucosa of a mild and firm palate, ulcer. Dermatitis of a nscrotum quite often develops. Enough often on the maiden week of illness the lymphadenitis nin occipital, cervical, axillary areas is marked. The lymph nodules enlarged up nto the pea size, mild, are a little morbid.  From the 5-7-th of day of illness nthe hemorrhagic set of symptoms more expressed is affixed than at Lassa fever; nfor the women – parent bleedings, spontaneous abortions. The psychics, nhyperesthesia, cramp is sometimes upset. Complications – bronchopneumonia, norchitis, panreatitis, uveitis. After petering fevers is long the external tags nof illness – deeply sunk down of an eye, cachexia labored gait are saved. In a nblood at first leukopenia, then leukocytosis with a left-shift, nthrombocytopenia. Immediate causes of death – infectous-toxic shock, heart nfailure, cerebral distresses. Lethality – 30-90 %.

http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/ebola.htm

http://www.cdc.gov/ncidod/dvrd/spb/mnpages/dispages/marburg.htm

Yellow fever. Aincubation period is 3-6 days. Distinguish two stages of illness. First stage nis characterized by the sudden beginning with strong chills, fever repeated nvomiting. Ill has pains in a head, back, lower back, bones. It are marked a nsharp hyperemia and edema of a face and neck, eye injected by a blood. A mucosa nof a or pharynx and tongue of bright red colour. The photophobia develops. nPatients are irritable and are provoked. Pulse is fast. From the 3-rd day of nillness there are yellow colouring of a skin and sclera, dot hemorrhages on a nskin, are enlarged a liver and spleen. Then there comes a remission continuing n1-2 days. Temperature of a body is reduced up to the norm, the state of health nis improved.

From the 5-th day of illness the condition of patient is nsharply degraded (stage of venous stasis). Temperature of a body up to 40 °С nand above is again increased, there can be a delirium. The icterus rises. The nface becomes pale yellow with cyanotic tint. Strengtheausea and vomiting. nEmesis masses are of dark brown or black colour. A feces are dark (melena). Oa skin of a trunk both extremities there are petechias and ecchymomas. The ncopious nasal and parent bleedings, bleeding gums are observed. The nephroses – noliguria or anuria, blood and barrels in urine, azotamia are struck.

The tachycardia is replaced by a nbradycardia (Faget’s sign). The arterial pressure is reduced. In the analysis nof a blood a leukopenia – up to 1,5-2,0-10 /l, neutropenia. Encreased ESR. Are ncharacteristic a hyperbilirubinemia (at the expense of both fractions of a npigment), enhancement of activity aminotransferase, in urine – bilirubin, nurobilin, it is a lot of albumin, erythrocytes, leucocytes, barrels.

The fever stage lasts 8-9 days. The death  ncan occure due to bleedings, shock, hepato–renal failure. The lethality makes n5-10 %, in the season of epidemics – up to 60 % and higher.

The abortive forms of illness without aicterus and hemorrhagic set of symptoms are possible mild, deleted.

Diagnosis

The diagnostic hemorrhagic fever is carried out with nallowance for of epidemiological anamnesis (seasonal prevalence, connectiowith the causative agent, contact with ticks, rodens and exotic animal) and nrepresentative clinical developments acute onset, fever, hemorrhagic syndromes. nThe diagnosis confirms virology and serological methods of research. Causative nagent of Lassa fever,  Ebola and Маrburg – on culture of cells Vero or oguinea pigs   epidemic parotitises. “The Gold standard” – detection of RNA of nthe originator. For serodiagnosis will use RCC, RN, RIA, RIIF, IFA with double nserums of patients, immunosorbent methods. With material of sick persons work nonly in the specially equipped labs, adhering to strick safety measures n(Fig.8).

Fig.8. Specially equipped department for treatment

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The differential diagnosis

As against hemorrhagic fever, for an ill flu the hemorrhagic ndevelopments are very seldom. The high contagiousness, more short feverish nseason(term), availability катарального of a set of symptoms,  Morozkin sign is ncharacteristic for him(it). In outwashes with a slimy nasopharynx by a method nfind antigens of a virus of a flu.

The virus hepatitises often start step-by-step, with npreicteric of the period, the flow which one is accompanied catarrhal,dyspeptic, nasteno-vegetative syndromes. In height of illness are not watched a hyperemia nand одутловатость of a face, горячка, озноб, lesion of nephroses. The nhemorrhagic set of symptoms arises only at a very serious degree of illness.

The тyphoid-paratyphoid diseases have a gradual beginning, nstepwise temperature rise, reference predominantly roseola eruption. Easy ndiagnostic confirming epidemiological anamnesis, research of a hemoculture, nserological tests.

At a canicola fever the strong muscle pains, specially iикроножных muscles are characteristic; a liver, often icteric forms(shapes) of nillness with the sharply expressed hyperbilirubinemia practically always nenlarged; in a blood on all stretch(extent) of illness – hyperleukocytosis with na neutrocytosis, shift of the formula to the left, very high ESR. The diagnosis nconfirms by the laboratory data – detection of the originator at a dark field nmethod of a blood and urine, serological tests RMA with leptospira.

For a hemorrhagic vasculitis are characteristic long-lived nrecurrent flow, lesion of joints, and localization of an eruption on extensor nsurfaces of top and bottom extremities.

At Q fever are struck mild with development of a pneumonia, nare enlarged a liver and lien.

For a malaria pathognomic representative attacks of a fever nwith definite periodicity. At examination find a splenomegaly, in a blood – nmalarial plasmodium.

The meningococcal infection contamination starts is acute, nbut in a clinical picture of the generalized form (shape) on the foreground nmore often the meningitis or sepsis with a copious hemorrhagic eruption acts, nit is a lot of members of the star-shaped form (shape) with a necrosis of aepithelium. In the analysis of a blood a hyperleukocytosis with shift of the nformula to the left, enlarged ESR. The diagnosis confirms by detectioменингококка in sowings from a nasopharynx, blood and liquor.

Treatment

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 All sick are subject to mandatory nhospitalization. The basis of treatment make desintoxication (i.v. 5-10 % nglucose, polyionic solutions, 5 % donor Albuminum), glucocorticoids, strife nwith a hemorrhagic set of symptoms (Ascorutinum, Vicasolum, Dicynonum, nEtamsylatum, calcium Dobesilat, Adroxonum, Acidum aminocapronicum;  blood). Icase of renal failure (for decreasing of remic intoxication a gastric lavage nand intestine with 2 % sodium of Sodium hydrogenum solutions; at increasing of nacute renal failure and infectious-toxic shock – extra corporal haemodialysis). nAntiviral drugs per the maiden days of illness assign virolex, ribavirin, ninducers of endogenic interferonogenesis (cycloferon, groprinosin), specific nimmunoglobulin or plasma. The antibiotics in case of bedding of a bacterial ninfection contamination.

Prophylaxis and measures in the locus

 At hemorrhagic fever with a renal nsyndrome the preventive measures are directed on strife with the gnawers. Are noffered inactivated cultural and cerebral vaccines (China, Russia, Japan), recombinant of a vaccine (USA, China), which one have appeared effective in endemial nterrains. With this purpose carry out a disinfestation in the natural locuses, nputtings, and also collect of tongs with animal and poultries. For a ndisinfestation will use gexachloran. In a burn-time in a field and on timber nloggings it is recommended to use a special protective clothing and repellents.

Medical observation in the focus for 10 ndays. Conduct mandatory final disinfection with 3 % Chloraminum solution and nchlorofos. For contact persons or one who was bitten by tongs in endemial ndistricts enter a specific immunoglobulin i.m. in doses 5-7.5 ml for adult, n2.5-3.5 ml – for children. Apply a vaccine, inactivated by formalinum for nspecific prophylaxis of Congo-Crimean hemorrhagic fever.

Primary antiepidemic measures after detectioof sick with contagious hemorrhagic fevers Lassa, Ebola and Marburg, and also nyellow fever same, as well as at other quarantine infection contaminations. nPatient will hospitalize in hermetic isolation ward with independent life nsupport, monitor behind absence of an air inflow from a zone of isolation ward, npaste vent holes. The staff should work in a protective clothing, including a nmask or respiratory supplied with a special inhaler. Conduct careful current nand final disinfection.

The specific prophylaxis contagious nhemorrhagic fever. The quarantine for arriving from epidemic areas lasts 17 nday. In endemial districts of  yellow fever vaccination of the population by aalive “Dakar” vaccine or 17-D is carried out.  The immunodefence is saved 10 nyears, and then make a revaccination.

Ebola nhemorrhaghic fever

Ebola nhemorrhaghic fever is a severe, often fatal disease in humans and other nprimates that has appeared sporadically since its was first seen in 1976 in Zaire, where it killed 318 people. It is caused by infection with the Ebola virus, named nafter a river near where it was first identified.

The nexact origin and location of the Ebola virus is unknown. But researchers nbelieve the virus is maintained in an animal host in Africa. Confirmed cases of nEbola in humans have been reported in Uganda, the Democratic Republic of Congo,Gabon, Sudan and the Ivory Coast. Ebola-Reston virus, a strain that causes ndisease ionhuman primates but not people, sparked a scare when it caused nsevere illness and death in monkeys imported to research facilities in the United States from the Phillipines. Several laboratory researchers became infected with the nvirus but did not become ill

The virus can be transmitted through blood or other bodily nsecretions. People can also be infected with Ebola through contact with ncontaminated objects such as needles. The virus has shown an ability to spread nthrough airborne particles under research conditions, but this type of ntransmission hasn’t been seen in a real-world setting.

Within a few days of infection, patients usually experience nhigh fever, headache, muscle aches, stomach pain, fatigue and diarrhea. nPatients may also experience less common symptoms such as a sore throat, nhiccups, rash, red and itchy eyes, vomiting blood and bloody diarrhea. Withione week of infection, patients often experience chest pain, shock and death. nOther symptoms may include blindness and bleeding.

There nis no standard treatment for Ebola fever. Currently, patients receive nsupportive therapy, including balancing their fluids and electrolytes, nmaintaining their blood pressure and breathing, and treating them for any ncomplicating infections.

Yellow fever

Yellow fever (YF) is a viral haemorrhagic fever transmitted nby infected mosquitoes.

Yellow fever can be recognized from historic texts stretching nback 400 years. Infection causes a wide spectrum of disease, from mild symptoms nto severe illness and death. The “yellow” in the name is explained by nthe jaundice that affects some patients, causing yellow eyes and yellow skin.

There nare three types of transmission cycle: sylvatic, intermediate and urban. nAll three cycles exist in Africa, but in South America, only sylvatic and urbayellow fever occur.

n

Sylvatic (or jungle) yellow fever noccurs in tropical rainforests where monkeys, infected by sylvatic mosquitoes, npass the virus onto other mosquitoes that feed on them; these mosquitoes, iturn bite and infect humans entering the forest. This produces sporadic cases, nthe majority of which are often young men working in the forest e.g. logging.

The nintermediate cycle of yellow fever transmission occurs in humid or nsemi-humid savannahs of Africa, and can produce small-scale epidemics in rural nvillages. Semi-domestic mosquitoes infect both monkey and human hosts and nincreased contact between man and infected mosquito leads to disease. This is nthe most common type of outbreak seen in recent decades in Africa.

Urban yellow fever results in large nexplosive epidemics when travellers from rural areas introduce the virus into nareas with high human population density. Domestic mosquitoes, most notably Aedes naegypti, carry the virus from person to person. These outbreaks tend to nspread outwards from one source to cover a wide area.

Yellow fever can be prevented by vaccination. In order to protect people living in areas at high risk of nyellow fever transmission, WHO’s dual strategy for prevention of yellow fever nepidemics relies on preventive mass immunization campaigns followed by infant nroutine immunization.

Yellow fever causes epidemics that can affect 20% of the npopulation. When epidemics occur in unvaccinated populations, case-fatality nrates may exceed 50%. No treatment beyond supportive care exists.

 

Photo nessay: Controlling the Marburg outbreak in Angola

The safe injection campaign in Uige, Angola 2005

 Disease Outbreak News: Marburg

 Marburg haemorrhagic fever – fact sheet

(French) (Spanish) (Portuguese)

 Controlling nthe Marburg outbreak in Angola: Marburg virus photo essay

 Images from the outbreak of Marburg haemorrhagic fever in Uige nProvince, Angola 2005

Marburg haemorrhagic fever is a severe and highly fatal disease ncaused by a virus from the same family as the one that causes Ebola nhaemorrhagic fever. These viruses are among the most virulent pathogens knowto infect humans. Both diseases are rare, but have a capacity to cause dramatic noutbreaks with high fatality.

Illness caused by Marburg virus begins abruptly, with severe nheadache and severe malaise. Many patients develop severe haemorrhagic nmanifestations between days 5 and 7, and fatal cases usually have some form of nbleeding, often from multiple sites. The disease has no vaccine and no specific ntreatment. Case fatality rates have varied greatly, from 25% in the initial nlaboratory-associated outbreak in 1967, to more than 80% in the Democratic nRepublic of Congo from 1998-2000, to even higher in the outbreak that began in Angola in late 2004.

For nmore information

– Risk Factors for Marburg Hemorrhagic Fever, Democratic Republic of nthe Congo Emerging Infectious Diseases Journal.Volume 9, Number 12, December 2003

– Viral haemorrhagic fever/Marburg, Democratic Republic of the Congo Weekly nEpidemiological Record. 21 May 1999, Vol 74, 20

– Infection control for viral haemorrhagic fevers in the Africahealth care setting

– Viral haemorrhagic fevers. Report of a WHO Expert Committee (pages n78-88)

– Surveillance of Ebola/Marburg fevers

– Viral haemorrhagic fevers of man. Bulletin of nthe World Health Organization, 56 (6): 819-832 (1978)

– Marburg and Ebola virus infections: a guide for their diagnosis, nmanagement, and control

Prophylaxis and measures in the locus. At nhemorrhagic fever with a renal set of symptoms the preventive measures are ndirected on strife with the gnawers. Are offered inactivated vaccines (China, Russia, Japan), recombinant of a vaccine n(USA, China), which one have appeared effective in endemial terrains. With this npurpose carry out a disinfestation in the natural locuses, puttings, and also ncollect of tongs with animal and poultries. For a disinfestation will use ngeksachloran. In a burn-time in a field and on timber loggings it is nrecommended to use a special protective clothing and repellents.

For focus of nhemorrhagic fever after hospitalization ill establish medical observation for n10 days. Carry out mandatory final disinfection with противоклещевой by processing n3 % by solution of Chloraminum and Chlorofos. To faces, former in a contact nwith ill, and also the one who was bitten by(with) tongs, in endemial districts nenter a specific immunoglobulin в/м in doses 5-7,5 mls for adult, 2,5-3,5 mls – for nchildren. In the endemial locuses Omsk hemorrhagic fever for an immunization of nthe people from group of risk will use also formolvaxine.

Primary antiepidemic measures after ndetection by ill contagious hemorrhagic fevers Lassa, Ebola and Marburg, and also nyellow fever same, as well as at other quarantine infection contaminations. The nintrahospital diffusion is peculiar to it горячкам, therefore nill will hospitalize in hermetic isolation ward with independent life support, nmonitor behind absence of an air inflow from a zone of isolation ward, paste nvent holes. The nosotrophy demands special opening-up. The staff should work ia protective clothing, including a mask or respiratory almuce supplied with a nspecial inhaler. Ill yellow fever isolate in a room reliably protected from nзалета of mosquitos. nFor strife with last will use insecticides. Carry out careful current and final ndisinfection.

The specific prophylaxis contagious nhemorrhagic fever. The quarantine for arriving from terrain, where they are nrecorded, lasts 17 day. In endemial districts of a yellow fever the nbacterination of the population by an alive vaccine “of «Dakar” or n17-D is carried nout. Both enter накожно or subcutaneously. The immunodefence is saved 10 years, and nthen make a revaccination. The compulsory vaccinations are subject faces nleaving in endemically districts of Africa or Southern America. The nbacterination is recorded in « the International testimony ». The not vaccinated nfaces arriving from endemial districts are subject to quarantine for 6 day, ntransportation facilities – processing by insecticides.

 

TETANUS

Definition

Tetanus is a disease of the nervous system characterized by persistent ntonic spasm, with violent brief exacerbations. The spasm almost always ncommences in the muscles of the neck and jaw. causing closure of the jaws (trismus, nlockjaw) and involves the muscles of trunk more than those of the limbs. It nis always acute in onset, and a very large proportion of those affected die.

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History

Nicolaier isolated a strychnine-like toxin from anaerobic soil bacteria nin 1884; 6 years later. Behring and Kitasato described active immunization with ntetanus toxoid. This latter discovery should have reduced tetanus to a nhistorical curiosity, but we still fail to fulfill this promise.

Epidemiology

The global incidence of tetanus is thought to be about one million cases nannually, or about 18 per 100,000 population. The U.S. Centers for Disease nControl and Prevention (CDC) receive reports of about 70 domestic cases per nyear; this represents underreporting of about 60 %. Most reported cases are ipatients over the age of 60: this is one of several indicators that waning nimmunity is an important risk factor. This may be a particularly serious nproblem in older women. In developing countries, mortality rates are as high as n28 per 100,000.

Neonatal ntetanus accounts for about half of the tetanus deaths in developing nations. Ia study of neonatal mortality in Bangladesh 112 of 330 deaths were attributed nto tetanus. Up to one-third of neonatal tetanus cases are in children born to nmothers of a previously afflicted child, highlighting failure to immunize as a nmajor cause of tetanus. Immunization programs clearly decrease neonatal tetanus ndeaths.

Acute injuries naccount for about 70 % of  cases, evenly divided between punctures and nlacerations. Other identifiable conditions are noted in 23 %, leaving about 7 % nof cases without an apparent source. Other studies cite rates of cryptogenic ntetanus as high as 23 %.

Etiology

Clostridium tetani is an obligate nanaerobic bacillus that is gram-positive in fresh cultures but that may have nvariable staining in older cultures or tissue samples (Fig.13). During growth, nthe bacilli possess abundant flagellae and are sluggishly motile. Two toxins, ntetanospasmin (commonly called tetanus toxin) and tetanolysin, are produced nduring this phase. Tetanospasmin is encoded on a plasmid, which is present iall toxigenic strains. Tetanolysin is of uncertain importance in the npathogenesis of tetanus. Mature organisms lose their flagellae and develop a nterminal spore, coming to resemble a squash racquet. The spores are extremely nstable in the environment, retaining the ability to germinate and cause disease nindefinitely. They withstand exposure to ethanol, phenol, or formalin, but cabe rendered noninfectious by iodine, glutaraldehyde. hydrogen peroxide, or nautoclaving at 121°C and 103 kPa for 15 minutes. Growth in culture is optimal nat 37°C under strictly anaerobic conditions, but culture results are of no ndiagnostic value. Antibiotic sensitivity is discussed below.

 

 

Fig.13. Clostridium ntetani

Pathogenesis

Tetanospasmin is synthesized as a single 151-kD chain that is cleaved nextracellularly by a bacterial protease into a 100-kD heavy chain and a 50-kD nlight chain (fragment A), which remain connected by a disulfide bridge. The nheavy chain can be further divided into fragments В and С by pepsin. The heavy nchain appears to mediate binding to cell surface receptors and transport proteins, nwhereas the light chain produces the presynaptic inhibition of transmitter nrelease, which produces clinical tetanus. The nature of the receptor to which ntetanospasmin binds, previously thought to be a ganglioside, remains debated. nThe toxin enters the nervous system primarily via the presynaptic terminals of nlower motor neurons, where it can produce local failure of neuromuscular ntransmission. Tetanospasmin appears to act by selective cleavage of a proteicomponent of synaptic vesicles, synaptobrevin II. It then exploits the nretrograde axonal transport system, and is carried to the cell bodies of these nneurons in the brain stem and spinal cord, where it expresses its major npathogenic action.

Once the toxienters the central nervous system, it diffuses to the terminals of inhibitory ncells, including both local glycinergic interneurons and descending GABAergic nneurons from the brain stem. By preventing transmitter release from these ncells, tetanospasmin leaves the motor neurons without inhibition. This produces nmuscular rigidity by raising the resting firing rate of motor neurons, and also ngenerates spasms by failing to limit reflex responses to afferent stimuli. nExcitatory transmitter release in the spinal cord can also be impaired, but the ntoxin appears to have greater affinity for the inhibitory systems. The nautonomic nervous system is affected as well: this is predominantly manifested nas a hypersympathetic state induced by failure to inhibit adrenal release of ncatecholamines.

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Clinical manifestations

Tetanus is classically divided into four clinical types: generalized, nlocalized, cephalic, and neonatal. These are valuable diagnostic and prognostic ndistinctions, but reflect host factors and the site of inoculation rather thadifferences in toxin action. Terms describing the initial stages of tetanus ninclude the incubation period (time from inoculation to the first symptom) and nthe period of onset (time from the first symptom to the generalized spasm). The nshorter these periods, the worse the prognosis. Various rating nscales are available. Certain portals of entry (e.g., compound fractures) are nassociated with poorer prognoses. Tetanus may be particularly severe inarcotic addicts, for unknown reasons.

Generalized tetanus is the most commonly recognized form, and oftebegins with trismus (“lockjaw”, masseter rigidity)(Fig.14) and a nrisus sardonicus (increased tone in the orbicularis oris)(Fig.15). Abdominal nrigidity may also be present. The generalized spasm resembles decorticate nposturing, and consists of opisthotonic posturing with flexion of the arms and nextension of the legs. The patient does not lose consciousness, and experiences nsevere pain during each spasm, which are often triggered by sensory stimuli. nDuring the spasm, the upper airway can be obstructed, or the diaphragm may nparticipate in the general muscular contraction. Either of these compromise respiration, nand even the first such spasm may be fatal. In the modern era of intensive ncare, however, the respiratory problems are easily managed, and autonomic ndysfunction, usually occurring after several days of symptoms, has emerged as nthe leading cause of death.

Fig.14. nExamination of chewing muscles reflex

 

The illness can progress for about 2 weeks, reflecting nthe time required to complete the transport of toxin, which is already intra-axonal nwhen antitoxin treatment is given. The severity of illness may be decreased by npartial immunity. Recovery takes an additional month, and is complete unless ncomplications supervene. Lower motor neuron dysfunction may not be apparent nuntil spasms remit, and recovery from this deficit ieuromuscular ntransmission may take additional weeks. Recurrent tetanus may occur if the patient ndoes not receive active immunization, because the amount of toxin produced is ninadequate to induce immunity.

 

Fig.15. Risus nsardonicus

 

Localized tetanus involves rigidity of the muscles associated with the nsite of spore inoculation. This may be mild and persistent, and often resolves nspontaneously. Lower motor neuron dysfunction (weakness and diminished muscle ntone) is often present in the most involved muscle. This chronic form of the ndisease probably reflects partial immunity to tetanospasmin. However, nlocalized tetanus is more commonly a prodrome of generalized tetanus, which noccurs when enough toxin gains access to the central nervous system.

Cephalic tetanus is a special form of localized disease affecting the ncranial nerve musculature. Although earlier reports linked cephalic tetanus to na poor prognosis, more recent studies have revealed many milder cases. A lower nmotor neuron lesion, frequently producing facial nerve weakness, if ofteapparent. Extraocular muscle involvement is occasionally noted.

Neonatal tetanus follows infection of the umbilical stump, most commonly ndue to a failure of aseptic technique where mothers are inadequately immunized. nCultural practices may also contribute. The condition usually presents with ngeneralized weakness and failure to nurse; rigidity and spasms occur later. The nmortality rate exceeds 90%, and developmental delays are common among nsurvivors. Poor prognostic factors include age less than 10 days, symptoms for nfewer than 5 days before presentation to hospital, and the presence of risus nsardonicus, fever, opistotonus (Fig.16).

Fig.16. nOpistotonus iew born

Diagnosis

Tetanus is diagnosed by clinical observation, and has a limited ndifferential diagnosis. Laboratory testing cannot confirm or exclude the ncondition, and is primarily useful for excluding intoxications that may mimic ntetanus. Electromyographic studies are occasionally useful in questionable ncases. Such testing becomes more important wheo portal of entry is apparent. nAntitetanus antibodies are undetectable in most tetanus patients, but many nreports document the disease in patients with antibody levels above the ncommonly cited “protective” concentration of 0.01 IU/liter. Rare npatients apparently develop antibodies that are not protective.

Attempts to culture C. tetuni from wounds are not useful idiagnosis, because (1) even carefully performed anaerobic cultures are nfrequently negative; (2) a positive culture does not indicate whether nthe organism contains the toxin-producing plasmid; and (3) a positive nculture may be present without disease in patients with adequate immunity.

Strychnine npoisoning, in which glycine is antagonized, is the only condition that truly nmimics tetanus; toxicologic studies of serum and urine should be performed whetetanus is suspected, and tetanus should be considered even if strychnine npoisoning appears likely. Because the initial treatment of tetanus and nstrychnine intoxication are similar, therapy is instituted before the assay nresults are available. Dystonic reactions to neuroleptic drugs or other central ndopamine antagonists may be confused with the neck stiffness of tetanus, but nthe posture of patients with dystonic reactions almost always involves lateral nhead turning, which is rare in tetanus. Treatment with anticholinergic agents n(benztropine or diphenhydramine) is rapidly effective against dystonic nreactions. Dental infections may produce trismus, and should be sought, but do nnot cause the other manifestations of tetanus.

 

Treatment

The patient with tetanus requires simultaneous attention to several nconcerns. Attention to the airway and to ventilation is paramount at the time nof presentation, but the other aspects of care, especially passive nimmunization, must be pursued as soon as the respiratory system is secure.

Tetanic spasms sometimes demand that the airway be secured before other nlines of therapy are possible. An orotracheal tube can be passed under sedatioand neuromuscular junction blockade; a feeding tube should be placed at the nsame time. Because the endotracheal tube may stimulate spasms, an early ntracheostomy may be beneficial.

Benzodiazepines nhave emerged as the mainstay of symptomatic therapy for tetanus. These drugs nare GАВА agonists, and thereby indirectly antagonize the effect of the toxin. nThey do not restore glycinergic inhibition. The patient should be kept free of nspasms, and may benefit from the amnestic effects of the drugs as well. nDiazepam has been studied most intensively, but lorazepam or midazolam appear nequally effective. Tetanus patients have unusually high tolerance for the nsedating effect of these agents, and commonly remain alert at doses normally nexpected to produce anesthesia.

Intravenous midazolam (5-15 mg/h or more) is effective and does not ncontain propylene glycol, but must be given as a continuous infusion because of nits brief half-life. Propofol infusion is also effective, but is currently very nexpensive, and the amount necessary to control symptoms may exceed the npatient’s tolerance of the lipid vehicle. When the symptoms of tetanus subside, nthese agents must be tapered over at least 2 weeks to prevent withdrawal. nIntrathecal baclofen is also effective in controlling tetanus, but has no clear nadvantage over benzodiazepines. Neuroleptic agents and barbiturates, previously nused for tetanus, are inferior for this indication and should not be used.

Most tetanus patients will still have the portal of entry apparent whethey present. If the wound itself requires surgical attention may be performed nafter spasms are controlled. However, the course of tetanus is not affected by nwound de-bridement.

Passive immunization with human tetanus immunoglobulin (HTIG) shortens nthe course of tetanus and may lessen its severity. A dose of 500 units appears nas effective as larger doses. There is no apparent advantage to nintrathecal HTIG administration. Intrathecal HTIG has also been showineffective ieonatal tetanus. Pooled intravenous immunoglobulin has beeproposed as an alternative to HTIG. Active immunization must also be initiated.

The role of antimicrobial therapy in tetanus remains debated. The ivitro susceptibilities of C. tetani include metronidazole, penicillins, ncephalosporins, imipenem. macrolides, and tetracy-cline. A study comparing oral nmetronidazole to intramuscular penicillin showed better survival, shorter nhospitalization, and less progression of disease in the metronidazole group. nThis may reflect a true advantage of metronidazole over penicillin, but it more nlikely corresponds to a negative effect of penicillin, a known GABA antagonist. nTopical antibiotic application to the umbilical stump appears to reduce the nrisk of neonatal tetanus.

Nutritional support should be started as soon as the patient is stable. nThe volume of enteral feeding needed to meet the exceptionally high caloric and nprotein requirements of these patients may exceed the capacity of the ngastrointestinal system.

The mortality nrate in mild and moderate tetanus is presently about 6 percent; for severe ntetanus, it may reach as high as 60%, even in expert centers. Among adults, age nhas very little effect on mortality, with octogenarians and nonagenarians nfaring as well as middle-aged patients. Tetanus survivors often have serious npsychological problems related to the disease and its treatment that persist nafter recovery, and that may require psychotherapy.

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Prophylaxis

Tetanus is preventable in almost all patients, leading to its descriptioas the “inexcusable disease.” A series of 3 monthly intramuscular injections of nalum-adsorbed tetanus toxoid provides almost complete immunity for at least 5 nyears. Patients less than 7 years of age should receive combined ndiphtheria-tetanus-pertussis vaccine, and other patients combined ndiphtheria-tetanus vaccine. Routine booster injections are indicated every 10 nyears; more frequent administration may increase the risk of a reaction. Some npatients with humoral immune deficiencies may not respond adequately to toxoid ninjection: such patients should receive passive immunization for tetanus-prone ninjuries regardless of the period since the last booster. Most young patients nwith human immunodeficiency virus (HIV) infection appear to retain antitetanus nantibody production if their primary immunization series was completed prior to nacquiring HIV. Vitamin A deficiency interferes with the response to tetanus ntoxoid. A recent report documented tetanus in babies of women immunized with ntoxoid later shown to be devoid of potency; this disconcerting report nunderscores the need for quality control in toxoid production.

Although any wound may be inoculated with tetanus spores. Some types of ninjury are more frequently associated with tetanus and are therefore deemed ntetanus-prone. These include wounds that are contaminated with dirt, saliva, or nfeces; puncture wounds, including unsterile injections; missile injuries; nburns; frostbite; avulsions; and crush injuries. Patients with these wounds who nhave not received adequate active immunization in the past 5 years, or in whom nimmunodeficiency is suspected. should receive passive immunization with HTIG n(250-500 IU, intramuscularly) in addition to active immunization.

Mild reactions to tetanus toxoid (e.g.. local tenderness, edema, nlow-grade fever) are common. More severe reactions are rare; some are actually ndue to hypersensitivity to the preservative thiomersal.

IV. Convalescent nstage: 2-6 weeks

 

ANTHRAX

Definition

Acute ninfection in both animals and humans in three forms: cutaneous, respiratory, nand gastrointestinal. The incidence of anthrax has decreased in developed ncountries but it remains a considerable health problem in developing countries.

Etiology

Pus or tissue from patients suspected to have anthrax should be stained nby both Gram stain, to reveal gram-positive bacilli, and polychrome nmethylene blue, to show the polypeptide capsule. Bacilli are usually nabundant in the specimen and easy to culture on standard blood or nutrient agar n(Fig.17).

Fig.17. Bacillus nantracis

 

 In heavily ncontaminated specimens such as stool it may be necessary to use selective agar nor decontamination methods that rely on the і resistance of the anthrax spores nto heat or ethanol. The colonies  are gray-white to white and nonhemolytic. nIdentification of the isolate depends on biochemical tests, presence of a ncapsule, і lack of motility, catalase positivity, lysis by nγ-bacteriophage, penicillin susceptibility, and aerobic endospore nproduction. Commercially available test strips (API Products, Plainview, NY) and fluorescent antibody staining can be used to aid identification.

Epidemiology

Anthrax is usually a disease of herbivores and only incidentally infects nhumans who come into contact with infected animals or their products. Because nanthrax remains a problem in developing countries, animal products imported nfrom these areas continue to pose a risk.

Human cases may occur in an industrial or in an agricultural environment. nIndustrial cases result from contact with anthrax spores that contaminate raw nmaterials that are used in manufacturing processes. In the United States, occasional epidemics occurred in industrial settings, probably related to nthe processing of batches of highly contaminated imported animal fibers, nparticularly goat hair. These epidemics were primarily of cutaneous anthrax.

One epidemic nwas recently reported in Switzerland. Within less than 3 years, 25 workers ione textile factory contracted the disease; 24 cases had cutaneous and 1 ninhalation anthrax. The infection was imported in goat hair from Pakistan. The rarity of the illness contributed to a general lack of experience and ntherefore hindered recognition of the clinical symptoms. In addition, repeated nattempts failed to identify the pathogenic agent conclusively.

Human cases of anthrax in an agricultural environment result from direct ncontact with animals that are sick or have died from anthrax.

In Africa there have been multiple epidemics of human disease associated with epizootics of nanthrax in cattle. The largest reported agricultural outbreak occurred in Zimbabwe, with more than 10,000 cases reported between 1979 and 1985. Endemic cases ncontinue to occur in the involved area. The majority of patients had cutaneous ninfections located primarily on the exposed parts of the body; some ngastrointestinal cases were also reported. Domestic cattle deaths were noted. A nsimilar large outbreak of human and animal anthrax occurred in Chad, mainly in the Department of Chari Baguirmi, from September to December 1988, ninfecting more than 50 % of donkeys and horses. There were 716 human cases nreported, with 88 deaths.

In Africawildlife, which cannot easily be vaccinated and in which the other aspects of ncontrol are not relevant, the disease remains a major cause of uncontrolled nmortality in herbivores.

Organisms caalso be transmitted by a common vehicle such as food (meat), although this is nmore rare. Large outbreaks have been reported in Thailand and Russia. This last outbreak of human anthrax occurred iorth central Russia in 1979, in which the government health authorities of the former U.S.S.R. reported nthat the source of infection was contaminated meat. Officially there were 96 ncases: 79 of gastrointestinal anthrax and 17 of cutaneous anthrax. However, nthere is novel evidence concerning the real nature of this anthrax outbreak. nIntelligence authorities in the United States had initially reported hundreds nof fatalities, including military personnel, and had suspected that aexplosion at a secret germ warfare facility in Sverdlovsk had sent deadly nanthrax spores airborne. The United States has repeated this allegation, but it nnever formally accused the former U.S.S.R. of violating the germ warfare treaty nor substantiated its charge. The hospital records of the patients affected by nthis outbreak including the autopsy reports have been unavailable.

Recently two nRussian pathologists published hidden secret information describing the nnecropsy of 42 cases, which consistently revealed pathologic lesions diagnostic nof inhalation anthrax. Main features include hemorrhagic necrosis of the nthoracic lymph nodes in the lymphatic drainage of the lungs and hemorrhagic nmediastinitis. This information underscores the potential use of B. nanthracis in biological warfare.

Pathogenesis

The virulence of B. anthracis is determined by the presence of nthree components: edema toxin, lethal toxin, and capsular material. To exert ntheir effect within cells, both edema and lethal toxin require participation of na common transport protein called protective antigen. The capsule material ncontains poly-D-glutamic acid, which helps protect the bacillus from ingestioby phagocytes. Production of the toxic factors is regulated by one plasmid and nthat of the capsular material by a second plasmid.

The effects of nanthrax toxin components on humaeutrophils have been studied in detail. nPhagocytosis of opsonized and radiation killed B. anthracis was not naffected by the individual anthrax toxin components. However, a combination of nlethal toxin and edema toxin inhibited bacterial phagocytosis and blocked the noxidative burst of polymorphonuclear neutrophils. The two-toxin combinatioalso increased intracellular cyclic AMP levels. These studies suggest that two nof the protein components of anthrax toxin increase host susceptibility to ninfection by suppressing polymorphonuclear neutrophil function and impairing nhost resistance.

Experiments nperformed in animals suggest that spores deposited beneath the skin or in the nrespiratory or intestinal mucosa germinate and the resulting vegetative forms nmultiply and produce a toxin. The local lesion results from the action of the ntoxin on the surrounding tissue, which causes tissue necrosis. The toxin or norganisms or both may disseminate by the vascular system, causing systemic nsymptoms and signs of toxicity or bacteremia. Organisms are also often picked nup by the lymphatic system, resulting in lymphangitis and lymphadenopathy.

Morbid nanatomy

The most significant findings at autopsy are those seen in patients who nhave died of inhalation anthrax. The classic finding is that of hemorrhagic nmediastinitis with enlarged, hemorrhagic lymphadenitis. There may be ninflammation of the pleura and some pleural effusion. Some patients may have nhemorrhagic meningitis, and hemorrhages may be seen in the gastrointestinal ntract.

In deaths due to gastrointestinal anthrax there is typically hemorrhagic nenteritis, with congestion, thickening, and edema of the intestinal walls. nMucosal ulcers with necrosis may be seen in the terminal ileum and cecum. The nregional lymph nodes are enlarged, edematous, and hemorrhagic with some nnecrosis. There may be acute splenitis. Peritonitis with ascitic fluid is oftepresent.

Clinical manifestations

Approximately 95 % of anthrax cases in developed counties are cutaneous nand 5 % are respiratory: confirmed epidemic cases of gastrointestinal anthrax nhave often been reported in “Third World” countries.

The clinical presentation of cutaneous anthrax is so ncharacteristic that the diagnosis is not often missed by physicians familiar nwith the disease. Most of the cases occur in exposed skin areas mostly on the narms and hands followed by the face and neck. The infection begins as a npruritic papule that resembles an insect bite. The papule enlarges and within 1 nor 2 days develops into an ulcer surrounded by vesicles. The lesion is usually n1-3 cm in diameter and usually remains round and regular (Fig.18, 19). A ncharacteristic black necrotic central eschar develops later with associated nedema (Fig.20, 21). The lesion is most often painless and may first be noticed nbecause of pruritus. After 1-2 weeks the lesion dries, and the eschar begins to nloosen and shortly thereafter separates, revealing a permanent scar. There may nbe regional lymphangitis and lymphadenopathy and some systemic symptoms such as nfever, malaise, and headache. Antibiotic therapy does not appear to change the nnatural progression of the lesion itself: however, it will decrease or inhibit ndevelopment of edema and systemic symptoms. Differential diagnosis include nconditions due to potential contact with infected animals such as plague and ntularemia.

 

Fig.18. nAnthrax carbuncle

Fig.19. nAnthrax carbuncle

 

Fig.20. Edema nof skin

 

Fig.21. Edema nof skin

 

Respiratory anthrax shows a biphasic clinical patterwith a benign initial phase followed by an acute, severe second phase that is nalmost always fatal. The initial phase begins as a nonspecific illness nconsisting of malaise, fatigue, myalgia, mild fever, nonproductive cough, and, noccasionally, a sensation of precordial oppression.

The illness may cause disorder of a mild upper respiratory tract ninfection such as a cold or viral influenza. After 2-4 days, the patient may show nsigns of improvement. However, there is then the sudden onset of severe nrespiratory distress characterized by severe hypoxia and dyspnea. In several ncases, subcutaneous edema of the chest and neck has been described. The pulse, nrespiratory rate. and temperature become elevated. Physical examination reveals nmoist, crepitant rales over the lungs and possibly evidence of pleural neffusion. Radiographic examination of the chest may reveal widening of the nmediastinum and pleural effusion. Patients soon become hypotensive and nsepticemia and meningitis may develop. Death occurs in most persons with ninhalation anthrax within 24 hours after the onset of the acute phase. nInhalation anthrax is very difficult to diagnose early.

The incubation period of gastrointestinal anthrax is commonly 3-7 ndays. There are two clinical presentations following ingestion of B. nantracis-contaminated food: abdominal and oropharyngeal.

The symptoms of abdominal anthrax are initially nonspecific and include nnausea, vomiting, anorexia, and fever. Lesions are frequently described in the ncecum and adjacent areas of the bowel. Some reports have described lesions ithe large bowel, and rarely in the duodenum. With progression of the disease nabdominal pain, hematemesis and bloody diarrhea develop. With further nprogression toxemia develops, with shock, cyanosis, and death. The time from nonset of symptoms to death has most frequently varied from 2 to 5 days.

In the noropharyngeal form edema and tissue necrosis occur in the cervical area. There nare several reports describing the development of an inflammatory lesioresembling a cutaneous lesion in the oral cavity involving the posterior wall. nthe hard palate, or the tonsils. The main clinical features are sore throat, ndysphagia, fever, regional lymphadenopathy in the neck and toxemia. Most of nthese patients die with toxemia and sepsis.

Treatment

It is estimated that approximately 20 % of untreated cases of cutaneous nanthrax will result in death, whereas inhalation anthrax is almost always nfatal. Deaths are, however, rare after antimicrobial treatment in the cutaneous nform.

Intravenous penicillin is the drug of choice, with a dose of 4 milliounits every 4-6 hours. Lesions become culture negative in a few hours but ntherapy should be continued for 7-10 days. For the penicillin allergic patient, nerythromycin, a tetracycline or chloramphenicol is satisfactory. Antibiotic ntherapy is designed to ameliorate systemic symptoms, although progression to neschar is not prevented. Excision of the lesion is contraindicated. Topical ntherapy is not effective. Systemic corticosteroids have been used for patients nwith extensive or cervical edema and in those with meningitis but indications nare not well established. Tracheotomy may be needed when cervical edema compromises nthe airway.

Dressings with drainage from the lesions should be incinerated, nautoclaved, or otherwise disposed of as biohazardous waste. Patients with ndraining lesions should be placed in “contact isolation.” although nthis is superfluous is hospitals using “universal precautions.” nPerson-to-person transmission has not been documented, including from patients nwith inhalation anthrax.

Diagnosis

For the detection of anthrax bacillus, sterile swabs should be nsoaked in the fluid of the vesicles, Vesicular fluid should reveal B. nanthacis organisms microscopically and on culture. Anthrax bacilli are neasily seen on Gram stain smears and cultures from vesicular fluid. The ndifferential diagnosis includes staphylococcal disease, plague, and tularemia.

An enzyme-lined immunosorbent assay (EL1SA) has been developed that nmeasures antibodies to the lethal and edema toxins. The diagnosis may be nconfirmed serologically by demonstrating a fourfold change in liter in acute nand convalescent-phase serum specimens collected 4 weeks apart or by a single ntiter of greater than 1:32.

Although extensive serologic studies have not been conducted, antibody nliters in some surveys of exposed individuals suggest some degree of previous nsubclinical infection.

Control and nprevention

The resistance nof the spore form of B. anthracis to physical and chemical agents is nreflected in the persistence of the organism in the inanimate environment. nOrganisms have been demonstrated to persist for years in factories in which the nenvironment became contaminated during the processing of contaminated imported nmaterials of animal origin. Accordingly, they may serve as the source of ninfection for people who work in the area. Special efforts are required to ndecontaminate this environment; one method is to use paraformaldehyde vapor, nwhich is successful in killing B. anthracis spores. In the nlaboratory, surfaces may be decontaminated with either 5% hypochlorite or 5% nphenol (carbolic acid); instruments and other equipment may be autoclaved.

Employees should be educated about the disease and the recommendations nfor working in a contaminated environment and for reducing the risk of ndeveloping the disease. Medical consultation services should be available to nthe employees. Adequate cleanup facilities and clothes-changing areas should be navailable so that workers do not wear contaminated clothes home.

It should be nnoted that the risk of industrial infection has been reduced significantly as nthe use of imported animal products decreased because of changing business nconditions, the increased use of synthetic materials, and the use of humavaccine.

Gastrointestinal nanthrax can be prevented by forbidding the sale for consumption of meat from nsick animals or animals that have died from disease. Depending on the ncircumstances, it may be important to alert individuals who may come in contact nwith contaminated meat about the disease and about the need to cook all meats nthoroughly. Prophylactic penicillin may be used if contaminated food has beeingested.

Animals that ngraze in areas known as anthrax districts should be vaccinated annually with nthe animal vaccine. All animals suspected of dying from anthrax should be nexamined microbiologically: blood or tissue smears can be examined nmicroscopically, and cultures can be set up from these same materials. nNecropsies with spillage of contaminated blood with resultant sporulation of norganisms should be avoided. All animals that have died with a confirmed ndiagnosis of anthrax should be thoroughly burned and the remaining bones and nother materials buried deeply.

Control of the disease in humans ultimately depends on control of the ndisease in animals. Effective animal vaccines are available, and all cases nshould be reported to state veterinary authorities.

Both an attenuated live vaccine and a killed vaccine have been developed. nHowever, the only human vaccine in current use in the United States is the killed vaccine derived from a component of the exotoxin. This vaccine nwas field tested in employees of four different textile mills in the United States, and an effectiveness of 92,5 percent was demonstrated. This vaccine should nbe used for all employees who may be exposed to contaminated materials or nenvironment. Additionally, anyone who comes into a mill processing B.antracis-contaminated nmaterials should also be vaccinated. Currently, the vaccine is giveparenterally with three doses given at 2-week intervals followed by three nbooster inoculations at 6-month intervals and the annual booster inoculations. nVeterinarians and other persons who, because of their occupation, have npotential contact with anthrax should also be immunized with the human anthrax nvaccine.

The ability to nprepare purified components of anthrax toxin by recombinant technology has nopened the possibility of new anthrax vaccines. For example, immunization with nprotective antigen (PA) toxoid vaccines or PA-producing live vaccines elicits npartial or complete protection against anthrax infection and these new vaccines ndeserve careful field testing.

 

Erysipelas

Definition

Erysipelas is a distinctive type of nsuperficial border serous or serous-hemorrhagic inflammation of the skin with nprominent lymphatic involvement with acute or chronic course of disease.

http://emedicine.medscape.com/article/1052445-overview#showall

Etiology

It nis almost always due to group A b–hemolytic nstreptococci (uncommonly, group С or G). Group В streptococci have produced erysipelas in the newborns.

http://www.merckvetmanual.com/mvm/index.jsp?cfile=htm/bc/202300.htm&word=Erysipelas

Epidemiology

Erysipelas nis more common in infants, young children, and older adults. Evidence of streptococcal ninfections (groups A, G, and C) was found in 26 of 27 patients with clinical nerysipelas, utilizing the combination of direct immunofluorescence and cultures nof punch biopsy specimens along with serologic titers. Very rarely, a similar nskin lesion is caused by S. aureus.

 Formerly, nthe face was most commonly involved, and an antecedent streptococcal nrespiratory tract infection preceded cutaneous involvement in about one-third nof patients even though streptococci might not be found on culture at the time nthe skin lesion became evident.

Source of disease is sick person with erysipelas and other streptococcal ninfections (tonsillitis, pneumonia, scarlet fever, streptodermia) and nhealthy carriers.

Contact mechanism of transmission. Increasing of morbidity nin summer-autumn period.

Pathogenesis

Most ninterest has focused on streptococcal pyrogenic exotoxins (SPEs). Iedition to mediating the scarlatinal rush, SPE exibit a variety of adverse nbiologic effects, including the multiorgan damage and lethal shock. There is aamino acid homology of 50 % and immunologic reactivity between SPE A and nstaphylococcal enterotoxins B and C. SPE of  group A streptococcus is a nsuperantigen and it is a potent inducer of tumor necrosis factor.

The antistreptolysin O response after cutaneous nstreptococcal infection is wea. There is experimental evidence to suggest that nthis may be due to local inactivation of streptolysin O by skin lipids. The nimmune response to antiDNase B is brisk, and antihyaluronidase reactivity is nalso a useful test in the serodiagnosis of erysipelas.

 

Clinical nmanifestations

Usual localization of erysipelas: 70-80 % of the lesions othe lower extremities and 5-20 % on the face. Portals of entry are commonly nskin ulcers, local trauma or abrasions, psoriatic or eczematous lesions, or nfungal infections; in the neonate, erysipelas may develop from an infection of nthe umbilical stump. Predisposing factors include venous stasis, paraparesis, ndiabetes mellitus, and alcohol abuse. Patients with the nephrotic syndrome are nparticularly susceptible. Erysipelas tends to occur in areas of preexisting nlymphatic obstruction or edema (after a radical mastectomy). Also, because nerysipelas itself produces lymphatic obstruction, it tends to recur in an area nof earlier infection. Over a 3-year period, the recurrence rate is about 30 %, npredominantly in individuals with venous insufficiency or lymphedema.

Streptococcal bacteremia occurs iabout 5 % of patients with erysipelas; group A, C, or G streptococci cabe isolated on throat culture from about 20 % of cases.

The face (often bilaterally)(Fig.22), an arm or a leg n(Fig.23) is most often involved. The lesion is well demarcated, shiny, red, nedematous and tender; vesicles and bullas often develop. Patches of peripheral nredness and regional lymphadenopathy are seen occasionally; high fever, chills nand malaise are common. Erysipelas may be recurrent and may result in chronic nlymph edema. A cause of infection may be an interdigital fungal infection of nthe foot that may require long-term therapy to prevent recurrent erysipelas.

Uncomplicated erysipelas remains confined primarily to the nlymphatics and the dermis. Occasionally, the infection extends more deeply, nproducing cellulitis, subcutaneous abscess, and necrotizing fasciitis.

Leukocytosis is common with erysipelas. Group A streptococci nusually cannot be cultured from the surface of the skin lesion, and only rarely ncan they be isolated from tissue fluid aspirated from the advancing edge of the nlesion. In cases of erysipelas complicating infected ulcers, group A streptococci nhave been isolated from the ulcerated area in 30 % of patients.

Fig.22. nErysipelas of face

Fig.23. nErysipelas of leg

 

Diagnosis

Diagnosis from the characteristic appearance is usually neasy. The causative organism is difficult to culture from the lesion, but it nmay occasionally be cultured from the blood.

http://emedicine.medscape.com/article/1052445-workup#showall

Therapy

 Mild early cases of erysipelas in the adult may be treated nwith intramuscular procaine penicillin (600,000 units once or twice daily) or nwith oral penicillin V (250-500 mg every 6 hours). Erythromycin (250-500 mg norally every 6 hours) is a suitable alternative. For more extensive erysipelas, npatients should be hospitalized and receive pare) aqueous penicillin G n(600,000-2 millions units every 6 hours).

Prophylaxis

Adherense to good regimens of personal hygiene, with nspecial attention to frequent scrubbing with soap and water, is the most neffective preventive measure currently available. The in time treatment of nstreptococcal pharyngitis is of much importance.

 

Salmonellosis

Salmonellae are widely dispersed niature, being found in the in the gastrointestinal tracts of domesticated nand wild mammals, reptiles, birds, and insects.

May present nclinically as gastroenteritis, enteric fever, a bacteremic syndrome, or focal ndisease. An asymptomatic carrier state may also occur.

http://www.cdc.gov/salmonella/

Historic reference

The  term  n“Salmonellosis”  unites  a  large  group  of  diseases, caused  by  multiply  nserotypes  of  bacteriums  from genus Salmonellae (more than 2000).

Sallmonellae nare named for the pathologist Salmon who nfirst isolated S. cholerae suis from porcine intestine. The nantigenic classification or serotyping of Salmonella used today nis the result of study of antibody interactions with bacterial surface antigens nby Kauffman and White in the 1920s to 1940s. Ames and coworkers in 1973 nreported the development of the test that uses S.typhimurium auxotrophic nmutants to test the mutagenic activity of chemical compounds.

Salmonellosis is ndisease of animals and humans. It is characterized by essential damage of ngastrointestinal tract, and more rarely by typhus-like or septicopyemic nduration.

Etiology

http://www.onlinemedicinetips.com/disease/s/salmonella/Etiology-Of-Salmonella.html

Salmonella nare non-spore-forming gram negative rods of the family Enterobacteriaceae. nSalmonella are motile by peritrichous flagella. Salmonella strains demonstrate nsufficient differences in biochemical reactions, antigenic structure, host nadaptations, and geographical distribution to be grouped into 10 distinct nsubgroups, which have been variously designated in proposed taxonomic schemes. nVirtually all strains isolated in clinical laboratories and implicated idisease in humans (more than 700 serotypes)(Fig.24).

 

 

Fig.24. Lactose-negative colonies of salmonella growing on MacConkey nagar

 

Like other enterobacteria, salmonella has somatic (0) nantigens, which are lipopolysaccharide components of the cell wall, and nflagella (H)  antigens, which are proteins. There  may  be  detached  some  nserological  groups  on  the  basic of  the  differences  in  structure  of  nO-antigens. Salmonella  preserve  viability  in  external environment  for  a  nlong  time: nin  water – 11-120 days, in  the  sea  water – 15-27 days, in  soil – 1-9 nmonths , in  sausage products – 60-130 days, in  the  eggs, vegetables  and  nfruits  till  2,5 months. The  optimal  temperature  for  reproduction is  n35-37 °C. There  are  serological  groups A, B, C, D, E  and  other.

Salmonella can be differentiated nfrom other Enterobacteriaceae on the basis of certain biochemical nreactions, including fermentation reactions with specific sugars.

Salmonella organisms grow readily non simple media in aerobic or anaerobic conditions. Cultures of specimens that nare normally sterile, such as blood, joint fluid, or cerebrospinal fluid, cabe done on ordinary media such as blood agar. Excretions or secretions, such as nfeces or sputum, which have high concentrations of  other microorganisms, are nusually grown on selective or differential media, such as bismuth sulfate agar nor desoxychlorate  agar, which contains inhibitors of growth of non-pathogenic norganisms of the normal flora.

Epidemiology

http://www.safe–poultry.com/salmonellaepidemiology.asp

Animals  suffering  from  primary  or  secondary  nsalmonellosis, water   swimming  birds and  also  human-sick  or  carries are nthe  main  sources  of infection    in  salmonellosis. Mechanism  of  ntransmission  of  infection  is  fecal-oral. The factors  of  the transmission  nof  the infection  are  food-stuffs  of  animal  origin  and  other  products  nwhich  are polluted  by excretions  of  animals  and  humans. The  promotive  nfactors  are  violation  of  the  preservation  and  preparing  of  the  food  nand  also sanitary.

The  diseases occur  as  separate  sporadic  cases  and  nas  outbreaks. Susceptibility  of  human depends  from  the  premorbidal state  nof  the  macroorganism and  from  the  quantity  and  variety (serotypes)  of   nSalmonella.

Salmonella are nprimarily pathogens of lower animals. The reservoir of infection in animals nconstitutes the principal source of nontyphoidal Salmonella organisms nthat infect man, although infection may be transmitted from person to person, Salmonella nhave been isolated from almost all animals species, including poultry n(chickens, turkeys and ducks), cows, pigs, pets (turtles, cats, dogs, mice, guinea npigs and hamsters), other birds (doves, pigeons, parrots, starlings, sparrows), nsheep,  seals, donkeys, lizards and snakes.

The most accurate ninformation on sources of human Salmonellosis is derived from studies of noutbreaks. Poultry (chickens, turkeys, ducks) and poultry products (primarily neggs) are the most important sources of human infection and are estimated to be nresponsible for about one-half of the common – vehicle epidemic. Salmonella ifeces of infected hens may contaminate the surface of egg shells or penetrate ninto the interior of the egg through hairline cracks. In hens with ovariainfection, organism may gain access to the yolk. Meat, especially beef and npork, are quite often implicated, accounting for about 13 % of the outbreaks,  and ndairy products, including raw and powdered milk account for about 4 % of the nepidemics.

Cross – infection with nspread by person – to – person is responsible for virtually all the outbreaks nieonatal nerseries  and in pediatric wards and is important in many noutbreaks among hospitalized adults.

The stage is set for cross-infectiowhen Salmonella are introduced into the hospital by admission, or for example, na patient with acute enterocolitis or as asymptomatic carrier with other  nmedical problem or by the introduction of a contaminated common- course nvehicle. Hospital personnel then may carry infection on hands or clothing from npatient to patient; in some cases fomites (dust, delivery room, furniture), may nbe implicated in transmission. Hospital personnel who are excreting Salmonella nin stools may also occasionally transmit infection to patient.

Pathogenesis

The ndevelopment of disease after ingestion of Salmonella is influenced by the nnumber and virulence of the organisms and by multiple host factors.

A large nnumber of Salmonella  must be swallowed in most instances to produce ndisease in healthy human being. However, in the event of infection with nunusually virulent organisms or in patients with reduced resistance, nsymptomatic infection may result from extremely small inocula. Ingested norganisms pass from the mouth to the stomach. In the stomach  Salmonella nare exposed to gastric acid and low PH, which reduce the number of viable norganisms. Most  Salmonella are perished rapidly at 2,0 PH, which is nreadily achieved in the normal stomach. Viable bacilli that survive then pass ninto the small intestine, where the organisms may be further reduced iumber nor eliminated entirely. The antimicrobial  activity observed in the small bowel nis related at least in part to the normal microbial flora of the intestine, nwhich elaborate short-chain fatty acids and perhaps other substances capable of nkilling or inhibiting growth of Salmonella. Studies in animals have nshown that the increased susceptibility to Salmonella infection produced by nadministration of antibiotics rapidly reverts to normal with reestablishment of nthe normal intestinal flora.

Salmonella that nsurvive the antibacterial mechanisms in the stomach and upper small bowel may nmultiply in the small intestine. Multiplication of Salmonella in the nintestinal tract may be asymptomatic, associated only with transient excretioof organism in stools, or symptomatic, associated with clinical manifestations nof either enterocolitis (acute gastroenteritis) enteric fever or bacteremia.

Blood stream ninvasion, which occurs with variable frequency, may lead to localization of ninfection and suppuration at almost any site.

Local factors in the nstomach and upper intestinal tract are important determinants of the disease. nFactors that neutralize the low PH of the stomach or decrease the time the npathogen is exposed to stomach acid diminish local bactericidal action and nincrease the probability that an infections inoculums will reach the small nintestine. The importance of gastric acidity as a defense mechanism is nemphasized by the increased incidence of severe Salmonella enterocolitis nin persons with achlorhydria, prior gastroectomy, gastroenterostomy, or nvagotomy, conditions that reduce acidity or cause faster gastric emptying time. n

The oral administratioof buffering compounds also increases susceptibility to intestinal infection. nIt has been suggested that ingestion  of organisms in food allows for longer nexposure to gastric acid, thereby necessitating the presence of a relatively larger ninoculums to produce disease, whereas water or other liquids, which have a nfast  gastric transit time, may be less heavily contaminated and still cause ndisease.

The small intestine nprovides other protective mechanisms through motility and normal flora. nAlteration of the intestinal flora by antibiotics markedly reduces the size of nthe inoculums required to produce   Salmonella infection in animals and humans nand prolongs the convalescent carrier state. Prior antimicrobial   therapy also nenhances the possibility of  infection with antibiotic – resistant Salmonella nstrains.

Age is an important ndeterminant of  disease produced by Salmonella. Salmonella enterocolitis noccurs with highest incidence in children less than 5 years old; newborns and ninfants less one year of age are especially susceptible. The influence of age non incidence may reflect immaturity of humoral and cellular immune mechanisms, ndiminished antibacterial action of the normal intestinal flora, a high nfrequently of fecal – oral contamination, or other factors. In some instances, nincreasing resistance with age is related to immunity consequent to previous nexposure to the organism, even though disease has not been produced.

Patient with nimpaired cellular and humoral immune mechanisms are at increased risk for ndevelopment of Salmonellosis. Impairments of host defenses caused by nmalnutrition, malignancy, infection with  human immunodeficiency virus or ntherapeutic measures such as corticosteroid or immunosuppressive therapy also npredispose to infection and disease.

Salmonella causing nenterocolitis are thought to produce diarrhea by a true infection with mucosal  ninvasion and possibly by elaboration of an enterotoxin that acts on upper nintestinal transport. Salmonella invasion of intestinal mucosa may lead to nlocal production of inflammatory exudates of mediators that stimulate nelectrolyte secretion and smooth muscle contraction (Fig.25).

Fig.25. nFlask-shaped ulcer with necrosis of epithelium and extrusion of necrotic ntissue, fibrin and mucus

There  are  ntwo types of toxins: exotoxins and endotoxins. Exotoxins are the toxic products nof bacteria which are actively secreted into environment. Endotoxins are toxic nsubstances which are liberated only during the lysis of microbial cells. The nprincipal factor responsible for development of this disease is endotoxical ncomplex of Salmonella, but we should remember that these bacteria produce eveexotoxins. Exotoxins and endotoxins have toxical properties.

Stages of salmonellosis development:

1.                      nColonization (setting) of pathogenic organism in the place of nthe inculcation.

2.                      nInvasion and reproduction.

3.                      nDeath of the pathogenic bacteria and endotoxins liberation.

Infectious process may stop at the stage nof colonization due to unknown reasons. Invasion may be limited by nearest ntissues. In majority cases it leads to development of gastrointestinal forms of nSalmonellosis. For development of the first stage of pathogenesis of nSalmonellosis the factors violating structural and functional state of ngastrointestinal tract play important role (dysbacteriosis, hypovitaminosis and nother). These conditions may promote to development of the disease even due to nsmall quantity of bacteria in food-stuffs.

Isalmonellosis the principal pathologoanatomical changes develop in the place of ninoculation of the agent in the small intestine. Data about changes of small nintestine in gastrointestinal forms of Salmonellosis may be received only as a nresult of its biopsy. But biopsy is not used in practice. Investigation of nmaterial during biopsy testifies dystrophical changes of epithelium, ninfiltration of epithelium  of mucous membrane by macrophages. Increased nquantity of interepithelial leukocytes, polymorphonuclear leukocytes and nmacrophages is marked.

Principal  changes develop in lamina npropria of mucous membrane of small intestine in Salmonellosis. These changes nare accompanied by hyperemia, hemorrhages, edema and intensification of cell ninfiltration. At the same time  the  changes of the different parts of ngastrointestinal tract develop. There is an acute inflammatory process, ndystrophic changes of epithelium, edema, hyperemia and cell infiltration istomach. There are dystrophy, erosions, hyperemia, edema in mucous of large nintestine. Changes in all parts of gastrointestinal tract are transient. They nare exposed to reverse development in clinical recovery of the patients.

In half of the patients with nSalmonellosis nonsharp violations of liver are marked. These changes are nconsidered as compensatory mechanism.

In connection with sufficient efficiency nof modern methods of treatment the fatal outcomes are rare. Dystrophic  changes nof parenchymatous organs were revealed in autopsy of deceaseds from ngastrointestinal forms of Salmonellosis. These changes were direct cause of ndeath. Inrarely, edema of the lungs and brain, hyperplasia of spleen and nmesenteric lymph nodes may develop.

Clinical  manifestations

http://www.bettermedicine.com/article/salmonella-infections

Iconnection with considerable variability of clinical duration of Salmonellosis nthere are multitude classifications of this disease. The next classification is nmore comfortable for practice use:

1)                     nLocalized (gastrointestinal) forms of Salmonellosis:

a)           nGastritic variant;

b)          nGastroenteritic variant;

c)           n Gastroenterocolitic variant.

2)                     nGeneralized forms:

a)           nTyphus-like form;

b)          nSeptic form (septicopyemia).

3)                     nCarrier state:

a)           nAcute carriers;

b)          nChronic carriers;

c)           nTransitory carriers.

Clinical nsymptoms of Salmonellosis are studied sufficiently completely.  nGastrointestinal forms of Salmonellosis are observed in most of cases of the ndisease. According data of different authors they occur from 79 to 85 %.

Incubatioperiod is from 4-6 hours up to some days. Onset of the disease is an acute. nProdromal period is not typical or very short. Weakness, malaise, and slight nchill characterize it. Then temperature increases to subfebrile in moderate and nsevere forms accordingly.

After ningestion of  contaminated food or water, illness begins in many patients with nnausea and vomiting; these symptoms usually resolve within a few hours. Myalgia nand headache are common. The cardinal manifestation is diarrhea, which may vary nfrom a few loose stools to fulminate diarrhea. In most cases, stools are loose, nof moderate volume,  without blood, swamp-like and bed smell (Fig.11).

 

Hand, foot nand mouth disease

Hand, foot and mouth disease (HFMD) is a nhuman syndrome ncaused by intestinal viruses of the Picornaviridae nfamily. The most common strains causing HFMD are Coxsackie nA virus and Enterovirus n71 (EV-71).^[1]

HFMD usually affects infants and children, and is quite common. nIt is moderately contagious and is spread through direct contact with the nmucus, saliva, or feces of an infected person. It typically occurs in small epidemics niursery schools or kindergartens, usually during the summer and autummonths. The usual incubation period is 3–7 days.

It is less common in adults, but those with immune deficiencies are very susceptible. HFMD nis not to be confused with foot-and-mouth disease (also called nhoof-and-mouth disease), which is a separate disease affecting sheep, cattle, nand swine (both are caused by members of the Picornaviridae family, but are not ntrans-communicable between Humans and livestock).

 

Fig.26. Typical lesions around the mouth of an 11 month old male

ICD–10 B08.4 ICD–9 074.3 DiseasesDB 5622 MedlinePlus 000965 eMedicine derm/175 MeSH D006232

 

Signs and symptoms

Fig.27. Rash on the hands.

 

Fig.28. Rash on the feet

Symptoms nof HFMD include:^[2]

·   Fever

·   Headache

·   Vomiting

·   Fatigue

·   Malaise

·   Referred ear pain

·   Sore throat

·   Painful oral lesions

·   body rash, followed by sores nwith blisters non palms of hand and soles of feet

o           nRash is nrarely itchy for children, but can be extremely itchy for adults

·   Oral ulcer

·   Sores or blisters may be npresent oose and nostrils

·   Sores or blisters may be npresent on the buttocks of small children and infants

·   Irritability in infants and ntoddlers

·   Loss of appetite.

·   Diarrhea

The ncommon incubation period (the time between infection and onset of symptoms) is nfrom three to seven days.

Early nsymptoms are likely to be fever often followed by a sore throat. nLoss of appetite and general malaise may also occur. Between one and two days after the nonset of fever, painful sores (lesions) may appear in the mouth or throat, or both. A rash nmay become evident on the hands, feet, mouth, tongue, inside of the cheeks, and noccasionally the buttocks (but generally, the rash on the buttocks will be ncaused by the diarrhea).

Treatment

There nis no specific treatment for hand, foot and mouth disease. Individual symptoms, nsuch as fever and pain from the sores, may be eased with the use of analgesics. nHFMD is a viral disease that has to run its course; many doctors do not nprescribe medicine for this illness. Infection in older children, adolescents, nand adults is typically mild and lasts approximately 1 week, occasionally nlonger. Fever reducers and luke-warm baths can help bring temperature down.

Only na very small minority of sufferers require hospital admission, mainly as a nresult of uncommon neurological complications (encephalitis, nmeningitis, nor acute flaccid paralysis) or pulmonary nedema/pulmonary hemorrhage.

Complications

·   Complications from the virus ninfections that cause HFMD are not common, but if they do occur, medical care nshould be sought.

·   Viral or aseptic meningitis ncan rarely occur with HFMD. Viral meningitis causes fever, headache, stiff nneck, or back pain. The condition is usually mild and clears without treatment; nhowever, some patients may need to be hospitalized for a short time.

·   Other more serious diseases, nsuch as encephalitis (swelling of the brain), a polio-like paralysis, result neven more rarely. Encephalitis can be fatal.

·   There have been reports of nfingernail and toenail loss occurring mostly in children within 4 weeks of ntheir having hand, foot, and mouth disease (HFMD). At this time, it is not nknown whether the reported nail loss is or is not a result of the infection. nHowever, in the reports reviewed, the nail loss has been temporary and nail ngrowth resumed without medical treatment.