See CDC

Cryptococcus neoformans is a fungus that lives in the environment throughout the world. People can become infected with C. neoformans after breathing in the microscopic fungus, although most people who are exposed to the fungus never get sick from it. C. neoformans infections are rare in people who are otherwise healthy; most cases occur in people who have weakened immune systems, particularly those who have advanced HIV/AIDS.

C Neoformans is monomorphic unlike other dimorphic pathogogens. It can be identified with India Ink (has a wide capsule) and is the leading cause of meningitis in AIDS patients. 

Treatment: 

Treatment is with amphotericin B or flucytosine

Fungi are nonmotile eukaryotes. They secrete exoenzymes into the environment, then absorb the digested nutrients. Most are saprophytes that decompose dead organic matter, but some are parasites of plants, animals, or humans.

Fungi, along with bacteria, are the principal decomposers in the biosphere. They break down organic materiasl and return the substances locked in those molecuels to circulation in the ecosystem. Fungi can break down cellulose na dlignin; lingin is an insoluble organic compound that is a major constituent of wood. By breaking down such substances, fungi release carbon, nitrogen, and phosphorus from living or dead organisms and make them available to other organisms.

Structure

Fungi are eukaryotes with a cell membrane that has ergosterol as a key component rather than cholesterol. This is an importance difference since many antifungal agents are directed towards ergosterol. Fungi also have a rigid cell wall that contains chitin as well as hyphae which are branching, threadlike tubular filaments.

Detection

Fungi can be detected by 1) microscopic examination with the use of fungal stains (ex.India ink) or with KOH which dissolves host tissue leaving alkali resistant fungi or by the unique morphology of fungi (e.g., hyphae), 2) culture (media that inhibits bacterial growth like Sabouraud’s agar), 3) DNA probes or 4) serology (detection of specific antibodies).

Classification and disease mechanisms: 

Fungi can cause health issues in numans by acting as allergens that trigger immune responses or by direct infection, usually of the skin or nails, or by producing toxins that are ingested.

Fungi are informally divided into unicellular yeasts and filamentous molds based on their overall appearance. Fungi are also sometimes classified as follows:

superficial mycoses which live on dead skin and hair and do not elicit an immune response. Superficial mycoses include Tinea versicolr, Tinea nigra, Black and White piedra which grow on hair shafts.

cutaneous mycoses which are caused by dermatophytes and infect keratinized skin, hair and nails. Cutaneous mycoses invoke an immune response. Diseases are very common and include ringworm or tinea (e.g., Tinea pedis).

–Dermatophytosis, (also called ringworm or tinea), is a common superficial fungal skin infection most often caused by Trichophyton, Microsporum, or Epidermophyton fungi and often treated using over-the-counter topical antifungal agents.

Tinea is a very common fungal infection of the skin. It is often called “ringworm” because the rash is circular, with a ring-like appearance.

Oral terbinafine is a first-line antifungal treatment for extensive skin infections, which typically occur in immunocompromised or older persons. Outbreaks of extensive, recalcitrant, and frequently terbinafine-resistant dermatophytosis in immunocompetent persons are ongoing in southern Asia because of the recently emerged dermatophyte Trichophyton indotineae (formerly Trichophyton mentagrophytes genotype VIII). T. indotineae typically causes tinea faciei, corporis, or cruris; easily spreads person-to-person; and has been reported globally, including in multiple US states. Laboratory identification requires advanced molecular techniques because culture-based methods cannot distinguish T. indotineae from other Trichophyton species. There is an emergence of antifungal-resistant T. indotineae as a cause of genital lesions and possible acquisition and transmission through sexual contact. Clinicians should be aware that visual inspection without diagnostic testing cannot reliably distinguish dermatophytosis from other causes of inflammatory skin conditions (e.g., contact dermatitis). Spivack “Potential Sexual Transmission of Antifungal-Resistant Trichophyton indotineae”

—-Tinea pdeis (foot) causes itching, scaling, flaking and sometimes blistering of the affected areas. Tinea pedis are fungi that are typically transmitted in moist communal areas where people go barefoot, such as around swimming pools or in showers and require a warm moist environment like the inside of a shoe to incubate. Tinea cruris (groin) also known as “crotch itch” or “jock itch” is a dermatophyte fungal infection of the groin region. Tinea corporis (body) is a superficial fungal infection of the arms and legs, especially on glabrous skin. However it may occur on any part of the body. It presents as a annual, marginated plaque with thin scale and clear center. Treatment includes grisofluvine, itraconazole and clotrimazole cream.

Ketoconazole is a synthetic imidazole antifungal drug that is used to treat fungal infections such as tinea.

Subcutaneous mycoses are lesions in deeper skin layers usually caused by a trauma such as a thorn. For example, sporotrichosis (“Rose grower’s disease”) typically occurs when one is pricked by a thorn which has the Sporothrix schenckii fungus agent. Other subcutaneous infections are Chromoblastomycosis and Mycetoma.

Systemic mycoses are inheritently infectious and include (1) Histoplasmosis otherwise known as “Darling’s” “cave” or “spelunker’s” disease. Histoplasmosis occurs in the midwest. Infection is due to inhalation of conidia or hyphal fragments which are phagocytized by pulmonary macrophages. It is usually found on bird dropping and is a dimorphic fungus in that it can exist in the yeast (e.g., macophages) or mold (e.g., soil) form. Treatment may include itraconazole and/or amphotericin B. (2) Blastomycosis otherwise known as “Gilchrist’s” or “Chicago” disease is endemic in Ohio and the Mississippi Valley. Treatment can again be amphotericin B. (3) Coccidioidomycosis otherwise known as “Posada-Wernicke” or “San Joaquin Valley vever” is endemic in California and Texas. Treatment can again include amphotericin

B. opportunistic mycoses are pathogenic in immunocompetent individuals and include (1) Aspergillosis such as A. fumigatus, A. flavus, A. niger are ubiquitous in damp basements and vegetation. It can cause blockage of airways from fungal masses. Treatment can include surgery, amphotericin B or itraconazole. (2) Cryptococcosis neoformans (3) Candidiasis is a dimorphic fungus with yeast on mucosal surfaces. It is actually part of one’s normal flora in skin, mouth and intestines and stays as yeast but it forms hyphae when invasive. Treatment includes cessation of antibiotic and can also include itraconzaole.

Most fungi are not pathogens but they can produce toxins and cause allergies (primarily IgE mediated). For example, spoiled peanuts and other grains contain coumarin derivatives produced by Aspergillus flavus and cause liver damage. Claviceps purpura also infects grains and produces lysergic acid diethylamide, commonly known as “LSD”.

Medically Important Fungus

Fungal infections kill more than 1.6 million people yearly, according to Global Action for Fungal Infections, a research and fundraising organization. Fungal infections are estimated to kill at least 1.6 million people yearly, according to Global Action for Fungal Infections, a research and fundraising organization. In the U.S., more than 75,000 people are hospitalized with fungal infections every year, the Centers for Disease Control and Prevention said.

WHO has said that some 19 species on the list merit urgent attention from public-health officials and drug developers. Four species were designated as threats of the highest priority: Aspergillus fumigatus, a mold found abundantly in nature; Candida albicans, which is commonly found in the human body; Candida auris, a highly deadly yeast; and Cryptococcus neoformans, a fungus that can cause deadly brain infections.

Fungi are adapting to rising temperatures in ways that may make them better suited to thrive in the human body, researchers said. And more people undergoing treatments that weaken their immune systems means a larger population vulnerable to severe fungal infections.

Aspergillus fumigatus: which most people inhale every day, can cause disease of the lungs but can also colonize other parts of the body including the brain, infectious-disease experts said. Hospitalizations related to severe Aspergillus infectionss are increasing.

Candida albicans causes oral thrush and vaginal yeast infections, and can also infect the blood, heart and other internal organs. The mortality rate of Candida auris, which often spreads in hospitals, can be as high as 60%, according to the CDC said.

Candidad albicans is normally present on the skin of the glans and can be a considered normal flora. The yeast can cause infection in certain cicumstances, especially when the patient has underlying conditions, poor hygiene, overgrowth, or changes in basline pH. Although yest infection is the most common cause, there are several other etiologies that exist and must be considered by the provider. These include the following infectious and noninfectious etiologies:

• Candidal species (most commonly associated with diabetes)
• Group B and group A beta-hemolytic streptococci
• Neisseria gonorrhea
• Chlamydia species
• Anaerobic infection
• Human papillomavirus
• Gardnerella vaginalis
• Treponema pallidum (syphilis)
• Trichomonas species
• Borrelia vincentii and Borrelia burgdorferiNoninfectious etiologies:
  • Poor personal hygiene (most common)
  • Chemical irritants (e.g.,  spermicides, detergents, perfumed soaps and shower gels, fabric conditioners)
  • Edematous conditions, including congestive heart failure (right-sided), cirrhosis, and nephrosis
  • Drug allergies (e.g., tetracycline, sulfonamide)
  • Morbid obesity
  • Allergic reaction (condom latex, contraceptive jelly)
  • Fixed-drug eruption (sulfa, tetracycline)
  • Plasma cell infiltration (Zoon balanitis)
  • Autodigestion by activated pancreatic transplant exocrine enzymes
  • Trauma
  • Neoplastic conditions

Some fungal infections can be passed on sexually – these include Thrush, Jock Itch (like athletes foot, but around the genitals) and Balanitis (inflammation of the end of the penis). Infectious etiologies of balanitis include certain fungi like yeast and certain bacteria or viruses (including those that cause STDs such as gonorrhea).

Affecting the Nervous System

Coccidioides species (Valley Fever): This fungus causes a condition that is often called “Valley Fever” in the U.S. Southwest. The morphology of Coccidioides is very distinctive. At 25C, it forms a most white to brown colony with abundant branching, septate hypae. These hyphae fragment into thick-walled blocklike arthroconidia (arthrospores) at maturity. This is a true systemic fungal infection of high virulence, as opposed to an opportunistic infection. It usually beings with pulmonary infection but can disseminate quickly throught the body. Coccidioidomycosis of the meniges is the most serious manifestation.

There are two species that casue this disease, found in different areas. C. immitis casues disease in California and C. posadasil in northern Mexico, Central and South America adn the American Southwest, especially Arizona. Sixty percent of all infections occur in Arizona. The highest incidence of coccidioidomycosis is estiamted at 100k cases per year.

Most people who breathe in the spores don’t get sick, but some people do. Usually, people who get sick with Valley fever will get better on their own within weeks to months, but some people will need antifungal medication.

See CDC

Fonsecaea spp.:

–F. monophora is known to infect the CNS and cause fungal brain abscess. Definitive identificaion is by molecular methods. Targeting hte ITS region of 18s rDNA, the unviersal fungal barcode, is usually sufficient. (Xess “Molecular identificaiton of Fonsecaea monophora, Novel agent of fungal brain abscess” Emerging Infectious Diseases, 30(6), June 2024).

(Xess “Molecular identificaiton of Fonsecaea monophora, Novel agent of fungal brain abscess” Emerging Infectious Diseases, 30(6), June 2024) disclosea a 3 year old pIndian patient experiencing headaches and seizures diagnosed with a fungal infection, initially misidentified as Cladophialophora bantiana. Follow up sequencing identified the isolate to be Fonsecaea monophora fungus. Contrast enhanced omputed tomography of chest and abdomen relevaed well defined nodules int he right lung and boht lobes of the liver. Cerebrospinal fluid examination showed a glucose level of 51 mg/dL (references range 40-70 mg/dL), protein level of 82 mg/dL (reference range 1-2-60 mg/dL) and leukocyte count of 45 cells/mm3 (reference range 0-20 cells/mm3) with 22% neutrophils. Persistent eosinophilia (up to 31%) was found.

–F. pedrosoi fungus: has been shown to cause brain abscesses.

Non-Aspergillus filamentous fungi:

Scedosporium spp. and Lomentospora prolificans: are non-Asperigillus filamentous fungi causing increasingly recognized invasive fungal disease (IFD) in both immunocompromised and immunocompetent patients. Scedosporium sppl includes S. apiospermum complex species, which includes S. apiospermum sensu stricto and S. boydii; L. proificans was previously known as S. prolifcans. In immunocompetent patients, localized infections have been described, such as mycetomas, osteoarticular infections, or central nervous system (CNS) infections after near-drowings. In immunocompromised hosts, scedosporiosis and lomentosporiosis mainy affect the lungs and CNS or are disseminated. Scedosporium spp. and L. prolificans can also cuase non-CNS vascular infections. Solid organ transplant was the main host risk factor.  The ability of molds to invade vessels is known; angioinvasion is a kety pathogenic characteristic of invasive asperillosis and mucormycosis as well. (Bronnimann, “Deciphering unexpected vascular locaitons of Scedosporium spp. and Lomentospora prolificans fungal infections, France” Emerging infectios Diseases, 30(6), 2024).

Affecting the Respiratory System

Coccidioidomycosis, histoplasmosis, and blastomycosis are underdiagnosed fungal diseases that often mimic bacterial or viral pneumonia and can cause disseminated disease and death. These diseases are caused by inhalation of fungal spores that have distinct geographic niches in the environment (e.g., soil or dust), and distribution is highly susceptible to climate changes such as expanding arid regions for coccidioidomycosis, the northward expansion of histoplasmosis, and areas like New York reporting cases of blastomycosis previously thought to be nonendemic. The national incidence of coccidioidomycosis, histoplasmosis, and blastomycosis is poorly characterized. CDC uses the National Notifiable Diseases Surveillance System (NNDSS) to track coccidioidomycosis and histoplasmosis from states where the diseases are reportable by mandate and from those where cases are reported voluntarily. Reportable fungal diseases are designated by the state or jurisdiction and require health care professionals and laboratories to notify public health departments of cases. Coccidioidomycosis, histoplasmosis, and blastomycosis cause substantial illness in the United States, particularly coccidioidomycosis in terms of the number of cases reported (20,061). Although substantially fewer histoplasmosis and blastomycosis cases were reported, surveillance for these two diseases occurred in fewer states than for coccidioidomycosis. Even in states where histoplasmosis and blastomycosis are reportable, missed cases are likely because milder illnesses might be less commonly detected than mild coccidioidomycosis, in part because of the broader and less concentrated geographic distributions of histoplasmosis and blastomycosis than of coccidioidomycosis (37,38). In 2019, a total of 249 histoplasmosis and 147 blastomycosis cases resulted in hospitalization. Coccidioidomycosis, histoplasmosis, and blastomycosis are frequently misdiagnosed as community-acquired pneumonia or other acute lower respiratory tract infections. Misdiagnoses can lead to inappropriate therapy with antibacterial medications and delayed antifungal treatment. See CDC

Invasive pulmonary-aspergillosis (IPA): has been increasingly reported as a serious and potentially lethan complicaiton in pateints who require ICU treatment for severe influenza or COVID 19 assocaited acute respiratory failure. During the COVID-19 pandemic and pervious epidemic waves of influenza, secondary pulmonary mold infections and especially aspergillosis gained increasing attention. Alhtough exact ICU admission rates and treatment characteristics (e.g., mechnicial ventiliation, hemodynamic shock) in the context of HFRS are lacking, hantaviruses ahve also been shown to cause direct damage to the airway epithelium, potentially enablig aspergillus to invade tissue. Krause, “Invasive Pulmonary Asperillosis in Critically Ill Patients with Hantavirus Infection, Austria” Emerging Infectious Diseases, 39)6), June 2024).

Blastomycosis: 

Coccidioidomycosis (Valley Fever): is caused by a fungus that lives in dust and soild, particularly in the SW United States. Symptoms include headaches, night sweats, muscle and joint pain.

Choanephora infundibulifera: can cause rhinosinusitis, aprticular in immunocompromised patients. Max, “Choanephora infundibulifera Rhinosinusitis in Man with Acute Lmphoblastic Leukemia, Tennesseee, USA” Emerging Infectious Diseases, 39(6), June 2024).

Histoplasmosis: is caused by a fungus that thrives in bird and bat droppings. It affects the lungs and respirtary tract. In the United States, an estimated 60% to 90% of people who live in areas surrounding the Ohio and Mississippi River valleys. See CDC.  See Dr.Fungus

Mucoymocetes: are fungi commonly found in soil or decarying matter. The fungal conidia may be inhaled form the air or introduced by skin trauma. Most humans are not affected by these spores, but those with impaired immune systomes are a great host for the fungus. In inhaled mucormycosis, hyphae invade the tissues and blood vessels of the sinuses, lungs, eyes and face. The infection is treated with intravenous antifungal medications. The fugaus spreads rapdily, often requring extensive repeated surgeries to restore affected facial bones and tissues. If not aggressively treated, the fungal infection may spread into the brain and is frequently fatal.

Pneumocystis Pneumonia (PCP) is considered one the most frequent opportunistic infections in patients with AIDS. However, this fungal infection does not limit itself to this patient population. The majority of the patients who get PCP have a weakened immune system which includes: cancer patients, people taking corticosteroids for long term (e.g. for chronic lung diseases), transplant patients, and patients with inflammatory/autoimmune diseases. PCP is a serious infection that is brought by the fungus Pneumocystis jirovecii. It is spread through the air or droplet contact. Healthy adults can carry the Pneumocystis fungus in their lungs and have no symptoms, and it can spread to other people, including those with weakened immune systems. See CDC

Affecting Wildlife:

Fungal pathogens have been implicated in wildlife population declines, posing a substantial challenge to the conservation of many species. In reptiles, most fungal pathogens are with the genera Namnizziopsis, Paranamnizziopsis and Ophidiomyces, members of the order onygenales. Of thsoe general, the most well documeted genus in wild reptiles is Ophidiomyces, consisting of the single species O. ophidiicola, which is respnosible for ophidiomycosis, also called sanke fungal disease. (Blanvillain, “Paranannizziopsis spp infection in wild vipers, Europe” Emerging Infectious Diseases, 30(5), May 2024).

Parannizziopsis spp. 

Blanvillain, (“Paranannizziopsis spp infection in wild vipers, Europe” Emerging Infectious Diseases, 30(5), May 2024) rope. They swabbed the ventral and dosal areas of the snakes in duplicae using a premoistened, sterile polyester-tipped applicator from Puritan, sotred frozen swab samples at -020C, extracted DNA from the samples uing PrepMan Ultra Sample preparation Reagent rom ThermoFisher as well as Qiagen blood and Tissue Kit. disclsoes describe the detection of Parannizziopsis sp. fungas in a wild population of vipers in Europe.

Affecting Plants (and sometimes mammals):

Mucorales Group: consists of over 260 sepcies in 55 genera that are ubiquitous in wet, organic evenironments, About 40 species are clincially isgnificant, cuasing invasive infection (mcormycosis) cheifly in persons with diabets and immuno-compromising conditions.

–Genus Choanephora (family Choanephoracae): contains 2 species, C. infundibulifera and C. cucurbitarum. These species are saprophtes or parasites of plants that can promote spoilage and disease. C. cucrbitarum, the more commonly recognized species, causes wet blight, flower rot blight, and leaft blight, chiefly on summer squash and other cucurbits.

The optimal treatment for infections caused by Choanephora speies is unkown. The minimal inhibitory conentraiton correlation with treamtnet response in vivo is unkown, but he in vitro antifungal minimal inhibitory conentrations against this isolate suggest amphoteric B might ahve greater activity than posaconazole and isavuconazole, which are used to treat mucormycosis caused by other species. Max, “Choanephora infundibulifera Rhinosinusitis in Man with Acute Lmphoblastic Leukemia, Tennesseee, USA” Emerging Infectious Diseases, 39(6), June 2024).

—-C. infundibulifera: infrequently causes plant disease but has been implicated in twig and leaf rot and blossom blight. On potato-carot or potato dexrose agar, colonies grow rapidly at 25C with abundant white, pale-yellow, or brown mycelia and sporangiophores, with sporangia arising from substrate mycelium or nonsepttate, unbrached, hyaline aerial hyphae. Definitive identificaiton is based on morphology and sequencing of the nuclear ribosomal internal transcribed spacer region and the D1 nad D2 domains on the 28S rRNA gene. (Max, “Choanephora infundibulifera Rhinosinusitis in Man with Acute Lmphoblastic Leukemia, Tennesseee, USA” Emerging Infectious Diseases, 39(6), June 2024).

Max, “Choanephora infundibulifera Rhinosinusitis in Man with Acute Lmphoblastic Leukemia, Tennesseee, USA” Emerging Infectious Diseases, 39(6), June 2024) disloses an 18 year old man with systemic symptoms and lymphadenopathy who received a diagnosis of ealry T cell precursor acute lymphoblastic leukemia. Induction chemotherpay was complicated by rhinosinusitis linked to speies of Alternaria and Curvularia and presumed funal pneumonia. The treatment consisted of debridement of his nasal and sinus passages and advinistration of liposomal amphotericin B, followed by oral posaconazole for 5 monhts. Thereafter, posaconazole secondary prophylaxis was prescirbed druing severe neutrophenia. Later on computed tomography of the sinuses showed evdience of rhinosinusiti. A magnetic resonance imaging scan revealed soft tissue swelling, right nodularity and irregular nasal septal mucosal thinning, sinus mucosal thickening, and enhanced right jugular lymph nodes. Computed tomography of the chest yeilded unremarkable resutls. The patient udnerwent nasal endoscopy and debridement, hmatoxyline and iosin-stained sections from a biopsy of the right nasal septum revealed necrotic tissue with numerous hyaline fungal elements with a wide, ribbon-like appearance. Two isolates form a fungal culture showed a curvularia speies on a lactophenol cotton blue stain. Further testing by matrix-assisted laser desorption/ionization time of flight mass spectrometry (Vitek MS V3.2; bioMerieux) revealed the isolate to be Curvalaria lunata. The other isolated was determeind to be Choanephora infundibulifera by phenotypic characterization and BAST searches using the nuclear ribosomal internal transcribed spacer region and the D1 and D2 domains of the 28S rRNA gene. BLAST search reuslts matched with srtains C. infundibulifera, C. infundibulifera.

Treatment:

There are four classes of antifungal medicines for invasive fungal disease, and most drugs in these classes are toxic, even at low doses, infectious-disease experts say. A new class to treat severe diseases hasn’t been approved in over 20 years. Fungal infections receive less than 1.5% of all infectious-disease research funding.

Several antifungal drugs in development, including Scynexis’ ibrexafungerp and Pfizer’s fosmanogepix, have been shown in clinical trials to be effective against Aspergillus and Candida infections. Cidara Therapeutics Inc. has submitted its drug rezafungin for Food and Drug Administration approval to treat Candida infections, including severe disease; and F2G Ltd. said its antifungal olorofim had been found effective at eradicating Aspergillus and other rare molds in a Phase 2 clinical trial.

Helpful Links:  CDC

Scabies is caused by skin infestation with the mite Sarcoptes scabiei which is an arthropod (member of the class Arachnida). Like many other infectious diseases, it is transmitted by contact (McCarthy, “Scabies: more than just an irritation” (2003). Poverty and overcorwding are often concomitant. However, scabies is not influenced by hygiene practices or the availability of water.

Life Cycle: The lifecycle of S scabiei begins with the mating of adult male and female mites, after which the adult male dies, while the female beings to lay eggs in the skin buttrow for her lifespan of 4-6 weeks. After 3-4 days the eggs hatch and six legged larvae cut through the roof of the burrow to reach the skin surface. They then dig burrows and pass through two further developmental stages before multing into either males or females.

Symptoms: Classical scabies presents as an intesnely pruirtic rash, particularly involving those region of the skin best suited for the mite, such as the interditial web spaces, wrists, anterior axilary folds, periumbilical skin, pelvic girdle including buttocks, ankles, the penis and the perioreolar region in femails. . Onset of these symptoms in a host with no prior infestation occurs after 3-4 weeks. Patients complain that the pruritis is more intense at night.

Diagnosis: can be made based on a typical history of pruritis, worse at night and the distribution of inflammatory papules. Confirmation can be made by gently scraping the skin off the burrow with a lunt scalpel blade, and placing the material on a glass slide with a drop of 10% potassium hydroxide or minieral oil, and seeking mites, eggs by low power microscopy.

Treatment: Permethrin 5% Lyclear) is considered the treatment of choice in the US.

Helminths that parasitize humans are diverse, ranging from barely visible roundworms (0.3 mm) to huge tapeworms (25 m long). Worm infection usually provokes an increase in granular leukocytes called eosinophils, which have a specialized capacity to destroy multicellular parasites. This increased, termed eosinophilia, is a hallmark of helminthic infection and is detectable in blood counts. Helminthic infections may be acquired through the fecal-oral route or through penetration of the skin. Helminths have numermous adaptations that allow them to survive in their host such as specialized mouthparts for attaching to tissue and for feeding as well as enzymes with which they liquefy and penetrate tissues. The damage they cause in the host is very often the result of the host’s response to the presence of the invader. Diagnosis includes the “O&P test” which is microscopic examination of a stool sample to look for ova or parasites. A differential blood count showing increased eosinophile and serological tests indicating sensitivity to helminthic antigens all provide indirect evidence of worm infection. A history of travel to the tropics or immigation from those regions is also helpful, even if it occurred years ago, because some flukes and nematodes persist for decades. There are no vaccines but prophylactic treatment twice a year with antihelminthic drugs has been shown to keep people healthy. Some anihlminthic drugs suppress a metabolic process that is more important to the worm than to the human.

Nematodes (Roundworms)

Intestinal roundworms acquired by ingestion

–Enterobius vermicularis (pinworm) The Pinword (Enterobius vermicularis) is is the most common worm disease of children in temperate zones. It is transmitted by the fecal-oral route (ingestion of ova) and treatment is mebendazole. Pinworms are white, parasitic worms that can live in the large intestine of humans. They are about one-half inch long. While the infected person sleeps, female pinworms leave the intestinal tract and lay their eggs on the skin around the anus. The eggs are laid in a sticky, jelly-like substance that, along with the wriggling of the female pinworm, causes severe itching. Fresly deposited eggs have a sticky coating that causes them to lodge beneath the fingernails and to adhere to fomites. Upon drying, the eggs become airbone and settle in house dust. Eggs are ingested from contaminated food or drink and from self inoculation from one’s own fingers. Eggs hatch in the small intestine and release larvae that migrate to the large intestine. When one member of the famaily is diagnosed, the entire family should be tested and/or treated because it is likely that multiple members are infected. Pinworms are thin and white, measuring about 1/4 to 1/2 inch (about 6 to 13 millimeters) in length.  The medications used for the treatment of pinworm are either mebendazole, pyrantel pamoate, or albendazole. Any of these drugs are given in one dose initially, and then another single dose of the same drug two weeks later. Pyrantel pamoate is available without prescription. The medication does not reliably kill pinworm eggs. Therefore, the second dose is to prevent re-infection by adult worms that hatch from any eggs not killed by the first treatment. Health practitioners and parents should weigh the health risks and benefits of these drugs for patients under 2 years of age.Mayo Clinic. See CDC  See NY Health Dept

–Ascaris lumbricoides can be a particular problem with persons who have AIDS. Infection is again by ingestion of ova and the worm may cause intestinal obstruction. Infective stages are found where human feces are used as a fertilizer. Ascaris lumbricoides is a nematode, or roundworm, that parasitizes the human gastrointestinal tract. Worldwide, ascariasis is among the most common helminthic human infections with an estimated 800 million to 1.2 billion people infected, and it causes more than 60,000 deaths annually,  In fact, ascariasis is considered one of the “neglected tropical diseases,” or NTDs – a diverse group of infectious diseases that exist in tropical and subtropical environments in 149 countries across the world, and which affect more than 1 billion individuals, costing developing economies billions of dollars each year.  In the life cycle of A. lumbricoides, the definitive host for infection is human and the mode of transmission is the fecal-oral transfer of embryonated eggs. After oral ingestion, via contaminated food or water, the eggs hatch in the small intestine within 4 days and release larvae. See Shaw

–Dracunculiasis (Guinea worm disease), caused by the parasite Dracunculus medinensis, is acquired by drinking water containing small crustacean copepods (water fleas) infected with D. medinensis larvae. Recent evidence suggests that the parasite also appears to be transmitted by eating fish or other aquatic animals. About 1 year after infection, the worm typically emerges through the skin on a lower limb of the host, causing pain and disability. No vaccine or medicine is available to prevent or treat dracunculiasis. Eradication relies on case containment* to prevent water contamination and other interventions to prevent infection, including health education, water filtration, treatment of unsafe water with temephos (an organophosphate larvicide), and provision of safe drinking water.  Cama, CDC

–Trichuris trichiura (whipworm) The whipworm (Trichuris trichiura): has its highest incidence in the areas of the tropics and subtropics that have poor sanitation. It is again transmitted by ingestion of the ova. Symptoms are asymptomatic unless the worm burden reaches a certain point at which time there is anemia, eosinophilia and bloody diarrhea. Transmission occurs where sanitation is poor and human feces are used for fertilizer.  Symptoms include localized hemorrhage of the bowel caused by worms burrowing and piercing intestinal mucosa. Thsi can also provide a portal of entry for secondary bacterial infection. Heavier infections can cause dysentery, loss of muscle tone and rectal prolapse, which can prove fatal in children.  An estimated 604-795 million people in the world are infected with whipworm. Whipworms live in the large intestine and whipworm eggs are passed in the feces of infected persons. If the infected person defecates outside (near bushes, in a garden, or field) or if human feces as used as fertilizer, eggs are deposited on soil. They can then mature into a form that is infective. Whipworm infection is caused by ingesting eggs. This can happen when hands or fingers that have contaminated dirt on them are put in the mouth or by consuming vegetables or fruits that have not been carefully cooked, washed or peeled. See CDC  Trichiura has a worldwide distribution, principally within the tropical and subtropical zones, although it may have been more widely distributed in the past. However, with improvements in sanitation and public health in the richer countries, it has been largely eliminated from areas such as Southern USA, Japan, and much of the Mediterranean basin. See Horton.  Trichuris trichiurareceived the common name of whipworm from their distinctive body shape. Whipworms have an elongated anterior end that contains the mouth and esophogus that stretches into a thread-like point.Trichuris trichiurareceived the common name of whipworm from their distinctive body shape. Whipworms have an elongated anterior end that contains the mouth and esophogus that stretches into a thread-like point.Trichuris trichiurareceived the common name of whipworm from their distinctive body shape. Whipworms have an elongated anterior end that contains the mouth and esophogus that stretches into a thread-like point.

Intestinal roundworms usually acquired by passage through skin

–Necator americanus and Ancylostoma duodenale usually penetrate the skin of the legs and feet (“ground itch”) and are usually found where the soil is shaded, but warm and the air is humid. Wearing shoes helps prevent exposure. Treatment is mebendazole or iron therapy to treat anemia. Ancylostoma brziliense is a dog and cat hookworm that penetrates human (inadvertant host) skin but cannot develop further. People often get infected after dogs have been brought to the beach.

–Strongyloides stercoralis (strongyloidiasis) is a particular problem for AIDS patients. Treatment is with thiabendazole. 

Tissue  Nemathelminths (Roundworms)

–Trichinella spiralis cause trichinosis after eating poorly cooked meat which contains encysted larval forms. No eggs are involved (just larvae)  in their life cycle. Freezing meat for longer than 20 days in a home freezer will kill larvae. 

–Toxocara canis and T. cati have a similar life cycle to A. lumbilcoides in humans. Corticosteroids may be helpful in treatment.

–wucheretia bancrofti and Brugia malayi are transmitted by mosquitoes and are not endemic to the US.

–onchocera volvulus are transmitted by blackflies and cause Onchocerciasis (river blindness) and are not endemic to the U.S.  see WHO.  Onchocerca volvulus,is spread by the bite of an infected Simulium blackfly. It is also called river blindness because the fly that transmits infection breeds in rapidly flowing streams, mostly near remote rural villages, and the disease that is caused by O. volvulus following repeated bites from infected blackflies can lead to blindness.

Cestodes (Tapeworms)

Tapeworms are long (mm to meters) and have an extensive reproductive system (proglottids). If man is the definitive host, disease is minor but if man is the intermediate host serious disease may develop. All tapeworms are hermophrodditic, with male and female reproductive organs present on each mature proglottid. Taeniasis is the infection of humans with the adult tapeworm of Taenia saginata or Taenia solium. Humans are the only definitive hosts for T. saginata and T. solium. Eggs or gravid proglottids are passed with feces,  The eggs can survive for days to months in the environment. Cattle (T. saginata) and pigs (T. solium) become infected by ingesting vegetation contaminated with eggs or gravid proglottids,  See CDC

–Taenia saginata (beef) contain sucking discs but no hooklets like the pork tapeworm. Niclosamide is the drug of choice for treatment.

–Taenia solium (pork):  Taenia solium (pig tapeworm) is a tapeworm and is usually 5 meters long and have a scolex swith hooklets and suckers to attach to the itnestine. T. solium is distributed worldwide but is concentrated in areas where human live in close proximity with pigs or eat undercooked pork. The cycle starts in the pigs, when the eggs hatch in the small intestine and the released larvae migrate throughout the organs. Ultimately, they encyste in the pig’s muscles, becoming cysticerci, young tapeworms that are the infective stage for humans. When humans ingest a live cysticercus in pork, the coat is digested and the organism is flushed into the intestine, where it firmly attaches by the scolex and develops into an adult tapeworm. Infection with T. solium can take another form when humans ingest the tape-worm eggs rather than infected meat. Then the human, instead of the tapeworm in the gut, becomes the host of the encysted alrvae, or cysticerci, leading to cysticercosis, one of the five neglected parasitic infections in the U.S. It is estimated that thens of thousands of Latinos living in the U.S. are affected by cysticercosis. Niclosamide can be used to treat it. Adult worms may cause mild gastrointestinal symptoms or passage of a motile segment in the stool. The tapeworm Taenia (T.) solium can be responsible for two different conditions: taeniasis and cysticercosis. Taeniasis is infection with an adult tapeworm, while cysticercosis is infection with larval stages (of T. solium) in body tissues. Taeniasis occurs only in the human host, after ingestion of undercooked pork infected with cysticerci. In taeniasis an adult worm is present in the intestine, and the infestation is usually asymptomatic and generally recognized when segments of proglottids are found in stool specimens. Cysticercosis is caused by ingestion of food contaminated with feces, or by autoinfection. In the latter case, a human infected with adult T. solium can ingest eggs produced by that tapeworm, either through fecal contamination or, possibly, from proglottids carried into the stomach by reverse peristalsis. Once eggs are ingested, oncospheres hatch in the intestine invade the intestinal wall, and migrate to striated muscles, as well as the brain, liver, and other tissues, where they develop into cysticerci. Cysticercosis is usually asymptomatic unless larvae invade the central nervous system, resulting in neurocysticercosis, which can cause seizures and various other neurologic signs.  Intestinal infection is treated with prazincuantel 5 to 10 mg/kg orally as a single dose to eliminate adult worms. See Merk Manual.  See Gangemi

–Diphyllobothrium latum (fish) results from eating improperly cooked fresh water fish (can occur in Florida). Diphyllobohrium latam has an intermediate host in fish. It is common in the Great Lakes, Alaska and Canada. It develops in the intestine and can cause long-term symtpoms. It can be transmitted in raw food such as sushi and sashimi made form salmon. It is the largest human tapeworm known, growing up to 30 feet. Diphyllobothrium latum and related species (the fish or broad tapeworm), the largest tapeworms that can infect people, can grow up to 30 feet long. Several other Diphyllobothrium species infect humans, but less frequently.  Most infections are asymptomatic. However symptoms can include abdominal discomfort, diarrhea, vomiting, and weight loss. Vitamin B12 deficiency leading to pernicious anemia may occur. Complications include intestinal obstruction and gall bladder disease caused by migration of proglottids. Diagnosis is made by identification of eggs or segments of the tapeworm in a stool sample with a microscope. Eggs are usually numerous, but more than one stool sample may be needed to find them. You got infected by eating raw or undercooked fish. Examples of fish include salmon, trout, perch, walleyed pike, and other species — usually freshwater fish. Some fish such as salmon live in both fresh and salt water and can harbor Diphyllobothrium larvae. Lightly salted, smoked, or pickled fish also may contain infectious organisms.  Effective medications are available to treat Diphyllobothrium infection (praziquantel or niclosamide are used most often). See CDC

–Echinococcus ganulosis (dog tapeworm): Man is an accidental/inadvertant host. Echinococcosis is a parasitic disease caused by infection with tiny tapeworms of the genus Echinocococcus. Echinococcosis is classified as either cystic echinococcosis or alveolar echinococcosis. Cystic echinocccosis (CE), also known as hydatid disease, is caused by infection with the larval stage of Echinococcus granulosus, a ~2–7 millimeter long tapeworm found in dogs (definitive host) and sheep, cattle, goats, and pigs (intermediate hosts). Although most infections in humans are asymptomatic, CE causes harmful, slowly enlarging cysts in the liver, lungs, and other organs that often grow unnoticed and neglected for years. Alveolar echinococcosis (AE) disease is caused by infection with the larval stage of Echinococcus multilocularis, a ~1–4 millimeter long tapeworm found in foxes, coyotes, and dogs (definitive hosts). Small rodents are intermediate hosts for E. multilocularis. Although cases of AE in animals in endemic areas are relatively common, human cases are rare. AE poses a much greater health threat to people than CE, causing parasitic tumors that can form in the liver, lungs, brain, and other organs. If left untreated, AE can be fatal.  See CDC.

–Hymenolpsis: species are small tapeworms and are the most common human tapeworm infections in the word (however in U.S. is only 0.4%). They follow a life cycle where the adult matures in the human intestine, eggs are released into the environment, eggs are then eaten by grazing animals, larval forms and incyst in tissue and then humans eating animal flesh are infected. People can also ingest the eggs, which become larval cysts in their tissues. Hymenolepiasis is caused by two cestodes (tapeworm) species, Hymenolepis nana (the dwarf tapeworm, adults measuring 15 to 40 mm in length) and Hymenolepis diminuta (rat tapeworm, adults measuring 20 to 60 cm in length). Hymenolepis diminuta is a cestode of rodents infrequently seen in humans and frequently found in rodents. Hymenolepsis nana, known as the “draft tapeworm” because it is only 1-540 mm in lenght, and H. diminuta (rat tapeworm) which is usually 20-60 cm in lenght as an adult. Hymenolepis nana is the most common cause of all cestode infections, and is encountered worldwide. In temperate areas its incidence is higher in children and institutionalized groups. Hymenolepis diminuta, while less frequent, has been reported from various areas of the world. Hymenolepis nana and H. diminuta infections are most often asymptomatic. Heavy infections with H. nana can cause weakness, headaches, anorexia, abdominal pain, and diarrhea.  See CDC

Trematodes (Flukes and Schistosomes)

Trematodes are hermaphroditic with both male and female reproductive organs in a single body, with the exception of schistosomes. They are broad, leaf-like flat worms. 2 intermediate hosts are required; snail and then man.

Three  schistosomes most frequently associated with human disease are mansoni, haematobium and japonicum. They collectively produce the disease schistosomiasis.  The female lives in the ventral groove of the male for life. The avian species is acquired by wading in fresh water where aquatic birds frequent.

Blood flukes (Schistosomiasis): When liver swelling or malfunction is accompanied by easinophilia, schistosomiasis should be suspected. Shistosomes are trematodies or flukes but they are more cylindrical than flat. The life cycle is complex and begins when infected humans release eggs into irrigation fields or ponds, either by deliberate fertilization with excreta or by defecating or urinating direclty into the water. The disease is endemic to 74 countries located in Afica, South America, the Middle East and the Far East. Schistosomiasis (including the urinary tract form) is the second most prominent parasitic disease after malaria, probably affecting 200 millin people at any one time worldwide.

–-Schistosomiasis mansoni: is a severe public health problemin many tropic countries, affecting more than 200 million worldwide. Two Schistosoma mansoni adult worm proteins, Sm31 and Sm32 have been found to be highly immunogenic in mice and humans and have also been proposed as potential serodiagnostic antigens for detection of infection by S. mansoni, Schistosoma japnicum and Schistosoma haematobium. Noya (Parasite Immunology, 2001, 23, 567-573) disclose the synthesise of 17 polymericable 20 amino acid long peptides comprising the entire Sm31 sequence, and the immunization of rabbits with a pool of 4-5 different synthetic peptides. Using a multiple antigen blot assay (MABA), Noya simultaneously identified that 10 out of the 17 synthetic Sm31 peptides were highly immunoglenic. The use of chemically synthesized peptides may imporve the performance of serological assays based on the detection of antibodies, by enhancing the sensitivity and specificity of the immunoassay.

—Schistosoma japonicum: is an important cause of intestinal schistosomiasis. It has been a particular problem in China and the Philippines. One problem is that the snail hosts are amphibious and can proliferate in a diverse array of microhabitats and that infection is a zoonosis transmitted from a diverse array of mammalin hosts, expercially water buffaloes in the marshland reigon of China.

Patients infected with Schistosoma japnicum in the CNS may present with an acute meningoencephalitis. CNS symptoms (headache, fever, stiff neck, vomiting, or seizures) may be noted within days after the apeparance of mucosanguienous stools in patients in the Philippines and within months in Japan and China. Partial seizures resutls form brain invasion by eggs or adult worms.

Diagnosis is by stool microscope. Praziquantel, an anticonvulsant and occasionally corticosteroids are used for treatment. The dosage of prziquantel may vary with the worm burden.

Leeches:

Most leeches live in freshwater, although a few are murine and some tropical leeches occupy terrestrail habitats. About half the known species of leeches eat detritus or devour small animals. The others suck blood or other fluids form their hosts. Blood sucking leeches secrete an anticoagulant into the wound to prevetn the blood from clotting, and vasodilators to keep the blood flowing. The leech’s powerful pharynx pumps the blood out quickly once a hole has been opened.

Leeches are used to remove excess blood after surgery or to keep blood from coagulating in severed appendages that have been reattached. Accumulations of blood can cause the tissue to die; when leeches remove such blood, new capillaries form in about a week, adn the tissues remain healthy.

–Hookworms: are gastrointestinal nematodies that infect about 600 million people in developing countries. Adult hookworms bury their ehads beneath the mucosa of the human intestine and feed on blood. Moderate to heavy infections result in iron deficiency anaemia,. The resulting hookworm disease and anemia has a serious deleterious impact on many aspects of the health of infected individuals, including child hood growth retardation and cognitive development,  and impaired fetal development during pregnancy. While anthelminthic drugs of the benzimidazole class are highly effective at eliminating existing hookworm infections, they do not protect against rapid re-infection. In areas of high transmission, hookworm re-infection will occur within 4-12 months. In addition, the efficacy of benzimidazole drugs decreases with frequent use.

Parasites encompasses fungi, protozoa, including amoebae and flagellates, as well as multicellular parasites such as (roundworms) and platyhelminthes (flatworms).

Lice

Lice are parasites that can be found on the body. See CDC

Head Lice: Pediculus humanus capitis causes head lice. Benzyl alcohol is used effectively for treating lice infestations as the active ingredient in lotion shampoo with 5% benzyl alcohol. (sold under the brane name Ulesfia)

Crabs: is caused by Pthirus pubis, 

Fungi

Ringworm: These mycoses are strictly confined to the nonliving epidermal tissues (statum corneum) and thei rderivatives (hair and nails). All these conditions have different names that begin with the word “tinea”.. Tinea Capitis results from the fungal invasion of the scalp and the hair of the head, eyebrows and eyelashes. Tinea Corporis is extremely prevalent infection that can apepar nearly anywhere on the body’s glabrous (smooth and bare) skin. Tinea Cruris also known as “jock itch” is a crutal ringworm that occurs mainly in males on the groin, preianal skin, scrotum and accoasinally the penis. The fungus thrives under conditions of mositure and humidity created by sweating. Tinea Pedis is ringword of the foot.

Protozoa (see outline)

Toxoplasma gondii 

Toxoplasma is a globally distributed pathogen of humans and animals. Between 30-80% of the human population carries latent infeciton with this opportunisitc parasite. T. Gondii develops in the intestinal cells of cats. Humans can become infected by ingestion of infective ooxycts from cat fecal contamination or by ingestion of improperly cooked meat from an intermediate host. Infection can be serious in immunocompromised people. This is a risk in AIDS patietns, where about 25% of those carring latent T. gondii infection undergo reactivating toxoplasmosis in the central nervous system.

Trypanosomes 

Trypanosomes are microscopic unicellular protozoa that are ubiqitous parasites of insects, plants and birds.  Trypanosomes differ from most other cells with respect to their mitochondrial DNA which is present in large amount, is condensed in the kinetoplast and called the kinetoplast DNA. It consists of thousands of interlocked circular molecules that seem to be held together by catenation.

Trypanosomes include include the following:

African trypanosomiasis which cause sleeping sickness

Trypanosoma cruzi is the causative agent of Chagas’ disease.

It is transitted by the reduuviid bug (kissing bug). After the bug bites on the face it deposits its feces which transmits the infection. It causes chagas disease and occurs mainly in children under 5. Trypanosoma is endemic in Central and South America, as well as in Mexico. In endemic areas, T. cruzi is transmitted mainly by blood-sucking triatomine insects. The disease can also be spread by blood transfusion, intravenous drug use, congenital transmission, by sexual activity, organ transplant or through breast milk.

After a mild acute phase, most infected people enter an indeterminate phase that is characterized by a lack of symptoms, low parasite count, and low titers of anti-T. cruzi antibodies. About 10-30% of persons with chronic T. cruzi infections, develop cardiac or gastrointestinal dysfunction.

Diagnosis of chronic T. cruzi infection refllects the complexity of the parasites’ lfie cycle. During period of high fever, diagnosis consists simply of identifying the parasites in blood, crebrospinal fluid, fixed tissue or lymph nodes. However, during latency the bug is difficult to detect. Serologic assays for antibodies to T. cruzi are well suited for rapid and inexpensive diagnosis. Brophy (US 2017/0023568) discloses antibodies that specifically bind Trypanosoma cruzi antigens and uses thereof.

An antibody has been generated that specifically inhibits the differentiation of one form of the parasite to another (epimastigote to trypomastigote stage) in vitro and which reacts with a cell surface glycoportein, however, this antigen is abesent form the mammalian bloodstream forms of the parasite (Sher, Nature, 300: 639-640, 1982).

To kill the parasite, Chagas disease can be treated with benznidazole or nifurtimox. Both medicines are nearly 100% effective in curing the disease if given soon after infection at the onset of the acute phase, including the cases of congenital transmission. The efficacy of both diminishes, however, the longer a person has been infected and the adverse reactions are more frequent at older age. See WHO

Treatment for Parasitic Infections Generally:

–—Fenbendazole, [5-(phenylthio)-1H-benzimidazol-2-yl]carbamic acid methyl ester, is widely used to treat pinworms, other helminthes, and a variety of parasitic infections in laboratory animals, livestock, companion animals, and people. Fenbendazole (brand names Panacur®, Safe-Guard®) is a medication used to treat a variety of parasites (e.g., roundworms, hookworms, lungworm, whipworm, and certain types of tapeworms) in dogs. Its use in cats for the treatment of parasites is ‘off label’. The mode of action works at the sub-cellular level, preventing cell division. Benzimidazoles binds to β-tubulin, 69 inhibiting the cell’s microtubule assembly responsible for intracellular transport and required for mitotic 70 cellular division.

—-Ivermectin: is a broad FDA approved anti-parasitic drug. Interesting it has also showed to be helpful for the Coronavirus.

Many factors affect whether you will be more or less suceptible to viral infection and the course of a viral infection. Factors which are important include the genotype of the virus, your own ethnic background, your gender and your age. Lets take genetic background as an example since it clearly is a major factor. See diseases mechanisms of viruses under “virology” for more information. Some will assume there is nothing that diet can do in such cases. Well this is not completely accurate. An example of this generally assumed belief is infection with coxsackieviru. Coxsackievirus induces a myocarditis in mice. A susceptible strain of mice (C3H/HeJ) fed a diet deficient in either Se or vitamin E develope increased cardiac pathology when infection with coxsackievirus B3 (CVB3) when compared with nutritionally adequate mice. A myocarditic strain of coxsackievirus B3 (CVB3/20) became more so and an amyocarditic strain of coxsackievirus B3 (CVB3/0) converted to virulence when the virus was inoculated into Se or vitamin E-deficient mice. In the case of the virus that converted from avirulent to virulent, the genome of the amyocarditic CVB3/0 mutated to a form closely resembling that of the myocarditic strains as a result of having been passed through either a Se or a vitamin E deficient host. Thus, the viral genotype was altered by the nature of the diet fed to the host. But what is even more intriguing is that mice that are normally resistant to coxsackievirus-induced myocarditis by virute of their genetic makeup (C57B1/6 strain) become susceptible to the virus when they are fed a diet that is deficient in both Se and vitamin E. This implied that host genetic background as a deteminant of viral infection otucome is superseded by feeding the host a diet nutritionally defiicent in both selenium and vitamin E.

Whatever the biochemical mechanism whereby dietary deficiency decreases the ability of a naturally resistant host to ward off viral infection, host nutritional status can have a profund effect on the course of viral disease. 

Cytokines (IL-8): Studies in human volunteers have established an association between IL-8 and common cold symptoms, In rhinovirus infections there is a direct correlation between the severtiy of common cold symptoms and the concentration of IL-8 in the nasal secretion.

IgA: Traditionally, immunoglobulin preparation for the prophylaxis and treatment of infection were largely compirsed of IgG. However, the successful use of breast milk for the prophylaxis and treatment of infant diarrhaea highlighted the potential benefits of plasma (monomeric) and mucosal (secretory) IgA for immunotherapeutic use. IgAbulin has also been administered in nose drops to reduct the incidence of Haemophilus influeanze in people identified as chronic nasopharynegal carriers (WO00/41721).

Treatment for the Flu

The main influenza strain circulating in the US has become resistant to two of the four drugs used to treat it (Amantadine and rimantadine).

Tamiflu: is the generic name for oseltamivir. It is approved for treatment of influenza (flu).

Relenza: is the generic name for zanamivir.

Amantadine and rimantadine: are among the few prescribed drugs used to shorten a flu attack and ease its symptoms, making the disease less dangerous for the elderly and those with compromised immune system. But in the 2006 flue season, 91% of samples of the main flu virus circulatingin the US, known as H3N2, that were tested by the CDC have shown resistance to the two drugs. This may be due either to a mutation in the flu virus in the US or importation of a virus that had gained resistance, psossibly from Asian countires where the drugs are sold over the counter.

Arbo Map (map by CDC of disease presence such as dengue, west nile). 

Maculopapular Rash Diseases caused by Viruses

Measles (Rubeola): Every year hundreds of thousands of childen in the developing world die from measles, even though an extremely effective vaccine has been available since 1963. 

–Signs and Symptoms: The intial symptoms are sore throat, dry coughing, headache, conjunctivities, lymph adenitis and fever. In a short time, typical oral lesions called Koplik’s spots appear as a prelude to the characteristic red maculopapular exanthem that erupts on the head and then progresses to the trum and extremities until most of the body is covered. The rash gradually coalexes into red patches that fade to brown. 

The most serious complication is subacute sclrosing panencephalitis (SSPe), a progressive neurological generation of the crebral cotrex, white matter, and brain stem. 

Measles implants in the respiratory mucosa and infects the tracheal and bronchial cells. From there, it travels to the lymphatic system, wehre it multiples and then enters the bloodstream, a condition known as viremia. The bloodstream carries the virus to the skin and to various organs. 

The measles virus induces the cell emmbranes of adjacent host cells to fuse into large syncytia, giant cells with many nuclei. These cells no longer perfromt their proper function. 

–Transmission: Measles is one of the most contagious infectious diseases, transmitted principally by respiratory droplets. There is no reservoir other than huans, and a person is infectious during the periods of incubation, prodrom phase, and the skin rash but usually not during convalescence. 

–Vaccination: The MMR vaccine (for measles, mumps and rubella) contains live attenuated measles virus which confers protection for up to 20 years. Measles immunization is recommended for all healthy children at the age of 12-15 months, with a booster before the child enters school. 

Roseola: is common in young children and babies. It can result in a maculopapular rash, but a high percentage of cases proceed without the rash stage. Children exhibit a high fever that comes on quickly and lasts for up to 3 days. On the fourth day, the fever disappears, and it is at this point that a rash can appear, first on the chest and trunk and less prominently on the face and limbs. Roseola is caused by a human herpesvirus called HHV-6. Like all herpesviruses, it can remain latent in its host indefinitely after the disease has cleared. Very occasionally, the virus reactivates in childhood or adulthood, leading to mononucleosis-like or hepatitis-like symptoms. It is thorught that 100% of the US population is infected with this virus by adulthood. Some people experience roseola when they became infection, and some of them did not. No vacine and no treatment exists. 

Rubells (German Measles): causes a relativey minor rash disease with few complications. Two clinical forms of rubella are referred to as postnatal infection, which develops in children or adults and congenital )prenatal) infection of the feturs. Postnatal Rubella presents itself as a rash of pink macules and papules on the face which progresses down the trunk and toward the extremities, advancing and resolving in about 3 days. The rash is milder looking than the measles rash. Adult rubella is often characterized by joint inflammation and pain rather than a rash. 

Vesicular or Pustular Rashes caused by Viral Diseases

Chickenpox: is very common and mostly benign. It has an inucubation period of 10-20 days when the first symptoms to appear are fever and an abundant rash that beings on the scalp, face and trunk and radiates in sparse crops to the extremities. Skin lesions progress quickly from macules and paules to itchy vesicles filled with a clear fluid. In several days, they encrust and drop off, usually healing completely but sometimes leaving a tiny pit or scar. 

About 0.1% of chickenpox cases are follwed by encephalopathy or inflammation of the brain. It can be fatal, but in most cases recovery is complete. 

Human herpesvirus 3 (HHV-3) also called varicella causes both chikenpox and shingles. Like other herpresviruses, it is an enveloped DNA virus. 

Shingles (Herpes Zoster): After recuperation from chickenpox, the virus enters into the sensory nerve endings and cuntaenous spinal nerve branches, especially those that serve the skin of the chest and head. From there, it becomes latent in the ganglia and may reemerge as shingles with its characteristic asymmetrical distribution on the skin of the trunk or head. 

Singles develops abruptly after reactivaiton by such stimuli as pshycholgical stress, x ray treatments, immunosuppresives and other drug therapy, sergery ro a developing malignancy. 

In2006, The FDA approved a unique vaccine called Zostavax. It is intended for adults age 60 and over. 

Smallpox: (see also Bioterrorism) Largely through the WHO global efforts, naturally occurring smallpox is a disease of the past. But it is a bioterrosism disease. Vaccination, which had been discontinued was once again offered to certain US populations. 

Infection begins with fever and malaise and later a rash begins in the pharynx, spreads to the face and prgoresses to the extremities. 

It is important for health care workers to recognize the early signs and symptoms as even a single suspected case must be treated as a health and law enforcement emergency. 

The causative agent of smallpox, the variola virus, is an orthopoxvirus, and enveloped DNA virus. 

In the early 1970s, smallpox was endemic in 31 countries. Every year, 10-15 million people contracted the disease and about 2 milion died form it. 

Affecting the Cardiovascular and Lymphatic System

HIV (see “viruses” and “retrovirsus”

Hemorrhagic Fever Diseases: a number of agents that infect the blood and lymphatics casue extreme fevers, some of which are accompanied by itnernal hemorrhaging. The presence of the virus in the bloodstream casues capillary fragility and disrupts the blood clotting system, which can even lead to death. All of these viruses are RNA enveloped viruses and include the Ebola virus. 

Yellow fever, chikungunya and dengue fever.  Yellow fever, chikungunya and engue are spread by the Aedes genus of mosquito and are common in South Americ and Africa.  In several places in the world trials are being conducted in which male A. aegypti mosquitoes infected with the bacterium Wolbachia are being released in areas with heavy dengue burden. When these males mate with females, the resultant eggs are not delivered. An ebola vaccine which has been shown to be safe and highly effective is also in phase III clinical trials. 

–Eboli Virus: Ebola virus is regarded as the prototype pathogen of viral haemorrhagic fever, causing severe disease and high case-fatality rates. Ebola virus and Marburg virus constitute the family Filoviridae in the order of Mononegavirales. Filoviruses are enveloped, non-segmented, negative-stranded RNA viruses of varying morphology. These viruses have characteristic filamentous particles that give the virus family its name. Ebola haemorrhagic fever is thought to be a classic zoonosis with persistence of the Ebola virus in a reservoir species generally found in endemic areas. Apes, man, and perhaps other mammalian species that are susceptible to Ebola virus infection are regarded as end hosts and not as reservoir species. The different species of Ebola virus seem to cause somewhat different clinical syndromes, but opportunities for close observation of the diseases under good conditions have been rare. Generally, the abrupt onset of Ebola haemorrhagic fever follows an incubation period of 2–21 days (mean 4–10) and is characterised by fever, chills, malaise, and myalgia. The subsequent signs and symptoms indicate multisystem involvement and include systemic (prostration), gastrointestinal (anorexia, nausea, vomiting, abdominal pain, diarrhoea), respiratory (chest pain, shortness of breath, cough, nasal discharge), vascular (conjunctival injection, postural hypotension, oedema), and neurological (headache, confusion, coma) manifestations. Haemorrhagic manifestations arise during the peak of the illness and include petechiae, ecchymoses, uncontrolled oozing from venepuncture sites, mucosal haemorrhages, and post-mortem evidence of visceral haemorrhagic effusions. A macropapular rash associated with varying severity of erythema and desquamate can often be noted by day 5–7 of the illness; this symptom is a valuable differential diagnostic feature and is usually followed by desquamation in survivors. Abdominal pain is sometimes associated with hyperamylasaemia and true pancreatitis. In later stages, shock, convulsions, severe metabolic disturbances, and, in more than half the cases, diffuse coagulopathy supervene. See Feldman

–Chikungunya virus (CHIKV) is an arthropod-borne virus that is transmitted by Aedes (Ae.) mosquitoes. It was first isolated in 1952 in the Makonde Plateau of the southern province of Tanzania (former Tanganyika). The virus transmission cycle requires infection of female mosquitoes via a viraemic bloodmeal taken from a susceptible vertebrate host and, following a suitable extrinsic incubation period, transmission to another vertebrate host during subsequent feeding. After an incubation period, most patients suffer from polyarthralgia and myalgia, with a significant impact on their quality of life. Chikungunya fever is characterised by a very high viraemic load and concomitant abnormalities such as pronounced lymphopenia and moderate thrombocytopenia. The rate of asymptomatic cases is lower, and the percentage of infected patients requiring medical attention is higher, than in most other common arboviral infections. After the acute stage, some patients experienced relapse, persistent arthralgia or musculoskeletal pains. Increase of age is the most obvious risk factor associated with severe disease or persistent symptoms in adults, whilst in paediatric populations, newborns have a higher risk of severe disease. The name “Chikungunya” in the Bantu language of the Makonde people refers to the stooped posture due to the frequent and debilitating joint pain induced during chikungunya fever. The virion has an icosahedral capsid enclosed by a lipid envelope and a diameter of 60–70 nm. It is sensitive to desiccation and to temperatures >58 °C. The genome is a single-stranded, positive sense, RNA molecule of approximately 12 kb in length. See Thimburville

No vaccine exists to prevent chikungunya fever, and there’s no effective antiviral treatment. However, the disease runs a limited course and rarely causes serious complications. Treatment is aimed at relieving symptoms with rest, fluids and medications — such as acetaminophen (Tylenol, others) and ibuprofen (Advil, Motrin IB, others) — to relieve joint pain and fever. Chikungunya outbreaks were first reported in Africa, Asia, Europe, and islands in the Indian and Pacific oceans. The first reported case of chikungunya in the Americas occurred in 2013, on islands in the Caribbean. Since then, more than 1.7 million suspected cases of chikungunya have been reported in the Caribbean islands, in Latin American countries and in the United States. Canada and Mexico also have reported cases of infection. See Mayo Clinic.   See WHO

–Yellow Fever: Yellow fever is a viral disease spread to humans, as well as between certain other primates and humans, by the bite of infected mosquitoes. The virus is called simply Yellow fever virus, named for the jaundice that affects some patients, and belongs to the virus family Flaviviridae. Yellow fever is endemic in areas of Latin America and Africa, while imported cases have appeared throughout the world. Globally, the disease infects about 200,000 people per year, causing fever, chills, nausea, vomiting, muscle pain, and headache, and has no cure. There is no direct treatment for yellow fever. Supportive care may be provided, including efforts to reduce pain and to lower the fever associated with the disease. Medications used for pain relief must be carefully selected, as some nonsteroidal anti-inflammatory drugs (including aspirin) may increase bleeding risk. While many yellow fever patients recover after 3-4 days of symptoms, approximately 15% enter a second phase of the illness after a remission. This second phase includes a return of high fever, as well as jaundice; abdominal pain and vomiting; bleeding from the mouth, nose, eyes, or stomach; and deteriorating kidney function. As many as half of the patients who experience the second phase may die. In all, yellow fever kills 30,000 people globally each year. The yellow fever vaccine provides protection for 30 years or more—possibly for life—and for 95% of those vaccinated, offers protective immunity against the disease within a week. See History of Vaccines

–Lassa Fever:  Though first described in the 1950s, the virus causing Lassa disease was not identified until 1969. The virus is a single-stranded RNA virus belonging to the virus family Arenaviridae. About 80% of people who become infected with Lassa virus have no symptoms. 1 in 5 infections result in severe disease, where the virus affects several organs such as the liver, spleen and kidneys.  Lassa fever is a zoonotic disease, meaning that humans become infected from contact with infected animals. The animal reservoir, or host, of Lassa virus is a rodent of the genus Mastomys, commonly known as the “multimammate rat.” Mastomys rats infected with Lassa virus do not become ill, but they can shed the virus in their urine and faeces. Because the clinical course of the disease is so variable, detection of the disease in affected patients has been difficult. When presence of the disease is confirmed in a community, however, prompt isolation of affected patients, good infection prevention and control practices, and rigorous contact tracing can stop outbreaks. Lassa fever is known to be endemic in Benin (where it was diagnosed for the first time in November 2014), Ghana (diagnosed for the first time in October 2011), Guinea, Liberia, Mali (diagnosed for the first time in February 2009), Sierra Leone, and Nigeria, but probably exists in other West African countries as well.  See WHO

Mononucleosis (“mono” or “kissing disease”):

–cause: This lymphatic system disease can be casued by a number of bacteria or viruses but the vast majority are casued by the Epstein-Barr virus (EBV), a member of the herpesvirus family. 

–signs and umptoms: are sore throat, high fever, and cervical lymphadenopathy, which develop after a long incubation period (30-50 days). Many patients also have a gray white exudate in the throat, a skin rash and enlarged spleen and liver. A notable sign of mononucleosis is sudden leukocytosis (an increase in number of white blood cells), consisting initially of infected B cells and later T cells. Fatigue for a period of weeks is a hallmark of the disease.  Eventually, the strong, cell mediated immune response is decisive in controlling the infection. 

–transmission and epidemiology: more than 90% of the world’s population is infected with EBV. In general, the virus casues no noticeable symptoms, but the time of life when the virus is first encountered seems to matter. In the case of EBV, infection during the teen eyars results in disease about 25% of the time. Direct oral contact and contamination with saliva are the principal modes of transmission, alhtough transfer through blood transfusions, sexual contact and organ transplants is possible. 

–prevention and treamtent: the usual treamtents is symptomatic relief of fever adn sore throat. 

Affecting the Gastrointestinal Tract

Hepatitis: See Outline under “viruses”. 

Affecting the Genitourinary System

Genital Herpes:

–cause: Herpes is caused by herpes implex viruses (HSVs). The types of HSV that have been identified are HSV-1 and HSV-2. Both HSV-1 and HSV-2 can cause gential herpes if the virus contacts the genital epithelium, although HSV-1 is thought of as a virus that infects the oral mucosa, resulting in cold sores or fever blisters. HSV-2 is thought of as the genital virus. In reality, either virus can infect either region. Herpresviruses have a strong tendency to become latent. During latency, some type of signal causes not of the HSV genome not to be transcribed. This allows the virus to be maintained within cells of the nervous system between epiosides.   See CDC

–Transmission:  Although hperes is not a nationally reportable disease, 50-80% of adults in the US are seropositive for HSV-1 and 20-40% are positive for HSV-2. Worldwide, the WHO estminates that 4 billion people are infected. Becasue the viruses are relatively sensitive to the environment, transmission is primarily through direct exposure to secretions containig the virus. People with active lesions are the most significant source of infection, but sutdies indicate that genital hperes can be transmitted even when no lesion are present. 

–symptoms: After initial infection one may notice no symptoms or the appearance of a single or multiple vesicles on the genitalia, perineum, thigh and buttocks. The vesicles are small and are filled with a clear fluid. They can be intensely painful to touch. The appearance of lesions the first time can be accompanied by malaise, anorexia, fever and bilateral swelling and tenderness in the groin. Occasionally central nervous system symptoms such as meningitis or encephalitis can develop. 

–Prevention: no vaccine is currenlty licended but one is being tested in clinical trails. Condoms provide good protection when they cover the site where the lesion is, but lesions can occur outside of the area covered by a condom. 

–Treatment: Acyclovir and its derivative , famiclovir or valacyclovir, are very effective. Topical formulations can be applied directly to lesions and pills are available as well.

Human Papillomavirus Infection (HPV):

–cause: HPVs are a group of nonenveloped DNA viruses belonging to the Papovaviridae family. There are more than 100 different types of HPV. Some types are specific for teh mucous membranes while others invade the skin. Some of these viruses are the cause of plantar warts, which often occur on the soles of the feet. Other HPVs cause the common warts and flat wards. Others colonize the genital tract such as on the cervix and can lead to cancerous changes. See FDA

–Transmission: nearly all sexually active adults will get HPV at some time in their lives. The mode of transmission is direct contact. Autoinoculation is also possible meaning that the virus can be spread to other parts of the body by touching warts.  See WHO

–Virulence: The major virulence factor for cancer cuasing HPV is their oncogenes, which code for proteins that interfer with normal host cell function, resulting in uncontrolled growth. 

–Prevention: Vaccines prevent infection by up to nine tyeps of HPV.  

–Detection: 

PCR based screening tests can be used to test samples form a pelvic exam ofr the presence of dangerous HPV types. The Pap smeear is still the best screening prcoedure and can detect all precancerous cells if conducted on the recommended schedule.

Most peope who receive abnormal cervical cancer screening results either have HPV ifections or have early cell changes that can be monitored (since they often go away on their own) or reated early (to prevent the development of cervical cancer). A negative HPV test results means that high risk HPV was not found. One should test i 5 years unless there were abnormal resutls in the past. A positive HPV test means that high risk HPV was found. Follow up steps can be taken based on one’s specific test result. ]Pap test results show whetehr cervical cells are normal or abnormal. Normal results indicate no abnormal cervical cells were found. Abnormal pap test results include 1) atyypical squamous cells of undertermined significant (ASC-US) which is the most common abnormal Pap test finding and means that some cells do not look completely normal but it is not clear if the changes are casued by HPV infection, atypical glandular cells (AGC) whgich indicates that some glandular cells were found that do not look normal, low-grade squamous intraepitheial lesions (LSIL) which indicates that there are low grade changes that are usually casued by an HPV infection an datypical squamous cells, cannot exlude high grade squamous intraepithelia lesion (ASC-H) which indicates that some abnormal squamous cells were found that may be a high grade squamous intraepiethelia lesion (HSIL), although it is not certain, high-rade squamous intraepithelialleisions (HSIL0 which indciates that there are moederately or severely abnormal cervical cells that culd become cancerous if not treated, adenocarcinoma in situ (AIS) which indicates an advanced lesion (area of abnormal growth) which was found in the glandular tissue of the cervix and cervical cancer cells (squamous cell carcinoma or adenocarcinoma) which indicates that cancer cells were found (this result is rare for people who ahve been screened at regulr intervals). (National Cancer Institute, “HPV and Pap Test Results: Next steps after an abnormal test”)

–Treatment:

Infection with any HPV is incurable, alhtough they may resolve over a period of months to years. Genital warts can be removed through a variety of methods, but that does not eliminate the virus. 

The most common treatment for high grade cervical cell changes is conization, the removal of a cone shaped pieces of tissue form the ervix and cervical canal. Tehre are two types of conization 1) loop electrosurgical excision proecure (LEEP) which sues a thin wire loop, through which an electrical current is passed to remove abnormal tissue and (2) cold knife conization which uses a scalpel to remove the abnormal tissue which is done at the hospital under general anesthesia. Laser therapy, cryotherapy and total hysterectomy are other options. (National Cancer Institute, “HPV and Pap Test Results: Next steps after an abnormal test”)

Molluscum Contagiosum:

–-cause. MC is caused by an unclassified virus in the fmaily Poxviridae. 

–transmission: MC can be transmitted through fomites such as clothing or towels and through autoinoculation. It can also be transmitted sexually. 

–symptoms: This disease can take the form of skin lesions. The wartlike growths that result from this infeciton can be found on the mucous membranes or the skin of the genital area. Few problems are associated with these growths beyond the warts themselves. 

–treatment: the warts can be removed but the virus is not treatable. 

Affecting the Nervous System

Meningitis: The majority of cases of viral meningitis occur in children, and 90% are casued by enteroviruses. A common cause of viral meningitis is initial infection with HSV-2, concurrent with a genital infection. But many other virsues also gain access to the CNS on occasion. Viral meningitis is generally milder than bacterial or fungal meningitis, and it is usually resolved within 2 weeks. 

Arbovirus Encephalitis: Encephalitis (inflammation of the brain) can present as acute or subacute. One category of viral encephalitis is casued by virsues borne by insects (called arboviruses, which is short for arthropod-borned virsues), including Wist Nile virus, Alternatively other virsues sucha s the JC virus and members fo the herpes family cre causative agents. The signs and tymptoms of encephalitis vary, but may include behaviro changes or confusion becasue of inflammation. Dcreased consciousness and seizures frequently occur. Symtpoms of meningitis are often also present. Few of these agents have specific treatments, but becasue sift initiation of acyclovir theraphy can save the life of a patient suffering from herpesvirus encephalitis, most physicians will begin empiric therapy with acryclovir in all seriously ill neonates adn msot other patients showing evidence of encephalitis. 

–—Eastern Equine Encephalitis Virus: is endemic to an area along eastern cost of North America and Canada. The pattern is sporadic but epidemics can occur in humans and horses. A vaccine exsits for horses and is strongly recommended to eliminate the virus from its reservoir in humans. The case fatality can be 70%. 

One case of eastern equine encephalitis virus disease was reported. The pateint was a woman >60 will illness onset in August. The patient expeirenced neuroinvasive disease and was hospitalized. (Sutter, “West Nile Virus and other nationally notifiable arboviral diseases -United States, 2022” MMWR, 2024, 73(21))

––La Cross Virus: has only been reproted in the eastern half of the U.S. adn in Texas. It is maintained by infection of small mammals, such as sequirrels and chipmunks. Mosquitoes are the vector. Worst form of the disease occurs primarily in children udner 16.

Twent-two cases of La Crosse virus disease were reported form 19 counties in 5 states. Twenty (91%) patients pericenced ilness onset during July-September. The median patient age was 9 years and 55% were male. Nineteen (86%) pateints had neuroinvasive disease. Twenty-one (95%) patients were hospitalized; none died. Ohio reported the highest number o neuroinvasive disease cases. (Sutter, “West Nile Virus and other nationally notifiable arboviral diseases -United States, 2022” MMWR, 2024, 73(21))

—-Jamestown Canyon Virus: is maintained in nature by cycling between mosquitos and der or moose. The virus is found throughout North American.

Among 12 cases of Jamestown Canyon virus disease reported form 12 counties in 5 states, ilness onset occurred most frequently during April-June. The median patient age was 60 and 9 of the 12 patietns were male. All but one patient had neuroinvasive disease and 1 patients were hospitalized; no deaths were reported. Wisconsin reported the highest number of neuroinvasive disease cases (4) and the highest incidence (0.18 per 100k) of neuroinvasive disease occurred in Rhode Island. (Sutter, “West Nile Virus and other nationally notifiable arboviral diseases -United States, 2022” MMWR, 2024, 73(21))

—-Powassan Virus: is maintained in nature by ticks and groundhogs. It is found int he Northeast and the Great Lakes tates. St. Luis Encephalitis Virus: shows no symptoms. The virus is maintained in birds, and transferred by mosquitos to the dead end host, humans. Severe nueroinvasive damage is more common in adults.

forty-seven cases of Powassan virus disease were reported form 39 counties in 9 states. In 2022, Powassan virus disease was reported form Vermont for the first time. Illness onset occurred most fequently during April-Une (45%). Modian patient age was 64 years, and 55% of patients were male. Forty-three (91%) patietns experience neuroinvasive disease, 45 (96%) patients were hospitalized and seven (15% died. States with the highest incidence of neuroinvasive disease included Main (0.29 per 100k), Connectivut (0.17) and Vermont (0.15). All patients who died were >60. (Sutter, “West Nile Virus and other nationally notifiable arboviral diseases -United States, 2022” MMWR, 2024, 73(21))

—-West Nile Virus: emerged in the U.S. in 1999. 70-80% who are infected ahve no symtpoms. Birds are the ampoliyfing hsots. Humans and other large mammals are dead-end hosts.  See Center for Health Production

–JC Virus (JCV) gets its name form the initials for the pateint in whom it was first diagnosed. In patietns with immune dysfunction such as AIDS patietns, it can casue a condition called “progressive multifocal leukoencephalopathy”. Thsi uncommon but generally fatal infection is a result of JC virus attack of accessory brain cells. The infection demyelinizes certain parts of the cerebrum. The virus should be considered when encephalitis symptoms are observed in AIDS pateints. Recently a few deaths from the condition ahve been prevented with high doses of zidovudine. 

 –Herpes Simplex Virus (HSV): Herpes simplex type 1 and 2 viruses can cause encephalitis in newbrons born to HSV positive mothers. Older children and young adults as well as older adults (over 50) are also suspeptible to herpes simplex encephalitis casued most commonly by HSV-1. In these cases, the HSV encephalitis usually represents a reactivation of dormant HSV form the trigeminal ganglion. The varicella-zoster virus (causes chickenpox and perpes zoster (shingles) can also reactive from the dormant state, and it is responsbile for rare cases of encephalitis. (see beow)

–-Oropouche virus can cause encephalitis. Oropouche virus disease in the Americas region, originating from endemic areas in the Amazon basin and new areas in South America and the Caribbean. Between January 1 and August 1, 2024, more than 8,000 cases of Oropouche virus disease were reported, including two deaths and five cases of vertical transmission associated with fetal death or congenital abnormalities. Countries reporting cases include Brazil, Bolivia, Peru, Colombia, and Cuba. It belongs to the Simbu serogroup of the genus Orthobunyavirus in the Peribunyaviridae family. The virus was first detected in 1955 in Trinidad and Tobago. Sylvatic (enzootic) transmission of Oropouche virus occurs in forested areas between mosquitoes and non-human vertebrate hosts (e.g., sloths, non-human primates, domestic and wild birds, and rodents). Humans can become infected while visiting forested areas and are likely responsible for introducing the virus into urban environments. Humans contribute to the transmission cycle in urban environments since infected humans develop sufficient viremia to serve as amplifying hosts. Biting midges (Culicoides paraensis) and possibly certain mosquitoes (Culex quinquefasciatus) are responsible for transmitting the virus from an infected person to an uninfected person in urban areas. Approximately 60% of people infected with Oropouche virus become symptomatic. he incubation period is typically 3–10 days. Initial clinical presentation is similar to diseases like Dengue such as acute onset of fever, chills, headache, myalgia, and arthralgia. See CDC

Varicella is an illness characterized by a generalized, pruritic rash adn transmitted thorugh airbonre, droplet, and contact transmission. Alhtough varicella causes mild to moderate systmptomes, serious complications, including pneumonia and death can occur. In October 2022, the NYC Department of Health and Mental Hygiene idneitfied a varicella outbreak primarily involving persons who recently migrated from or thorugh Central and South America and lived in an NYC shelter or residentail facility.

–-Varicella-zoster virus (VZV) is responsible for both varicella (chickenpox) and herpes zoster (shingles). During varicella, the virus establishes latency within the sensory ganglia and can reactivate to cause herpes zoster, but the immune responses that occur in ganglia during herpes zoster have not previously been defined. See Stainne

Varicella-zoster virus (VZV) is a human alphaherpesvirus that infects >90% of people worldwide. Primary VZV infection, typically acquired during early childhood, leads to varicella (chickenpox) and establishment of a lifelong latent infection in neurons of trigeminal ganglia (TG) and dorsal root ganglia (DRG). Later in life, VZV reactivates in approximately one third of infected individuals to cause herpes zoster ([HZ] shingles). See Laing

Varicella-zoster virus (VZV) is a medically important human alphaher-pesvirus that causes varicella and zoster. VZV initiates primary infection by inoculation of the respiratory mucosa. In the course of primary infection, VZV establishes a life-long persistence in sensory ganglia; VZV reactivation from latency may result in zoster in healthy and immunocompromised patients. The VZV genome has at least 70 known or predicted open reading frames (ORFs), but understanding how these gene products function in virulence is difficult because VZV is a highly human-specific pathogen. See Arvin

Poliomyelitis (polio): is an acute enterovival infection of the spinal cord that casue casue neuromuslular paralysis. Becasue it often affects small children, in the past it was called “infantile paralysis”. Most infections are contained as short term, mild viremia. In paralytic disease, invasion of motor neurons casues various degress of flaccid (floppy) paralysis over a period of a few hours to several days. The poliovirus is int he fmaily Picornaviridae, genus Enterovirus, named for its small (pico) size and its RNA genome. It is a nonenveloped and nonsegmented. Human are the only known reservoir. The virsu is passed within the population through food, water, hands, obtects contaminated with feces, adn mechincal vectors. Although the 20th centruy saw a very large rise in paralytic polio cases, effective vaccines were developed. The infection was eliminated form teh Western Hemisphere in the late 20th centrue. Since the virus cannot exist outside of a human, it is possible to totally eradicate the disease if we vaccinate all susceptible hosts. 

Rabies: is a slow, progressive zoonatic disease characterized by a fatal encephalitis. The average incubation period of rabies is 1-2 months or more, dpending on the wound site, its severity and inoculation dose. The incubation period is shorter in facila, scalp or neck wounds becasue of clsoer proximity to the brain. The prodromal pahse starts with fever, nausea, vomiting, headache, fatigue and other nonspecific symptoms. Infection with rabies virus typically begins when an infected animal’s saliva enters a puncture site. The virus occasionally is inhaled or inoculated through the membrnes of the ye. The virus remains up to a week at the trauma site, where it multiples. The virus then gradually enters never endings and advances toward the ganglia, spinal cord and brain. Globally, over 905 of human rabies cases are still azquired from dogs. A bite from a wild or stray animal demands assessment of the animal, meticulous care of the wound, and a specific treatment regimen. A wild mammal, especially a skunk, raccon, fox or coyote that bites without provocation is presumed to be rabid, and therapy for rabies is immediately started. A combination of passive and active postexposure immunization is successful. Initially the wound is infused with human rabies immune globulin to impede the spread of the virus, and globulin is also injected intramuscularly to provide immediate systemic protection. A full course of vaccination is started simultaneously. The routine postexposure vaccination enails intramuscular or intradermal injection on days 0, 3, 7 and 14, sometimes with two additional boosters. 

Tick-borne Encephalitis (TBE) virus: is a tickborne flavivrus taht is focally endemic in a geographic region extending form westerna nd northern Europe thorugh to northern and eastern Asia. TBE virus is a single=stranded RNA virus in the genus Flavivirus family Faviviridae. TBE virus is closely related to Powassan virus, a tickborne flavirus transmitted in parts of the U.S. The three main antigenic subtypes of TBE virus (e.e., European, Siberian, and Far Eastern) differ in the severity of disease they cause and geographic distribution. The most recognized clinical manifestation of TBE virus infection is acute neurologic disease, which usually results in hospitalization, often permanent neurologic or cognitive sequelae, and sometimes death. TBE is rare among travelers and laboratory workers. In August 2021, the FDA approved an inactivated TBE vaccine for use in persons aged more than 1. The TBE virus is primarily transmitted to humans by the bites of infected txodes sp. ticks. The preferred habitats for the vector ticks are woodland enviornments. (MMWR, “Tick-borne encephalitis vaccine: recommendations of the advisory committee on immunizaiton practices, United States, 2023”. 

Zika Virus: Starting in 2015 adn continuing into 2016, an epidemic of babies born with abnromally small heads, a condition called microcephaly, became obvious in Brazil. The cause was quickly determinedto be the Zika virus. Zika virus is an RNA virus is int he Flaviviridae family. It is closely related to viruses casuing dengue fever, West Nile fever and yellow fever.

 During 2016, the virus spread rapidly through the Americas adn cotninues to do so. Its mosquito host, the genus Aedes, is spread throughout the world. The best way to prevent Zika is to prevent mosquito bites by using insect repellent, wearing long-sleeved shirts and pants and staying in places with air conditioning or window and door screens. Remvoing standing water is also very improtant.

When adults are infected with Zika, they can experience a range of symptoms, from none at all, to a skin rash, conjunctivitis, and muscle and joint pian. The virus also appears to trigger Guillain-Barre syndrome (GBS) in some adutls. GBS is a neurological conditions that can occur after infections with certain bacteria and viues, adn soemtimes after exposure to vaccines. 

Affecting the Respiratory System 

See “Respiratory Viruses” under “viruses”

Bronchiolitis is a common lung infection in young children and infants. It causes inflammation and congestion in the small airways (bronchioles) of the lung. Bronchiolitis is almost always caused by a virus. Typically, the peak time for bronchiolitis is during the winter months. Most cases of bronchiolitis are caused by the respiratory syncytial virus (RSV). RSV is a common virus that infects just about every child by 2 years of age. Outbreaks of RSVinfection occur every winter, and individuals can be reinfected, as previous infection does not appear to cause lasting immunity. Bronchiolitis also can be caused by other viruses, including those that cause the flu or the common cold. See Mayo Clinic. 

See CDC

Introduction:

Pneumococcal disease is a name for any infection caused by bacteria called Streptococcus pneumoniae or pneumococcus. Bacteria called Streptococcus pneumoniae, or pneumococcus, can cause many types of infections. Some of these infections like pneumonia below can be life threatening. Today, the pneumococcus is thought to be responsible for at least half of all community-acquired pneumonia and otitis media and remains a significant cause of bacteremia and meningitis (together referred to as invasive pneumococcal disease [IPD])

Pneumococcal infections are casued by Streptococcus pneuonia (pneumococcus), a gram-positive, facultative anaerobic bacterium. Pneumococcus can colonize the upper respiratory tract, most commonly in young children, and is transmitted to others through contact with respiratory droplets from a person with pneumococcal colonization in the upper respiratory tract. Certain persons with pneumococcal colonization might develop invasive pneumococcal disease (IPD). IPD is infection of normally sterile sites, including pneumonia with bacteremia, meingitis, osteomyelitis, septic arthritis and bacteremica without a focus of infection. Examples of noninvasive disease include pneumonia without bacteremia, sinusitits, or otitis mediate. In adults, pneumococccal pneumonia is the most common type of pneumococcal disease, and pneumococccus is the most common bacterial cause of pneumonia that resutls in hospitalizaiton. (Kabayashi, “Pneumococcal vaccine for adults aged > 18 years: Recommendations of the advisory committe on immunization practices, United States, 2023”).

In adults, the risk for pneumococcal disease increased with age. Pneumococcal pneumonia is the most common form of pneumococcal disease in adults and is estimated to account for about 10% of hospitalized community acquired pneumonia. (Kabayashi, “Pneumococcal vaccine for adults aged > 18 years: Recommendations of the advisory committe on immunization practices, United States, 2023”).

In 2020, a decline in IPD incidence was observed globally and the decline is thought to be a result of the introduciton of nonpharmaceutical interventions to contain COVID-19 such as mask wearing and restrictions on indoor gathering whic

Biochemical and Morphological Characteristics

Streptococcus pneumonia (S.p.) or pneumococcus is a gram-positive, alpha-hemolytic member of the genus Streptococcus.

Pneumococci are classified into seroptyes depending on their capsular polysaccharide, which is a main virulence factor for pneumococcus. At least 100 pneumococcal serotypes were documeted as of 2020. During 2018-2019, about 60-75% of all IPD in adults was caused by the 24 pneumococcal serotyeps that were included in formulations of commercially available polysaccharide conjugate vaccine (PCV) or pneumococcal polysaccharide vaccine (PPSV) vaccines (i.e., PCV13, PCV15, PCV20, and PPSV23). Current pneumococcal vaccines use the pneumococcal capsular polysaccharides as antigens to generate serotype specific antibodies, which facilitate serotype specific clearance of pneumococci through opsonophagocytosis. (Kabayashi, “Pneumococcal vaccine for adults aged > 18 years: Recommendations of the advisory committe on immunization practices, United States, 2023”).

What it causes

It is an important human pathogen that colonizes the upper respiratory tract. S pneumoniae is the most common etiologic agent in community acquired pneumonia, as well as bacterial meningitis, otitis media and sepsis. It is responsible for more than 500k cases of lower respiratory tract infection in the US each year. Despite the widespread use of antibiotics, the mortality rate from S.p remains highest during the first 48 hours of hospitalization and has not decreased appreciably over the past 30 years. Successful treatment has been hampered by the increasing prevalence of antibiotic resistant strains worldwide. The earliest stage is seldom recognized and is most likely to be found in patients who die after illness lasting only a short time period because of the very rapid progress of the disease.

Acute Otitis Media (Ear Infection):

Although the middle ear normally has no biota, bacteria can migrate along the eustachian tube form the upper respiratory tract. Wehn bacterai encounter mucus and fluid buildup in the middle ear, they multiply rapidy. Their presence increases the inflammatory response, leading to pus production and continued fluid secretion. Another condition, known as chronic otitis media occurs when fluid reamins in the middle ear.

The single most common bacterium seen in acute otitis media is Streptococcus pneumoniae, although new dat suggest that it is caused by a mixed biofilm of bacteria which are also less usceptible to antibiotics.

Pneumonia

Pneumonia is an inflammatory condition of the lung in which fluid fills the alveoli. It can be caused by a wide variety of different microorganisms but S pneumoniae accounts for up to 40% of community-acquired bacterial pneumonia cases.

Worldwide more children under the age of 5 die from pneumonia than any other infectious disease. In the US there are 2-3 million cases of pneumonia and more than 45,000 deaths eacy year. It is much more common in the winter.

Symptoms: 

Histologically, the initial phase of pneumococcal pneumonia is characterized by acute lung injury (ALI) which is an inflammatory disorder of the lung, characterized by hypoxemia, diffuse biolateral infiltrate on chest radiograph and absence of atrial hypertension. Although numerous bacterial are present, few inflammatory cells are seen in serous exudates of these lesions because leukocytes have not had time to reach the alveoli in the advance edema zone.

Etiology: 

Following adherence and colonization, Sp will infrequently cause more invasive disease such as pneumonia. The pneumococcus can gain access to the alveolar space and set in motion a series of events leading to inflammation and clinical pneumonia. Although the pneumococcus can bind to many epithelial cell types in the nasopharynx, it cannot adhere to the cilated epithelium lining the tracheo-bronchial tree and ultizes an entirely different set of cell surface receptors in the alveolus. How the pneumococcus changes from a passive colonizing agent in the nasopharynx to a destructive invader of the lower respiratory tract is incompletely understood.  (McCullers, “Molecular Pathogenesis of Pneumococcal Pneumonia, Frontiers in Bioscience, 6, 2001).

1. Virulence Factors

pneumolysis (PLY), a 53 kDa protein produced by virtually all clinical isolates of Sp, plays an important role in mortality by inducing hemorrhage. PLY is a member of a family of cholesterol-binding toxins (CBTs, known as cholesterol-dependent cytolysin), which also includes numerous toxins from four general of Gram-positive bacteria.

2. Protecting Factors:

CYLD: Studies have also shown that a deficiency of the deubiquitinating enzyme CYLD protects mice from Sp pneumonia pneumolysis induced ALI and lethality. CYLD was initially identified as a tumor suppressor because loss of its activity causes a benign human syndrome called cylindromatosis. In vitro studies have indicated that CYLD is a member of the deubiquitinating (cleavage of ubiquitin from protein) enzyme family. Transfection studies have that CYLD deubiquitinates TRAF2and TRAF6 and acts as a negative regulator for activation of NF-?B by tumor necrosis factor receptor and Toll-like receptor.

Type-1 plasminogen activator inhibitor-1 (PAI-1) deficient mice are hyper-susceptible to several Sp infection and exogenous administration of PAI-1 protects against alveolar hemorrhage and early lethality in mice (WO 2009/018010). PAI-1 is a principal inhibitor of tissue plasminogen activator (tPA) and urokinase (uPA), the activators of plasminogen and hence fibrinolysis (the physiological breakdown of blood clots). CYLD (above) has been shown to act as a negative regulator for PAI-1 expression. CYLD, highly induced by pneumolysin, negatively regulates MKK3-p38 MAPK-dependent expression of PAI-1 in lung tissue, which in turn leads to potentiation of lung hemorrhage and increased mortality.

Capsule: Streptococcus pneumoniae (the pneumococcus) virulence is largely due to its polysaccharide capsule, which shields it from the host immune system. Capsular PS is critical to pneumococcal survival by shielding the organism from complement and subsequent phagocytic killing. It is the virulence factor most necessary for invading the host and causing disease. Most protective antibodies are specific to serotypes or serogroups, and because of this, the famous immunologist Charles Janeway, Jr., stated, “from the point of view of the adaptive immune system, each serotype of S. pneumoniae represents a distinct organism”.  Not all capsule types appear to be equally effective in shielding. Only 20 to 30 serotypes of the more than 90 show significant invasiveness. Most pneumococcal capsules are anionic which is thought to help prevent clearance by mucus. CAs pneumococcal vaccines provide serotype-specific protection, it is important that vaccines prevent disease caused by the most clinically relevant serotypes.

Thus, vaccines provide the greatest impetus for recognizing capsular diversity and serotype epidemiology. See Geno

Using unencapsulated serotype 2 and 4S. pneumoniaemutants, Hyams have confirmed that the capsule has several effects on complement activity. The capsule impaired bacterial opsonization with C3b/iC3b by both the alternative and classical complement pathways and also inhibited conversion of C3b bound to the bacterial surface to iC3b. There was increased binding of the classical pathway mediators immunoglobulin G (IgG) and C-reactive protein (CRP) to unencapsulatedS. pneumoniae, indicating that the capsule could inhibit classical pathway complement activity by masking antibody recognition of subcapsular antigens, as well as by inhibiting CRP binding. Cleavage of serum IgG by the enzyme IdeS reduced C3b/iC3b deposition on all of the strains, but there were still marked increases in C3b/iC3b deposition on unencapsulated TIGR4 and D39 strains compared to encapsulated strains, suggesting that the capsule inhibits both IgG-mediated and IgG-independent complement activity againstS. pneumoniae. Unencapsulated strains were more susceptible to neutrophil phagocytosis after incubation in normal serum, normal serum treated with IdeS, complement-deficient serum, and complement-deficient serum treated with IdeS or in buffer alone, suggesting that the capsule inhibits phagocytosis mediated by Fcγ receptors, complement receptors, and nonopsonic receptors. Overall, these data show that theS. pneumoniaecapsule affects multiple aspects of complement- and neutrophil-mediated immunity, resulting in a profound inhibition of opsonophagocytosis. See Hyams

Prevention and Treatment:

Vaccination:

Before October 2024, the Advisory Committee on Immunization Practices (ACIP) recommended use of a pneumococcal conjugate vaccine (PCV) for all adults aged ≥65 years, as well as for those aged 19–64 years with risk conditions for pneumococcal disease who have not received a PCV or whose vaccination history is unknown. Options included either 20-valent PCV (PCV20; Prevnar20; Wyeth Pharmaceuticals) or 21-valent PCV (PCV21; CAPVAXIVE; Merck Sharp & Dohme) alone or 15-valent PCV (PCV15; VAXNEUVANCE; Merck Sharp & Dohme) in series with 23-valent pneumococcal polysaccharide vaccine (PPSV23; Pneumovax23; Merck Sharp & Dohme). On October 23, 2024, ACIP recommended a single dose of PCV for all PCV-naïve adults aged ≥50 years. See CDC

Widespread use of pneumococcal conjugate vaccine (PCV) in children reduced the incidence of pneumococcal disease, both among children through direct effects and among older children and adults who have not received PCV through indirect effects (i.e., reduction in disease incidence in the population because of decreased transmission of pneumococcus from children).

The PPSV and PCV vaccines induce immune responses in different ways. Studies in mice have found that the polysaccharide vaccine induces a T cell independent immune response and stimulated immediate B cell resposes. As a result, B cells differentiate to plasma cells that produce antibodies. However, a T cell independent immune response does not result in creation of serotope specific memory cells. On the other hand, conjugate vaccines induce a T cell dependent response. The polysaccharide antigen binds to the B cells, and the peptides form the carrier protein are presented to carrier peptide specific helper T cells which enhance the immune response by the B cells and memory Beclls are also created. All PCVs use CRM197 (genetically detoxified diphteria toxin) as a carrier protein. (Kabayashi, “Pneumococcal vaccine for adults aged > 18 years: Recommendations of the advisory committe on immunization practices, United States, 2023”).

Use of azithromycin, benzathine penicillin G, amoxicillin or levofloxacin has been reported in recent outbreaks to prevent additional cases. If an exposed person has received vaccines that contain the serotype of the circulating pneumococcus, they are expected to have longer term proteion against pneumococcal diasese than if they were to receive antimicrobial chemoprophylaxis. PCVs have advantages ofver PPSV23 because these vaccines can induce high levels of serotype specific iIgG to help protect vaccinated persons from vaccine type pneumococcal carriage. (Kabayashi, “Pneumococcal vaccine for adults aged > 18 years: Recommendations of the advisory committe on immunization practices, United States, 2023”).

Treatment:

The current treatment recommendation for uncomplicated acute otitis media with a fewer below 104F is “watchful waiting” for 72 hours to allow the body to clear the infection, avoiding the use of antibiotics.

Since the introduction of sulfonamides and penicilin in the first half of the 20th century, antibiotic therpay has been the primary treatment. However, antibotic resistance could be detected in clinical isolates as early as 1941, 12 years after the discvoery of penicillin.

See CDC

Pneumonia is common across all age groups but it is a leading cause of death among the old and immunosupressed. There are two broad classifications, community acquired pneumonia (CAP) and hospital acquired pneumoniae (HAP).

pneumonia can be caused by the flue, COVID-19 or many other infectious agents. Health providers make a distinction between viral pneumonia and bacterial pneumonia. Viral pneumonia follows on from a cold or flue that persists. Bacterail pneumonia is caused by bacteria and may be accompanied by a mucus-y cough, high fever and severe chest paints. 

Community acquired pneumonia (CAP): 

CAP is infectious pneumonia in a person who has not been recently hospitalized. It is the most common type of pneumonia. Causes of CAP include gram positive bacteria such as Streptococcus pneumoniae and staphylococcus aureus. Gram negative bacteria causes include Haemophilus influenza, Klebsiella pneumonia, Escherichia coli, Pseudomonas aeruginosa, and Moraxella catarrhalis. These bacteria often live in the stomach or intestines and may enter the lungs if vomit is inhaled. Atypical bacterial causes include Chlamydophila pneumoniae, Mycoplasma pneumonia (also called “walking pneumonia which is less severe), and Legionella pneuophila. Viral causes include influenza, respitory syncytial virus (RSV), adenovirus, and parainfluenza. Viruses account for about 20% of pneumonia according to some studies.

Hospital acquired pneumoniae (HAP):

HAP also called nosocomial pneumonia is acquired during or after hospitalization for another illness or procedure with an onset 72 hours after admission. Hospital acquired microorganisms can include resistant bacteria such as , Pseudomonas, Enterobacter, and Serratia. Because individuals with HAP are immunosuppressed to start with, this type of infection is typically more deadly then CAP. Nationwide, about 6% of hospitals have problems with “superbugs” known as carbapenem-reistant bacteria such as Klebsiella pneumonia. For example, the NIH in 2011 had such an outbreak which killed 11 of their patients. 6 of the patients had immune systems weakened by cancer and drugs given after organ transplants.

Symptoms: Pneumonia is an inflammatory condition of the lung which is often is characterized by air sacs (alveoli) filling with fluid. Symptoms of pneumonia include cough, chest pain, fever, and difficulty breathing. Other symptoms include coughing up blood, blueness of the skin, nausea, vomiting, and joint pains.

Specific Types of Bacteria that cause Pneumoniae

Klebsiella species cause a wide range of diseases including pneumonia, urinary tract infections (UTIs), bloodstream infections and sepsis. These infections are particularly a problem among neonates, elderly and immunocompromised individuals. Klebsiella is also responsible for a significant number of community-acquired infections. A defining feature of these infections is their morbidity and mortality, and the Klebsiellastrains associated with them are considered hypervirulent. lebsiella species are ubiquitously found in nature including water, soil and animals, and they can colonise medical devices and the healthcare environment See Pessoa

–Klebsiella pneumonia is a type of Gram-negative bacteria that can cause different types of healthcare-associated infections, including pneumonia, bloodstream infections, wound or surgical site infections, and meningitis. Increasingly, Klebsiella bacteria have developed antimicrobial resistance. See CDC

The capsular polysaccharide and type 1 fimbriae are two of the major surface-located virulence properties associated with the pathogenesis of Klebsiella pneumoniae. The capsule is an elaborate polysaccharide matrix that encases the entire cell surface and provides resistance against many host defense mechanisms. See Klemm

Carbapenem-resistant (CR) Klebsiella pneumoniae has emerged as an urgent public health threat in many industrialized countries worldwide, including the United States. Infections caused by CR K. pneumoniae are difficult to treat because these organisms are typically resistant to multiple antibiotics, and the patients have significant comorbidities. Notably, there is high (∼50%) mortality among individuals with bacteremia caused by CR K. pneumoniae. See Deleo

Treatment: 

Symptoms of pneumonia needs immediate medical attention. Treatment includes antibiotics. If a patient’s condition does not improve or if there is doubt about the diagnosis, a culture of the sputum may be tested.

Many people with pneumonia need antibiotics even if an infectio had a viral origin becasue a bacterial infection may have set in. 

A vaccine against Streptococcus pneumoniae is available and is recommended for all adults over 65. A repeat vaccine may be required after 5- 10 years. Influenza vaccines should be given at the same time.

Complications: 

Ventilator-associated pneumonia (VAP): is a frequent complication in patients requiring mechanical ventilation with an incidence rate of 10-25% and a crude mortality ranging from 10% to 40%. M