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.

Among the maternal risk factors for Neonatal HSV-1: White non-Hispanic race, young maternal age (<25), primary infection in third trimester

, first pregnancy, HSV (1&2) seronegative, discordant partner, gestation <38 weeks, receptive oral sex in third trimester.

Neonatal HSV-2 maternal risk factors: Black race, young maternal age (<21), discordant partner, primary or non primary first episode infection in third trimester, four or more lifetime sexual partners, lower level of education, history of previous STD, history of pregnancy wastage, first viable pregnancy, gestation <38 weeks.

Developing countries are more severely affected by TORCH syndrome.

Congenital disease occurs due to the acquisition of the organism by a pregnant woman exposed to tissue cysts or oocytes in uncooked meat or substances contaminated with cat feces. Spontaneous abortion may result if the disease is acquired during the first trimester.

Congenital toxoplasmosis may lead to hydrocephalus, seizures, lymphadenopathy, hepatosplenomegaly, rash, and fever. However, retinochoroiditis is the most common manifestation, occurring in 3/4 of cases.

In congenital toxoplasmosis, the disease is bilateral in 65–85% of cases and involves the macula in 58%.

Chronic or recurrent maternal infection during pregnancy is not thought to confer a risk of congenital toxoplasmosis because maternal immunity protects against fetal transmission. In contrast, pregnant women without serologic evidence of prior exposure to Toxoplasma should take sanitary precautions when cleaning up after cats and avoid undercooked meats.

TORCH syndrome can be prevented by treating an infected pregnant person, thereby preventing the infection from affecting the fetus.

"Toxoplasma" infection can be prevented in large part by:

- cooking meat to a safe temperature (i.e., one sufficient to kill "Toxoplasma")

- peeling or thoroughly washing fruits and vegetables before eating

- cleaning cooking surfaces and utensils after they have contacted raw meat, poultry, seafood, or unwashed fruits or vegetables

- pregnant women avoiding changing cat litter or, if no one else is available to change the cat litter, using gloves, then washing hands thoroughly

- not feeding raw or undercooked meat to cats to prevent acquisition of "Toxoplasma"

Prolonged and intense rainfall periods are significantly associated with the reactivation of toxoplasmic retinochoroiditis. Changes promoted by this climatic condition concern both the parasite survival in the soil as well as a putative effect on the host immune response due to other comorbidities.

The formation of gummata is rare in developed countries, but common in areas that lack adequate medical treatment.

Syphilitic gummas are found in most but not all cases of tertiary syphilis, and can occur either singly or in groups. Gummatous lesions are usually associated with long-term syphilitic infection; however, such lesions can also be a symptom of benign late syphilis.

If a pregnant mother is identified as being infected with syphilis, treatment can effectively prevent congenital syphilis from developing in the fetus, especially if he or she is treated before the sixteenth week of pregnancy. The fetus is at greatest risk of contracting syphilis when the mother is in the early stages of infection, but the disease can be passed at any point during pregnancy, even during delivery (if the child had not already contracted it). A woman in the secondary stage of syphilis decreases her fetus's risk of developing congenital syphilis by 98% if she receives treatment before the last month of pregnancy. An afflicted child can be treated using antibiotics much like an adult; however, any developmental symptoms are likely to be permanent.

Kassowitz’s law is an empirical observation used in context of congenital syphilis stating that the greater the duration between the infection of the mother and conception, the better is the outcome for the infant. Features of a better outcome include less chance of stillbirth and of developing congenital syphilis.

The Centers for Disease Control and Prevention recommends treating symptomatic or babies born to infected mother with unknown treatment status with procaine penicillin G, 50,000 U/kg dose IM a day in a single dose for 10 days. Treatment for these babies can vary on a case by case basis. Treatment cannot reverse any deformities, brain, or permanent tissue damage that has already occurred.

Death from congenital syphilis is usually due to bleeding into the lungs.

Individuals with a weak immune system are most at risk. This includes individuals taking immunosuppressive medication, cancer patients, HIV patients, premature babies with very low birth weight, the elderly, etc.

People who are at an increased risk of acquiring particular fungal infections in general may also be at an increased risk of developing fungal meningitis, as the infection may in some cases spread to the CNS. People residing in the Midwestern United States, and Southwestern United States and Mexico are at an increased risk of infection with "Histoplasma" and "Coccidioides", respectively.

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.

Meningeal syphilis (as known as syphilitic aseptic meningitis or meningeal neurosyphilis) is a chronic form of syphilis infection that affects the central nervous system. Treponema pallidum, which is a spirochate bacterium, is the main cause of syphilis, which spreads drastically throughout the body and can infect all the systems of the body if not treated appropriately. The bacterium is the main cause of the onset of meningeal syphilis and other treponemal diseases, and it consists of a cytoplasmic and outer membrane that can cause a diverse array of diseases in the central nervous system and brain.

Early symptomatic neurosyphillis (or acute syphilitic meningitis or neurorecurrence) is the onset of meningeal syphilis. The symptoms arise as a result of inflamed meninges, which eventually lead up to signs of meningitis.

"Treponema pallidum" invades the nervous system within three to eighteen months after the primary infection. The initial series of events is asymptomatic meningitis, which can remain in the human body system and produce more damage within the body. Every form of neurosyphilis has meningitis as a component; however, every case differs in severity. The individual is infected with syphilis through a gram negative bacteria that only humans can obtain. Syphilis has four stages of infection, which are primary, secondary, latent, and tertiary. If syphilis is not treated, the disease can affect various other systems in the body, including the brain, heart, and vessels. The infection of the heart and vessels leads to meningovascular syphilis, which is usually presented during the secondary stage of syphilis. If syphilis is prolonged, it can affect the nervous system, which is known as neurosyphilis. Meningeal syphilis is a component of neurosyphilis, which usually occurs in the tertiary stage of syphilis.

Congenital syphilis is that which is transmitted during pregnancy or during birth. Two-thirds of syphilitic infants are born without symptoms. Common symptoms that develop over the first couple of years of life include enlargement of the liver and spleen (70%), rash (70%), fever (40%), neurosyphilis (20%), and lung inflammation (20%). If untreated, late congenital syphilis may occur in 40%, including saddle nose deformation, Higoumenakis sign, saber shin, or Clutton's joints among others. Infection during pregnancy is also associated with miscarriage.

In syphilis, the gumma is caused by reaction to spirochaete bacteria in the tissue.

It appears to be the human body's way to slow down the action of this bacteria, it is a unique immune response that develops in humans after the immune system fails to kill off syphilis.

It can be treated with systemic antiviral drugs, such as aciclovir or valganciclovir. Foscarnet may also be used for immunocompromised host with Herpes simplex and acyclovir-resistant Herpes simplex.

Prognosis depends on the pathogen responsible for the infection and risk group. Overall mortality for "Candida" meningitis is 10-20%, 31% for patients with HIV, and 11% in neurosurgical cases (when treated). Prognosis for "Aspergillus" and coccidioidal infections is poor.

Progressive disseminated histoplasmosis is an infection caused by Histoplasma capsulatum, and most people who develop this severe form of histoplasmosis are immunocompromised or taking systemic corticosteroids. Skin lesions are present in approximately 6% of patients with dissemination.

The duration of the visible blistering caused by varicella zoster virus varies in children usually from 4 to 7 days, and the appearance of new blisters begins to subside after the fifth day. Chickenpox infection is milder in young children, and symptomatic treatment, with sodium bicarbonate baths or antihistamine medication may ease itching. It is recommended to keep new infants from birth up to age 6 months away from an infected person for 10 to 21 days because their immune systems are not developed enough to handle the stress it can bring on. Paracetamol (acetaminophen) is widely used to reduce fever. Aspirin, or products containing aspirin, should not be given to children with chickenpox, as it can cause Reye's Syndrome.

In adults, the disease is more severe, though the incidence is much less common. Infection in adults is associated with greater morbidity and mortality due to pneumonia (either direct viral pneumonia or secondary bacterial pneumonia), bronchitis (either viral bronchitis or secondary bacterial bronchitis), hepatitis, and encephalitis. In particular, up to 10% of pregnant women with chickenpox develop pneumonia, the severity of which increases with onset later in gestation. In England and Wales, 75% of deaths due to chickenpox are in adults. Inflammation of the brain, or encephalitis, can occur in immunocompromised individuals, although the risk is higher with herpes zoster. Necrotizing fasciitis is also a rare complication.

Varicella can be lethal to adults with impaired immunity. The number of people in this high-risk group has increased, due to the HIV epidemic and the increased use of immunosuppressive therapies. Varicella is a particular problem in hospitals, when there are patients with immune systems weakened by drugs (e.g., high-dose steroids) or HIV.

Secondary bacterial infection of skin lesions, manifesting as impetigo, cellulitis, and erysipelas, is the most common complication in healthy children. Disseminated primary varicella infection usually seen in the immunocompromised may have high morbidity. Ninety percent of cases of varicella pneumonia occur in the adult population. Rarer complications of disseminated chickenpox include myocarditis, hepatitis, and glomerulonephritis.

Hemorrhagic complications are more common in the immunocompromised or immunosuppressed populations, although healthy children and adults have been affected. Five major clinical syndromes have been described: febrile purpura, malignant chickenpox with purpura, postinfectious purpura, purpura fulminans, and anaphylactoid purpura. These syndromes have variable courses, with febrile purpura being the most benign of the syndromes and having an uncomplicated outcome. In contrast, malignant chickenpox with purpura is a grave clinical condition that has a mortality rate of greater than 70%. The cause of these hemorrhagic chickenpox syndromes is not known.

Congenital syphilis in the newborn can be prevented by screening mothers during early pregnancy and treating those who are infected. The United States Preventive Services Task Force (USPSTF) strongly recommends universal screening of all pregnant women, while the World Health Organization recommends all women be tested at their first antenatal visit and again in the third trimester. If they are positive, it is recommend their partners also be treated. Congenital syphilis is still common in the developing world, as many women do not receive antenatal care at all, and the antenatal care others receive does not include screening. It still occasionally occurs in the developed world, as those most likely to acquire syphilis (through drug use, etc.) are least likely to receive care during pregnancy. Several measures to increase access to testing appear effective at reducing rates of congenital syphilis in low- to middle-income countries. Point-of-care testing to detect syphilis appeared to be good although more research is needed to assess its effectiveness and into improving outcomes in mothers and babies.

Disseminated disease refers to a diffuse disease-process, generally either infectious or neoplastic. The term may sometimes also characterize connective tissue disease.

A disseminated infection, for example, has extended beyond its origin or nidus and involved the bloodstream to "seed" other areas of the body. Similarly, one can view metastatic cancer as a disseminated infection in that it has extended into the bloodstream or into the lymphatic system and thus "seeded" distant sites (a process known as metastasis).

Disseminated disease often contrasts localized disease.

Chancroid is a bacterial infection caused by the fastidious Gram-negative streptobacillus "Haemophilus ducreyi". It is a disease found primarily in developing countries, most prevalent in low socioeconomic groups, associated with commercial sex workers. In the United States socioeconomic status has not been found to be a factor in the spread of sexually transmitted diseases.

Chancroid, caused by H. ducreyi has infrequently been associated with cases of Genital Ulcer Disease in the US, but has been isolated in up to 10% of genital ulcers diagnosed from STD clinics in Memphis and Chicago.

Infection levels are very low in the Western world, typically around one case per two million of the population (Canada, France, Australia, UK and US). Most individuals diagnosed with chancroid have visited countries or areas where the disease is known to occur frequently, although outbreaks have been observed in association with crack cocaine use and prostitution.

Chancroid is a risk factor for contracting HIV, due to their ecological association or shared risk of exposure, and biologically facilitated transmission of one infection by the other.

Eczema herpeticum is a rare but severe disseminated infection that generally occurs at sites of skin damage produced by, for example, atopic dermatitis, burns, long term usage of topical steroids or eczema. It is also known as Kaposi varicelliform eruption, Pustulosis varioliformis acute and Kaposi-Juliusberg dermatitis.

Some sources reserve the term "eczema herpeticum" when the cause is due to human herpes simplex virus, and the term "Kaposi varicelliform eruption" to describe the general presentation without specifying the virus.

This condition is most commonly caused by herpes simplex virus type 1 or 2, but may also be caused by coxsackievirus A16, or vaccinia virus. It appears as numerous umbilicated vesicles superimposed on healing atopic dermatitis. it is often accompanied by fever and lymphadenopathy. Eczema herpeticum can be life-threatening in babies.

CNS demyelinating autoimmune diseases are autoimmune diseases which primarily affect the central nervous system.

Examples include:

- Diffuse cerebral sclerosis of Schilder

- Acute disseminated encephalomyelitis

- Acute hemorrhagic leukoencephalitis

- Multiple sclerosis (though the cause is unknown, it is sure that immune system is involved)

- Transverse myelitis

- Neuromyelitis optica

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.

Uveitis may be an immune response to fight an infection inside the eye. While representing the minority of patients with uveitis, such possible infections include:

- brucellosis

- leptospirosis

- Lyme disease

- presumed ocular histoplasmosis syndrome

- syphilis

- toxocariasis

- toxoplasmic chorioretinitis

- tuberculosis

- Zika fever