Serological testing is typically used to obtain a definitive diagnosis. Most serological tests would succeed only after a certain period of time past the symptom onset (usually a week). The differential diagnosis list includes typhus, ehrlichiosis, leptospirosis, Lyme disease and virus-caused exanthema (measles or rubella).

The diagnosis of relapsing fever can be made on blood smear as evidenced by the presence of spirochetes. Other spirochete illnesses (Lyme disease, syphilis, leptospirosis) do not show spirochetes on blood smear. Although considered the gold standard, this method lacks sensitivity and has been replaced by PCR in many settings.

Tetracycline-group antibiotics (doxycycline, tetracycline) are commonly used. Chloramphenicol is an alternative medication recommended under circumstances that render use of tetracycline derivates undesirable, such as severe liver malfunction, kidney deficiency, in children under nine years and in pregnant women. The drug is administered for seven to ten days.

The treatment for bacillary angiomatosis is erythromycin given for three to four months.

Currently, no vaccine against relapsing fever is available, but research continues. Developing a vaccine is very difficult because the spirochetes avoid the immune response of the infected person (or animal) through antigenic variation. Essentially, the pathogen stays one step ahead of antibodies by changing its surface proteins. These surface proteins, lipoproteins called variable major proteins, have only 30–70% of their amino acid sequences in common, which is sufficient to create a new antigenic "identity" for the organism. Antibodies in the blood that are binding to and clearing spirochetes expressing the old proteins do not recognize spirochetes expressing the new ones. Antigenic variation is common among pathogenic organisms. These include the agents of malaria, gonorrhea, and sleeping sickness. Important questions about antigenic variation are also relevant for such research areas as developing a vaccine against HIV and predicting the next influenza pandemic.

Diagnosis during the acute phase can be made by obtaining a peripheral blood smear with Giemsa stain, Columbia blood agar cultures, immunoblot, indirect immunofluorescence, and PCR. Diagnosis during the chronic phase can be made using a Warthin-Starry stain of wart biopsy, PCR, and immunoblot.

The CDC states that PCR testing from a single blood draw is not sufficiently sensitive for "B." "henselae" testing, and can result in high false negative rates due to a small sample volume and levels below the limit of molecular detection.

"Bartonella" spp. are fastidious, slow-growing bacteria that are difficult to grow using traditional solid agar plate culture methods due to complex nutritional requirements and potentially a low number of circulating bacteria. This conventional method of culturing "Bartonella" spp. from blood inoculates plated directly onto solid agar plates requires an extended incubation period of 21 days due to the slow growth rate.

"Bartonella" growth rates improve when cultured in an enrichment inoculation step in a liquid insect-based medium such as "Bartonella" α-Proteobacteria Growth Medium (BAPGM) or Schneider’s Drosophila-based insect powder medium. Several studies have optimized the growing conditions of "Bartonella" spp. cultures in these liquid media, with no change in bacterial protein expressions or host interactions "in vitro". Insect-based liquid media supports the growth and co-culturing of at least seven "Bartonella" species, reduces bacterial culturing time and facilitates PCR detection and isolation of "Bartonella" spp. from animal and patient samples. Research shows that DNA may be detected following direct extraction from blood samples and become negative following enrichment culture, thus PCR is recommended after direct sample extraction and also following incubation in enrichment culture. Several studies have successfully optimized sensitivity and specificity by using PCR amplification (pre-enrichment PCR) and enrichment culturing of blood draw samples, followed by PCR (post-enrichment PCR) and DNA sequence identification.

Carrion's disease is caused by "Bartonella bacilliformis".

Recent investigations show that "Candidatus Bartonella ancashi" may cause verruga peruana, although it may not meet all of Koch's postulates. There has been no experimental reproduction of the Peruvian wart in animals and there is little research on the disease's natural spread or impact in native animals.

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.

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.

The Warthin–Starry stain can be helpful to show the presence of "B. henselae", but is often difficult to interpret. "B. henselae" is difficult to culture and can take 2–6 weeks to incubate. The best diagnostic method currently available is polymerase chain reaction, which has a sensitivity of 43-76% and a specificity (in one study) of 100%.

Cat-scratch disease is characterized by granulomatous inflammation on histological examination of the lymph nodes. Under the microscope, the skin lesion demonstrates a circumscribed focus of necrosis, surround by histiocytes, often accompanied by multinucleated giant cells, lymphocytes, and eosinophils. The regional lymph nodes demonstrate follicular hyperplasia with central stellate necrosis with neutrophils, surrounded by palisading histiocytes (suppurative granulomas) and sinuses packed with monocytoid B cells, usually without perifollicular and intrafollicular epithelioid cells. This pattern, although typical, is only present in a minority of cases.

The diagnosis of group A beta-hemolytic streptococcus (GABHS) tonsillitis can be confirmed by culture of samples obtained by swabbing both tonsillar surfaces and the posterior pharyngeal wall and plating them on sheep blood agar medium. The isolation rate can be increased by incubating the cultures under anaerobic conditions and using selective growth media. A single throat culture has a sensitivity of 90–95% for the detection of GABHS (which means that GABHS is actually present 5–10% of the time culture suggests that it is absent). This small percentage of false-negative results are part of the characteristics of the tests used but are also possible if the patient has received antibiotics prior to testing. Identification requires 24 to 48 hours by culture but rapid screening tests (10–60 minutes), which have a sensitivity of 85–90%, are available. Older antigen tests detect the surface Lancefield group A carbohydrate. Newer tests identify GABHS serotypes using nucleic acid (DNA) probes or polymerase chain reaction. Bacterial culture may need to be performed in cases of a negative rapid streptococcal test.

True infection with GABHS, rather than colonization, is defined arbitrarily as the presence of >10 colonies of GABHS per blood agar plate. However, this method is difficult to implement because of the overlap between carriers and infected patients. An increase in antistreptolysin O (ASO) streptococcal antibody titer 3–6 weeks following the acute infection can provide retrospective evidence of GABHS infection and is considered definitive proof of GABHS infection.

Increased values of secreted phospholipase A2 and altered fatty acid metabolism in patients with tonsillitis may have diagnostic utility.

This disease is diagnosed mainly by the appearance of well-demarcated rash and inflammation. Blood cultures are unreliable for diagnosis of the disease, but may be used to test for sepsis. Erysipelas must be differentiated from herpes zoster, angioedema, contact dermatitis, and diffuse inflammatory carcinoma of the breast.

Erysipelas can be distinguished from cellulitis by its raised advancing edges and sharp borders. Elevation of the antistreptolysin O titer occurs after around 10 days of illness.

Depending on the severity, treatment involves either oral or intravenous antibiotics, using penicillins, clindamycin, or erythromycin. While illness symptoms resolve in a day or two, the skin may take weeks to return to normal.

Because of the risk of reinfection, prophylactic antibiotics are sometimes used after resolution of the initial condition. However, this approach does not always stop reinfection.

Treatments to reduce the discomfort from tonsillitis include:

- pain and fever reducing medications such as paracetamol (acetaminophen) and ibuprofen

- warm salt water gargle, lozenges, or warm liquids

When tonsillitis is caused by a virus, the length of illness depends on which virus is involved. Usually, a complete recovery is made within one week; however, symptoms may last for up to two weeks.

Many cases of croup have been prevented by immunization for influenza and diphtheria. At one time, croup referred to a diphtherial disease, but with vaccination, diphtheria is now rare in the developed world.

The most commonly used system for classifying the severity of croup is the Westley score. It is primarily used for research purposes rather than in clinical practice. It is the sum of points assigned for five factors: level of consciousness, cyanosis, stridor, air entry, and retractions. The points given for each factor is listed in the adjacent table, and the final score ranges from 0 to 17.

- A total score of ≤ 2 indicates "mild" croup. The characteristic barking cough and hoarseness may be present, but there is no stridor at rest.

- A total score of 3–5 is classified as "moderate" croup. It presents with easily heard stridor, but with few other signs.

- A total score of 6–11 is "severe" croup. It also presents with obvious stridor, but also features marked chest wall indrawing.

- A total score of ≥ 12 indicates impending respiratory failure. The barking cough and stridor may no longer be prominent at this stage.

85% of children presenting to the emergency department have mild disease; severe croup is rare (<1%).

Vaccination is available against tick-borne and Japanese encephalitis and should be considered for at-risk individuals. Post-infectious encephalomyelitis complicating smallpox vaccination is avoidable, for all intents and purposes, as smallpox is nearly eradicated. Contraindication to Pertussis immunization should be observed in patients with encephalitis.

People should only be diagnosed with encephalitis if they have a decreased or altered level of consciousness, lethargy, or personality change for at least twenty-four hours without any other explainable cause. Diagnosing encephalitis is done via a variety of tests:

- Brain scan, done by MRI, can determine inflammation and differentiate from other possible causes.

- EEG, in monitoring brain activity, encephalitis will produce abnormal signal.

- Lumbar puncture (spinal tap), this helps determine via a test using the cerebral-spinal fluid, obtained from the lumbar region.

- Blood test

- Urine analysis

- Polymerase chain reaction (PCR) testing of the cerebrospinal fluid, to detect the presence of viral DNA which is a sign of viral encephalitis.

Laboratory testing includes white blood cell count, ESR, and CRP. These values are usually elevated in those with septic arthritis; however, these can be elevated by other infections or inflammatory conditions and are, therefore, nonspecific. Procalcitonin may be more useful than CRP.

Blood cultures can be positive in up to half of patients with septic arthritis.

Outbreaks of zoonoses have been traced to human interaction with and exposure to animals at fairs, petting zoos, and other settings. In 2005, the Centers for Disease Control and Prevention (CDC) issued an updated list of recommendations for preventing zoonosis transmission in public settings. The recommendations, developed in conjunction with the National Association of State Public Health Veterinarians, include educational responsibilities of venue operators, limiting public and animal contact, and animal care and management.

Imaging such as x-ray, CT,MRI, orultrasoundarenonspecific. They can help determine areas of inflammation but cannot confirm septic arthritis.

When septic arthritis is suspected,x-raysshould generally be taken. This is used to assess for involvement of surrounding structures such as bone and also for comparison purposes when future x-rays are taken.While x-rays may not be helpful early in the diagnosis/treatment, they may show subtle increase in joint space and tissue swelling. Later findings include joint space narrowing due to destruction of the joint.

Ultrasoundcan be done and is effective at detecting joint effusions.

CTandMRI are not required for diagnosis but can be used if diagnosis is unclear or in joints that are hard to examine (ie.sacroiliacorhip joints). They can can help assess for inflammation/infection in or about the joint (ie.osteomyeltis).

Diagnosis of FVR is usually by clinical signs, especially corneal ulceration. Definitive diagnosis can be done by direct immunofluorescence or virus isolation. However, many healthy cats are subclinical carriers of feline herpes virus, so a positive test for FHV-1 does not necessarily indicate that signs of an upper respiratory tract infection are due to FVR. Early in the course of the disease, histological analysis of cells from the tonsils, nasal tissue, or nictitating membrane (third eyelid) may show inclusion bodies (a collection of viral particles) within the nucleus of infected cells.

Prophylaxis and treatment with an anti-inflammatory agent may stop progression of the reaction. Oral aspirin or ibuprofen every four hours for a day or 60 mg of prednisone orally or intravenously has been used as an adjunctive treatment . However, steroids are generally of no benefit. Patients must be closely monitored for the potential complications (collapse and shock) and may require IV fluids to maintain adequate blood pressure. If available, meptazinol, an opioid analgesic of the mixed agonist/antagonist type, should be administered to reduce the severity of the reaction. Anti TNF-a may also be effective.