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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.
The gold standard for diagnosis is visualization of the amastigotes in splenic aspirate or bone marrow aspirate. This is a technically challenging procedure that is frequently unavailable in areas of the world where visceral leishmaniasis is endemic.
Serological testing is much more frequently used in areas where leishmaniasis is endemic. A 2014 Cochrane review evaluated different rapid diagnostic tests. One of them (the rK39 immunochromatographic test) gave correct, positive results in 92% of the people with visceral leishmaniasis and it gave correct, negative results in 92% of the people who did not have the disease. A second rapid test (called latex agglutination test) gave correct, positive results in 64% of the people with the disease and it gave correct, negative results in 93% of the people without the disease. Other types of tests have not been studied thoroughly enough to ascertain their efficacy.
The K39 dipstick test is easy to perform, and village health workers can be easily trained to use it. The kit may be stored at ambient temperature and no additional equipment needs to be carried to remote areas. The DAT anti-leishmania antigen test, standard within MSF, is much more cumbersome to use and appears not to have any advantages over the K39 test.
There are a number of problems with serological testing: in highly endemic areas, not everyone who becomes infected will actually develop clinical disease or require treatment. Indeed, up to 32% of the healthy population may test positive, but not require treatment. Conversely, because serological tests look for an immune response and not for the organism itself, the test does not become negative after the patient is cured, it cannot be used as a check for cure, or to check for re-infection or relapse. Likewise, patients with abnormal immune systems (e.g., HIV infection) will have false-negative tests.
Other tests being developed include detects erythrosalicylic acid.
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".
Leishmaniasis is diagnosed in the hematology laboratory by direct visualization of the amastigotes (Leishman-Donovan bodies). Buffy-coat preparations of peripheral blood or aspirates from marrow, spleen, lymph nodes, or skin lesions should be spread on a slide to make a thin smear and stained with Leishman stain or Giemsa stain (pH 7.2) for 20 minutes. Amastigotes are seen within blood and spleen monocytes or, less commonly, in circulating neutrophils and in aspirated tissue macrophages. They are small, round bodies 2–4 μm in diameter with indistinct cytoplasm, a nucleus, and a small, rod-shaped kinetoplast. Occasionally, amastigotes may be seen lying free between cells. However, the retrieval of tissue samples is often painful for the patient and identification of the infected cells can be difficult. So, other indirect immunological methods of diagnosis are developed, including enzyme-linked immunosorbent assay, antigen-coated dipsticks, and direct agglutination test. Although these tests are readily available, they are not the standard diagnostic tests due to their insufficient sensitivity and specificity.
Several different polymerase chain reaction tests are available for the detection of "Leishmania" DNA. With this assay, a specific and sensitive diagnostic procedure is finally possible.
Most forms of the disease are transmitted only from nonhuman animals, but some can be spread between humans. Infections in humans are caused by about 21 of 30 species that infect mammals; the different species look the same, but they can be differentiated by isoenzyme analysis, DNA sequence analysis, or monoclonal antibodies.
Diagnosis is based on the characteristic appearance of non-healing raised, scaling lesions that may ulcerate and become secondarily infected with organisms such as "Staphylococcus aureus", in someone who has returned from an endemic area.
The gold standard for diagnosis is PCR (polymerase chain reaction) helps DNA polymerase to create new strands of DNA equivalent to template given.
The best treatment for cutaneous leishmaniasis is not known. Treatments that work for one species of leishmania may not work for another; it is recommended that advice of a tropical medicine or geographical medicine specialist be sought. Ideally, every effort should be made to establish the species of leishmania by molecular techniques (PCR) prior to starting treatment. In the setting of a developing country, there is often only one species present in a particular locality, so it is usually unnecessary to speciate every infection. Unfortunately, leishmaniasis is an orphan disease in developed nations, and almost all the current treatment options are toxic with significant side effects. The most sound treatment for cutaneous leishmaniasis thus far is prevention.
- "Leishmania major" :"L. major" infections are usually considered to heal spontaneously and do not require treatment, but there have been several reports of severe cases caused by "L. major" in Afghanistan. In Saudi Arabia, a six-week course of oral fluconazole 200 mg daily has been reported to speed up healing. In a randomized clinical trial from Iran, fluconazole 400 mg daily was shown to be significantly more effective than fluconazole 200 mg daily in the treatment of cutaneous leishmaniasis.
- "Leishmania braziliensis" :Treatment with pentavalent antimonials or amphotericin is necessary, because of the risk of developing disfiguring mucocutaneous lesions.
- "Leishmania infantum" :"L. infantum" causes cutaneous leishmaniasis in southern France.
New treatment options are arising from the new oral drug miltefosine (Impavido) which has shown in several clinical trials to be very efficient and safe in visceral and cutaneous leishmaniasis. Recent studies from Bolivia show a high cure rate for mucocutaneous leishmaniasis. Comparative studies against pentavalent antimonials in Iran and Pakistan are also beginning to show a high cure rate for "L. major" and "L. tropica". It is registered in many countries of Latin America, as well in Germany. In October 2006 it received orphan drug status from the US Food and Drug administration. The drug is generally better tolerated than other drugs. Main side effects are gastrointestinal disturbances in the 1–2 days of treatment which does not affect the efficacy.
Secondary bacterial infection (especially with "Staphylococcus aureus") is common and may require antibiotics. Clinicians who are unfamiliar with cutaneous leishmaniasis may mistake the lesion for a pure bacterial infection (especially after isolation of "S. aureus" from bacterial skin swabs) and fail to consider the possibility of leishmaniasis.
There are no vaccines or preventive drugs for visceral leishmaniasis. The most effective method to prevent infection is to protect from sand fly bites. To decrease the risk of being bitten, these precautionary measures are suggested:
- Outdoors:
1. Avoid outdoor activities, especially from dusk to dawn, when sand flies generally are the most active.
2. When outdoors (or in unprotected quarters), minimize the amount of exposed (uncovered) skin to the extent that is tolerable in the climate. Wear long-sleeved shirts, long pants, and socks; and tuck your shirt into your pants.
3. Apply insect repellent to exposed skin and under the ends of sleeves and pant legs. Follow the instructions on the label of the repellent. The most effective repellents generally are those that contain the chemical DEET (N,N-diethylmetatoluamide).
- Indoors:
1. Stay in well-screened or air-conditioned areas.
2. Keep in mind that sand flies are much smaller than mosquitoes and therefore can get through smaller holes.
3. Spray living/sleeping areas with an insecticide to kill insects.
4. If you are not sleeping in a well-screened or air-conditioned area, use a bed net and tuck it under your mattress. If possible, use a bed net that has been soaked in or sprayed with a pyrethroid-containing insecticide. The same treatment can be applied to screens, curtains, sheets, and clothing (clothing should be retreated after five washings)."
On February 2012, the nonprofit Infectious Disease Research Institute launched a clinical trial of the visceral leishmaniasis vaccine. The vaccine is a recombinant form of two fused Leishmania parasite proteins with an adjuvant. Two phase 1 clinical trials with healthy volunteers are to be conducted. The first one takes place in Washington (state) and is followed by a trial in India.
The treatment is determined by where the disease is acquired, the species of "Leishmania", and the type of infection.
For visceral leishmaniasis in India, South America, and the Mediterranean, liposomal amphotericin B is the recommended treatment and is often used as a single dose. Rates of cure with a single dose of amphotericin have been reported as 95%. In India, almost all infections are resistant to pentavalent antimonials. In Africa, a combination of pentavalent antimonials and paromomycin is recommended. These, however, can have significant side effects. Miltefosine, an oral medication, is effective against both visceral and cutaneous leishmaniasis. Side effects are generally mild, though it can cause birth defects if taken within 3 months of getting pregnant. It does not appear to work for "L. major" or "L. braziliensis".
The evidence around the treatment of cutaneous leishmaniasis is poor. A number of topical treatments may be used for cutaneous leishmaniasis. Which treatments are effective depends on the strain, with topical paromomycin effective for "L. major", "L. tropica", "L. mexicana", "L. panamensis", and "L. braziliensis". Pentamidine is effective for "L. guyanensis". Oral fluconazole or itraconazole appears effective in "L. major" and "L. tropica".
In order to ascertain if an individual has activated PI3K delta syndrome, usually one finds atypical levels of immunoglobulins. Methods to determine the condition are the following:
- Genetic testing
- Laboratory findings
- Symptoms exhibited
"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.
Diagnosis is often made by visualization of yeast cells in tissue, or superficial scrapings. Radiography of the chest reveals interstitial infiltrates in the majority of cases.
Opportunistic infections caused by Feline Leukemia Virus and Feline immunodeficiency virus retroviral infections can be treated with Lymphocyte T-Cell Immune Modulator.
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.
Viscerotropic leishmaniasis is a systemic infection reported in soldiers fighting in Operation Desert Storm in Saudi Arabia.
The main candidates for testing are those with a close relative who has suffered an episode of MH or have been shown to be susceptible. The standard procedure is the "caffeine-halothane contracture test", CHCT. A muscle biopsy is carried out at an approved research center, under local anesthesia. The fresh biopsy is bathed in solutions containing caffeine or halothane and observed for contraction; under good conditions, the sensitivity is 97% and the specificity 78%. Negative biopsies are "not" definitive, so any patient who is suspected of MH by their medical history or that of blood relatives is generally treated with non-triggering anesthetics, even if the biopsy was negative. Some researchers advocate the use of the "calcium-induced calcium release" test in addition to the CHCT to make the test more specific.
Less invasive diagnostic techniques have been proposed. Intramuscular injection of halothane 6 vol% has been shown to result in higher than normal increases in local among patients with known malignant hyperthermia susceptibility. The sensitivity was 100% and specificity was 75%. For patients at similar risk to those in this study, this leads to a positive predictive value of 80% and negative predictive value of 100%. This method may provide a suitable alternative to more invasive techniques.
A 2002 study examined another possible metabolic test. In this test, intramuscular injection of caffeine was followed by local measurement of the ; those with known MH susceptibility had a significantly higher (63 versus 44 mmHg). The authors propose larger studies to assess the test's suitability for determining MH risk.
In terms of the treatment for ativated PI3K delta syndrome, generally primary immunodeficiencies see the following used:
- Bacterial infection should be treated rapidly(with antibiotics)
- Antiviral therapy
- Modify lifestyle(exposure to pathogens need to be minimized)
Genetic testing is being performed in a limited fashion to determine susceptibility to MH. In people with a family history of MH, analysis for "RYR1" mutations may be useful.
Individuals at higher risk are often prescribed prophylactic medication to prevent an infection from occurring. A patient's risk level for developing an opportunistic infection is approximated using the patient's CD4 T-cell count and sometimes other markers of susceptibility. Common prophylaxis treatments include the following:
Successful diagnosis of XDR-TB depends on the patient’s access to quality health-care services. If TB bacteria are found in the sputum, the diagnosis of TB can be made in a day or two, but this finding will not be able to distinguish between drug-susceptible and drug-resistant TB. To evaluate drug susceptibility, the bacteria need to be cultivated and tested in a suitable laboratory. Final diagnosis in this way for TB, and especially for XDR-TB, may take from 6 to 16 weeks. To reduce the time needed for diagnosis, new tools for rapid TB diagnosis are urgently needed.
The original method used to test for MDR-TB and XDR-TB was the Drug Susceptibility Testing (DST). DST is capable of determining how well four primary antitubercular drugs inhibit the growth of Mycobacterium Tuberculosis. The four primary antitubercular drugs are Isoniazid, Rifampin, Ethambutol and Pyrazinamide. Drug Susceptibility testing is done by making a Lowenstein-Jensen medium plate and spreading the bacteria on the plate. Disks containing one of the four primary drugs are added to the plate. After weeks of allowing the bacteria to grow the plate is checked for clear areas around the disk. If there is a clear area, the drug has killed the bacteria and most likely the bacteria is not resistant to that drug.
As "Mycobacterium tuberculosis" evolved new strains of resistant bacteria were being found such as XDR-TB. The problem was that primary DST was not suitable for testing bacteria strains that were extensively drug resistant. This problem was starting to be fixed when drug susceptibility tests started including not just the four primary drugs, but secondary drugs. This secondary test is known as Bactec MGIT 960 System. Although Bactec MGIT 960 System was accurate it was still slow at determining the level of resistance.
Diagnosis of MDR and XDR-TB in children is challenging. With an increasing number of cases being reported worldwide there is a great need for better diagnostic tools available for pediatric patients.
In recent years drug resistant tuberculosis testing has shown a lot of progress. Some studies have found an in-house assay that could rapidly detect resistance to drugs involved in the definition of XDR-TB directly from smear-positive specimens. The assay is called Reverse Line Blot Hybridization Assay also known as RLBH. The study showed that the results of RLBH were as accurate as other drug susceptibility tests, but at the same time didn`t take weeks to get results. RLBH testing only took 3 days to determine how resistant the strain of bacteria was.
The current research has shown progress in the testing of drug resistance. A recent study found that a research technique known as direct nitrate reductase assay (D-NRA) showed efficient accuracy for the rapid and simultaneous detection of resistance to isoniazid (INH), rifampicin (RIF), kanamycin (KAN) and ofloxacin (OFL). D-NRA results were obtained in 16.9 days, comparably less than other drug susceptibility testing. At the same time the study mentioned how D-NRA is a low-cost technology, easy to set up in clinical laboratories and suitable to be used for DST of M. tuberculosis in all smear-positive samples.
Pregnant women are more severely affected by influenza, hepatitis E, herpes simplex and malaria. The evidence is more limited for coccidioidomycosis, measles, smallpox, and varicella. Pregnancy may also increase susceptibility for toxoplasmosis.
During the 2009 H1N1 pandemic, as well as during interpandemic periods, women in the third trimester of pregnancy were at increased risk for severe
disease, such as disease requiring admission to an intensive care unit or resulting in death, as compared with women in an earlier stage of pregnancy.
For hepatitis E, the case fatality rate among pregnant women has been estimated to be between 15% and 25%, as compared with a range of 0.5 to 4% in the population overall, with the highest susceptibility in the third trimester.
Primary herpes simplex infection, when occurring in pregnant women, has an increased risk of dissemination and hepatitis, an otherwise rare complication in immunocompetent adults, particularly during the third trimester. Also, recurrences of herpes genitalis increase in
frequency during pregnancy.
The risk of severe malaria by "Plasmodium falciparum" is three times as high in pregnant women, with a median maternal mortality of 40% reported in studies in the Asia–Pacific region. In women where the pregnancy is not the first, malaria infection is more often asymptomatic, even at high parasite loads, compared to women having their first pregnancy. There is a decreasing susceptibility to malaria with increasing parity, probably due to immunity to pregnancy-specific antigens. Young maternal age and increases the risk. Studies differ whether the risk is different in different . Limited data suggest that malaria caused by "Plasmodium vivax" is also more severe during pregnancy.
Severe and disseminated coccidioidomycosis has been reported the occur in increased frequency in pregnant women in several reports and case series, but subsequent large surveys, with the overall risk being rather low.
Varicella occurs at an increased rate during pregnancy, but mortality is not higher than that among men and non-pregnant women.
Listeriosis mostly occurs during the third trimester, with Hispanic women appearing to be at particular risk. Listeriosis is a vertically transmitted infection that may cause miscarriage, stillbirth, preterm birth, or serious neonatal disease.
Some infections are vertically transmissible, meaning that they can affect the child as well.
Sulfonamides are the traditional remedies to paracoccidiodomycosis. They were introduced by Oliveira Ribeiro and used for more than 50 years with good results. The most-used sulfa drugs in this infection are sulfadimethoxime, sulfadiazine, and co-trimoxazole. This treatment is generally safe, but several adverse effects can appear, the most severe of which are the Stevens-Johnson syndrome and agranulocytosis. Similarly to tuberculosis treatment, it must be continued for up to three years to eradicate the fungus, and relapse and treatment failures are not unusual.
Antifungal drugs such as amphotericin B or itraconazole and ketoconazole are more effective in clearing the infection, but are limited by their cost when compared with sulfonamides.During therapy, fibrosis can appear and surgery may be needed to correct this. Another possible complication is Addisonian crisis. The mortality rate in children is around 7-10%.
Diagnosis is based on the demonstration of vascular lesions in large and middle-sized vessels on angiography, CT scan, magnetic resonance angiography or FDG PET. FDG PET can help in diagnosis of active inflammation not just in patients with active Takayasu arteritis prior to treatment but also in addition in relapsing patients receiving immunosuppressive agents.
Contrast angiography has been the gold standard. The earliest detectable lesion is a local narrowing or irregularity of the lumen. This may develop into stenosis and occlusion. The characteristic finding is the presence of "skip lesions," where stenosis or aneurysms alternate with normal vessels. Angiography provides information on vessel anatomy and patency but does not provide information on the degree of inflammation in the wall.
The age at onset helps to differentiate Takayasu's arteritis from other types of large vessel vasculitis. For example, Takaysu's arteritis has an age of onset of 60 years.
Takayasu arteritis is not associated with ANCA, rheumatoid factor, ANA, and anticardiolipin antibodies.
There are currently only two donor-funded non-governmental organizations that focus exclusively on NTDs: the Schistosomiasis Control Initiative and Deworm the World. Despite under-funding, many neglected diseases are cost-effective to treat and prevent. The cost of treating a child for infection of soil transmitted helminths and schistosomes (some of the main causes of neglected diseases), is less than US$0.50 per year, when administered as part of school-based mass deworming by Deworm the World. This programme is recommended by Giving What We Can and the Copenhagen Consensus Centre as one of the most efficient and cost-effective solutions. The efforts of Schistosomiasis Control Initiative to combat neglected diseases include the use of rapid-impact packages: supplying schools with packages including four or five drugs, and training teachers in how to administer them.
An alternative model to the profit-driven drug development emerged in the years 2000 to provide an answer to the needs of these neglected patients. Product development partnerships (PDPs) aim at implementing and accelerating the research and development (R&D) of safe and effective health tools (diagnostics, vaccines, drugs) to notably combat diseases that are neglected. Drugs for Neglected Diseases "initiative" (DNDi) is one of these PDPs that has already developed new treatments for NTDs
The Sabin Vaccine Institute, founded in 1993, works to address the issues of vaccine-preventable diseases as well as NTDs. They run three main programs, Sabin Vaccine Development, Global Network for Neglected Tropical Diseases, and Vaccine Advocacy and Education. Their product development partnership affiliates them with the Texas Children's Hospital as well as the Baylor College of Medicine. Their major campaign, End7, aims to end seven of the most common NTDs (elephantiasis, river blindness, snail fever, trachoma, roundworm, whipworm and hookworm) by 2020. Through End7, college campuses undertake fundraising and educational initiatives for the broader goals of the campaign.
WIPO Re:Search was established in 2011 by the World Intellectual Property Organization in collaboration with BIO Ventures for Global Health (BVGH) and with the active participation of leading pharmaceutical companies and other private and public sector research organizations. It allows organizations to share their intellectual property, compounds, expertise, facilities and know-how royalty-free with qualified researchers worldwide working on new solutions for NTDs, malaria and tuberculosis.
In 2013, the Government of Japan, five Japanese pharmaceutical companies, the Bill and Melinda Gates Foundation, and the UNDP established a new public-private partnership, Global Health Innovative Technology Fund. They pledged over US$100 million to the fund over five years, to be awarded as grants to R&D partnerships across sectors in Japan and elsewhere, working to develop new drugs and vaccines for 17 neglected diseases, in addition to HIV, malaria and tuberculosis. Affordability of the resulting drugs and vaccines is one of the key criteria for grant awards.
Mendelian susceptibility to mycobacterial disease, also called familial disseminated atypical mycobacterial infection, is a rare genetic disease characterized by susceptibility to mycobacteria and Salmonella infection outside of the intestinal tract.