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"Penicillium marneffei" demonstrates in vitro susceptibility to multiple antifungal agents including ketoconazole, itraconazole, miconazole, flucytosine, and amphotericin B. Without treatment patients have a poor prognosis; death occur by liver failure as the fungus releases toxins in the bloodstream. The elevation of liver enzyme in the blood helps to establish a diagnosis.
In the United States, certain breed clubs are strongly recommending screening for "Leishmania", especially in imported breeding stock from endemic locations. For reasons yet unidentified The Foxhound and Neapolitan Mastiff seem to be predisposed or at higher risk for disease. The Italian Spinone Club of America is also requesting all breeders and owners to submit samples for testing; the club reported 150 Spinone Italiano dogs have tested positive in the United States.
In the United States, the following veterinary colleges and government bodies assist with testing and treatment of "Leishmania"-positive dogs:
- Centers for Disease Control and Prevention on Leishmaniasis in dogs
- Iowa State University Department of Pathology
- North Carolina State University College of Veterinary Medicine
Diagnostic testing includes molecular biology and genetic techniques which provide high accuracy and high sensitivity/specificity. The most commonly employed methods in medical laboratories include Enzyme-Linked Immunosorbent Assays, aka ELISA (among other serological assays) and DNA amplification via Polymerase Chain Reaction (PCR).
The Polymerase Chain Reaction(PCR) method for detecting "Leishmania" DNA is a highly sensitive and specific test, producing accurate results in a relatively short amount of time.
A study completed in which Foxhounds were tested using PCR showed that approximately 20% of the tested dogs were positive for leishmaniasis; the same population tested with serological/antibody assays showed only 5% positive.
Diagnosis can be complicated by false positives caused by the leptospirosis vaccine and false negatives caused by testing methods lacking sufficient sensitivity.
Diagnosis of mycetoma is usually established clinically in endemic areas.
X rays and ultrasonography may be employed in evaluating the extent of the disease. X rays findings are extremely variable. The disease is most often observed at an advanced stage that exhibits extensive destruction of all bones of the foot. Rarely, a single lesion may be seen in the tibia where the picture is identical with chronic osteomyelitis. Cytology of fine needle aspirate or pus from the lesion, and tissue biopsy may be undertaken sometimes. Some publications have claimed a "dot in a circle sign" as a characteristic MRI feature for this condition (this feature has also been described on ultrasound).
The following clinical conditions may be considered before diagnosing a patient with mycetoma:
1. Tuberculous ulcer
2. Kaposi's sarcoma, a vascular tumour of skin usually seen in AIDS.
3. Leprosy
4. Syphilis
5. Malignant neoplasm
6. Tropical ulcer
7. Botryomycosis, a skin infection usually caused by the bacteria Staphylococcus aureus.
In areas where the known vector is a sandfly, deltamethrin collars worn by the dogs has been proven to be 86% effective. The sandfly is most active at dusk and dawn; keeping dogs indoors during those peak times will help minimize exposure.
Unfortunately, there is no one answer for leishmaniasis prevention, nor will one vaccine cover multiple species. "Different virulence factors have been identified for distinct "Leishmania" species, and there are profound differences in the immune mechanisms that mediate susceptibility/resistance to infection and in the pathology associated with disease."
In 2003, Fort Dodge Wyeth released the Leshmune vaccine in Brazil for "L. donovani" (also referred to as "kala-azar" in Brazil). Studies indicated up to 87% protection. Most common side effects from the vaccine have been noted as anorexia and local swelling.
The president of the Brazil Regional Council of Veterinary Medicine, Marcia Villa, warned since vaccinated dogs develop antibodies, they can be difficult to distinguish from asymptomatic, infected dogs.
Studies also indicate the Leshmune vaccine may be reliable in treating "L. chagasi", and a possible treatment for dogs already infected with "L. donovani".
There is no cure for CPL; the aim of treatment is to relieve the signs of the disease, and to slow the progression. Management requires daily care to prevent infection of the affected skin. The first step is to trim the feather from the lower leg, to ensure no affected areas are missed, and to allow application of treatments directly to the affected skin. Bacterial infections can be treated by gentle washing and drying of the skin. Topical treatments are required to treat chorioptic mange (caused by the mite "Chorioptes equi"), as the mites are not vulnerable to oral or systemic treatments when they are within the crusts on the skin. Daily exercise assists with the flow of lymph. Combined decongestive therapy involves massage of the leg to move the lymph, followed by specialized compression bandaging which creates a pressure gradient up the leg.
Horses with CPL often have poor-quality hoof, so regular trimming is required to help keep the hoof healthy.
Diagnosis is usually made by identification of the fungi from clinical specimens. Biopsies of skin lesions, lymph nodes, and bone marrow demonstrate the presence of organisms on histopathology.
The most common symptoms are fever, skin lesions, anemia, generalized lymphadenopathy, and hepatomegaly.
This disease is caused by problems in the circulatory system, so when it is presented, in the beginning it is important to follow several recommendations. The person needs to keep the legs elevated as much as possible to help the return of the blood. Whenever sitting down, the person needs to keep the legs on a foot stool. At night it is advisable to sleep with a pillow under the lower legs. In the evening, t is not unusual for legs to be swollen. The volume of the lower leg can increase to up to 100ml after a long working day or up to 200ml after a long-haul flight without moving.
In the example of the 41-year-old Japanese man the lesions were much improved by washing and topical use of corticosteroids for two months, also oral antibiotics like cephalexin are used if cellulitis is present. Moist exudative inflammation and moist ulcers respond to tepid wet compresses of Burow’s solution or just saline or water for 30 to 60 minutes several times a day. But in worse cases, edema that does not disappear spontaneously within a few hours or after a walk, is described as pathological, so it needs to have a special treatment. It is very important to say that Papillamitosis, bilateral and marked edema with few symptoms is mostly caused by the systemic circulation (heart, kidneys, liver).
Papillamitosis is associated, as has been mentioned before, with symptoms and/or clinical signs such as dilated superficial veins, varicose veins and changes in the skin. Edema and its complication Papillamitosis are only partially reversible and soon becomes hard, which is mainly confirmed on palpation. All skin structures are affected and this is characterized by the term. Lymphoedema may develop in many cases accompanied by acral thickening of the skin folds, hyperkeratosis and papillomatosis.
The most informative test is to scrape the lesion and add potassium hydroxide (KOH), then examine under a microscope. (KOH scrapings are commonly used to examine fungal infections.) The pathognomonic finding is observing medlar bodies, sclerotic cells. Scrapings from the lesion can also be cultured to identify the organism involved. Blood tests and imaging studies are not commonly used.
On histology, chromoblastomycosis manifests as pigmented yeasts resembling "copper pennies". Special stains, such as periodic acid schiff and Gömöri methenamine silver, can be used to demonstrate the fungal organisms if needed.
The diagnostic criteria for tropical pulmonary eosinophilia include:
- a history supportive of exposure to lymphatic filariasis;
- a peripheral eosinophilia count greater than 3 × 10/L);
- an elevated serum IgE levels (> 1000 kU/L);
- increased titers of antifilarial antibodies;
- peripheral blood negative for microfilariae; and
- a clinical response to diethylcarbamazine.
High antifilarial IgG titers to microfilariae often result in cross reactivity with other nonfilarial helminth antigens, such as strongyloides and schistosoma antigens, as demonstrated in reported cases. It is important to exclude other parasitic infections before tropical pulmonary eosinophilia is diagnosed, by serological tests, examination of stool specimens in a laboratory experienced in parasitic infections, or a trial of anthelminthic medication. Other parasitic infections, such as the zoonotic filariae, dirofilariasis, ascariasis, strongyloides, visceral larva migrans and hookworm disease, may also be confused with tropical pulmonary eosinophilia because of overlapping clinical features, serological profile and response to diethylcarbamazine. Radiological findings are nonspecific, with normal appearance on chest X-ray in up to 20% of patients. Lung biopsy is not part of the routine diagnostic workup of tropical pulmonary eosinophilia.
Treatment consists of antibiotics, elevation of the affected limb, and compression. For persons with elephantiasis nostras who are overweight or obese, weight loss is recommended. Oral retinoids have been used to treat the cutaneous manifestations of the disease.
Affected breeds include the Shire, Clydesdale, Belgian, Gypsy cob, and Friesian. Signs are usually only seen in horses older than two years. Both sexes are affected.
No preventive measure is known aside from avoiding the traumatic inoculation of fungi. At least one study found a correlation between walking barefoot in endemic areas and occurrence of chromoblastomycosis on the foot.
Tender or enlarged inguinal lymph nodes or swelling in the extremities can alert physicians or public health officials to infection.
With appropriate laboratory equipment, microscopic examination of differential morphological features of microfilariae in stained blood films can aid diagnosis—in particular the examination of the tail portion, the presence of a sheath, and the size of the cephalic space. Giemsa staining will uniquely stain "B. malayi" sheath pink. However, blood films can prove difficult given the nocturnal periodicity of some forms of "B. malayi".
PCR based assays are highly sensitive and can be used to monitor infections both in the human and the mosquito vector. However, PCR assays are time-consuming, labor-intensive and require laboratory equipment. Lymphatic filariasis mainly affects the poor, who live in areas without such resources.
The ICT antigen card test is widely used in the diagnosis of "W. bancrofti", but commercial antigens of "B. malayi" have not been historically widely available. However, new research developments have identified a recombinant antigen (BmR1) that is both specific and sensitive in the detection of IgG4 antibodies against "B. malayi" and "B. timori" in ELISA and immunochromatographic rapid dipstick (Brugia Rapid) test. However, it appears that immunoreactivity to this antigen is variable in individuals infected with other filarial nematodes. This research has led to the development of two new rapid immunochromatographic IgG4 cassette tests – WB rapid and panLF rapid – which detect bancroftian filariasis and all three species of lymphatic filariasis, respectively, with high sensitivity and selectivity.
Diagnosis is usually clinical, but as with yaws and bejel, serological tests for syphilis, such as rapid plasma reagin (RPR) and TPHA, will be positive, and the spirochetes can be seen on dark field microscopy of samples taken from the early papules.
Identification of microfilariae by microscopic examination is a practical diagnostic procedure. Examination of blood samples will allow identification of microfilariae of "Loa loa". It is important to time the blood collection with the known periodicity of the microfilariae (between 10 am and 2 pm). The blood sample can be a thick smear, stained with Giemsa or haematoxylin and eosin (see staining). For increased sensitivity, concentration techniques can be used. These include centrifugation of the blood sample lyzed in 2% formalin (Knott's technique), or filtration through a Nucleopore membrane.
Antigen detection using an immunoassay for circulating filarial antigens constitutes a useful diagnostic approach, because microfilaremia can be low and variable. Interestingly, the Institute for Tropical Medicine reports that no serologic diagnostics are available. While this was once true, and many of recently developed methods of Antibody detection are of limited value—because substantial antigenic cross reactivity exists between filaria and other parasitic worms (helminths), and a positive serologic test does not necessarily distinguish between infections—up and coming serologic tests that are highly specific to "Loa loa" were furthered in 2008. They have not gone point-of-care yet, but show promise for highlighting high-risk areas and individuals with co-endemic loiasis and onchocerciasis. Specifically, Dr. Thomas Nutman and colleagues at the National Institutes of Health have described the a luciferase immunoprecipitation assay (LIPS) and the related QLIPS (quick version). Whereas a previously described LISXP-1 ELISA test had a poor sensitivity (55%), the QLIPS test is both practical, as it requires only a 15 minutes incubation, and has high sensitivity and specificity (97% and 100%, respectively). No report on the distribution status of LIPS or QLIPS testing is available, but these tests would help to limit complications derived from mass ivermectin treatment for onchocerciasis or dangerous strong doses of diethylcarbamazine for loiasis alone (as pertains to individual with high "Loa loa" microfilarial loads).
Physically, Calabar swellings (see image; needs image) are the primary tool for diagnosis. Identification of adult worms is possible from tissue samples collected during subcutaneous biopsies. Adult worms migrating across the eye are another potential diagnostic, but the short timeframe for the worm's passage through the conjunctiva makes this observation less common.
In the past, health care providers use a provocative injection of "Dirofilaria immitis" as a skin test antigen for filariasis diagnosis. If the patient was infected, the extract would cause an artificial allergic reaction and associated Calabar swelling similar to that caused, in theory, by metabolic products of the worm or dead worms.
Blood tests to reveal microfilaremia are useful in many, but not all cases, as one third of loiasis patients are amicrofilaremic. By contrast, eosinophilia is almost guaranteed in cases of loiasis, and blood testing for eosinophil fraction may be useful.
The disease can be treated with penicillin, tetracycline (not to be used in pregnant women), azithromycin or chloramphenicol, and can be prevented through contact tracing by public health officials. A single intramuscular injection of long-acting penicillin is effective against endemic treponematoses including pinta, yaws, and bejel
Lumbar puncture should always be done is cases of suspected meningitis. In cases of eosiniphilc meningitis it will rarely produce worms even when they are present in the CSF, because they tend to cling to the end of nerves. Larvae are present in the CSF in only 1.9-10% of cases. However, as a case of eosiniphilic meningitis progresses, intracranial pressure and eosiniphil counts should rise. Increased levels of eosinophils in the CSF is a trademark of the eosiniphilic meningitis.
Elephantiasis is a symptom of a variety of diseases, where parts of a person's body swell to massive proportions.
Some conditions that have this symptom include:
- Elephantiasis nostras, due to longstanding chronic lymphangitis
- Elephantiasis tropica or lymphatic filariasis, caused by a number of parasitic worms, particularly "Wuchereria bancrofti". More than 120 million people, mostly in Africa and Southeast Asia, are affected.
- Nonfilarial elephantiasis or podoconiosis, an immune disease affecting the lymph vessels
- Elephantiasis, Grade 3 lymphedema which may occur in people with breast cancer.
- Genital elephantiasis, end result of lymphogranuloma venereum
- Proteus syndrome, the genetic disorder of the so-called Elephant Man.
The cornerstone of prevention and treatment of podoconiosis is avoidance of exposure to irritant soils. Wearing shoes in the presence of irritant soils is the primary method of exposure reduction. In Rwanda, a country of high disease prevalence, the government has banned walking barefoot in public, in order to curtail podoconiosis and other soil-borne diseases.
Once the disease has developed, rigorous foot hygiene including daily washing with soap and water, application of an emollient, and nightly elevation of the affected extremity has been shown to reduce swelling and disability. Compression wrapping and decongestive physiotherapy of the affected extremity has been shown to be effective in other forms of lymphedema, but the benefits of these therapies have not been rigorously studied in podoconiosis. Nodules will not resolve with these conservative measures, although surgical removal of the nodules can be performed.
The differential diagnosis for podoconiosis includes other causes of tropical lymphedema, such as filariasis or leprosy, and mycetoma pedis. Podoconiosis begins almost exclusively in the foot, as opposed to filariasis, where the initial edema can appear anywhere in the lower extremities. Podoconiosis is usually asymmetrically bilateral, whereas filariasis and mycetoma are usually unilateral. Additionally, groin involvement with podoconiosis is extremely rare and is usually indicative of filariasis.
If a clinical distinction between podoconiosis and filariasis cannot be made based on history and examination alone, blood smears and ELISA antigen testing can be useful to screen for filariasis.
The disfigurement associated with podoconiosis can include soft or firm edema, and in later stages firm nodules and a mossy appearance, whereas mycetoma is characterized by firm nodules and edema, usually without the mossy appearance of podoconiosis. Additionally, the edema of podoconiosis is typically more striking and extends more proximally than the edema of mycetoma. Radiology can help distinguish between podoconiosis and mycetoma if the diagnosis is questionable.
Local epidemiology can also be a clue to diagnosis, as podoconiosis is typically found in higher altitude areas with volcanic soils, whereas mycetoma is found along the "mycetoma belt" between latitudes 15 south and 30 north, and filariasis is uncommon at higher altitudes and other environments in which the mosquito vector is less prevalent.
Podoconiosis can be distinguished from leprosy by the preservation of sensation in the affected limb and the isolation of disease to the lower extremities.
Coccidioidomycosis diagnosis relies on a combination of an infected person's signs and symptoms, findings on radiographic imaging, and laboratory results.
The disease is commonly misdiagnosed as bacterial community-acquired pneumonia. The fungal infection can be demonstrated by microscopic detection of diagnostic cells in body fluids, exudates, sputum and biopsy tissue by methods of Papanicolaou or Grocott's methenamine silver staining. These stains can demonstrate spherules and surrounding inflammation.
With specific nucleotide primers, "C.immitis" DNA can be amplified by polymerase chain reaction (PCR). It can also be detected in culture by morphological identification or by using molecular probes that hybridize with "C.immitis" RNA. "C. immitis" and "C. posadasii" cannot be distinguished on cytology or by symptoms, but only by DNA PCR.
An indirect demonstration of fungal infection can be achieved also by serologic analysis detecting fungal antigen or host IgM or IgG antibody produced against the fungus. The available tests include the tube-precipitin (TP) assays, complement fixation assays, and enzyme immunoassays. TP antibody is not found in cerebrospinal fluid (CSF). TP antibody is specific and is used as a confirmatory test, whereas ELISA is sensitive and thus used for initial testing.
If the meninges are affected, CSF will show abnormally low glucose levels in CSF, an increased level of protein in the CSF, and lymphocytic pleocytosis. Rarely, CSF eosinophilia is present.
Mortality rate in treated cases
- 0-2% in treated cases among immunocompetent patients
- 29% in immunocompromised patients
- 40% in the subgroup of patients with AIDS
- 68% in patients presenting as acute respiratory distress syndrome (ARDS)
Once suspected, the diagnosis of blastomycosis can usually be confirmed by demonstration of the characteristic broad based budding organisms in sputum or tissues by KOH prep, cytology, or histology. Tissue biopsy of skin or other organs may be required in order to diagnose extra-pulmonary disease. Blastomycosis is histologically associated with granulomatous nodules. Commercially available urine antigen testing appears to be quite sensitive in suggesting the diagnosis in cases where the organism is not readily detected. While culture of the organism remains the definitive diagnostic standard, its slow growing nature can lead to delays in treatment of up to several weeks. However, sometimes blood and sputum cultures may not detect blastomycosis.
Brain lesions, with invasion of both gray and white matter, can be seen on a CT or MRI. However MRI findings tend to be inconclusive, and usually include nonspecific lesions and ventricular enlargement. Sometimes a hemorrhage, probably produced by migrating worms, is present and of diagnostic value.