Overview of Pathogenic Microorganisms: Bacteria, Fungi, Protozoa, and Viruses
Pathogenic microorganisms are responsible for a wide range of infectious diseases in humans, animals, and plants.
Classification of infections
∙ Primary infection: initial infection with a parasite in a host is termed as primary infection.
∙ Re-infection: Subsequent infections by the same parasite in the host are termed as re-infections.
∙ Secondary infection: A secondary infection is a bacterial or viral illness that occurs after or during treatment for another infection. It can be caused by the first treatment or by changes to the body or immune system. A secondary infection can make the first infection more severe.
∙ Cross-infection: When in a patient already suffering from a disease a new infection is set up from another host or another external source is termed as cross-infection. ∙ Nosocomial infection: Cross-infections occurring in hospitals are called nosocomial infections.
∙ Iatrogenic infection: refers to physician induced infections resulting from investigative, therapeutic or other procedures.
Methods of transmission of infection
Contact
∙ Infection may be acquired by contact which may be direct or indirect. ∙ Sexually transmitted diseases such as syphilis and gonorrhea illustrate spread by direct contact.
∙ Indirect contact may be through the agency of fomites, which are inanimate objects such as clothing, pencils or toys which may be contaminated by a pathogen from one person and acts as a vehicle for its transmission to another.
∙ Pencils shared by school children may act as fomites in the transmission of diphtheria.
Inhalation
∙ Respiratory infections such as influenza and tuberculosis are transmitted by inhalation of the pathogen.
∙ Such microbes are shed by the patients into the environment, in secretions from the nose or throat during sneezing, speaking or coughing.
∙ Large drops of such secretions fall to the ground and dry there.
∙ Pathogens resistant to drying may remain viable in the dust and act as sources of infection.
∙ Small droplets, under 0.1 mm in diameter, evaporate immediately to become minute particles or droplet nuclei which remain suspended in the air for long periods acting acts sources of infection.
Ingestion
∙ Intestinal infections are generally acquired by the ingestion of food or drink contaminated by pathogens.
∙ Infection transmitted by ingestion may be waterborne (cholera), foodborne (food poisoning) or hand borne (dysentery).
∙ The importance of finger borne transmission is being increasingly recognized, not only in the case of pathogens entering through the mouth, but also those that enter through the nose and eyes.
Inoculation
∙ Pathogens in some instances, may be inoculated directly into the tissues of the host. ∙ Tetanus spores implanted in deep wounds, rabies virus deposited subcutaneously by dog bite and arboviruses injected by insect vectors are examples.
∙ Infection by inoculation may be iatrogenic when unsterile syringes and surgical equipment are employed. Hepatitis B and the human immunodeficiency virus (HIV) may be transmitted through transfusion of infected blood, or the use of contaminated syringes and needles, particularly among addicts of injectable drugs.
Insects
∙ Insects may act as mechanical or biological vectors of infectious diseases.
Congenital infections
Some pathogens are able to cross the placental barrier and infect the fetus in utero. This is known as vertical transmission. This may result in abortion, miscarriage or stillbirth. Live infants may be born with manifestations of a disease, as in congenital syphilis.
Iatrogenic and laboratory infections
Infection may sometimes be transmitted during administration of injections, lumbar puncture and catheterization, if meticulous care in asepsis is lacking. Modern methods of treatment such as exchange transfusion, dialysis and organ transplant surgery have increased the possibilities for iatrogenic infections. Laboratory personnel handling infectious material are at risk and special care should be taken to prevent laboratory infection.
Pathogenic Bacteria
Pathogenic mechanisms
∙ Pathogenicity is generally employed to refer to the ability of a microbial species to produce disease. Virulence is applied to the same property in a strain of microorganism.
∙ The virulence of a strain is not constant and may undergo spontaneous or induced variation.
∙ Enhancement of virulence is called exaltation and reduction of virulence is called attenuation.
∙ Adhesins: The initial event in the pathogenesis of many infections is the attachment of bacteria to body surfaces. This attachment is not a chance event but a specific reaction between surface receptors on host cells and adhesive structures(ligands)on the surface of bacteria. These adhesive structures are called adhesins. Adhesins may occur as organized structures, such as fimbriae or pili or as colonization factors. This specific adhesin may account for the tissue tropisms and host specificity exhibited by many pathogens. Adhesins serve as virulence factors, and loss of adhesins often renders the strain avirulent.
∙ Invasiveness: This refers to the ability of a pathogen to spread in the host tissues after establishing infection. High invasive pathogens characteristically produce spreading or generalized lesions while less invasive pathogens cause more localized infections.
∙ Toxigenicity: Bacteria produce two types of toxins- exotoxins and endotoxins ∙ Exotoxins: These are heat labile proteins which are secreted by certain species of bacteria and diffuse readily into the surrounding medium. They are highly potent in minute amounts and constitute some of the most poisonous substances known. They exhibit specific tissue affinities and pharmacological activities, each toxin producing a typical effect which can be made out by characteristic clinical manifestations or autopsy appearances. Exotoxins are generally formed by Gram positive bacteria but may also be produced by some gram negative organisms such as Shiga’s dysentery, bacillus, Vibrio cholera and enterotoxigenic E. coli. ∙ Endotoxins: These are stable lippolysaccharides (LPS) which form an integral part of the cell wall of Gram negative bacteria. Their toxicity depends on the lipid component (lipid A). They are not secreted outside the bacterial cell and are released only by the disintegration of the cell wall. They are poor antigens and their toxicity is not completely neutralized by the homologous antibodies. They are active only in relatively large doses. They do not exhibit specific pharmacological activities. Intravenous injections of large doses of endotoxin and massive Gram negative septicemias cause endotoxic shock marked by fever, leucopenia,
thrombocytopenia, significant fall in blood pressure, circulatory collapse and bloody diarrhea leading to death.
∙ Distinguishing features of exotoxins and endotoxins
∙ Other bacterial products: Pathogenic Staphylococci produce a thrombin like enzyme which prevents phagocytosis by forming a fibrin barrier around the bacteria and walling off the lesion. Fibrinolysins promote the spread of infections by breaking down the fibrin barrier in tissues. Hyaluronidases split hyaluronic acid which is a component of intercellular connective tissue and thus facilitate the spread of infection along the tissue spaces.
∙ Bacterial appendages: Capsulated bacteria such as Pneumococci, K pneumoniae and H influenzae are not readily phagocytosed. Some bacterial surface antigens such as the Vi antigen of S typhi and K antigens of E coli also help the bacteria to withstand phagocytosis and the lytic activity of complements.
Typhoid fever
It is caused by Salmonella typhi and is acquired by ingestion of food or water contaminated by feces of infected humans or person-person contact. In earlier centuries the disease occurred in great epidemics. A milder form of the disease, Parathyphoid fever is caused by Salmonella paratyphi. The incubation period is about 10 to 14 days. The bacteria colonize the small intestine, penetrate the epithelium and spread to the lymphoid tissue, blood, liver and gall bladder. Symptoms include fever, headache, abdominal pain, anorexia, and malaise which last several weeks. After approximately 3 months, most individuals stop shedding bacteria in their feces. However, a few individuals continue to shed S typhi for extended periods but show no symptoms. In these carriers, the bacteria continue to grow in the gallbladder and reach the intestine through the bile duct.
Laboratory diagnosis of typhoid fever is by demonstration of typhoid bacilli in the blood, urine, or stools and serology. Treatment with ceftriaxone or ciprofloxacin has reduced the mortality rate to less than 1%. Recovery from typhoid confers permanent immunity. Purification of drinking water, prevention of food handling by carriers, and complete isolation of patients are the most successful prophylactic measures.
Q fever
It is an acute zoonotic disease caused by the bacteria Coxiella burnetti, an intracellular, gram negative bacterium. C burnetti can survive outside host cells by forming a resistant, endospore like body. This bacterium infects both wild animals and livestock. Cattle, sheep and goats are the primary reservoirs. In animals, ticks transmit C burnetti, whereas human transmission is primarily by inhalation of dust contaminated with bacteria from dried animal feces or urine, or consumption of unpasteurized milk.
In humans,Q fever is an acute illness characterized by the sudden onset of severe headache, malaise, confusion, sore throat, chills, sweats, nausea, chest pain, myalgia (muscle pain) and high fever. Diagnosis is most commonly made using indirect immunofluorescence assay or PCR. Treatment is with doxycycline or quinolone antibiotics.
Cholera
Cholera is caused by the comma-shaped, gram negative Vibrio cholera bacterium. Individuals acquire cholera by ingesting food or water contaminated by fecal material from patients or carriers. Once the bacteria enter the body, the incubation period is 12 to 72 hours. The bacteria adhere to the intestinal mucosa of the small intestine, where they are not invasive but secrete choleragen, a cholera toxin which enters the intestinal epithelial cells and activates the enzyme adenylate cyclase and stimulates hypersercetion of water and chloride ions while inhibiting absorption of sodium ions.
The patient loses massive quantities of fluid and electrolytes, causing abdominal muscle cramps, vomiting, fever and watery diarrhea. Death may result from the elevated concentrations of blood proteins, caused by reduced fluid levels, which leads to circulatory shock and collapse. Laboratory diagnosis is by culture of the bacterium from feces and subsequent identification by agglutination reactions. Treatment is by oral rehydration therapy with NaCl plus Glucose. The antibiotics of choice are tetracycline or ciprofloxacin. The most reliable control methods are based on proper sanitation, especially of water supplies.
∙ Streptococcus pneumonia causes pneumonia, meningitis, and bacteremia. ∙ Mycobacterium tuberculosis Causes tuberculosis (TB), a serious respiratory infection.
∙ Escherichia coli (E. coli) - Certain strains cause urinary tract infections, gastroenteritis, etc
∙ Bordetella pertussis - Whooping cough
∙ Cornybacterium diphtheria - Diphtheria
Pathogenic Fungi
Pathogenic mechanisms
1. Adherence and Colonization: Fungi attach to host tissues through adhesion molecules, allowing them to colonize on skin, mucous membranes, and internal organs.
2. Invasion: Some fungi produce enzymes like proteases, lipases, and keratinases that degrade host tissues, facilitating tissue invasion. For example, dermatophytes break down keratin in the skin, nails, and hair.
3. Toxin Production: Fungi can produce mycotoxins, which can cause cell damage, immune suppression, or toxic effects when ingested or inhaled by the host. 4. Immune Evasion: Fungi can evade the host’s immune response by producing a capsule (as in Cryptococcus neoformans) or altering their surface antigens. 5. Dimorphism: Many pathogenic fungi, like Histoplasma and Candida, can switch between different forms (yeast and mold), aiding survival inside the human body. 6. Biofilm Formation: Fungi, like Candida, can form biofilms, which provide protection from the immune system and increase resistance to antifungal treatments.
Blastomycosis
It is caused by Blastomyces dermatitidis, a fungus that grows as a budding yeast in humans but as a mold on culture media and in the environment. The initial infection begins when blastospores are inhaled into the lungs. The fungus can then spread rapidly, especially to the skin, where cutaneous ulcers and abscess formation occur. B dermatitidis can be isolated from pus and biopsy sections. Diagnosis requires the demonstration of thick
walled yeast –like cells, 8 to 15 micrometer in diameter. Amphotericin B, Itaconazole or ketoconazole are the drugs of choice for treatment.
Cryptococcosis
This is a systemic mycosis caused by Cryptococcus neoformans. The fungus enters the body through the respiratory tract, causing a minor pulmonary infection that is usually transitory. Some pulmonary infections spread to the skin, bones, viscera and central nervous system. Once the central nervous system is involved, cryptococcal meningitis
results. Diagnosis is accomplished by detection of thick walled, spherical yeasts cells in pus, sputum, etc. The fungus can be easily cultured on Sabouraud dextrose agar. Treatment includes amphotericin B or itraconazole.
Histoplasmosis
It is caused by Histoplasma capsulatum. This fungus is seen on rotting trees and in soil. Inhalation of spores liberated in air causes infection. Most of the infections are asymptomatic, but sometimes the fungus can cause intracellular infection of the reticuloendothelial system. This infection results in lymphadenopathy, hepatosplenomegaly, fever and anaemia which is highly fatal. Some people develop pulmonary disease resembling tuberculosis or TB. Laboratory diagnosis is accomplished by complement-fixation tests and isolation of the fungus from tissue specimens. Currently the most effective treatment is with amphotericin B, ketoconazole or itraconazole .
∙ Candida albicans causes candidiasis, including oral thrush, vaginal yeast infections, and systemic candidiasis.
∙ Aspergillus fumigatus causes aspergillosis, including allergic bronchopulmonary aspergillosis, invasive aspergillosis, and aspergilloma.
∙ Trichophyton rubrum causes dermatophytosis (ringworm), affecting the skin, hair, and nails.
Pathogenic Protozoa
Pathogenic mechanisms
1. Adherence and Invasion: Protozoa can attach to host tissues using surface proteins or structures like flagella. Some protozoa, such as Entamoeba histolytica, invade tissues by secreting enzymes that degrade host cell membranes, allowing them to penetrate and destroy cells.
2. Immune Evasion: Protozoa have evolved various ways to evade the host's immune response. For example, Plasmodium (which causes malaria) hides inside red blood cells while Trypanosoma undergoes antigenic variation, constantly changing its surface proteins to evade the immune system.
3. Toxin Production: Some protozoa, such as Entamoeba histolytica, secrete cytotoxins that directly damage host tissues, leading to cell death and tissue destruction.
4. Nutrient Deprivation: Many protozoa deprive host cells of nutrients. For instance, Giardia lamblia attaches to the intestinal wall, interfering with nutrient absorption, leading to malnutrition and diarrhea.
5. Host Cell Destruction: Certain protozoa, like Plasmodium in malaria, replicate inside host cells (red blood cells) and cause them to burst
6. Modulation of Host Immune Response: Some protozoa manipulate the host’s immune system. Leishmania can survive inside macrophages by suppressing the host’s immune response.
Amoebiasis
Infection is caused by the amoeba Entamoeba histolytica. Entamoeba histolytica infection does not always result in disease. It may remain in colon asymptomatically and the persons act as carriers. When the amoeba invades the intestinal tissue, they cause disease which occurs in 10 % cases of infection only. This results in ulcers and destroy tissues by necrosis and forms abscess. Amoebic ulcer is flask shaped with narrow mouth and neck and large round base. These ulcers release necrotic material containing the pathogen. Some amoeba may get released into blood circulation during intestinal wall invasion and reach liver. In liver they multiply and cause necrosis and inflammatory response. Results in liver enlargement and is known as amoebic hepatitis. Untreated abscess may result in release of amoebae to other organs such as stomach, pericardium, skin, lung etc. The incubation period varies from 4 days to one year. Lab diagnosis is done by Macroscopic observation – semiliquid, brownish black foul smelling fecal matter containing blood and pus or by Microscopic observation of pus cells, epithelial cells, etc in the stool or sputum of patients. Treatment is done by using amoebicides such as iodoquinol, paromomycin, emetine, chloroquine.
Malaria
Malaria is a mosquito-borne infectious disease of humans and other animals caused by protozoa of the genus Plasmodium. Four species of Plasmodium cause malaria - Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale and Plasmodium malariae. P falciparum and P vivax most commonly cause infections. The vector for plasmodium is female anopheles’ mosquito. When an infective female Anopheles mosquito bites man, it inoculates saliva containing sporozoites (infective stage) to human. Sporozoites reach the blood stream and within 30 minutes enter the parenchymal cells of the liver and multiplication occurs. RBC’s or other parenchymal liver cells are also infected. Incubation period varies and an average is 8-40 days. Malarial symptoms are periodic bouts of fever with rigor (shaking and shivering), followed by anaemia and splenomegaly. Serologic procedures such as ELISA, RIA, heamagglutination, immunoflourescence are available but they are used for epidemiological surveys or for screening blood donors.
∙ Trypanosoma brucei Causes African sleeping sickness (trypanosomiasis), leading to neurological symptoms and death if untreated.
∙ Giardia lamblia Causes giardiasis, leading to diarrhea, malabsorption, and abdominal cramps.
∙ Toxoplasma gondii Causes toxoplasmosis, which is particularly dangerous in pregnant women and immunocompromised individuals.
Pathogenic Viruses
Pathogenic mechanisms
1. Cell Damage and Lysis: Viruses can cause direct damage by destroying host cells during replication. Many viruses cause cell lysis, releasing new viral particles by bursting the host cell, leading to tissue damage.
2. Immune Evasion: Viruses have evolved mechanisms to evade the host immune response. They may downregulate host immune responses or undergo antigenic variation to escape immune detection.
3. Latency and Reactivation: Some viruses, like herpesviruses, establish a latent infection, remaining dormant in host cells for long periods. These viruses can reactivate under certain conditions, causing recurrent infections.
4. Exaggerated host Immune Response: An excessive immune response (cytokine storm) cause widespread inflammation and tissue damage, as seen in severe cases of COVID-19.
Mumps
It is an acute, generalized disease that occurs primarily in school children. The virus is transmitted in saliva and respiratory droplets. The port of entry is the respiratory tract. The virus replicates in the nasopharynx and lymph nodes of an infected person. The most prominent manifestations of mumps are swelling and tenderness of the salivary glands 16 to 18 days after infection by virus. The swelling usually lasts for 1 to 2 weeks and is accompanied by a low grade fever. Severe complications of mumps are rare, however, meningitis and inflammation of the epididymis and testes may occur as complications associated with this disease-especially in male. Therapy of mumps is limited to symptomatic and supportive measures. A live, attenuated mumps virus vaccine is available. It usually is given as part of the trivalent MMR vaccine.
Rubella (German measles)
It was first described in Germany in the 1800s and was subsequently called German measles. It is a moderately contagious disease that occurs primarily in children 5 to 9 years of age. It is caused by the rubella virus. This virus is spread in droplets that are shed from the respiratory secretions of infected individuals. Once the virus is inside the body, the incubation period ranges from 12 to 23 days. A rash of small red spots, usually lasting no more than 3 days and a light fever are the normal symptoms. Rubella can be a dangerous disease in the first trimester of pregnancy and can lead to fetal death, premature delivery, or a wide array of congenital defect that affect the heart, eyes and ears of the baby. The live attenuated rubella vaccine is recommended.
Poliomyelitis
Poliomyelitis or polio or infantile paralysis is caused by the poliovirus, a member of the family Picronaviridae.The poliovirus can remain infectious for relatively long periods in food and water-its main routes of transmission. The average incubation period is 6 to 20 days. Once ingested, the virus multiplies in the mucosa of the throat or small intestine.
Generally, there are either no symptoms or a brief illness characterized by fever, headache, sore throat, vomiting and loss of appetite. In minority of cases the viremia persists and the virus enters the central nervous system and causes paralytic polio and results in motor and muscle paralysis. Formalin inactivated salk vaccine or the attenuated virus sabin vaccine is used for vaccination
Hepatitis A
The disease is caused by the Hepatitis A virus. Hepatitis A usually is transmitted by fecal –oral contamination of food, drink or shellfish that live in contaminated water and contain the virus in their digestive system. Once in the digestive system, the viruses multiply within the intestinal epithelium. Usually only mild intestinal symptoms result. Occasionally viremia occurs and the viruses may spread to the liver. The virus reproduces in the liver, enter the bile and are released into the small intestine. Symptoms last from 2 to 20 days and include anorexia, general malaise, nausea, diarrhea, fever and chills. If the liver becomes infected, jaundice ensues. Laboratory diagnosis is by detection of anti hepatitis A antibody. Control of infection can be done by simple hygienic measures.
∙ Influenza Virus Causes influenza (flu), characterized by fever, cough, and body aches.
∙ Human Immunodeficiency Virus (HIV) Causes acquired immunodeficiency syndrome (AIDS), leading to severe immune system compromise and opportunistic infections.
∙ Hepatitis B Virus (HBV) Causes hepatitis B, leading to liver inflammation, cirrhosis, and hepatocellular carcinoma.
∙ Herpes Simplex Virus (HSV) Causes oral and genital herpes, characterized by painful blisters and ulcers.
∙ SARS-CoV-2 Causes COVID-19, characterized by respiratory symptoms, fever, and in severe cases, acute respiratory distress syndrome (ARDS).
