Since its first description in the 1960s, only seven people worldwide have been reported to have survived PAM as of 2015, with three in the United States and one in Mexico; one of the US survivors had brain damage that is probably permanent. Less than 1% of people with naegleriasis survive.

The disease is rare and highly lethal: there have only been 300 cases as of 2008. Drug treatment research at Aga Khan University in Pakistan has shown that "in-vitro" drug susceptibility tests with some FDA approved drugs used for non-infectious diseases have proved to kill "Naegleria" "fowleri" with an amoebicidal rate greater than 95%. The same source has also proposed a device for drug delivery via the transcranial route to the brain.

The number of cases of infection could increase due to climate change, and was posited as the reason for 3 cases in Minnesota in 2010, 2012, and 2015. In 2016, an infection was contracted in Maryland, four miles south of the Pennsylvania border;

As of 2013, numbers of reported cases were expected to increase, simply because of better informed diagnoses being made both in ongoing cases and in autopsy findings.

Experimental infection in immunocompetent and immunocompromised mice has produced intestinal inflammation, altered bowel habits, lethargy and death. Chronic diarrhea has been reported in non-human higher primates.

Humans contract "Blastocystis" infection by drinking water or eating food contaminated with feces from an infected human or animal. "Blastocystis" infection can be spread from animals to humans, from humans to other humans, from humans to animals, and from animals to animals. Risk factors for infection have been reported as following:

- International travel: Travel to less developed countries has been cited in development of symptomatic Blastocystis infection. A 1986 study in the United States found that all individuals symptomatically infected with "Blastocystis" reported recent travel history to less developed countries. In the same study, all hospital employees working in New York who were screened for "Blastocystis" were found to have asymptomatic infections.

- Military service: Several studies have identified high rates of infection in military personnel. An early account described infection of British troops in Egypt in 1916 who recovered following treatment with emetine. A 1990 study published in "Military Medicine" from Lackland AFB in Texas concluded symptomatic infection was more common in foreign nationals, children, and immunocompromised individuals. A 2002 study published in "Military Medicine" of army personnel in Thailand identified a 44% infection rate. Infection rates were highest in privates who had served the longest at the army base. A follow-up study found a significant correlation between infection and symptoms, and identified the most likely cause as contaminated water. A 2007 newspaper article suggested the infection rate of US military personnel returning from the Gulf War was 50%, quoting the head of Oregon State University's Biomedicine department.

- Consumption of Untreated Water (well water): Many studies have linked "Blastocystis" infection with contaminated drinking water. A 1993 study of children infected symptomatically with "Blastocystis" in Pittsburgh indicated that 75% of them had a history of drinking well water or travel in less developed countries. Two studies in Thailand linked "Blastocystis" infection in military personnel and families to drinking of unboiled and untreated water. A book published in 2006 noted that in an Oregon community, infections are more common in winter months during heavy rains. A research study published in 1980 reported bacterial contamination of well water in the same community during heavy rainfall. A 2007 study from China specifically linked infection with "Blastocystis sp. subtype 3" with drinking untreated water. Recreational contact with untreated water, for example though boating, has also been identified as a risk factor. Studies have shown that "Blastocystis" survives sewage treatment plants in both the United Kingdom and Malaysia. "Blastocystis" cysts have been shown to be resistant to chlorination as a treatment method and are among the most resistant cysts to ozone treatment.

- Contaminated Food: Contamination of leafy vegetables has been implicated as a potential source for transmission of "Blastocystis" infection, as well as other gastrointestinal protozoa. A Chinese study identified infection with "Blastocystis sp. subtype 1" as specifically associated with eating foods grown in untreated water.

- Daycare facilities: A Canadian study identified an outbreak of "Blastocystis" associated with daycare attendance. Prior studies have identified outbreaks of similar protozoal infections in daycares.

- Geography: Infection rates vary geographically, and variants which produce symptoms may be less common in industrialized countries. For example, a low incidence of "Blastocystis" infection has been reported in Japan. A study of individuals infected with "Blastocystis" in Japan found that many (43%, 23/54) carried "Blastocystis sp. subtype 2", which was found to produce no symptoms in 93% (21/23) of patients studied, in contrast to other variants which were less common but produced symptoms in 50% of Japanese individuals. Studies in urban areas of industrialized countries have found "Blastocystis" infection associated with a low incidence of symptoms. In contrast, studies in developing countries generally show "Blastocystis" to be associated with symptoms. In the United States, a higher incidence of "Blastocystis" infection has been reported in California and West Coast states.

- Prevalence over Time: A 1989 study of the prevalence of "Blastocystis" in the United States found an infection rate of 2.6% in samples submitted from all 48 states. The study was part of the CDC's MMWR Report. A more recent study, in 2006, found an infection rate of 23% in samples submitted from all 48 states. However, the more recent study was performed by a private laboratory located in the Western US, and emphasized samples from Western states, which have previously been reported to have a higher infection rate.

Research studies have suggested the following items are not risk factors for contracting "Blastocystis" infection:

- Consumption of municipal water near water plant (not a risk factor): One study showed that municipal water was free of "Blastocystis", even when drawn from a polluted source. However, samples taken far away from the treatment plant showed cysts. The researchers suggested that aging pipes may permit intrusion of contaminated water into the distribution system.

- Human-to-Human transmission among adults (not a risk factor): Some research suggests that direct human-to-human transmission is less common even in households and between married partners. One study showed different members of the same household carried different subtypes of Blastocystis.

Patients with the following conditions, treatments or situations are at increased risk for invasive candidiasis.

- Critical illness

- Long-term intensive care unit stay

- Abdominal surgery (aggravated by anastomotic leakage or repeat laparotomies)

- Immunosuppressive diseases

- Acute necrotizing pancreatitis

- Malignant hematologic disease

- Solid-organ transplantation

- Hematopoietic stem cell transplantation

- Solid-organ tumors

- Neonates (especially low birth weight and preterm infants)

- Broad-spectrum antibiotic treatment

- Central venous catheter

- Internal prosthetic device

- Total parenteral nutrition

- Hemodialysis

- Glucocorticoid use

- Chemotherapy

- Noninvasive "Candida" colonization (particularly if multifocal)

There is no vaccine to control "Cyclospora" infection in humans at present, but one is available for reduction of fetal losses in sheep.

Invasive candidiasis is a nosocomial infection with the majority of cases associated with hospital stays.

There are many different forms on prevention of syphilis and other sexually transmitted diseases in general. Prevention of syphilis includes avoiding contact of bodily fluids with an infected person. This can be particularly difficult because syphilis is usually transmitted by people who are unaware that they have the disease because they do not have any visible sores or rashes that may denote having an infection in general. Being abstinent or having mutually monogamous sex with a person who is uninfected with any type of sexually transmitted disease is the greatest guarantee of not becoming infected with syphilis or any form of a sexually transmitted disease. Using latex condoms can however reduce the risk of obtaining syphilis. In order to prevent further contamination to other individuals, benzathine penicillin is given to any contacts. Washing, douching, or urinating cannot prevent the transmission of a sexually transmitted disease in general.

Individuals obtain syphilis through a variety of circumstances. In general, syphilis can be transmitted from individual to individual through direct contact with sores that are present on the external genitals, vagina, rectum, anus, lips, or mouth. Transmission can occur through any form of sexual contact, including vaginal, anal, and oral sex. In addition, women who are pregnant and infected with syphilis can transmit the disease onto their child as well. If transmission has occurred, it is important to check up immediately with a physician to avoid further damage.

When an oocyst of "Cyclospora cayetanensis" enters the small intestine, it invades the mucosa, where it incubates for about one week. After incubation, the infected person begins to experience severe watery diarrhea, bloating, fever, stomach cramps, and muscle aches.

The parasite particularly affects the jejunum of the small intestine. Of nine patients in Nepal who were diagnosed with this illness, all had inflammation of the lamina propria along with an increase of plasma in the lamina propria. Of this sample, Oocysts were observed in the duodenal aspirates.

Oocysts are often present in the environment as a result of using contaminated water or human feces as fertilizer. Cyclosporiasis primarily affects humans and primates.

Bats recovering from white-nose syndrome (WNS) may be the first natural occurrence of IRIS, in a report released by the USGS. WNS is typified by a cutaneous infection of the fungus "Pseudogymnoascus destructans" during hibernation, when the immune system is naturally suppressed to conserve energy through the winter. This study suggests that bats undergoing an intense inflammation at the site of infection after a return to euthermia is a form of IRIS.

Although it is classified as a protozoal disease in ICD-10, their phylogenetic placement has been resolved to be within the Fungi, and some sources classify microsporidiosis as a mycosis, however, they are highly divergent and rapidly evolving.

There are five main causes of infections of the central nervous system (CNS): bacterial, viral, fungal, protozoal, and prionic.

The majority of cases (85%) occur during birth when the baby comes in contact with infected genital secretions in the birth canal, most common with mothers that have newly been exposed to the virus (mothers that had the virus before pregnancy have a lower risk of transmission), an estimated 5% are infected in utero, and approximately 10% of cases are acquired postnatally. Detection and prevention is difficult because transmission is asymptomatic in 60% - 98% of cases.

Fumagillin has been used in the treatment.

Another agent used is albendazole.

The most popular treatment forms for any type of syphilis uses penicillin, which has been an effective treatment used since the 1940s.

Other forms also include Benzathine penicillin, which is usually used for primary and secondary syphilis (it has no resistance to penicillin however). Benzathine penicillin is used for long acting form, and if conditions worsen, penicillin G is used for late syphilis.

Many viral infections of the central nervous system occur in seasonal peaks or as epidemics, whereas others, such as herpes simplex encephalitis, are sporadic. In endemic areas it is mostly a disease of children, but as the disease spreads to new regions, or nonimmune travelers visit endemic regions, nonimmune adults are also affected.

Neonatal HSV rates in the U.S. are estimated to be between 1 in 3,000 and 1 in 20,000 live births. Approximately 22% of pregnant women in the U.S. have had previous exposure to HSV-2, and an additional 2% acquire the virus during pregnancy, mirroring the HSV-2 infection rate in the general population. The risk of transmission to the newborn is 30-57% in cases where the mother acquired a primary infection in the third trimester of pregnancy. Risk of transmission by a mother with existing antibodies for both HSV-1 and HSV-2 has a much lower (1-3%) transmission rate. This in part is due to the transfer of significant titer of protective maternal antibodies to the fetus from about the seventh month of pregnancy. However, shedding of HSV-1 from both primary genital infection and reactivations is associated with higher transmission from mother to infant.

HSV-1 neonatal herpes is extremely rare in developing countries because development of HSV-1 specific antibodies usually occurs in childhood or adolescence, precluding a later genital HSV-1 infection. HSV-2 infections are much more common in these countries. In industrialized nations, the adolescent HSV-1 seroprevalance has been dropping steadily for the last 5 decades. The resulting increase in the number of young women becoming sexually active while HSV-1 seronegative has contributed to increased HSV-1 genital herpes rates, and as a result, increased HSV-1 neonatal herpes in developed nations. A recent three-year study in Canada (2000–2003) revealed a neonatal HSV incidence of 5.9 per 100,000 live births and a case fatality rate of 15.5%. HSV-1 was the cause of 62.5% of cases of neonatal herpes of known type, and 98.3% of transmission was asymptomatic. Asymptomatic genital HSV-1 has been shown to be more infectious to the neonate, and is more likely to produce neonatal herpes, than HSV-2, However, with prompt application of antiviral therapy, the prognosis of neonatal HSV-1 infection is better than that for HSV-2.

Meningitis is a very common in children. Newborns can develop herpes virus infections through contact with infected secretions in the birth canal. Other viral infections are acquired by breathing air contaminated with virus-containing droplets exhaled by an infected person. Arbovirus infections are acquired from bites by infected insects (called epidemic encephalitis). Viral central nervous system infections in newborns and infants usually begin with fever. The inability of infants to communicate directly makes it difficult to understand their symptoms. Newborns may have no other symptoms and may initially not otherwise appear ill. Infants older than a month or so typically become irritable and fussy and refuse to eat. Vomiting is common. Sometimes the soft spot on top of a newborn's head (fontanelle) bulges, indicating an increase in pressure on the brain. Because irritation of the meninges is worsened by movement, an infant with meningitis may cry more, rather than calm down, when picked up and rocked. Some infants develop a strange, high-pitched cry. Infants with encephalitis often have seizures or other abnormal movements. Infants with severe encephalitis may become lethargic and comatose and then die. To make the diagnosis of meningitis or the diagnosis of encephalitis, doctors do a spinal tap (lumbar puncture) to obtain cerebrospinal fluid (CSF) for laboratory analysis in children.

Granulomatous amoebic encephalitis (GAE) is a central nervous system disease caused by certain species of free-living amoebae, especially species of "Acanthamoeba" and "Balamuthia mandrillaris".

The term is most commonly used with "Acanthamoeba". In more modern references, the term "balamuthia amoebic encephalitis" (BAE) is commonly used when "Balamuthia mandrillaris" is the cause.

The preventative measure of keeping cats inside in areas with high infection rates can prevent infection. Approved tick treatments for cats can be used but have been shown not to fully prevent tick bites.

The most often used treatments for cytauxzoonosis are imidocarb dipropionate and a combination of atovaquone and azithromycin. Although imidocarb has been used for years, it is not particularly effective. In a large study, only 25% of cats treated with this drug and supportive care survived. 60% of sick cats treated with supportive care and the combination of the anti-malarial drug atovaquone and the antibiotic azithromycin survived infection.

Quick referral to a veterinarian equipped to treat the disease may be beneficial. All infected cats require supportive care, including careful fluids, nutritional support, treatment for complications, and often blood transfusion.

Cats that survive the infection should be kept indoors as they can be persistent carriers after surviving infection and might indirectly infect other cats after being themselves bitten by a vector tick.

Cytauxzoon felis is a protozoal organism transmitted to domestic cats by tick bites, and whose natural reservoir host is the bobcat. "C. felis" has been found in other wild felid species such as Florida bobcat, eastern bobcat, Texas cougar, and a white tiger in captivity. "C. felis" infection is limited to the family felidae which means that "C. felis" poses no zoonotic (transmission to humans) risk or agricultural (transmission to farm animals) risk. Until recently it was believed that after infection with "C. felis", pet cats almost always died. As awareness of "C. felis" has increased it has been found that treatment is not always futile. More cats have been shown to survive the infection than was previously thought. New treatments offer as much as 60% survival rate.

Even with treatment, the condition is often fatal, and there are very few recorded survivors, almost all of whom suffered permanent neurocognitive deficits. Antifungal drugs including ketoconazole, miconazole, 5-flucytosine and pentamidine have been shown to be effective against GAE-causing organisms in laboratory tests.

IRIS is particularly problematic in cryptococcal meningitis as IRIS is fairly common and can be fatal.

IRIS has been described in immunocompetent hosts who have meningitis caused by "Cryptococcus gattii" and "Cryptococcus neoformans" var. "grubii", environmental fungi which often affect immunocompetent hosts. Several weeks or even months into appropriate treatment, there is a sudden onset deterioration with worsening meningitis symptoms and progression or development of new neurological symptoms.

Magnetic resonance imaging shows increase in the size of brain lesions, and CSF abnormalities (white cell count, protein, glucose) increase. CSF culture is typically sterile, and there is no increase in CSF cryptococcal antigen titer.

The increasing inflammation can cause brain injury or be fatal.

The general mechanism behind IRIS is increased inflammation as the recovering immune system recognizes the antigens of the fungus as immunosuppression is reversed. Cryptococcal IRIS has three phases:

1. before HAART, with a paucity of cerebrospinal fluid (CSF) inflammation and defects in antigen clearance;

2. during initial HAART immune recovery, with pro-inflammatory signaling by antigen-presenting cells without an effector response; and

3. at IRIS, a cytokine storm with a predominant type-1 helper T-cell interferon-gamma response.

Three clinical predictors of cryptococcal-related paradoxical IRIS risk include:

1. lack of initial CSF pleocytosis (i.e. low CSF white blood cell count);

2. elevated C-reactive protein;

3. failure to sterilize the CSF before immune recovery.

IRIS may be the cause of paradoxically worse outcomes for cryptococcal meningitis in immunocompetent compared with immunocompromised hosts, in whom "Cryptococcus neoformans" is the usual pathogen. Treatment with systemic corticosteroids during IRIS may be beneficial in preventing death or progressive neurological deterioration. Steroids given to persons with anti-fungal treatment failure / cryptococcal relapse (in whom CSF cultures are not sterile) can be a fatal iatrogenic error.

The mortality rate of the virus largely depends on the immune status of the infected dogs. Puppies experience the highest mortality rate, where complications such as pneumonia and encephalitis are more common. In older dogs that develop distemper encephalomyelitis, vestibular disease may present. Around 15% of canine inflammatory central nervous system diseases are a result of CDV.

Chagas disease affects 8 to 10 million people living in endemic Latin American countries, with an additional 300,000–400,000 living in nonendemic countries, including Spain and the United States. An estimated 41,200 new cases occur annually in endemic countries, and 14,400 infants are born with congenital Chagas disease annually. in 2010 it resulted in approximately 10,300 deaths up from 9,300 in 1990.

The disease is present in 18 countries on the American continents, ranging from the southern United States to northern Argentina. Chagas exists in two different ecological zones. In the Southern Cone region, the main vector lives in and around human homes. In Central America and Mexico, the main vector species lives both inside dwellings and in uninhabited areas. In both zones, Chagas occurs almost exclusively in rural areas, where triatomines breed and feed on the more than 150 species from 24 families of domestic and wild mammals, as well as humans, that are the natural reservoirs of "T. cruzi".

Although Triatominae bugs feed on them, birds appear to be immune to infection and therefore are not considered to be a "T. cruzi" reservoir. Even when colonies of insects are eradicated from a house and surrounding domestic animal shelters, they can re-emerge from plants or animals that are part of the ancient, sylvatic (referring to wild animals) infection cycle. This is especially likely in zones with mixed open savannah, with clumps of trees interspersed by human habitation.

The primary wildlife reservoirs for "Trypanosoma cruzi" in the United States include opossums, raccoons, armadillos, squirrels, woodrats, and mice. Opossums are particularly important as reservoirs, because the parasite can complete its life cycle in the anal glands of this animal without having to re-enter the insect vector. Recorded prevalence of the disease in opossums in the U.S. ranges from 8.3% to 37.5%.

Studies on raccoons in the Southeast have yielded infection rates ranging from 47% to as low as 15.5%. Armadillo prevalence studies have been described in Louisiana, and range from a low of 1.1% to 28.8%. Additionally, small rodents, including squirrels, mice, and rats, are important in the sylvatic transmission cycle because of their importance as bloodmeal sources for the insect vectors. A Texas study revealed 17.3% percent "T. cruzi" prevalence in 75 specimens representing four separate small rodent species.

Chronic Chagas disease remains a major health problem in many Latin American countries, despite the effectiveness of hygienic and preventive measures, such as eliminating the transmitting insects. However, several landmarks have been achieved in the fight against it in Latin America, including a reduction by 72% of the incidence of human infection in children and young adults in the countries of the Southern Cone Initiative, and at least three countries (Uruguay, in 1997, and Chile, in 1999, and Brazil in 2006) have been certified free of vectorial and transfusional transmission. In Argentina, vectorial transmission has been interrupted in 13 of the 19 endemic provinces, and major progress toward this goal has also been made in both Paraguay and Bolivia.

Screening of donated blood, blood components, and solid organ donors, as well as donors of cells, tissues, and cell and tissue products for "T. cruzi" is mandated in all Chagas-endemic countries and has been implemented. Approximately 300,000 infected people live in the United States, which is likely the result of immigration from Latin American countries, and there have been 23 cases acquired from kissing bugs in the United States reported between 1955 and 2014. With increased population movements, the possibility of transmission by blood transfusion became more substantial in the United States. Transfusion blood and tissue products are now actively screened in the U.S., thus addressing and minimizing this risk.