SPECIFICAL INFLAMMATORY  PROCESSES OF THE MFA (ACTINOMYCOSIS, TUBERCULOSIS, SYFILIS), AIDS: CLASSIFICATION, CLINICAL COURSE, DIAGNOSIS, TREATMENT.

Cervicofacial Actinomycosis

Cervicofacial actinomycosis is a disease that is characterized by the formation of abscess, fistulae, tissue fibrosis and draining sinus tracts. This disease can mimic many other conditions such as granulomatous disease and malignancy. They show soft tissue swelling in the neck and head.Cervicofacial actinomycosis is caused by bacteria known as Actinomyces israelii. This type of bacteria is usually present in the mouth, however it is capable of causing disease once it enters the tissues from an injured portion of the body. Actinomyces israelii anaerobic meaning it dislikes oxygen and grows deep inside the tissues where oxygen level is low. Root canal treatment, tooth extraction, poor dental hygiene or jaw surgery are some of the reasons which allow access to Actinomyces israelii thus causing an infection.

 

 

Actinomycosis Actinomycosis – the chronic illness caused by various kinds of Actinomyces. It is characterised by a lesion of various organs and tissues with formation of dense infiltrates which then abscess with the advent of fistulas and an original lesion of a skin. Actinomycosis aetiology Originators – various kinds of Actinomyces, or radiant mushrooms. The cores from them is the following: Actinomyces israelu, Actinomyces bovis, Actinomyces albus, Ac. violaceus. Actinomyces well grow outrient mediums, forming colonys of the irregular form, is frequent with radiant edges. Are pathogenic for many kinds of agricultural and laboratory animals. In a pathological stuff meet in the form of druses which represent yellowish lumps in diameter of 1-2 mm. At microscopy in the centre of druses the clump of strands of a mycelium, and on periphery – flasklike inflations is found. At a coloration a hematoxylin – eosine the central part of druse is imbued in dark blue colour, and flasks in the pink. There are druses at which the border from flasklike cells is absent. Actinomyces are sensitive to a benzylpenicillin (20 Unit/ml), streptomycin (20 mkg/ml), Tetracyclinum (20 mkg/ml), Levomycetinum (10 mkg/ml) and erythromycin (1,25 mkg/ml). Actinomycosis epidemiology The actinomycosis is extended in all countries. With it humans and agricultural animals are ill. However cases of infestation of the human from sick humans or animals it is not described. Originators of an actinomycosis eurysynusic in the nature (hay, straw, bedrock, etc.). Actinomyces often find in healthy humans in an oral cavity, a debris, lacunas of tonsils, on a mucosa of a gastrointestinal tract. Matters both exogenous, and endogenous infestation means. Actinomycosis pathogenesis The most frequent is the endogenous path of an infection contamination. Actinomyces eurysynusic in the nature, in particular on plants, can get with plants to an organism and be on mucosas as a saprophyte. Transition of Actinomyces from saprophytical in a parasitic state is promoted by inflammatory diseases of mucosas of an oral cavity, a respiratory and gastrointestinal tract. On a place of introduction of Actinomyces the infectious granuloma which sprouts in surrounding tissues is formed. In granulations there are abscesses which, breaking, form fistulas. The skin lesion has secondary character. In formation of pyeses the role and secondary, mainly staphylococcal infection contamination plays. Antigens of radiant mushrooms lead to a specific sensibilization and allergic rearrangement of an organism (a hypersensibilization of the slowed down phylum), and also to antibody formation (complement-linked, agglutinins, precipitin, etc.). Symptoms and actinomycosis flow Duration of an incubation interval is not known. He can fluctuate over a wide range and reach till several years (from time of a becoming infected development of demonstrative forms of an actinomycosis). The basic clinical forms of an actinomycosis: 1.     An actinomycosis of a head, tongue and a neck 2.     A thoracal actinomycosis 3.     The abdominal 4.     An actinomycosis of genitourinary organs 5.     A skin actinomycosis 6.     A mycetoma 7.     An actinomycosis of the central excitatory system The actinomycosis concerns to initially-persistent infections with long progressing flow. At infiltrate growth the skin is involved in process. In the beginning very dense and almost painless infiltrate is defined, the skin becomes tsianotichno-crimson, there is a fluctuation, and then educe is long not healing fistulas. In pus find belovato-yellowish fine lumps (druses). Cervicofacial actinomycosis meets most often. On expression of process it is possible to secure the deep (muscular) form when process is localised in an intermuscular fat, hypodermic and dermal forms of an actinomycosis. At the muscular form process is localised mainly in masseters, under a fascia covering them, forming dense, cartilaginous consistences an infiltrate in the field of a mandible angle. The person becomes azygomorphous, the masticatory spasm of various intensity educes. Then in an infiltrate there are locuses of a ramollissement which are spontaneously dissected, forming the fistulas abjointing purulent or krovjanisto-purulent fluid, sometimes with an admixing of yellow grains (druses). A cyanotic coloration of a skin round fistulas it is long remains and is characteristic implication of an actinomycosis. On a neck original changes of a skin in the form of cross-section located platens are formed. At the dermal form of an actinomycosis infiltrates ball-shaped or semiball-shaped, localised in a hypodermic fat. A masticatory spasm and disturbances of processes of chewing it is not observed. The dermal form meets seldom. Actinomycotic process can grasp cheeks, labiums, tongue, tonsils, a trachea, orbits, a larynx. Flow rather congenial (in comparison with other forms). Thoracal actinomycosis (an actinomycosis of organs of a thoracal lumen and a thoracal side), or an actinomycosis of lungs. The beginning gradual. There is a delicacy, subfebrile temperature, tussis, in the beginning dry, then with a mucopurulent sputum, is frequent with a blood admixing (the sputum has an odour of the earth and taste of copper). Then the peribronchitis picture educes. The infiltrate extends from the centre to periphery, grasps a pleura, a thoracal side, a skin. There is a tumescence with extremely expressed stinging morbidity at a palpation, the skin becomes bagrovo-cyanotic. Fistulas educe, in pus druses of Actinomyces are found. Fistulas intercommunicate with bronchuses. They settle dowot only on a thorax, but can appear on a loin and even on a hip. Flow serious. Without treatment patients die. On frequency the thoracal actinomycosis takes the second place. Abdominal actinomycosis also meets often enough (takes the third place). The primary locuses are more often localised in ileocecal range and in the field of an appendix (over 60 %), then there are other departments of a colon and the stomach or a thin intestine, an esophagus is very seldom amazed initially. The abdominal wall is amazed again. The primary infiltrate is localised in ileocecal range more often, quite often imitates surgical diseases (an appendicitis, impassability of an intestine, etc.). Extending, the infiltrate grasps also other organs: the liver, nephroses, a column, can reach an abdominal wall. In the latter case there are characteristic changes of a skin, the fistulas intercommunicating with an intestine. Are located usually in inguinal range. At an actinomycosis of a rectum infiltrates cause occurrence of specific paraproctites, fistulas are dissected in perianal range. Without etiotropic treatment the lethality reaches 50 %. Genital actinomycosis and Pelvic actinomycosis meets rare. As a rule, it is secondary lesions at infiltrate diffusion at an abdominal actinomycosis. Primary actinomycotic lesions of generative organs meet very seldom. Actinomycosis of bones and joints meets rare. This form arises or as a result of transition of an actinomycotic infiltrate from the next organs, or is a consequence of hematogenous drift of a mushroom. Osteomyelites of bones of an anticnemion, a basin, a column, and also a lesion patellar and other joints are described. Quite often process is preceded by a trauma. Osteomyelites proceed with a destruction of bones, formation of sequesters. Attracts attention, that despite the expressed osteal changes, sick keep ability to move, at lesions of joints function seriously is not broken. At formation of fistulas there are characteristic changes of a skin. Skin actinomycosis arises, as a rule, again at primary localisation in other organs. Skin changes become appreciable when actinomycotic infiltrates reach a hypodermic fat and are especially characteristic at formation of fistulas. Mycetoma – an original variant of an actinomycosis. This form was known for a long time, often enough met in the tropical countries. Disease begins with appearance on stop, mainly on a sole, one or several dense circumscribed knots in size from a pea and more, covered at first not variated skin, further over inspissations the skin becomes red-violet or brownish. In the neighbourhood with pristine knots appear new, the skin swells, autopodium is enlarged in volume, changes the form. Then knots are softened and dissected with formation of deeply going fistulas excreting purulent or is serous-purulent, sometimes bloody fluid, is frequent with a fetor. In abjointed fine grains of usually yellowish colour (druse) are appreciable. Knots are almost painless. Process slowly progresses, all sole is penetrated by knots, toes turn up. Then knots and fistulous courses appear and on autopodium back. All autopodium turns to the deformed and pigmented mass penetrated by fistulas and lumens. Process can pass to muscles, tendons and bones. The atrophy of muscles of an anticnemion is sometimes observed. Usually process grasps only one autopodium. Disease proceeds very longly (10-20 years). Complications. Stratification of a secondary bacteriemic infection contamination. The diagnosis and the differential diagnosis. In far come cases with formation of fistulas and characteristic changes of a skin the diagnosis of difficulties does not represent. It is more difficult to diagnose initial forms of an actinomycosis. For diagnostics the intracutaneous test with actinolysathos has some value. However in attention it is necessary to accept only positive and sharply positive assays as weakly positive intracutaneous tests often happen at patients to diseases of dens (for example at an alveolar pyorrhea). Assay Negative takes not always allow to exclude an actinomycosis as at patients with serious forms they can be negative owing to sharp oppression of cellular immunodefence, they are always negative at a HIV-infected. Abjection of culture of Actinomyces from a sputum, a mucosa of a fauces, a nose has no diagnostic value as Actinomyces are quite often found and in healthy faces. The reaction of binding complement with actinolysathos which happens positive at 80 % of patients has diagnostic value. The greatest diagnostic value has abjection (detection) of Actinomyces in pus from fistulas, in biopsy samples of the amazed tissues, in druses, in the last is sometimes microscopically mycelium strands are found only. In these cases it is possible to try to secure culture of Actinomyces by stuff sowing on medium of the Aloe. Actinomycosis of lungs is necessary for differentiating from neoplasms of lungs, abscesses, other deep mycoses (an aspergillosis, a nocardiosis, a histoplasmosis), and also from a pulmonary tuberculosis. The abdominal actinomycosis should be differentiated from various surgical diseases (an appendicitis, a peritonitis and so forth). A lesion of bones and joints-from of purulent diseases. Actinomycosis treatment The best results are given by a combination of a causal treatment (antibiotics) and immunotherapies. At the is cervical-maxillofacial form prescribe inside a phenoxymethylpenicillin for 2 grammes/days and at duration of a course not less than 6 weeks. It is possible to prescribe also Tetracyclinum in the big doses (on 0,75 gramme 4 times a day within 4 weeks or on 3 gramme a day only in the first 10 days, and then on 0,5 gramme 4 times a day within last 18 days). Erythromycin is prescribed on 0,3 gramme by 4 times a day within 6 weeks. At abdominal forms and at an actinomycosis of lungs prescribe the big doses of a benzylpenicillin (10000000 Unit/day and more) intravenously within 1-1,5 months with the subsequent transition to a phenoxymethylpenicillin in a daily dose of 2-5 gramme within 2-5 months. At consecutive infection stratification (staphilococcuses, an anaerobic microflora) prescribe long courses of a dicloxacillin or antibiotics of tetracycline bunch, at a mephitic gangrene – metronidazole. For an immunotherapy actinolysathos it is possible to introduce subcutaneously or intradermally, and also it is intramuscular. Under a skin and intramusculary introduce on 3 ml actinolysathos 2 times a week. On a course of 20-30 injections, duration of a course 3 months At an abscess, an empyema spend surgical treatment (dissecting and a drainage). At extensive damages of a pulmonary tissue sometimes resort to a lobectomy. From antibiotics the most effective are Tetracyclinums, then go a phenoxymethylpenicillin and erythromycin is less effective. Refractory to these antibiotics of strains of Actinomyces did not meet. Actinomycosis forecast Without etiotropic treatment the forecast serious. At an abdominal actinomycosis 50 % of patients died, at the thoracal all patients perished. Rather the is cervical-maxillofacial actinomycosis is easier proceeded. All it causes necessity of early diagnostics and the beginning of therapy before development of serious anatomical damages. Considering possibility of relapses, convalescents should be under long observation (6-12 months). Actinomycosis preventive maintenance and actions in the locus Hygiene of an oral cavity, timely treatment of dens, inflammatory changes of tonsils and an oral cavity mucosa. Specific preventive maintenance is not developed. Actions in the locus do not spend.

 

Actinomycosis

Actinomycosis is a long-term (chronic) bacterial infection that commonly affects the face and neck.

Causes

Actinomycosis is usually caused by an anaerobic bacteria called Actinomyces israelii, which is a common and normally not disease-causing (nonpathogenic) organism found in the nose and throat.

Because of the bacteria’s normal location in the nose and throat, actinomycosis most commonly appears in the face and neck. However, the infection can sometimes occur in the chest (pulmonary actinomycosis), abdomen, pelvis, or other areas of the body. The infection is not contagious.

Symptoms occur when the bacteria enters the facial tissues after trauma, surgery, or infection. Common triggers include dental abscess or oral surgery. The infection has also been seen in certain women who have had an intrauterine device (IUD) to prevent pregnancy.

Once in the tissue, it forms an abscess, producing a hard, red to reddish-purple lump, often on the jaw, from which comes the condition’s commoame, “lumpy jaw.”

Eventually, the abscess breaks through the skin surface to produce a draining sinus tract.

Symptoms

A patient with Actinomycosis on the right side of the face.

Actinomycosis of Maxilla. The disease spread to opposite side; finally implicated base of skull, and proved fatal. Treated by radium.

• Draining sores in the skin, especially on the chest wall from lung infection with Actinomyces
• Fever
• Minimal or no pain
• Swelling or a hard, red to reddish-purple lump on the face or upper neck
• Weight loss

Exams and Tests

• Culture of the tissue or fluid shows Actinomyces species.
• Examination of drained fluid under a microscope shows “sulfur granules” in the fluid. They are yellowish granules made of clumped organisms.
• Examination under a microscope shows the Actinomyces species of bacteria.

Treatment

Treatment of actinomycosis usually requires antibiotics for several months to a year. Surgical drainage or removal of the lesion may be needed. If the condition is related to an IUD, the device must be removed.

Outlook (Prognosis)

With treatment, you should recover fully.

Possible Complications

Meningitis can rarely develop from this infection.

When to Contact a Medical Professional

Call your health care provider if you develop any of the symptoms of this disorder. Beginning treatment promptly helps quicken the recovery.

Prevention

Good oral hygiene and regular dentist visits may help prevent some forms of actinomycosis.

Alternative Names

Lumpy jaw

Actinomycosis: Causes, Symptoms and Treatment

Actinomycosis is an infection caused by a bacterium called Actinomyces israelii (A. israelii).

Actinomycosis (also known as Rivalta disease, big jaw, clams, lumpy jaw or wooden tongue) is an infection, commonly of the face and neck, that produces abscesses (collections of pus) and open-draining sinuses (tracts in the skin).

Actinomycosis is caused by a bacterium called Actinomyces israelii (A. israelii). It occurs normally in the mouth and tonsils. This bacterium may cause infection when it is introduced into the soft tissues by trauma, surgery or another infection. Once in the tissues, it may form an abscess that develops into a hard red to reddish purple lump. When the abscess breaks through the skin, it forms pus-discharging lesions.

Causes of Actinomycosis

Actinomycosis is caused by a strain of bacteria called actinomycetales. Actinomycetales are found in many of the body’s cavities, such as inside the mouth and less commonly the bowel.

In women, they can also be found in the womb and the fallopian tubes (through which eggs are released into the womb).

How actinomycosis spreads

Actinomycetales are anaerobic bacteria, which means they cannot survive in oxygen-rich environments. Therefore, they do not present a problem when they are in one of the body’s cavities, such as the mouth or the intestinal tract.

However, if actinomycetales break through the protective lining (mucus membrane) that surrounds the cavities, they can penetrate deep into your body’s tissue. As the deep layers of human tissue are low in oxygen, the bacteria are able to reproduce quickly and infect healthy tissue.

Abscesses

In an attempt to combat the infection, your immune system (the body’s natural defence against infection and illness) will send infection-fighting cells to the source of the infection. However, these cells do not have the ability to kill the bacteria and will quickly die.

As the infection-fighting cells die, they accumulate into a yellowish-coloured liquid called pus. Having failed to kill the infection, your immune system will attempt to limit its spread by using healthy tissue to form a protective barrier around the pus. This is how a pus-filled swelling, known as an abscess, is formed.

Unfortunately, the actinomycetales strain of bacteria has the ability to penetrate the protective barrier of an abscess and move into more healthy tissue. Your immune system will attempt to counter the infection by producing more abscesses.

Sinus tracts

Your body will eventually need to get rid of the accumulation of pus. To do this, small channels called sinus tracts will develop that lead from the abscesses to the surface of your skin.

The sinus tracts will leak pus, as well as ‘sulphur granules’, which are a yellow, powdery substance. The sulphur granules are actually made up of lumps of bacteria, but they are known as sulphur granules as they are the same colour as the chemical sulphur.

Opportunistic infection

Actinomycosis is an opportunistic infection that does not cause any symptoms unless an opportunity arises for it to penetrate into the body‘s tissue.

Oral cervicofacial actinomycosis

Opportunities for oral cervicofacial actinomycosis include:

• tooth decay – particularly if the decay is left untreated for many years
• gum disease
• dental abscess
• tonsillitis
• inner ear infection
• dental surgery, such as a tooth extraction, or root canal treatment
• jaw surgery

Thoracic actinomycosis

Most cases of thoracic actinomycosis are thought to be caused by small particles of food or other ingested material that get mixed up with the actinomycosis bacteria. Rather than passing harmlessly down into the stomach, the particles are mistakenly passed down into the windpipe and the airways of the lungs.

People with long-term drug or alcohol problems are particularly at risk of developing thoracic actinomycosis for two reasons:

• being drunk or intoxicated increases your risk of accidentally ingesting material into your lungs
• long-term drug and alcohol misuse weakens the immune system, which makes a person more vulnerable to developing an infection

Abdominal actinomycosis

Abdominal actinomycosis occurs when something tears the wall of the intestine (bowel), allowing the bacteria to penetrate into deep tissue.

The intestine can tear as a result of an infection, such as a burst appendix that damages the wall of the intestine. Or it can be damaged through injury – for example, when someone mistakenly swallows a fish bone.

There have also been some reported cases of abdominal actinomycosis occurring as a complication of bowel or abdominal surgery.

Pelvic actinomycosis

Most cases of pelvic actinomycosis have been recorded in women who were using the intrauterine device (IUD) form of contraception. The IUD is a small, T-shaped contraceptive device made from plastic and copper that fits inside the womb. The women affected tend to be long-term users of the IUD (eight years or more).

One explanation for the high number of cases of pelvic actinomycosis in women who are using the IUD is that over time the IUD may damage the womb lining, allowing bacteria to penetrate into deep tissue. However, no research has yet been done to find out whether or not this is the case.

It should be stressed that developing pelvic actinomycosis as a result of using an IUD is very unlikely. In England, millions of women use the IUD device and there have only been a handful of reported cases of pelvic actinomycosis.

Actinomycosis Symptoms

The list of signs and symptoms mentioned in various sources for Actinomycosis includes the 17 symptoms listed below:

* Symptoms of facial actinomycosis:
o Swollen jaw
o Jaw pain
o Tooth pain
o Pus in the mouth
* Symptoms of other abscesses:
o Pain
o Fever
o Weight loss
* Varies depending on site
* Commonly includes the mouth
* Rectum and vagina
* Fever
* Pain
* Abscess formation
* Weight loss
* Abnormal vaginal bleeding and vaginal discharge

Actinomycosis Treatment

Medical Care

In most cases of actinomycosis, antimicrobial therapy is the only treatment required, although surgery can be adjunctive in selected cases. Penicillin G is the drug of choice for treating infections caused by actinomycetes.

Surgical Care

Attempt to cure actinomycosis, including extensive disease, with aggressive antimicrobial therapy alone initially. Surgical therapy may include incision and drainage of abscesses, excision of sinus tracts and recalcitrant fibrotic lesions, decompression of closed-space infections, and interventions aimed at relieving obstruction (eg, when actinomycotic lesions compress the ureter).

Consultations

1)    Interventional radiologist

2)    Surgeon

3)    Infectious diseases specialist

 

Diet

No specific dietary precautions are indicated in patients with actinomycosis.

Activity

Patients with actinomycosis may be active to the degree tolerated.

Clinical synopsis

 

A 58-year-old previously healthy man presented to the emergency center with a 12-month history of progressive right-sided facial swelling. The patient reported only mild pain exacerbated by eating and difficulty opening his mouth. He denied fever, chills, or weight loss. He had a 40-pack per year history of smoking tobacco and consumed 40 ounces of beer per day. The patient had no significant past medical history, and denied diabetes, hypertension, or cancer. He had lived his entire life in Texas, and worked as a farmer. Physical examination revealed an 8 × 8 cm area of facial swelling and indurated nodularity in the right parotidomasseteric region. There was no skin breakdown or drainage at his initial visit. No fluctuance was noted; however, there was firm induration surrounding the mass as well as slight erythema of the overlying skin. A small right tonsillar mass was observed along with poor dentition. The rest of the head and neck exam was normal. The patient was admitted for further work up of the facial mass. Laboratory workup revealed an erythrocyte sedimentation rate of 37 mm/hr. Other laboratory values, a urinalysis, and chest x-ray were all withiormal limits. An excisional biopsy by an otolaryngologist revealed only dense fibrosis of the dermal and subcutaneous tissues. A computerized axial tomography scan revealed right sided soft-tissue swelling, small focal micro-abscesses, dental caries, and a right tonsillar mass. No neoplastic process was identified on laryngoscopic guided biopsies. The patient was discharged with outpatient followup by both ENT and the dermatology service. At his dermatology visit, which was approximately 1 month after his initial presentation, the patient was noted to have a few small sinus tracts without obvious drainage and a new indurated red papule. Two 6 mm punch biopsies of the sinus tract as well as from the new papule were obtained, and each was split for routine histology and tissue culture. Routine histology revealed chronic granulomatous inflammation with a mixed inflammatory infiltrate. Clusters of thin filamentous bacteria within a large granule were noted in the deep dermis with a surrounding neutrophilic abscess. The bacteria were morphologically compatible with an Actinomyces spp. Culture confirmed the diagnosis by growing Actinobacillus actinomycetemcomitans. The patient was started on oral amoxicillin and doxycycline with close outpatient followup by the otolaryngology, dermatology, and infectious disease services.

ORAL MANIFESTATIONS OF TB DISEASE

The estimated prevalence of oral tuberculous lesions ranges from 0.05 to 5%.  Oral lesions are usually secondary, reflecting oral inoculation with infected sputum or as a result of hematogenous spread.  Rare cases of primary tuberculous involvement of oral structures have been reported.  In one study evaluating patients with TB disease and co-infection with HIV, the prevalence of oral tuberculous lesions was found to be 1.33%. Oral tuberculous lesions are nonspecific in their clinical presentation, and their consideration in the differential diagnosis requires a high degree of awareness. While all oral tissues may be affected, in the cohort of patients with both TB disease and HIV-infection, the palate and dorsum of the tongue (Figure 2) were the most frequent sites of oral involvement.

These data are in agreement with those reported by other investigators in patients with TB disease without HIV-infection. Pain and cervical lymphadenopathy are common but not universal findings. A rare case of tuberculous osteomyelitis of the mandible and several cases of tuberculous parotitis have been documented.

Diagnosis

Early diagnosis of infection with MBT is important because of the nature of the disease. The tuberculin skin test (TST) or a blood assay for Mycobacterium tuberculosis (BAMT) are useful for screening groups of people for LTBI with exposure rates that substantially exceed those of the general population (Table 1).

The TST, which is the Mantoux intradermal test, using 5 tuberculin units of Tween-stabilized purified protein derivative (PPD)-tuberculin is the traditional method of diagnosing LTBI.  The antigen is injected intracutaneously into either the volar or dorsal surface of the forearm.  In patients with LTBI, the TST evokes a delayed hypersensitivity reaction to the tuberculin mediated by T-lymphocytes producing an area of redness and swelling.  The test is read at 48 to 72 hours.  Erythema is disregarded, and the diameter of the induration is measured (Table 3).

While the relative specificity of the TST skin test is high, both false positive and false negative reactions have been reported. False-positive reactions may be due to previous sensitization with mycobacterial antigens, as may be seen following vaccination with Bacille Calmette-Guerin (BCG). False-negative reactions to the TST have been reported in immunocompromised patients, in patients with recent exposure to MBT, and in very young children. 

The CDC recommends persons with a positive TST undergo further evaluation.⁴⁶ In recent years a number of in vitro diagnostic tests in the form of BAMT have been developed. However, the QuantiFERON®-TB Gold (QFT-G) test is the only such test approved by the Food and Drug Administration (FDA) for the detection of latent TB infection. This test detects the release of interferon-gamma in fresh heparinized blood from sensitized persons when it is incubated with mixtures of synthetic peptides representing two proteins present in MBT. The sensitivity of QFT-G is statistically similar to that of TST for detecting TB infection. However, the QFT-G measures cell-mediated response to peptides from two MBT proteins that are not present in any BCG vaccine strains and are absent from the majority of mycobacteria other than MBT. Hence, the QFT-G has greater selectivity.

Although the history, physical examination, TST and/or QFT-G data, and other studies such as chest radiographs are helpful and at times may strongly suggest TB disease, definitive diagnosis usually requires the demonstration of MBT in the patient’s tissues or secretions.¹ Bacteriologic examination, which includes obtaining a specimen of sputum, detection of acid-fast bacilli (AFB) in stained (Ziehl-Neelsen method) smears examined microscopically, may provide the first bacteriologic clue to TB disease. However, not all AFB are tubercle bacilli, therefore, a positive bacteriologic culture for MBT is essential to confirm the diagnosis. DNA probes specific for the genus Mycobacterium now are used routinely to identify specific mycobacterium. When the presence of MBT has been confirmed, it is theecessary to perform drug susceptibility testing on positive cultures.

Immunization with viable Mycobacterium bovis BCG is the most widely used preventive measure to control tuberculosis worldwide. Administered to newborns in a single dose, it prevents severe disease and reduces mortality among children from miliary and meningeal disease. However, BCG does not protect against pulmonary tuberculosis in children or adults. As mentioned earlier, optimal immune response to MBT infection appears to involve both CD4+ and CD8+ T-cells. BCG activates CD4+ T-cells by being taken up by macrophages and residing within phagosomes which are membrane-enclosed vacuoles. These antigens, once processed in the phagosomes, then readily interact with MHC class II molecules. However, the ability of the bacillus to block acidification of the phagosomes precludes its release into the cytoplasm and for an antigen to bind to MHC class I molecules it must be processed in the cytoplasm of the infected cells. Consequently, BCG fails to elicit a CD8+ T-cell response. A recently developed recombinant bacillus with an impaired ability to counter the acidification of phagosomes will soon enter phase 1 clinical trials. This new vaccine is likely to be more effective because it targets both CD4+ and CD8+ T-cells.

The goal of antibacterial chemotherapy is to induce selective toxicity. Selectivity can be realized by attacking targets that are:

• unique to the pathogen,
• similar to but not identical to those of the host,
• shared by the host but that vary in importance between pathogen and host.

One target is the bacterial cell wall, a structure that is both unique and essential for the survival of most pathogenic bacteria. The bacterial cell wall is a three-dimensional meshwork of peptide-crosslinked sugar polymer (peptidoglycan or murein) surrounding the cell just outside its cytoplasmic membrane.

Bacteria may be conveniently divided into two groups, Gram-positive and Gram-negative, based on the relative abilities of bacteria to retain purple Gram-stain after being washed with an organic solvent such as acetone. Gram-positive bacteria retain the stain and appear purple, whereas Gram-negative bacteria lose the stain and appear pink. The ability to retain stain results from two distinguishing characteristics of cell wall architecture. In Gram-positive bacteria, the cell wall is composed of a thick layer of murein (Figure 3A). The murein layer in Gram-negative bacteria is thinner but it is surrounded by a second, outer lipid bilayer membrane (Figure 3B). The cell wall of mycobacteria, which include the causative agent of tuberculosis, is similar to that of Gram-negative bacteria (Figure 3C).

Both Gram-negative bacteria and mycobacteria are enclosed by an inner cytoplasmic membrane, a thin murein layer, and an outer membrane. The main difference is that, in mycobacteria, the outer membrane is thick, composed of two leaflets that are asymmetrical in size and composition. The inner leaflet is composed of arabinogalactan and mycolic acid, and the outer leaflet is composed of extractable phospholipids. Cell wall biosynthesis takes place in the following three major steps:

1.     Synthesis of murein monomers from amino acids and sugar building blocks (N-acetylglucosamine [NAG] and N-acetylmuramic acid [NAM]).

2.     Polymerization of the monomers into linear peptidoglycans.

3.     Crosslinking of the polymers into a three-dimensional meshwork.

In mycobacteria the NAM residues of the cell wall are modified by the addition of a long chain consisting of a NAG-arabinogalactan linker topped with mycolic acid. The addition of arabinose units is catalyzed by the enzyme arabinosyl transferase. The synthesis of mycolic acid includes the formation of saturated hydrocarbon chains catalyzed by the enzyme fatty acid synthetase 1 (FAS1), which are then linked by the enzyme fatty acid synthetase 2 (FAS2). The linked products undergo further enzymatic transformations to become mycolic acid.

Standard antimycobacterial treatment regimens include antibiotics that target unique targets such as the synthesis of NAG-arabinogalactan and the early steps in mycolic acid synthesis (Table 4).

The treatment of infections with MBT can be divided into treatment of LTBI and treatment of TB disease. Guidelines with detailed management recommendations are published and updated regularly.

The risk for progression from LTBI to TB disease is highest during the first two years after infection and is often predicated on concomitant medical conditions that alter the ability of the immune system to maintain the isolation of MBT (Table 2).  HIV infection is the most important risk factor.  It has been estimated persons infected with MBT and co-infected with HIV have a 6-10% risk per year of developing TB disease, while an immunocompetent person infected with MBT has a 10% life-time risk for TB disease.  Isoniazid, given for nine months in a single daily dose, is the drug of choice for the treatment of LTBI.  Persons exposed to patients with known isoniazid resistant TB disease and those with intolerance to isoniazid may be treated with rifampin for four months.  For patients with known exposure to multi-drug resistant TB disease, a regimen with two drugs to which MBT is susceptible is recommended for nine to 12 months.

Tuberculosis (TB) – Prevention

Active tuberculosis (TB) is very contagious. The World Health Organization (WHO) estimates that one-third of the world’s population is infected with the bacteria that cause TB.

To avoid getting an active TB infection:

• Do not spend long periods of time in stuffy, enclosed rooms with anyone who has active TB until that person has been treated for at least 2 weeks.
• Use protective measures, such as face masks, if you work in a facility that cares for people who have untreated TB.
• If you live with someone who has active TB, help and encourage the person to follow treatment instructions.

Can the TB vaccine help?

A TB vaccine (bacille Calmette-Guerin, or BCG) is used in many countries to prevent TB. But this vaccination is almost never used in the United States because:

• The risk of getting TB is low in the U.S.
• The vaccine is not effective in adults who receive it.
• The BCG vaccine may cause a tuberculin skin test to indicate a TB infection even if a person is not infected with TB. This complicates the use of the tuberculin skin test to check people for TB.

Oral manifestations of syphilis

The past decade has shown a significant rise in the prevalence of infective syphilis in the developed world, and striking increases in its frequency have occurred in Eastern Europe, particularly the UK, and in the US. Although oral manifestations of syphilis are most likely to be observed during secondary disease, all stages of the disease can give rise to oral lesions. Significant oral lesions such as gumma-associated bony destruction and a possible predisposition to oral squamous cell carcinoma are associated with tertiary disease. Since the prevalence of infective syphilis in heterosexuals has been increasing, there has now been a gradual rise in the number of children born with congenital syphilis. Consequently, the congenital disease gives rise to dental anomalies as well as bone, skin, and neurological anomalies of the face. The aim of this report is to review syphilis-related oral lesions, as well as to summarize the relations between human immunodeficiency virus (HIV) and syphilis.

CHANGING EPIDEMIOLOGY OF INFECTIVE SYPHILIS

Infective syphilis is caused by the anaerobic filamentous spirochete, Treponema pallidum. In the past decade there has been a significant rise in the prevalence of infective syphilis in the developed world. Striking increases in the frequency of syphilis have occurred in Eastern Europe, and smaller rises have been reported in Western Europe and the US. The changing epidemiology of syphilis reflects the falling use of barrier methods of contraception, high numbers of sexual partners,⁷ sexual promiscuity, lack of relevant knowledge, the sex industry, the health care breakdown in former Communist communities, and the deterioration of public health responses to sexually transmitted infection (STI) control (e.g. faster notification). In Eastern Europe, the increased frequency of syphilis has been predominantly in heterosexuals, while in the UK and US, the outbreaks have occurred in heterosexuals and in men having sex with men. Outbreaks in the US have sometimes been associated with the use of crack cocaine, and rapid spread of syphilis has occurred in prisons where recent arrestees may already be infected.

PRIMARY SYPHILIS

The mouth, perhaps surprisingly, is rarely the site of primary syphilis, and because of its transient nature, the oral ulceration of primary syphilis often goes unnoticed by the patient or by any unsuspicious clinician. In addition, albeit rarely, the lesions of primary disease may be confused with other pre-existing mucocutaneous disease. A chancre develops within 1 to 3 weeks of acquisition. Primary syphilis is usually the consequence of orogenital or oroanal contact with an infectious lesion. Kissing may, very rarely, cause transmission; indeed, it has been suggested that intrafamilial oral acquisition of syphilis in a child may have occurred via this route, although more usually oral syphilis in a child is indicative of sexual abuse.

Primary syphilis of the mouth manifests as a solitary ulcer usually of the lip or, more rarely, the tongue. The upper lip is more commonly affected than the lower in males, while the opposite occurs in females—probably reflecting the anatomy involved with fellatio and cunninlingus. The pharynx or tonsils may rarely be affected. The ulceration is usually deep, with a red, purple, or brown base and an irregular raised border. There is usually an accompanying cervical lymphadenopathy. The ulceration of primary syphilis may be confused with other solitary ulcerative disorders, most notably traumatic ulceration, squamous cell carcinoma, and non-Hodgkin’s lymphoma.

The diagnosis of primary syphilis may be aided by detailed analysis of the sexual and/or social lifestyles of the patient and of any of the available sexual partner; however, often the diagnosis of early disease can be difficult. Affected patients often do not have a positive nonspecific reaginic test, eg, Rapid Plasma Reagin (RPR) or Venereal Disease Reference Laboratory (VDRL) tests. The specific tests for IgG antibodies to T. pallidum become positive before the reaginic tests, and thus should be carried out when the nonspecific tests prove negative but a diagnosis of primary disease is still likely.

Treponemes are present in primary lesions and can be detected by dark field microscopy; however, this test is fraught with the risk of nosocomial transmission and is thus no longer considered suitable. In addition, there can be confusion between the spirochetes of T. pallidum with the normal commensals of the mouth.

Histopathology is not always helpful, as there are no specific histopathological features, and the detection of T. pallidum with Warthin-Starry stain or silver nitrate stain may not be possible. Monoclonal anthodyl immunoperoxidase staining techniques can detect T. pallidum and is a relatively routine clinical investigation of biopsy material. However, molecular methods such as in situ and tissue PCR still remaionroutine investigations for all types of syphilis. The tests used to detect IgM antibodies to T. pallidum may detect early infection.

OUTCOMES OF THERAPY

The primary chancres spontaneously heal within 7 to 10 days, although they can persist much longer, only resolving with appropriate antimicrobial therapy.

SECONDARY SYPHILIS

The features of secondary syphilis reflect the hematogenous spread of T. pallidum, and similarly to its other mucocutaneous features, the oral manifestations of secondary syphilis can be more extensive and/or variable than those of the primary disease. Oral lesions arise in at least 30% of patients with secondary syphilis, although very rarely oral ulceration may be the only manifestation of infection. The 2 principal oral features of secondary syphilis are mucous patches and maculopapular lesions, although nodular lesions may rarely arise.

MACULOPAPULAR LESIONS

• Macular syphilides: Macular lesions tend to arise on the hard palate and manifest as flat-to-slightly raised, firm, red lesions.
• Papular syphilides: These are rare. They manifest as red, raised, firm round nodules with a grey center that may ulcerate. The papules usually arise on the buccal mucosa or commissures.
•  Mucous patches: A variety of descriptions of mucous patches have been reported, but in general these manifest as oval-to-crescenteric erosions or shallow ulcers of about 1 cm diameter, covered by a grey mucoid exudate and with an erythematous border. The patches usually arise bilaterally on the mobile surfaces of the mouth although the pharynx, gingivae, tonsils, and very rarely the hard palate can be affected. At the commissures, the mucous patches may appear as split papules, while on the distal and lateral aspects of the tongue, they tend to ulcerate or manifest as irregular fissures. The mucous patches may coalesce to give rise to, or arise de novo as, serpiginous lesions, sometimes termed snail track ulcers.

ULCERONODULAR DISEASE (LUES MALIGNA)

Ulceronodular disease is an explosive generalized form of secondary syphilis characterized by fever, headache, and myalgia, followed by a papulopustular eruption that rapidly transforms into necrotic, sharply demarcated ulcers with hemorrhagic brown crusts, organized in rupioid layers commonly on the face and scalp. The mucosa is involved in about one third of affected patients. Lues maligna gives rise to crateriform or shallow ulcers on the gingivae, palate or buccal mucosa, with multiple erosions on the hard and soft palates, tongue and lower lip.

NODULAR DISEASE

Rarely, secondary syphilis can manifest as nodules alone. This nodular eruption of syphilis has a predilection for the face, mucous membranes, palms of the hands and soles of the feet.²⁶ Lesions may occur on the vermillion, mimicking squamous cell carcinoma or keratoacanthoma.

DETECTION OF INFECTION IN SECONDARY DISEASE

Treponema pallidum can usually be detected on the surface of erosions or ulcers by darkfield microscopy, although as noted above, this test should be avoided. The patient will have positive serological tests.

The histopathological features of secondary syphilis are variable. Often the changes are nonspecific, although they may include perivascular infiltrates with a preponderance of plasma cells and epidermal psoriasiform hyperplasia. Warthin-Starry strains will only detect spirochetes in about a third of instances, although newer methods may increase the in situ detection of the causative agent.

OUTCOMES OF THERAPY

The lesions of secondary syphilis will resolve spontaneously within 3 to 12 weeks, regardless of therapy, and about 25% of untreated patients will have recurrence of secondary disease.

LATENT SYPHILIS

In early latent syphilis, usually the first 12 months after secondary disease, affected patients are infectious. In late latent syphilis the infectivity falls.

TERTIARY SYPHILIS

Clinical disease arises in about one third of patients with untreated secondary syphilis. The oral complications of tertiary syphilis center upon gumma formation, and much more rarely, syphilitic leukoplakia (and risk of oral squamous cell carcinoma) and neurosyphilis.

GUMMA FORMATION

Gummas tend to arise on the hard palate and tongue, although very rarely they may occur on the soft palate, lower alveolus, and parotid gland.^27-30 A gumma manifests initially as 1 or more painless swelling.¹⁶ When multiple, they tend to coalesce, giving rise to serpigninous lesions. The swellings eventually develop into areas of ulceration, with areas of breakdown and healing. There may be eventual bone destruction, palatal perforation, and oro-nasal fistula formation. Rarely, a gumma may erode into blood vessels—eg, the inferior alveolar artery. Gumma manifests radiologically as ill-defined radiolucencies that may resemble malignancy. The areas of ulceration eventually heal, although the resultant scarring can, at least on the tongue, cause fissuring.

SYPHILITIC LEUKOPLAKIA AND RISK OF SQUAMOUS CELL CARCINOMA

Syphilitic leukoplakia would appear to be a homogenous white patch affecting large areas of the dorsum of the tongue. There are few good descriptions of syphilitic leukoplakia, and it is unclear whether this lesion truly reflects syphilis, or more likely a tobacco smoking habit—indeed this was observed by Hutchinson in the 19th century.

An association between tertiary syphilis and oral squamous cell carcinoma—particularly of the tongue—has been suggested for many years. Both clinically- and serologically-based studies have suggested an increased prevalence of syphilis in patient groups with squamous cell carcinoma of the tongue (up to 60% in one study), the association being stronger in males than females.³¹ A relatively recent study of 16,420 people with syphilis resident in the US found a significantly raised frequency of cancer of the tongue (and Kaposi’s sarcoma) in males.³² A noncontrolled study found that 5 of 63 UK patients with squamous cell carcinoma of the tongue had serological evidence of past syphilis as detected by both specific and nonspecific tests.³³ However, it remains unclear whether any risk of oral squamous cell carcinoma in syphilis is a direct consequence of infection (which seems unlikely) or is the effect of recognized causative factors for oral malignancy, ie, tobacco, alcohol, and malnourishment.

NEUROSYPHILIS

Aside from the well-recognized Argyll Robertson pupil, tertiary syphilis can give rise to both unilateral and bilateral trigeminal neuropathy and facial nerve palsy. Potentially, syphilitic osteomyelitis may give rise to trigeminal neuropathy.

DETECTION OF INFECTION IN TERTIARY DISEASE

Gummas are characterized histopathologically by endarteritis obliterans, necrosis with epithelioid and giant cells and a plasma cell infiltrate. Spirochetes are difficult to detect. In tertiary disease, the nonspecific tests may not be positive; the most reliable test is FTA, although this may remain positive even after successful therapy.

CONGENITAL SYPHILIS

As discussed previously, in some communities there is a rising prevalence of congenital syphilis. Treponema pallidum crosses the placenta only after the 16th week of intrauterine life; hence, depending upon the time of infection, it may variably affect the facial structures. Resembling its systemic features, the orofacial manifestations of congenital syphilis can be split into early and late. Early features include diffuse maculopapular rash, periostitis (frontal bossing of Parrot), and rhinitis. Late features, manifesting at least 24 months after birth, comprise the Hutchinsonian triad of interstitial keratitis of the cornea, sensorineural hearing loss, and dental anomalies.

The dental anomalies of congenital syphilis only arise in teeth in which calcification occurs during the first year of life, hence typically the permanent incisors and first molars. Of note, the maxillary incisors are more commonly affected than the mandibular ones. The incisors have a screwdriver shape, there being a convergence of the lateral margins towards the incisal edge. In some, there may be notching of the incisal edge, while in others, there may be a depression on the labial surface. The first molar may be bud-shaped and reduced to the size of the adjacent second molar. The normal mesiodistal convexity of the crown may be reduced. Enamel hypoplasia may occur. Yellow discoloration of the skin about the lips can arise soon after birth; the area then becomes increasingly rigid with crack formation and eventual (Parrot’s) radial scars—rhagades—of the lips. There may be a loss of the well-circumscribed border of the vermillion.

Other, less common orofacial features include atrophic glossitis and a high, narrow palatal vault. Facial neuropathies may rarely occur as can palatal gumma in adulthood.

INTERACTIONS BETWEEN HIV AND SYPHILIS

According to WHO, Brazil had about 660,000 people living with human immunodeficiency virus (HIV) at the end of 2003, and 15,000 people had died of AIDS during that year. Heterosexual transmission, sex between men, and injecting drug users (IDU) continue to be almost equally responsible for the burden of HIV infection. However, the HIV epidemic in Brazil has changed over the last decade, with IDU being responsible for almost 30% of all HIV cases.

Strong evidence supports several biologic mechanisms through which sexually transmitted diseases (STDs) facilitate HIV transmission by increasing both HIV infectiousness and HIV susceptibility. Thus, the detection of STDs and the establishment of effective treatment is an important strategy of HIV control.

INFLUENCE OF HIV DISEASE UPON SYPHILIS

It was initially suggested that concurrent HIV infection and syphilis is not uncommon, particularly in young adults, men having sex with men, and traders of commercial sex. HIV disease might significantly influence the clinical source of syphilis, as it does for some STDs and other conditions related to HIV-associated immune deficiency, and the associated infection is often more aggressive than the mono-infection. A Nigerian study of 31 people with concurrent HIV infection and syphilis found that 64.2% of the patients had developed unusual lesions affecting more than 50% of the body. Also, the chancres seen at the sites of inoculation had an atypical appearance.

However, a recent detailed study suggests that other than an increased number and frequency of genital ulcers in secondary disease, HIV disease does not greatly impact the clinical care of syphilis. Nevertheless, there have been reports of prolonged primary disease and secondary disease; additionally, neurosyphilis may present more quickly and ulceronodular disease is more likely in patients infected with HIV than in those not infected.

INFLUENCE OF ORAL SYPHILIS UPON HIV DISEASE

Patients with concurrent HIV infection and syphilis usually have a history of sexually transmitted infection, and it is common that these patients have more than 1 condition (eg, genital ulcers, injected drug addition, etc) that are potential sources of exposure. The genital ulceration of syphilis increases the risk of HIV transmission. Nonulcerative STD, however, also have the capacity of increasing the likelihood of HIV transmission, and the detection and treatment of syphilis can probably help to reduce HIV transmission. While there are no data to support the notion, it is likely that oral syphilis principally influences HIV disease by increasing the likelihood of HIV transmission (and other related viruses) by oral sexual routes. A recent study found no association between early syphilis and changes in blood or semen viral load or CD4 count in HIV-positive individuals. According to the study, increased HIV-1 infectivity associated with early syphilis is unlikely to be associated with increased levels of HIV-1 RNA in blood or semen. There is now compelling evidence, based upon case and epidemiological studies, that HIV can be transmitted via orogenital contact. In addition, as persons in high-risk groups for HIV move away from high-risk sexual activities, there is likely to be an increased frequency of orogenital contact, and hence oral sex will contribute to a greater frequency of new infections than previously. Oral ulcerative disease, such as that of all the stages of syphilis, will increase the HIV load in the mouth, and hence the potential for HIV transmission via oral sex.⁴⁴ In addition, this increased risk of HIV transmission will be further worsened by ulcerative disease secondary to the use of the recreational drugs, crack cocaine⁴⁵ and cocaine powder. Finally the oral ulcerative disease of syphilis is likely to increase the nonsexual spread of human herpes virus 8 (HHV-8).

HOW DOES HIV AFFECT THE MOUTH?

In the early years of the HIV epidemic, dentists were often the first health professionals to notice signs of a weak immune system. These signs were infections that are normally controlled by a healthy person. When people get tested for HIV infection and get treatment, most of these infections never show up. However, many people do not get tested for HIV. They may be infected and now know it. Regular dental care is an important way they may learn they have a weak immune system.

According to the US Health Resources and Services Administration, over one third of people with HIV will have at least one major oral health problem, and almost two thirds do not receive regular dental care.

DON’T IGNORE MOUTH PROBLEMS!

Pain or bleeding in your mouth can be a sign of infection. It can keep you from eating normally. Severe pain makes some people skip taking their medications. Serious infections in your mouth can cause other health problems. Be sure to see a dentist or let your health care provider know if you have trouble swallowing, changes in how food tastes, or pain or other problems with your mouth or teeth.

Some dentists or their office staffers do not want to treat patients with HIV. This goes against community standards and violates the Americans with Disabilities Act. Dental health care workers know how to protect themselves from diseases carried in the blood of their patients, including HIV.

WHAT ARE THE SIGNS OF HIV IN THE MOUTH?

Several problems with the teeth, mouth and gums can show up in people with HIV. These are discussed below.

• Dry Mouth and Tooth Decay
• Candidiasis (thrush)
• Canker sores (apthous ulcers)
• Cold sores (herpes simplex)
• Gum disease (periodontitis)
• Hairy leukoplakia
• Kaposi’s Sarcoma
• Enlarged saliva glands
• Shingles (herpes zoster)
• Oral warts (human papillomavirus):

Dry Mouth and Tooth Decay
Many people with HIV have dry mouth. They don’t make enough saliva to chew and swallow comfortably. Saliva protects teeth and gums from infection and decay.

HIV infection can cause dry mouth. So can some medications, as well as coffee, carbonated beverages, alcohol, and smoking. If you have dry mouth, take frequent drinks of water. You can talk to your health care provider about using sugar-free gum or candy, or a saliva substitute.

Candidiasis (thrush) This infection is caused by a fungus (yeast) called Candida. It shows up as red patches on the tongue or roof of the mouth or white lumps that look like cottage cheese that can form anywhere in the mouth. Candidiasis infection can move into the throat. It can also cause painful cracks at the corners of the mouth called angular chelitis. Many anti-fungal treatments can treat thrush. However, some cases of thrush are resistant to the usual medications.

Canker sores (apthous ulcers) are small, round sores on the inside the cheek, under the tongue, or in the back of the throat. They usually have a red edge and a gray center. The sores can be quite painful. They can be caused by stress or by certain foods such as eating too many tomatoes. Hot and spicy or acidic foods or juices make them hurt more. Some ointments, creams or rinses can help.

Cold sores are caused by herpes simplex a common infection. In people with HIV, cold sores can be more severe and can keep coming back. The most common treatment is the antiviral drug acyclovir.

Gum Disease (periodontitis or gingivitis) is swelling of the gums. Sometimes painful and bloody, it can progress from gum loss to loosening and even loss of teeth. This can happen as quickly as 18 months. Dry mouth and smoking can make gum disease worse. Brush your teeth, floss, and see a dentist regularly.

Recently, gum disease has been linked to higher levels of inflammation, throughout the body. This can increase the risk of heart disease and stroke.

Hairy Leukoplakia is an irritation that usually shows up as painless, fuzzy white patches on the side of the tongue. It can be an early sign of HIV infection.

Kaposi’s Sarcoma (KS), usually shows up as dark purple or red spots on the gums, the roof of the mouth, and the back of the tongue. It is rarely seen when people are tested early and start using antiretroviral therapy for HIV infection. It can be the first sign of HIV infection in people who have not been tested for HIV. The best treatment for oral KS in someone with HIV is effective antiretroviral therapy.

Oral Warts – Human Papillomavirus, HPV is a sexually transmitted disease. Some strains of HPV cause warts or cancer. HPV warts can show up in the mouth. The warts can be frozen or cut out.

THE BOTTOM LINE

Signs of HIV infection often show up in the mouth. You might know people who haven’t been tested for HIV. Encourage them to pay attention to any mouth problems.

Keep your mouth healthy by brushing your teeth and flossing. Get your teeth cleaned regularly by a dental health professional. See a health or dental care provider about any serious issues.

The following may be warning signs of infection with HIV:

·         Rapid weight loss

·         Dry cough

·         Recurring fever or profuse night sweats

·         Profound and unexplained fatigue

·         Swollen lymph glands in the armpits, groin or neck

·         Diarrhea that lasts for more than a week

·         White spots or unusual blemishes on the tongue, in the mouth or in the throat

·         Pneumonia

·         Red, brown, pink or purplish blotches on or under the skin or inside the mouth, nose or eyelids

·         Memory loss, depression and other neurological disorders

 

Fungal Infections

Candidiasis(Thrush)

 

Thrush is a common problem for infants since their immune systems are not yet fully developed. In healthy adults, however, thrush infections happen only rarely, and usually are an indication of a lowered immune response.  Often it is due to illnesses other than AIDS such as general viral infections or stress related fatigue.  It is characterized by creamy white, soft plaques that are easily scraped off the mucosa (the lining of the mouth) revealing a red, inflamed patch underneath.  This type is seen in the picture to the right.  It is easily treated with topical antibiotics like Nystatin.

The image above, top left shows pharyngeal candidiasis.  The pharynx is the throat, and pharyngeal candidiasis is an indication of the severe immune system depression characteristic of AIDS.  This form of yeast infection was considered pathognomonic of AIDS until it was realized that persons who use inhaled steroid medications for the treatment of asthma are also prone to this sort of infection.  (Once again, the presence of pathognomonic signs of a disease, –which means observable things that are frequently associated with a particular disease– do not necessarily mean that the patient has that disease, but a blood test is strongly recommended in such cases.)   Oral and pharyngeal candidiasis are not contagious.

Angular Cheilitis

Angular cheilitis is a very common condition.  It is a fungal infection of the corners of the lips.  It can plague healthy people who tend to have moist lips, especially in the cold winter months.  This condition is caused by a persistent fungal infection, and left untreated, tends to remain active for many months.  It generally looks like a reddened,  dry area at the corners of the l

ips.  The severe, white, ulcerated variety shown to the left is more indicative of the type seen in AIDS.  Even a severe case like this, by itself, does not indicate that the patient has AIDS.  It is easily treated with Nystatin cream which is simply an antibiotic that kills the fungus.  Angular cheilitis is not contagious.  click the image on the left to see more images of angular cheilitis.

Viral associated signs of HIV

Hairy Leukoplakia

Hairy leukoplakia is one of the most common HIV associated oral signs.  It is a white, corrugated or “hairy” “coating” on the lateral borders of the tongue.  Unlike thrush, it is not easily scraped off.  It is painless, but patients occasionally complain of its appearance and texture.  It is caused by the body’s reaction to the Epstein-Barr virus (responsible for Mononucleosis), and can be eliminated with a viral antibiotic like acyclovir (Zovirax®), famciclovir (Famvir®) or valacyclovir (Valtrex®).  This condition is rarely seen in patients not infected with  HIV.  However, some healthy patients may develop a “callous”  on the lateral borders of the tongue due to the nervous habit of continually scraping the tongue over the teeth.  This can lead to embarrassment if the dentist suggests an AIDS test to a person who believes such a suggestion is an insult!  It is never meant as a value judgment.  Hairy Leukoplakia is not contagious.  click the image to see a larger version of this image and more information on hairy leukoplakia.   

Herpes Zoster (Shingles)

Herpes Zoster (better known as shingles) is caused by the same virus that causes Chicken Pox.    Herpes zoster “hides out” in a somatic nerve branch after the initial Chicken Pox infection (which usually happens in childhood), and flares up again later in life when the immune system begins to fail.  Shingles is common in otherwise healthy elderly persons.  It generally does not occur in younger people unless they are concurrently infected with the AIDS virus.  The distribution of the rash on the body is the key to the diagnosis of shingles, and distinguishes the herpes zoster virus from other forms of herpes viruses.  The distribution of the rash caused by herpes zoster in shingles is almost always on one side of the body, and is confined to the distribution of a single nerve root.  The skin surface distribution of each spinal or cranial nerve is called a dermatome.  The image on the left shows a rash which is confined to the dermatome defined by the third branch of the trigeminal nerve.  It is outlined in blue to make it easier to see.  Click the image to see larger images, as well as a great deal more on the concept of somatic dermatomes.  Shingles infections are quite painful, and they generally go away after four or five weeks, but shingles may reoccur again at a later date.  It frequently leaves those so afflicted with “postherpetic neuralgia” (PHN),  which is severely sensitive skin, well after the infection.  

Persons infected with HIV are prone to this disease if they have previously been infected with Chicken Pox.  For people with AIDS, this condition can be severe and even life threatening.  In the mouth, it is identified by its distribution. It is limited to one side of the affected organ.  The image to the right shows the Herpes zoster virus infecting half of the upper posterior palate.  It is easy to confuse Herpes zoster with Herpes simplex which may occur in the same distribution purely by chance.  While the Herpes simplex virus is contagious, Shingles, surprisingly is not.  Since a large percentage of the population already has been exposed to Chicken pox, most people harbor an immunity to Herpes zoster, and the probability that anyone will develop this disease depends more on the state of their immune system than on recent exposure to the virus.

Herpes Simplex (the “cold sore” or “fever blister” virus)

Herpes Simplex (type I) is the virus that causes  cold sores iormal, healthy adults.  The image at the right shows a typical cold sore, sometimes called a fever blister due to its propensity to appear when the patient has a cold or other febrile (fever causing) illness.  This is another bug that, like Shingles, tends to “hang out” in a nerve root for  the life of the patient after the initial infection, which often occurs in childhood.  Once infected, the patient remains infected for life.  However the  virus remains dormant inside the nerve root most of the time until the patient suffers an illness or other problem which lowers his immune response.  The virus takes advantage of the drop in immune response to flare up in the typical cold sore seen in this image.  Click the image above for more on Herpes simplex.

This image is what the initial infection may look like when a child, or young adult is first infected with the Herpes Simplex virus.  This is called “Primary Herpes stomatitis“, and as you can see, it can look quite severe with blisters both inside and outside the mouth.  (“Stomatitis” means inflammation of the entire mouth.)  The patient is quite sick, but this primary infection will disappear after 10-14 days with rest and lots of fluids.  In healthy people, this infection happens only once in a lifetime.  The presence of the virus only becomes apparent in adulthood whenever a cold sore appears.  

Whenever an adult appears in a clinic with a case of Primary Herpes Stomatitis, this infers a severely depressed immune response, and the dentist might consider referring the patient to a physician for diagnosis of an underlying disorder.  Adults presenting with severe herpes stomatitis should consider being tested for HIV.  It must be remembered, however, that a primary herpes stomatitis can happen at any time of life if the patient has never before had a cold sore.  Click on the image to see larger views of this condition.

Patients with AIDS have immune systems much more depressed thaormal people with a cold or the flu.  AIDS victims may get not only recurrent cold sores, but recurrent (repeating) cases of full blown Herpes Stomatitis as well.  Whenever an adult appears in a clinic with a case of Primary Herpes Stomatitis, this infers a severely depressed immune response, and the treating physician or dentist may suspect an undiagnosed HIV infection underlying the Herpes infection. New antibiotics like acyclovir (Zovirax®), famciclovir (Famvir®) or valacyclovir (Valtrex®) are effective in suppressing the Herpes. 

Herpes simplex blisters can sometimes occur in the oral cavity on tissues not generally associated with cold sores.  They always happen on tissue that is firmly bound down to underlying bone, such as the gums immediately around the teeth or on the roof of the mouth.  As you can see, the appearance of this infection in the mouth can easily be confused with Herpes Zoster (shingles), especially if it occurs on only one side of the mouth.  The viruses are closely related, and the blisters in the oral cavity can look identical.

The presence of this type of infection in the mouth does not indicate the presence of HIV, although this infection is more common in AIDS patients than in the non-HIV population.  This can happen to anyone who harbors the Herpes Simplex virus.  Left alone, provided the patient is not immunologically compromised, it disappears in 10 to 14 days and may be treated with acyclovir (Zovirax®), famciclovir (Famvir®) or valacyclovir (Valtrex®) for quicker recovery.  The herpes simplex virus is very contagious and if one person in a family develops a cold sore, then others in the family may develop one as well. 

For more basic information on the various forms herpes simplex takes, visit HerpesEductaion.Org.

A Note on Genital Herpes

Herpes Simplex type I (HSV-1) tends to infect the face and oral cavity. This virus is the one responsible for traditional cold sores, as well as primary herpes stomatitis.  However, there is a second variety of Herpes that prefers to infect the genital areas.  Herpes Simplex Type II (HSV-2)  is called “genital Herpes” because of its tendency to be transmitted sexually.  Both HSV-1 and HSV-2 produce similar lesions.  The difference between them is their site specific preferences.  Both varieties establish latency (in other words, they take up permanent residence) ierve roots and once established, tend to cause occasional recurrent outbreaks with active lesions (sores) in areas of the body serviced by that particular somatic nerve root.   Herpes Simplex type 1 prefers to live in the trigeminal nerve root where it causes lesions in the mouth and on the face.  HSV-2 takes up residence in the sacral ganglion, located at the base of the spine, where it may cause genital lesions (see the dermatome chart on the Herpes zoster page).

Even though each type of Herpes virus has site specific preferences, they are genetically similar, and can take up residence ierve roots in other parts of the body, including in each other’s territory.  However, outside of their own home territories neither virus is especially virulent, and rarely cause recurrent outbreaks. 

HSV-2 (genital herpes) causes approximately 90% of all cases of genital herpes outbreaks.  The other 10% is caused buy HSV-1.  Genital herpes caused by HSV-1 is generally much milder than that caused by HSV-2.   HSV-1, the “cold sore virus”,  is usually transferred to the genital area by direct oral/genital contact, but upon occasion can be transferred from a patient’s mouth to their own genitals (or someone else’s) by simple manual transfer.  Thus the use of saliva as a lubricant can transfer HSV-1 to the genital area.  Most people infected with HSV-1 in the genital area have few, if any, outbreaks after the initial episode.  HSV-2 prefers to live in this area and causes a much more virulent infection there. 

On the other hand, HSV-1 causes almost all cases of oral and facial herpes.  Oral herpes caused by HSV-2 is not likely to cause recurrent infections, except in immunocompromised patients.

Human Papillomavirus lesions (warts)

Warts are caused by a virus.  In the oral cavity, they tend to be somewhat flatter than the type occurring on hands, but if they are dried with air, the tiny projections characteristic of regular warts become evident.  The causative agent is the Human Papillomavirus (HPV).  These growths generally are not painful and can be ignored unless they interfere with appearance or function.  Persons infected with HIV may develop very large, multiple warts.  They may be removed using lasers, cautery or cold steel blades.  The presence of oral warts is not in itself an indication of AIDS, although some strains of the virus are associated with squamous cell carcinoma (oral cancer).  HPV is contagious. Click on the image for more information on HPV and its association with oral and cervical cancer

Neoplasms (tumors, or “growths” )

Kaposi’s Sarcoma (KS) (pronounced “cap-o-zeez”)

Kaposi’s Sarcoma is a form of cancer consisting  of an overgrowth of tiny blood vessels.  It is generally dark red or deep purple.  It may be flat, but sometimes presents as a swollen mass.  The lesions are rarely painful, unless they become secondarily infected.  Thus good oral hygiene is important in the management of these tumors when they occur in the mouth. 

Kaposi’s Sarcoma is most frequently seen on the skin.   However tumors can occur in the gastrointestinal tract and the oral cavity as well.  Lesions in the oral cavity occur mostly on the palate (the roof of the mouth).  Kaposi’s  is technically a form of cancer, however there is evidence that it is actually the result of a secondary infection with Herpes virus type VIII.  An abundance of this virus is found in the saliva of infected individuals.   However, the virus causes Kaposi’s Sarcoma only in patients with very compromised immune systems.  It is believed that in most

modern cases, Herpes virus type VIII is transferred through deep kissing.

Kaposi’s tumors were once seen exclusively in elderly men with compromised immune systems.  Today, however, they are seen more frequently in young men with AIDS.  The occurrence of one of these lesions anywhere on the body of a young man is indicative of the presence of HIV. Kaposi’s is rarely seen in women, even women infected with HIV.  It is also rarely found in men who have contracted AIDS by way of intravenous drug use.  It is not known why women and heterosexual males with AIDS do not generally get Kaposi’s sarcoma, although there is probably an association between the gay lifestyle and the transfer of the herpes type VIII virus. Kaposi’s occurs as the initial manifestation of AIDS in approximately 11% of patients.

Lymphoma (lymphatic cancer)

Non Hodgkin’s Lymphoma (NHL) is a form of cancer.  It starts in a lymph node and then  spreads to other areas of the body through the  blood vessels and the lymphatic system.  Before the era of AIDS, Non Hodgkin’s lymphoma usually affected older individuals (median age 67).  Unfortunately, since the beginning of the AIDS epidemic the incidence of NHL has increased substantially in younger persons.  Lesions like those in the image to the right, especially when present in a younger person, may be the first indication that a patient has an HIV infection.   NHL is usually accompanied by a generalized lymphadenopathy (generalized swelling of the lymph nodes).  However, persons with no history of immunosuppression (or HIV)  may contract the  disease.  Click the image for more information on this condition and its relation to HIV.

Bacterial diseases associated with AIDS

Periodontal Disease

In order to understand how periodontal disease  (gum disease) affects persons with AIDS, it will be helpful to read my explanation of regular periodontal disease, since the process in HIV infected people is the same (albeit more severe and much more rapidly  progressing) as in otherwise healthy people.  The treatment for HIV infected persons is also the same as the treatment for otherwise healthy persons with

Periodontal disease, except that irrigation with Betadine (an Iodine solution) and more aggressive antibiotics are used.

In light of the fact that Gum Disease in HIV infected patients is so similar to the variety seen in the normal population, it is unlikely that a dentist would draw a parallel  between the presence of this process and the presence of HIV until the condition presented itself like the picture below and to the right.

The image to the right shows a case of necrotizing ulcerative periodontitis.  The difference between periodontitis and gingivitis is the degree of bony involvement and the depth of the pocketing.  The white, red and bleedy area under the necks of the lower teeth is indicative of necrotizing  (in the process of dying) tissue. While the process can be halted by aggressive intervention from a dentist and periodontal health maintained by good oral hygiene, the damage to the gums and bone is permanent. Periodontal disease is caused by poor oral hygiene and is not contagious.

Acute Necrotizing Ulcerative gingivitis (trench Mouth)

A less severe form of this condition  found in the non HIV infected population (also seen in early stages of AIDS) is called Acute Necrotizing Ulcerative Gingivitis (ANUG), formerly called “Trench mouth“.  In ANUG,  only the  gingiva immediately surrounding the teeth becomes necrotic.  ANUG is often found in people with poor oral hygiene who are either ill or under extreme physical or emotional stress. (It was named “trench mouth” because it was common in soldiers who fought in the trenches during world war I.  These men were certainly under extreme physical and emotional stress, and had little opportunity to brush their teeth.)

ANUG, being a bacterial infection, is very easily treated by gentle cleaning of the teeth and irrigation of the affected gums with 3% hydrogen peroxide.  The bacteria that take advantage of a patient’s run-down condition tend to be anaerobic which means that they die in the presence of oxygen.  Hydrogen peroxide liberates oxygen (hence the bubbles) when it is exposed to blood, and the oxygen acts as an antiseptic and speeds healing of the damaged gum tissue.  The patient is sent home with a prescription for Penicillin and instructions on cleaning the teeth to prevent further problems.  ANUG is not contagious.

Dentists today rarely see cases of ANUG, however the disease is making a comeback in communities in which there is a lot of drug addiction.  It is especially prevalent in populations of methamphetamine addicts and is a part of the syndrome now known as Meth Mouth.

Acute Necrotizing Oral Stomatitis

This condition is never seen except in a hospital setting.  If the immune system is severely compromised, the body is unable to fight off bacterial infections that a normal immune system is able to combat easily.  Without a functioning immune system, normal environmental bacteria can attack a living body in the same way they would attack a dead body.  HIV attacks the immune system, immobilizing it.  Without a properly functioning immune system, there is no defense against parasitic bacteria and viruses, and a living body can start to decay.

 

Other indications of immune deficiency

Geographic tongue–This condition is thought to be an oral form of psoriasis (a common skin condition), and is characterized by the disappearance of the filiform papillae from irregular patches on the top surface of the tongue.  These patches then “heal” up and reoccur on another part of the tongue at a later date.  One can see lesions in varying stages of healing over large expanses of the tongue.  The cause of this condition is unknown.  These patients often complain of pain when eating sharp foods.  The condition can be treated with topical application of steroid gels or mouth rinses.  In general, however, it is not treated.  Geographic tongue is not a contagious condition.  This condition might be seen more frequently in AIDS patients, however the presence of geographic tongue does NOT mean that the patient has AIDS.  It may be more prevalent in persons with HIV because the virus attacks the immune system, and psoriasis is caused by a mal fun ti on of the immune system.  Click the image on the right for a larger view.

Syphilis Prevention and Treatment

Syphilis is a sexually transmitted disease (STD), once responsible for devastating epidemics. It is caused by a bacterium called Treponema pallidum. The rate of primary and secondary syphilis in the United States declined by 89.2 percent from 1990 to 2000. The number of cases rose, however, from 5,979 in 2000 to 6,103 in 2001. The U.S. Centers for Disease Control and Prevention reported in November 2002 that this was the first increase since 1990.

Of increasing concern is the fact that syphilis increases by 3- to 5-fold the risk of transmitting and acquiring HIV (human immunodeficiency virus), the virus that causes AIDS (acquired immunodeficiency syndrome).

How Is Syphilis Transmitted?

The syphilis bacterium is very fragile, and the infection is almost always transmitted by sexual contact with an infected person. The bacterium spreads from the initial ulcer (sore) of an infected person to the skin or mucous membranes (linings) of the genital area, mouth, or anus of an uninfected sexual partner. It also can pass through broken skin on other parts of the body.

In addition, a pregnant woman with syphilis can pass T. pallidum to her unborn child, who may be born with serious mental and physical problems as a result of this infection.

What Are The Symptoms Of Syphilis?

The initial infection causes an ulcer at the site of infection. The bacteria, however, move throughout the body, damaging many organs over time. Medical experts describe the course of the disease by dividing it into four stages-primary, secondary, latent, and tertiary (late). An infected person who has not been treated may infect others during the first two stages, which usually last 1 to 2 years. In its late stages, untreated syphilis, although not contagious, can cause serious heart abnormalities, mental disorders, blindness, other neurologic problems, and death.

Primary Syphilis

The first symptom of primary syphilis is an ulcer called a chancre (“shan-ker”). The chancre can appear within 10 days to 3 months after exposure, but it generally appears within 2 to 6 weeks. Because the chancre may be painless and may occur inside the body, the infected person might not notice it. It usually is found on the part of the body exposed to the infected partner’s ulcer, such as the penis, vulva, or vagina. A chancre also can develop on the cervix, tongue, lips, or other parts of the body. The chancre disappears within a few weeks whether or not a person is treated. If not treated during the primary stage, about one-third of people will go on to the chronic stages.

Secondary syphilis

A skin rash, with brown sores about the size of a penny, often marks this chronic stage of syphilis. The rash appears anywhere from 3 to 6 weeks after the chancre appears. While the rash may cover the whole body or appear only in a few areas, it is almost always on the palms of the hands and soles of the feet.

Because active bacteria are present in the sores, any physical contact-sexual or nonsexual-with the broken skin of an infected person may spread the infection at this stage. The rash usually heals within several weeks or months.

Other symptoms also may occur, such as mild fever, fatigue, headache, sore throat, patchy hair loss, and swollen lymph glands throughout the body. These symptoms may be very mild and, like the chancre of primary syphilis, will disappear without treatment. The signs of secondary syphilis may come and go over the next 1 to 2 years of the disease.

Latent syphilis

If untreated, syphilis may lapse into a latent stage during which the disease is no longer contagious and no symptoms are present. Many people who are not treated will suffer from no further signs and symptoms of the disease.

Tertiary syphilis

Approximately one-third of people who have had secondary syphilis go on to develop the complications of late, or tertiary, syphilis, in which the bacteria damage the heart, eyes, brain, nervous system, bones, joints, or almost any other part of the body. This stage can last for years, or even for decades. Late syphilis can result in mental illness, blindness, other neurologic problems, heart disease, and death.

How Is Syphilis Diagnosed?

Syphilis is sometimes called “the great imitator” because its early symptoms are similar to those of many other diseases. Sexually active people should consult a doctor or other health care worker about any rash or sore in the genital area. Those who have been treated for another STD, such as gonorrhea, should be tested to be sure they do not also have syphilis.

There are three ways to diagnose syphilis.

• Recognizing the signs and symptoms
• Examining blood samples
• Identifying syphilis bacteria under a microscope

The doctor usually uses all these approaches to diagnose syphilis and decide upon the stage of infection.

Blood tests also provide evidence of infection, although they may give false-negative results (not show signs of an infection despite its presence) for up to 3 months after infection. False-positive tests (showing signs of an infection when it is not present) also can occur. Therefore, two blood tests are usually used. Interpretation of blood tests for syphilis can be difficult, and repeated tests are sometimes necessary to confirm the diagnosis.

How Is Syphilis Treated?

Unfortunately, the early symptoms of syphilis can be very mild, and many people do not seek treatment when they first become infected.

Doctors usually treat patients with syphilis with penicillin, given by injection. They use other antibiotics for patients allergic to penicillin. A person usually can no longer transmit syphilis 24 hours after starting treatment. Some people, however, do not respond to the usual doses of penicillin. Therefore, it is important that people being treated for syphilis have periodic blood tests to check that the infectious agent has been completely destroyed.

People with neurosyphilis may need to be retested for up to 2 years after treatment. In all stages of syphilis, proper treatment will cure the disease. But in late syphilis, damage already done to body organs cannot be reversed.

What Are The Effects Of Syphilis In Pregnant Women?

A pregnant woman with untreated, active syphilis is likely to pass the infection to her unborn child. In addition, miscarriage may occur in as many as 25 to 50 percent of women acutely infected with syphilis during pregnancy. Between 40 to 70 percent of women with active syphilis will give birth to a syphilis-infected infant.

Some infants with congenital syphilis may have symptoms at birth, but most develop symptoms between 2 weeks and 3 months later. These symptoms may include

• Skin ulcers
• Rashes
• Fever
• Weakened or hoarse crying sounds
• Swollen liver and spleen
• Yellowish skin (jaundice)
• Anemia (low red blood cell count)
• Various deformities

People who care for infants with congenital syphilis must use special cautions because the moist sores are infectious.

Rarely, the symptoms of syphilis go undetected in infants. As infected infants become older children and teenagers, they may develop the symptoms of late-stage syphilis, including damage to their bones, teeth, eyes, ears, and brains.

Can Syphilis Cause Other Complications?

Syphilis bacteria frequently invade the nervous system during the early stages of infection. Approximately 3 to 7 percent of persons with untreated syphilis develop neurosyphilis, a sometimes serious disorder of the nervous system. In some instances, the time from infection to developing neurosyphilis may be up to 20 years.

Some people with neurosyphilis never develop any symptoms. Others may have headache, stiff neck, and fever that result from an inflammation of the lining of the brain. Some people develop seizures. People whose blood vessels are affected may develop symptoms of stroke with numbness, weakness, or visual problems. Neurosyphilis may be more difficult to treat, and its course may be different, in people with HIV infection or AIDS.

How Can Syphilis Be Prevented?

The open sores of syphilis may be visible and infectious during the active stages of infection. Any contact with these infectious sores and other infected tissues and body fluids must be avoided to prevent spread of the disease. As with many other STDs, using latex male condoms properly during sexual intercourse may give some protection from the disease.

Screening and treatment of infected individuals, or secondary prevention, is one of the few options for preventing the advanced stages of the disease. Testing and treatment early in pregnancy are the best ways to prevent syphilis in infants and should be a routine part of prenatal care.

References

1. Dupin N, Jdid R, N’Guyen YT, Gorin I, Franck N, Escande J P. Syphilis and gonorrhoea in Paris: the return. AIDS. 2001;15:814-5.        

2. Fenton K A, Nicoll A, Kinghorn, G. Resurgence of syphilis in England: time for more radical and nationally coordinated approaches. Sex Transm Infect. 2001;77:309-10.        

3. Hopkins S, Lyons F, Coleman C, Courtney G, Bergin C, Mulcahy F. Resurgence in infectious syphilis in Ireland: an epidemiological study. Sex Transm Dis. 2004;31:317-21.        

4. Hughes G, Paine T, Thomas D. Surveillance of sexually transmitted infections in England and Wales. Euro Surveill. 2001;6:71-80.        

5. Nicoll A, Hughes G, Donnelly M, Livingstone S, De Angelis D, Fenton K, et al. Assessing the impact of national anti-HIV sexual health campaigns: trends in the transmission of HIV and other sexually transmitted infections in England. Sex Transm Infect. 2001;77:242-7.        

6. Ashton M, Sopwith W, Clark P, McKelvey D, Lighton L, Mandal D. An outbreak no longer: factors contributing to the return of syphilis in Greater Manchester. Sex Transm Infect. 2003;79:291-3.        

7. Koumans EH, Farley TA, Gibson JJ, Langley C, Ross MW, McFarlane M,et al. Characteristics of persons with syphilis in areas of persisting syphilis in the United States: sustained transmission associated with concurrent partnerships. Sex Transm Dis. 2001;28:497-503.        

8. Poulton M, Dean G L, Williams D I, Carter P, Iversen A, Fisher M. Surfing with spirochaetes: an ongoing syphilis outbreak in Brighton. Sex Transm Infect. 2001;77;319-21.        

9. Okwumabua JO, Glover V, Bolden D, Edwards S. Perspectives of low-income African Americans on syphilis and HIV: implications for prevention. J Health Care Poor Underserved. 2001;12:474-89.        

10. Lopes F, Latorre MR, Campos Pignatari AC, Buchalla CM. HIV, HPV, and syphilis prevalence in a women’s penitentiary in the city of Sao Paulo, 1997-1998. Cad Saude Publica. 2001;17:1473-80.        

11. Mindel A, Tovey SJ, Timmins DJ, Williams P. Primary and secondary syphilis, 20 years’ experience. 2. Clinical features. Genitourin Med. 1989;65:1-3.        

12. Meljanac N, Dippel E, Zouboulis CC. Superimposed primary chancre in a patient with Adamantiades-Behcet’s disease. Sex Transm Infect. 1999;75:124-5.        

13. Neinstein LS, Goldenring J, Carpenter S. Nonsexual transmission of sexually transmitted diseases: an infrequent occurrence. Pediatrics. 1984;74: 67-76.        

14. Ozturk F, Gurses N, Sancak R, Bay A, Baris S. Acquired secondary syphilis in a 6-year-old girl with no history of sexual abuse. Cutis. 1998;62:150-1.        

15. Alam F, Argiriadou AS, Hodgson TA, Kumar N, Porter SR. Primary syphilis remains a cause of oral ulceration. Br Dent J. 2000;189:352-4.        

16. Laskaris G. Oral manifestations of infectious diseases. Dent Clin North Am, 1996;40:395-423.        

17. Kurien J, Kuriakose S. Doomed angels—a case report. J Indian Soc Pedod Prev Dent. 1997;15:10-12.        

18. Thomas P, Schuck A, Meurer M, Kind P. Angina specifica and mucous plaques of the mouth cavity in lues II. Hautarzt. 1994;45:639-41.        

19. Ban M, Ohtani M, Seishima M. A case of secondary syphilis with mucous patches on the hard palate. J Dermatol. 1995;22:52-54.        

20. Kleidermacher P, Vito KJ, Strome M. Otolaryngologic manifestations of acquired syphilis. Otolaryngol Head Neck Surg. 1998;119:399-402.        

21. Mani NJ. Secondary syphilis initially diagnosed from oral lesions. Report of three cases. Oral Surg Oral Med Oral Pathol. 1984;58:47-50.        

23. Meyer I, Shklar G. The oral manifestations of acquired syphilis. A study of eighty-one cases. Oral Surg Oral Med Oral Pathol. 1967;23:45-57.        

23. Ficarra G, Zaragoza AM, Stendardi L, Parri F, Cockerell CJ. Early oral presentation of lues maligna in a patient with HIV infection. A case report. Oral Surg Oral Med Oral Pathol. 1993;75:728-32.        

24. Rodriguez-Diaz E, Moran-Estefania M., Lopez-Avila A., Piris JB, Fernandez-Blasco G, Garcia JI, et al. Clinical expression of secondary syphilis in a patient with HIV infection. J Dermatol. 1994;21:111-6.        

 25. Sands M, Markus A. Lues maligna, or ulceronodular syphilis, in a man infected with human immunodeficiency virus: case report and review. Clin Infect Dis. 1995;20:387-90.        

26. Baniandres RO, Nieto PO, Moya AL, Carrillo GR, Harto CA Nodular secondary syphilis in a HIV patient mimicking cutaneous lymphoma]. An Med Interna. 2004;21:241-3.        

27. Huebsch RF Gumma of the hard palate, with perforation; report of a case. J Oral Surg. 1955;8:690-3.        

28. Kirwald H, Montag A. Stage 3 syphilis of the mouth cavity. Laryngorhinootologie.1999;78:254-8.        

29. Ramstad T, Traaholt L. Destruction of the soft palate and nose by tertiary ‘benign’ syphilis. A case report. J Oral Rehabil. 1980;7:111-5.        

30. Taylor RG, Hipple W. Gumma of palate with negative standard tests for syphilis. Oral Surg Oral Med Oral Pathol. 1961;14:788-92.        

31. Trieger N, Ship II, Taylor GW, Weisberger D. Cirrhosis and other predisposing factors in carcinoma of the tongue. Cancer. 1958;11:357-62.        

32. Michalek AM, Mahoney MC, McLaughlin CC, Murphy D, Metzger BB. Historical and contemporary correlates of syphilis and cancer. Int J Epidemiol. 1994;23:381-5.

33. Dickenson AJ, Currie WJ, Avery BS. Screening for syphilis in patients with carcinoma of the tongue. Br J Oral Maxillofac Surg. 1995;33:319-20.        

34. Keane JR. Melkersson’s syndrome associated with syphilis. J Clin Neuroophthalmol. 1988;8:249-53.        

35. Housego T, Wood RE, Grotepass F, Nortje CJ. Repair of a palatal defect associated with late congenital syphilis using a tongue flap. J Oral Maxillofac Surg. 1998;46:70-3.        

36. UNAIDS. Epidemiological fact sheets on HIV/AIDS and sexually transmited Infections: Brazil, 2004. 2004:1-20.        

37. Nnokura EN, Ezeoke ACJ. Evaluation of syphilis in patients with HIV infections in Nigeria. Trop Med Int Health. 2005;10:58-64.        

38. Johns DR, Tierney M, Felsenstein D. Alteration in the natural history of neurosyphilis by concurrent infection with the human immunodeficiency virus. N Engl J Med. 1987;316:1569-72.        

39. Kumar B, Gupta S, Muralidhar S. Mucocutaneous manifestations of secondary syphilis in north Indian patients: a changing scenario? J Dermatol. 2001;28:137-44.        

40. Kumar B, Muralidhar S. Malignant syphilis: a review. AIDS Patient Care STDS. 2001;12:921-5.        

41. Kumwenda NI, Taha TE, Hoover DR, Markakis D, Liomba GN, Chiphangwi JD, et al. HIV-1 incidence among male workers at a sugar estate in rural Malawi. J Acquir Immune Defic Syndr. 2001;27:202-8.       

42. Clottey C, Dallabetta G. Sexually transmited diseases and human immunodeficiency virus, epidemiologic synergy. Infec Dis North Am, 1993;7:753-70.        

43. Sadig ST, McSorley J, Copas AJ, Bennett J, Edwards SJ, Kaye S, et al. The effects of early syphilis on CD4 counts and HIV-1 RNA viral loads in blood and semen. Sex Transm Infect. 2005;81:213-6.        

44. Mbopi-Keou FX, Belec L, Teo CG, Scully C, Porter SR. Synergism between HIV and other viruses in the mouth. Lancet Infect Dis. 2002;2:416-24.        

45. Faruque S, Edlin BR, McCoy CB, Word CO, Larsen SA, Schmid DS, et al. Crack cocaine smoking and oral sores in three inner-city neighborhoods. J Acquir Immune Defic Syndr Hum Retrovirol. 1996;13:87-92.

46. Cook RD, Hodgson TA, Waugh AC, Molyneux EM, Borgstein E, Sherry A, et al. Mixed patterns of transmission of human herpesvirus-8 (Kaposi’s sarcoma-associated herpesvirus) in Malawian families. J Gen Virol 2002; 83: 1613-9.