Early localized infection can occur when the infection has not yet spread throughout the body. Only the site where the infection has first come into contact with the skin is affected. The classic sign of early local infection with Lyme disease is a circular, outwardly expanding rash called erythema chronicum migrans (EM), which occurs at the site of the tick bite three to 32 days after the tick bite. The rash is red, and may be warm, but is generally painless. Classically, the innermost portion remains dark red and becomes indurated (is thicker and firmer), the outer edge remains red, and the portion in between clears, giving the appearance of a bull's eye. However, partial clearing is uncommon, and the bull's-eye pattern more often involves central redness.

The EM rash associated with early infection is found in about 70–80% of people infected. It can have a range of appearances including the classic target bull's-eye lesion and nontarget appearing lesions. The 20–30% without the EM and the nontarget lesions can often cause misidentification of Lyme disease. Affected individuals can also experience flu-like symptoms, such as headache, muscle soreness, fever, and malaise. Lyme disease can progress to later stages even in people who do not develop a rash.

Within days to weeks after the onset of local infection, the "Borrelia" bacteria may begin to spread through the bloodstream. EM may develop at sites across the body that bear no relation to the original tick bite. Another skin condition, apparently absent in North American patients, but found in Europe, is borrelial lymphocytoma, a purplish lump that develops on the ear lobe, nipple, or scrotum.

Various acute neurological problems, termed neuroborreliosis, appear in 10–15% of untreated people. These include facial palsy, which is the loss of muscle tone on one or both sides of the face, as well as meningitis, which involves severe headaches, neck stiffness, and sensitivity to light. Inflammation of the spinal cord's nerve roots can cause shooting pains that may interfere with sleep, as well as abnormal skin sensations. Mild encephalitis may lead to memory loss, sleep disturbances, or mood changes. In addition, some case reports have described altered mental status as the only symptom seen in a few cases of early neuroborreliosis. The disease may adversely impact the heart's electrical conduction system and can cause abnormal heart rhythms such as atrioventricular block.

Diagnosis is based on a circular "bull's-eye" rash at the site of infection called erythema chronicum migrans, which is very similar to that seen in Lyme disease. However, the symptoms of STARI are mild, and resemble influenza, with fatigue, muscle pains, and headache. Fever is sometimes seen, but is not characteristic.

Southern tick-associated rash illness (STARI) or Masters' disease is an emerging infectious disease related to Lyme disease that occurs in southeastern and south-central United States. It is spread by tick bites, but the organism that causes the infection is unknown.

In general, specific laboratory tests are not available to rapidly diagnose tick-borne diseases. Due to their seriousness, antibiotic treatment is often justified based on clinical presentation alone.

The Baggio–Yoshinari syndrome (BYS), formerly known as the Brazilian Lyme-like disease and Brazilian human borreliosis, is a disease transmitted by the "Amblyomma cajennense" tick, but the organism that causes the infection is still unknown. Clinical features resemble those of Lyme disease (LD).

Tick-borne diseases, which afflict humans and other animals, are caused by infectious agents transmitted by tick bites. Tick-borne illnesses are caused by infection with a variety of pathogens, including rickettsia and other types of bacteria, viruses, and protozoa. Because individual ticks can harbor more than one disease-causing agent, patients can be infected with more than one pathogen at the same time, compounding the difficulty in diagnosis and treatment. As of 2016, 16 tick-borne diseases of humans are known (four discovered since 2013).

As the incidence of tick-borne illnesses increases and the geographic areas in which they are found expand, health workers increasingly must be able to distinguish the diverse, and often overlapping, clinical presentations of these diseases.

The virus can infect the brain (encephalitis), the meninges (meningitis) or both (meningoencephalitis).

In general, mortality is 1% to 2%, with deaths occurring 5 to 7 days after the onset of neurologic signs.

In dogs, the disease also manifests as a neurological disorder with signs varying from tremors to seizures and death.

In ruminants, neurological disease is also present, and animals may refuse to eat, appear lethargic, and also develop respiratory signs.

Symptoms manifest within 7–10 days and include fever, headache, partial paralysis, confusion, nausea and even coma.

A distinct feature of the syndrome is its prolonged clinical evolution, with relapsing episodes and autoimmune dysfunction. If diagnosed in its early stages, the symptoms respond well to antibiotics. If the disease evolves to a chronic phase, it can potentially cause oligoarthritis, cognitive impairment, meningoencephalitis and erythema nodosum, with the patient risking to develop both articular and neurological sequelae.

The neurological manifestations of BYS were first described by Yoshinari et al. including patients with peripheral neuritis, meningitis and cranial neuritis (facial nerve palsy, diplopia and deafness).

Likely transmission vectors of BYS belong to the "Amblyomma" and "Rhipicephalus" genera, which could help to explain all the particularities observed in BYS versus LD.

Some features of BYS also resemble those found in the Southern tick-associated rash illness (STARI, also known as Masters' disease), which is found in the Southern USA.

Chronic Lyme disease is a generally unrecognised diagnosis that encompasses "a broad array of illnesses or symptom complexes for which there is no reproducible or convincing scientific evidence of any relationship to "B. burgdorferi" infection." There is no clinical evidence that "chronic" Lyme disease is caused by a persistent infection. It is distinct from post-treatment Lyme disease syndrome, a set of lingering symptoms which may persist after successful treatment of infection with Lyme spirochetes. The symptoms of "chronic Lyme" are generic and non-specific "symptoms of life".

A number of alternative treatments are promoted for "chronic Lyme disease", of which possibly the most controversial and harmful is long-term antibiotic therapy, particularly intravenous antibiotics. Most medical authorities advise against long-term antibiotic treatment for Lyme disease, though they agree that some patients do experience lingering symptoms. Following disciplinary proceedings by State medical licensing boards in the United States, a subculture of "Lyme literate" physicians has successfully lobbied for specific legal protections, exempting them from the standard of care and Infectious Diseases Society of America treatment guidelines. This "troubling" political interference in medical care has been criticised as an example of "legislative alchemy", the process whereby pseudomedicine is legislated into practice.

Tick-borne encephalitis (TBE) is a viral infectious disease involving the central nervous system. The disease most often manifests as meningitis, encephalitis, or meningoencephalitis. Although TBE is most commonly recognized as a neurological disorder, mild fever can also occur. Long-lasting or permanent neuropsychiatric consequences are observed in 10 to 20% of infected patients.

The number of reported cases has been increasing in most countries.

The tick-borne encephalitis virus is known to infect a range of hosts including ruminants, birds, rodents, carnivores, horses, and humans. The disease can also be spread from animals to humans, with ruminants and dogs providing the principal source of infection for humans.

TBE, like Lyme disease, is one of the many tick-borne diseases.

Missouri Lyme disease is a cutaneous condition. The cause of ‘Missouri Lyme disease’ has been a source of controversy. True Lyme disease probably occurs in Missouri and other southern states, although Lyme disease-like illnesses not related to Borrelia burgdorferi also occur. Strains of B. burgdorferi have been isolated from A. americanum in Missouri, but the ticks are not efficient disease vectors.

Powassan encephalitis, caused by the Powassan virus (POWV), as flavivirus also known as the deer tick virus, is a form of arbovirus infection that results from tick bites. It can occur as a co-infection with Lyme disease since both are transmitted to humans by the same species of tick. There has been a surge in the number of cases and geographic range in the last decade. In the United States, cases have been recorded in the northeast. The disease was first isolated from the brain of a boy who died of encephalitis in Powassan, Ontario, in 1958. The disease is a zoonosis, an animal disease, usually found in rodents and ticks, with spillover transmission to humans. The virus is antigenically related to the Far Eastern tick-borne encephalitis viruses.

Neuroborreliosis is often preceded by the typical symptoms of Lyme disease, which include erythema migrans and flu-like symptoms such as fever and muscle aches. Neurologic symptoms of neuroborreliosis include the meningoradiculitis (which is more common in European patients), cranial nerve abnormalities, and altered mental status. Sensory findings may also be present. Rarely, a progressive form of encephalomyelitis may occur. In children, symptoms of neuroborreliosis include headache, sleep disturbance, and symptoms associated with increased intracranial pressure, such as papilledema, can occur. Less common childhood symptoms can include meningitis, myelitis, ataxia, and chorea. Ocular Lyme disease has also been reported, as has neuroborreliosis affecting the spinal cord, but neither of these findings are common.

The most common symptoms include headache, muscle aches, and fatigue. A rash may occur, but is uncommon. Ehrlichiosis can also blunt the immune system by suppressing production of TNF-alpha, which may lead to opportunistic infections such as candidiasis.

Most of the signs and symptoms of ehrlichiosis can likely be ascribed to the immune dysregulation that it causes. A "toxic shock-like" syndrome is seen in some severe cases of ehrlichiosis. Some cases can present with purpura and in one such case the organisms were present in such overwhelming numbers that in 1991 Dr. Aileen Marty of the AFIP was able to demonstrate the bacteria in human tissues using standard stains, and later proved that the organisms were indeed Ehrlichia using immunoperoxidase stains.

Experiments in mouse models further supports this hypothesis, as mice lacking TNF-alpha I/II receptors are resistant to liver injury caused by ehrlichia infection.

3% of human monocytic ehrlichiosis cases result in death; however, these deaths occur "most commonly in immunosuppressed individuals who develop respiratory distress syndrome, hepatitis, or opportunistic nosocomial infections."

Neuroborreliosis, also known as Lyme neuroborreliosis (LNB), is a disorder of the central nervous system. A neurological manifestation of Lyme disease, neuroborreliosis is caused by a systemic infection of spirochetes of the genus "Borrelia." Symptoms of the disease include erythema migrans and flu-like symptoms. The microbiological progression of the disease is similar to that of neurosyphilis, another spirochetal infection.

The majority of infections result in mild illness, including fever and headache. When infection is more severe the person may experience headache, high fever, neck stiffness, stupor, disorientation, coma, tremors, occasional convulsions and spastic paralysis. Fatality ranges from . Aged people are more likely to have a fatal infection.

Saint Louis encephalitis is a disease caused by the mosquito borne Saint Louis encephalitis virus. Saint Louis encephalitis virus is related to Japanese encephalitis virus and is a member of the Flaviviridae subgroup. This disease mainly affects the United States. Occasional cases have been reported from Canada and Mexico.

Signs and symptoms may include:

- fever

- severe headache

- muscle aches (myalgia)

- chills and shaking, similar to the symptoms of influenza

- nausea

- vomiting

- loss of appetite

- unintentional weight loss

- abdominal pain

- cough

- diarrhea,

- aching joints

- sensitivity to light

- weakness

- fatigue

- change in mental status (extreme confusion, memory loss, inability to comprehend environment- interaction, reading, etc.)

- temporary loss of basic motor skills

Symptoms may be minor, as evidenced by surveillance studies in high-risk areas. Gastrointestinal tract symptoms occur in less than half of patients and a skin rash is seen in less than 10% of patients. It is also characterized by a low number of platelets, a low number of white blood cells, and elevated serum transaminase levels in the majority of infected patients. Even though people of any age can get HGA, it is usually more severe in the aging or immune-compromised. Some severe complications may include respiratory failure, kidney failure, and secondary infections.

Infections associated with diseases are those that are associated with possible infectious etiologies, that meet the requirements of Koch's postulates. Other methods of causation are described by the Bradford Hill criteria and Evidence-based medicine. Koch's postulates have been altered by some epidemiologists based upon sequence-based detection of distinctive pathogenic nucleic acid sequences in tissue samples. Using this method, absolute statements are not always possible regarding causation. Since this is true, higher amounts of distinctive pathogenic nucleic acid sequences would be in those exhibiting disease compared to controls since inoculating those without the pathogen is unethical. In addition, the DNA load should drop or become lower with the resolution of the disease. The distinctive pathogenic nucleic acid sequences load should also increase upon recurrence.

Other conditions are met to establish cause or association including studies in disease transmission. This means that there should be a high disease occurrence in those carrying an pathogen, evidence of a serologicalresponse to the pathogen, and the success of vaccination prevention. Direct visualization of the pathogen, the identification of different strains, immunological responses in the host, how the infection is spread and, the combination of these should all be taken into account to determine the probability that an infectious agent is the cause of the disease. A conclusive determination of a causal role of an infectious agent for in a particular disease using Koch's postulates is desired yet this might not be possible.

The leading cause of death worldwide is cardiovascular disease, but infectious diseases are the second leading cause of death worldwide and the leading cause of death in infants and children.

An emerging infectious disease (EID) is an infectious disease whose incidence has increased in the past 20 years and could increase in the near future. Emerging infections account for at least 12% of all human pathogens. EIDs are caused by newly identified species or strains (e.g. Severe acute respiratory syndrome, HIV/AIDS) that may have evolved from a known infection (e.g. influenza) or spread to a new population (e.g. West Nile fever) or to an area undergoing ecologic transformation (e.g. Lyme disease), or be "reemerging" infections, like drug resistant tuberculosis. Nosocomial (hospital-acquired) infections, such as methicillin-resistant Staphylococcus aureus are emerging in hospitals, and extremely problematic in that they are resistant to many antibiotics. Of growing concern are adverse synergistic interactions between emerging diseases and other infectious and non-infectious conditions leading to the development of novel syndemics. Many emerging diseases are zoonotic - an animal reservoir incubates the organism, with only occasional transmission into human populations.

Half of all children and a quarter of previously healthy adults are asymptomatic with "Babesia" infection. When people do develop symptoms, the most common are fever and hemolytic anemia, symptoms that are similar to those of malaria. People with symptoms usually become ill 1 to 4 weeks after the bite, or 1 to 9 weeks after transfusion of contaminated blood products. A person infected with babesiosis gradually develops malaise and fatigue, followed by a fever. Hemolytic anemia, in which red blood cells are destroyed and removed from the blood, also develops. Chills, sweats, and thrombocytopenia are also common symptoms. Symptoms may last from several days to several months.

Less common symptoms and physical exam findings of mild-to-moderate babesiosis:

In more severe cases, symptoms similar to malaria occur, with fevers up to 40.5 °C (105 °F), shaking chills, and severe anemia (hemolytic anemia). Organ failure may follow, including adult respiratory distress syndrome. Severe cases occur mostly in people who have had a splenectomy. Severe cases are also more likely to occur in the very young, very old, and persons with immunodeficiency, such as HIV/AIDS patients.

A reported increase in human babesiosis diagnoses in the 2000s is thought to be caused by more widespread testing and higher numbers of people with immunodeficiencies coming in contact with ticks, the disease vector. Little is known about the occurrence of "Babesia" species in malaria-endemic areas, where "Babesia" can easily be misdiagnosed as "Plasmodium". Human patients with repeat babesiosis infection may exhibit premunity.

Ehrlichiosis is a tickborne

bacterial infection, caused by bacteria of the family Anaplasmataceae, genera "Ehrlichia" and "Anaplasma". These obligate intracellular bacteria infect and kill white blood cells.

The average reported annual incidence is on the order of 2.3 cases per million people.

Human granulocytic anaplasmosis (HGA) is a tick-borne, infectious disease caused by "Anaplasma phagocytophilum", an obligate intracellular bacterium that is typically transmitted to humans by ticks of the "Ixodes ricinus" species complex, including "Ixodes scapularis" and "Ixodes pacificus" in North America. These ticks also transmit Lyme disease and other tick borne diseases.

The bacteria infect white blood cells called neutrophils, causing changes in gene expression that prolong the life of these otherwise short-lived cells.