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Abnormal laboratory findings seen in patients with Rocky Mountain spotted fever may include a low platelet count, low blood sodium concentration, or elevated liver enzyme levels. Serology testing and skin biopsy are considered to be the best methods of diagnosis. Although immunofluorescent antibody assays are considered some of the best serology tests available, most antibodies that fight against "R. rickettsii" are undetectable on serology tests the first seven days after infection.
Differential diagnosis includes dengue, leptospirosis, and, most recently, chikungunya and Zika virus infections.
Biopsies or cultures of a person's tick wound (eschar) are used to diagnose ATBF. However, this requires special culture media and can only be done by a laboratory with biohazard protection. There are more specialized laboratory tests available that use quantitative polymerase chain reactions (qPCR), but can only be done by laboratories with special equipment. Immunofluorescence assays can also be used, but are hard to interpret because of cross-reactions with other rickettsiae bacteria.
Diagnosis of ATBF is mostly based on symptoms, as many laboratory tests are not specific for ATBF. Common laboratory test signs of ATBF are a low white blood cell count (lymphopenia) and low platelet count (thrombocytopenia), a high C-reactive protein, and mildly high liver function tests.
Presumptive diagnosis is made by characteristic clinical signs, post mortem lesions, and presence of competent vectors. Laboratory confirmation is by viral isolation, with such techniques as quantitative PCR for detecting viral RNA, antigen capture (ELISA), and immunofluorescence of infected tissues. Serological tests are only useful for detecting recovered animals, as sick animals die before they are able to mount effective immune responses.
The Coggins test (agar immunodiffusion) is a sensitive diagnostic test for equine infectious anemia developed by Dr. Leroy Coggins in the 1970s.
Currently, the US does not have an eradication program due to the low rate of incidence. However, many states require a negative Coggins test for interstate travel. In addition, most horse shows and events require a negative Coggins test. Most countries require a negative test result before allowing an imported horse into the country.
Horse owners should verify that all the horses at a breeding farm and or boarding facility have a negative Coggins test before using the services of the facility. A Coggins test should be done on an annual basis. Tests every 6 months are recommended if there is increased traveling.
On infection the microorganism can be found in blood and cerebrospinal fluid (CSF) for the first 7 to 10 days (invoking serologically identifiable reactions) and then moving to the kidneys. After 7 to 10 days the microorganism can be found in fresh urine. Hence, early diagnostic efforts include testing a serum or blood sample serologically with a panel of different strains.
Kidney function tests (blood urea nitrogen and creatinine) as well as blood tests for liver functions are performed. The latter reveal a moderate elevation of transaminases. Brief elevations of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and gamma-glutamyltransferase (GGT) levels are relatively mild. These levels may be normal, even in children with jaundice.
Diagnosis of leptospirosis is confirmed with tests such as enzyme-linked immunosorbent assay (ELISA) and polymerase chain reaction (PCR). The MAT (microscopic agglutination test), a serological test, is considered the gold standard in diagnosing leptospirosis. As a large panel of different leptospira must be subcultured frequently, which is both laborious and expensive, it is underused, especially in developing countries.
Differential diagnosis list for leptospirosis is very large due to diverse symptoms. For forms with middle to high severity, the list includes dengue fever and other hemorrhagic fevers, hepatitis of various causes, viral meningitis, malaria, and typhoid fever. Light forms should be distinguished from influenza and other related viral diseases. Specific tests are a must for proper diagnosis of leptospirosis.
Under circumstances of limited access (e.g., developing countries) to specific diagnostic means, close attention must be paid to the medical history of the patient. Factors such as certain dwelling areas, seasonality, contact with stagnant contaminated water (bathing, swimming, working on flooded meadows, etc.) or rodents in the medical history support the leptospirosis hypothesis and serve as indications for specific tests (if available).
"Leptospira" can be cultured in Ellinghausen-McCullough-Johnson-Harris medium (EMJH), which is incubated at 28 to 30 °C. The median time to positivity is three weeks with a maximum of three months. This makes culture techniques useless for diagnostic purposes but is commonly used in research.
Diagnosis is achieved most commonly by serologic testing of the blood for the presence of antibodies against the ehrlichia organism. Many veterinarians routinely test for the disease, especially in enzootic areas. During the acute phase of infection, the test can be falsely negative because the body will not have had time to make antibodies to the infection. As such, the test should be repeated. A PCR (polymerase chain reaction) test can be performed during this stage to detect genetic material of the bacteria. The PCR test is more likely to yield a negative result during the subclinical and chronic disease phases. In addition, blood tests may show abnormalities in the numbers of red blood cells, white blood cells, and most commonly platelets, if the disease is present. Uncommonly, a diagnosis can be made by looking under a microscope at a blood smear for the presence of the "ehrlichia" morulae, which sometimes can be seen as intracytoplasmic inclusion bodies within a white blood cell.
In endemic areas, diagnosis is generally made on clinical grounds alone. However, overshadowing of the diagnosis is quite often as the clinical symptoms overlap with other infectious diseases such as dengue fever, paratyphoid, and pyrexia of unknown origin (PUO). If the eschar can be identified, it is quite diagnostic of scrub typhus, but this is very unreliable in the native population who have dark skin, and moreover, the site of eschar which is usually where the mite bites is often located in covered areas. Unless it is actively searched for, the eschar most likely would be missed. History of mite bite is often absent since the bite does not inflict pain and the mites are almost too small to be seen by the naked eye. Usually, scrub typhus is often labelled as PUO in remote endemic areas, since blood culture is often negative, yet it can be treated effectively with chloramphenicol. Where doubt exists, the diagnosis may be confirmed by a laboratory test such as serology. Again, this is often unavailable in most endemic areas, since the serological test involved is not included in the routine screening tests for PUO, especially in Burma (Myanmar).
The choice of laboratory test is not straightforward, and all currently available tests have their limitations. The cheapest and most easily available serological test is the Weil-Felix test, but this is notoriously unreliable. The gold standard is indirect immunofluorescence, but the main limitation of this method is the availability of fluorescent microscopes, which are not often available in resource-poor settings where scrub typhus is endemic. Indirect immunoperoxidase, a modification of the standard IFA method, can be used with a light microscope, and the results of these tests are comparable to those from IFA. Rapid bedside kits have been described that produce a result within one hour, but the availability of these tests is severely limited by their cost. Serological methods are most reliable when a four-fold rise in antibody titre is found. If the patient is from a nonendemic area, then diagnosis can be made from a single acute serum sample. In patients from endemic areas, this is not possible because antibodies may be found in up to 18% of healthy individuals.
Other methods include culture and polymerase chain reaction, but these are not routinely available and the results do not always correlate with serological testing, and are affected by prior antibiotic treatment. The currently available diagnostic methods have been summarised.
In lymph node biopsies, the typical histopathologic pattern is characterized by geographic areas of necrosis with neutrophils and necrotizing granulomas. The pattern is non specific and similar to other infectious lymphadenopathies.
The laboratorial isolation of "F. tularensis" requires special media such as buffered charcoal yeast extract agar. It cannot be isolated in the routine culture media because of the need for sulfhydryl group donors (such as cysteine). The microbiologist must be informed when tularemia is suspected not only to include the special media for appropriate isolation, but also to ensure that safety precautions are taken to avoid contamination of laboratory personnel.
Serological tests (detection of antibodies in the serum of the patients) are available and widely used. Cross reactivity with "Brucella" can confuse interpretation of the results, so diagnosis should not rely only on serology. Molecular methods such as PCR are available in reference laboratories.
The prognosis is good for dogs with acute ehrlichiosis. For dogs that have reached the chronic stage of the disease, the prognosis is guarded. When bone marrow suppression occurs and there are low levels of blood cells, the animal may not respond to treatment.
Rocky Mountain spotted fever can be a very severe illness and patients often require hospitalization. Because "R. rickettsii" infects the cells lining blood vessels throughout the body, severe manifestations of this disease may involve the respiratory system, central nervous system, gastrointestinal system, or kidneys.
Long-term health problems following acute Rocky Mountain spotted fever infection include partial paralysis of the lower extremities, gangrene requiring amputation of fingers, toes, or arms or legs, hearing loss, loss of bowel or bladder control, movement disorders, and language disorders. These complications are most frequent in persons recovering from severe, life-threatening disease, often following lengthy hospitalizations
Doxycycline has been provided once a week as a prophylaxis to minimize infections during outbreaks in endemic regions. However, there is no evidence that chemoprophylaxis is effective in containing outbreaks of leptospirosis, and use of antibiotics increases antibiotics resistance. Pre-exposure prophylaxis may be beneficial for individuals traveling to high-risk areas for a short stay.
Effective rat control and avoidance of urine contaminated water sources are essential preventive measures. Human vaccines are available only in a few countries, such as Cuba and China. Animal vaccines only cover a few strains of the bacteria. Dog vaccines are effective for at least one year.
There is currently no treatment for AHS.
Control of an outbreak in an endemic region involves quarantine, vector control and vaccination. To prevent this disease, the affected horses are usually slaughtered, and the uninfected horses are vaccinated against the virus. Three vaccines currently exist, which include a polyvalent vaccine, a monovalent vaccine, and a monovalent inactivated vaccine. This disease can also be prevented by destroying the insect vector habitats using insecticides.
Vaccines against anaplasmosis are available. Carrier animals should be eliminated from flocks. Tick control may also be useful although it can be difficult to implement.
There are no safe, available, approved vaccines against tularemia. However, vaccination research and development continues, with live attenuated vaccines being the most thoroughly researched and most likely candidate for approval. Sub-unit vaccine candidates, such as killed-whole cell vaccines, are also under investigation, however research has not reached a state of public use.
Optimal preventative practices include limiting direct exposure when handling potentially infected animals, such as wearing gloves and face masks while handling potentially infected animals (importantly when skinning deceased animals).
A definitive diagnosis is made by culturing the organism from any clinical sample, because the organism is never part of the normal human flora.
A definite history of contact with soil may not be elicited, as melioidosis can be dormant for many years before manifesting. Attention should be paid to a history of travel to endemic areas in returned travellers. Some authors recommend considering possibility of melioidosis in every febrile patient with a history of traveling to and/or staying at endemic areas.
A complete screen (blood culture, sputum culture, urine culture, throat swab, and culture of any aspirated pus) should be performed on all patients with suspected melioidosis (culture on blood agar as well as Ashdown's medium). A definitive diagnosis is made by growing "B. pseudomallei" from any site. A throat swab is not sensitive, but is 100% specific if positive, and compares favourably with sputum culture. The sensitivity of urine culture is increased if a centrifuged specimen is cultured, and any bacterial growth should be reported (not just growth above 10 organisms/ml which is the usual cutoff). Very occasionally, bone marrow culture may be positive in patients who have negative blood cultures for "B. pseudomallei", but these are not usually recommended. A common error made by clinicians unfamiliar with melioidosis is to send a specimen from only the affected site (which is the usual procedure for most other infections) instead of sending a full screen.
Ashdown's medium, a selective medium containing gentamicin, may be required for cultures taken from nonsterile sites. "Burkholderia cepacia" medium may be a useful alternative selective medium in nonendemic areas, where Ashdown's is not available. A new medium derived from Ashdown, known as Francis medium, may help differentiate "B. pseudomallei" from "B. cepacia" and may help in the early diagnosis of melioidosis, but has not yet been extensively clinically validated.
Many commercial kits for identifying bacteria may misidentify "B. pseudomallei" ("see" "Burkholderia pseudomallei" for a more detailed discussion of this topic).
A serological test for melioidosis (indirect haemagglutination) is available, but not commercially in most countries. A high background titre may reduce the positive predictive value of serological tests in endemic countries. A specific direct immunofluorescent test and latex agglutination, based on monoclonal antibodies, are used widely in Thailand, but are not available elsewhere. Cross-reactivity with "B. thailandensis" is almost complete. A commercial ELISA kit for melioidosis appears to perform well. but no ELISA test has yet been clinically validated as a diagnostic tool.
It is not possible to make the diagnosis on imaging studies alone (X-rays and scans), but imaging is routinely performed to assess the full extent of disease. Imaging of the abdomen using CT scans or ultrasound is recommended routinely, as abscesses may not be clinically apparent and may coexist with disease elsewhere. Australian authorities suggest imaging of the prostate specifically due to the high incidence of prostatic abscesses in northern Australian patients. A chest X-ray is also considered routine, with other investigations as clinically indicated. The presence of honeycomb abscesses in the liver is considered characteristic, but is not diagnostic.
The differential diagnosis is extensive; melioidosis may mimic many other infections, including tuberculosis.
Some conventional parasitological techniques (CPT) such as wet blood film, and stained blood smears are used because so far, the best identifier is looking at the blood of the potentially infected host. Other tissues can be looked at, but the gold standard is identifying trypanosomes in the blood. Before the infection becomes severe, it is difficult to catch as many times these cryptic infections are undetectable by direct microscopy. Since CPT is not very sensitive, it cannot be used as a sole method of diagnosis.
The Haematocrit Centrifugation Technique (HCT) is a much better alternative. Using HCT trypanosomes can be detected in the blood even in field conditions. Buffy coat can be used to increase detection. Detection with this method is approx 85 trypanosomes per millilitre.
Rather than using live animals as test subjects, Canada used serological tests such as complement fixation tests to detect trypanosomes, and have been very successful. Other tests used look at detecting antibodies generated by the host species against T.evansi antigens. This is done using the enzyme-linked immunosorbent assays (ELISA) method. Now polymerase chain reaction (PCR) and DNA probes are being used to detect Surra in animals.
Person-to-person transmission is exceedingly unusual; and patients with melioidosis should not be considered contagious. Lab workers should handle "B. pseudomallei" under BSL-3 isolation conditions, as laboratory-acquired melioidosis has been described.
In endemic areas, people (rice-paddy farmers in particular) are warned to avoid contact with soil, mud, and surface water where possible. Case clusters have been described following flooding and cyclones and probably relate to exposure. Other case clusters have related to contamination of drinking water supplies. Populations at risk include patients with diabetes mellitus, chronic renal failure, chronic lung disease, or an immune deficiency of any kind. The effectiveness of measures to reduce exposure to the causative organism have not been established. A vaccine is not yet available.
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.
Providing basic sanitation and safe drinking water and food is the key for controlling the disease. In developed countries, enteric fever rates decreased in the past when treatment of municipal water was introduced, human feces were excluded from food production, and pasteurization of dairy products began. In addition, children and adults should be carefully educated about personal hygiene. This would include careful handwashing after defecation and sexual contact, before preparing or eating food, and especially the sanitary disposal of feces. Food handlers should be educated in personal hygiene prior to handling food or utensils and equipment. Infected individuals should be advised to avoid food preparation. Sexually active people should be educated about the risks of sexual practices that permit fecal-oral contact.
Those who travel to countries with poor sanitation should receive a live attenuated typhoid vaccine—Ty21a (Vivotif), which, in addition to the protection against typhoid fever, and may provide some protection against paratyphoid fever caused by the "S. enterica" serotypes A and B. In particular, a reanalysis of data from a trial conducted in Chile showed the Ty21a vaccine was 49% effective (95% CI: 8–73%) in preventing paratyphoid fever caused by the serotype B. Evidence from a study of international travelers in Israel also indicates the vaccine may prevent a fraction of infections by the serotype A, although no trial confirms this. This cross-protection by a typhoid vaccine is most likely due to O antigens shared between different "S. enterica" serotypes.
Exclusion from work and social activities should be considered for symptomatic, and asymptomatic, people who are food handlers, healthcare/daycare staff who are involved in patient care and/or child care, children attending unsanitary daycare centers, and older children who are unable to implement good standards of personal hygiene. The exclusion applies until two consecutive stool specimens are taken from the infected patient and are reported negative.
One study using the medicinal plant "Peganum harmala" showed it to have a lifesaving effect on cattle infected with East Coast fever.
The classical treatment with tetracyclines (1970–1990) cannot provide efficiency more than 50%.
Since the early 1990s, buparvaquone is used in bovine theileriosis with remarkable results (90 to 98% recovery).
Other than the buparvaquones, other chemotherapeutic options are the parvaquones, e.g. Clexon. Halofuginone lactate has also been shown to have an 80.5% efficacy against "Theirelia parva parva" infections. The ultimate factor that causes death is pulmonary edema.
In May 2010, a vaccine to protect cattle against East Coast fever reportedly had been approved and registered by the governments of Kenya, Malawi and Tanzania. This consists of cryopreserved sporozoites from crushed ticks, but it is expensive and can cause disease.
Control of the disease relies on control of ticks of domestic animals, particularly disease-resistant ticks. This is a major concern in tropical countries with large livestock populations, especially in the endemic area. Pesticides (acaricides) are applied in dipping baths or spray races, and cattle breeds with good ability to acquire immune resistance to the vector ticks are used.
Yellow fever is most frequently a clinical diagnosis, made on the basis of symptoms and the diseased person's whereabouts prior to becoming ill. Mild courses of the disease can only be confirmed virologically. Since mild courses of yellow fever can also contribute significantly to regional outbreaks, every suspected case of yellow fever (involving symptoms of fever, pain, nausea and vomiting six to 10 days after leaving the affected area) is treated seriously.
If yellow fever is suspected, the virus cannot be confirmed until six to 10 days after the illness. A direct confirmation can be obtained by reverse transcription polymerase chain reaction where the genome of the virus is amplified. Another direct approach is the isolation of the virus and its growth in cell culture using blood plasma; this can take one to four weeks.
Serologically, an enzyme linked immunosorbent assay during the acute phase of the disease using specific IgM against yellow fever or an increase in specific IgG-titer (compared to an earlier sample) can confirm yellow fever. Together with clinical symptoms, the detection of IgM or a fourfold increase in IgG-titer is considered sufficient indication for yellow fever. Since these tests can cross-react with other flaviviruses, like dengue virus, these indirect methods cannot conclusively prove yellow fever infection.
Liver biopsy can verify inflammation and necrosis of hepatocytes and detect viral antigens. Because of the bleeding tendency of yellow fever patients, a biopsy is only advisable "post mortem" to confirm the cause of death.
In a differential diagnosis, infections with yellow fever must be distinguished from other feverish illnesses like malaria. Other viral hemorrhagic fevers, such as Ebola virus, Lassa virus, Marburg virus, and Junin virus, must be excluded as cause.
A vaccine is available, called "Chinese Live Attenuated EIA vaccine", developed in China and widely used there since 1983. Another attenuated live virus vaccine is in development in the United States.
Reuse of syringes and needles is a risk factor for transfer of the disease. Currently in the United States, all horses that test positive must be reported to federal authorities by the testing laboratory. EIA-positive horses are infected for life. Options for the horse include sending the horse to a recognized research facility, branding the horse and quarantining it at least 200 yards from other horses for the rest of its life, and euthanizing the horse. Very few quarantine facilities exist, which usually leads to the option of euthanizing the horse. The Florida Research Institute for Equine Nurturing, Development and Safety (a.k.a. F.R.I.E.N.D.S.) is one of the largest such quarantine facilities and is located in south Florida.
The horse industry and the veterinary industry strongly suggest that the risks posed by infected horses, even if they are not showing any clinical signs, are enough of a reason to impose such stringent rules. The precise impacts of the disease on the horse industry are unknown.
Without treatment, the disease is often fatal. Since the use of antibiotics, case fatalities have decreased from 4–40% to less than 2%.
The drug most commonly used is doxycycline or tetracycline, but chloramphenicol is an alternative. Strains that are resistant to doxycycline and chloramphenicol have been reported in northern Thailand. Rifampicin and azithromycin are alternatives. Azithromycin is an alternative in children and pregnant women with scrub typhus, and when doxycycline resistance is suspected. Ciprofloxacin cannot be used safely in pregnancy and is associated with stillbirths and miscarriage.
Combination therapy with doxycycline and rifampicin is not recommended due to possible antagonism.
No vaccine is licensed for use in the U.S. Infection with either of these bacteria results in nonspecific symptoms and can be either acute or chronic, impeding rapid diagnosis. The lack of a vaccine for either bacterium also makes them potential candidates for bioweaponization. Together with their high rate of infectivity by aerosols and resistance to many common antibiotics, both bacteria have been classified as category B priority pathogens by the US NIH and US CDC, which has spurred a dramatic increase in interest in these microorganisms. Attempts have been made to develop vaccines for these infections, which would not only benefit military personnel, a group most likely to be targeted in an intentional release, but also individuals who may come in contact with glanders-infected animals or live in areas where melioidosis is endemic.