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0900L - MODULE 7.0 INFECTIOUS EXPOSURES

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Copyright by Professor Omar Hasan Kasule Sr


MODULE OUTLINE

7.1 CONCEPTS
7.1.1 Epidemiological Characterization
7.1.2 The Agent: Micro-Organism
7.1.3 The Host
7.1.4 The Disease
7.1.5 Control and Prevention of Communicable Disease

7.2 VIRUSES
7.2.1 Viral Infections: Feco-Oral
7.2.2 Viral Infections: Air-Borne
7.2.3 Viral Infections: Vector-Borne
72.4 Viral Infections: Parenteral
7.2.5 Viral Infections: Others

7.3 PROKARYOTES
7.3.1 Bacteria Infections: Feco-Oral
7.3.2 Bacterial Infections: Droplet Spread
7.3.3 Bacterial Infections: Sexually Transmitted
7.3.4 Bacterial Infections: Others
7.3.5 Chlamydial & Rickettsial Infections

7.4 EUKARYOTES
7.4.1 Protozoal Infections
7.4.2 Helminthic Infestations
7.4.3 Fungal Infections

7.5 EMERGING and RE-EMERGING INFECTIONS
7.5.1 Over-View
7.5.2 Sexually Transmitted Diseases
7.5.3 Viral Diseases
7.5.4 Bacterial Diseases
7.5.5 Parasitic Diseases:


UNIT 7.1

CONCEPTS


Learning Objectives:


·    Incidence and prevalence
·    Attack rates (primary & secondary), case fatality ratio.
·    The causal triangle: agent (types of micro-organisms, transmission routes with examples for each route), host (susceptibility), and disease (natural history, clinical features)
·    Methods of transmission
·    Difference between control and eradication of communicable disease
·    Prevention of communicable disease (primary, secondary, tertiary) and surveillance
·    Investigation and management of a disease out-break


Key Words and Terms:


·    Agent
·    Anti-biosis
·    Attack rate
·    Bacteria
·    Carrier state
·    Case fatality ratio
·    Communicable disease
·    Contagion
·    Cross-infection
·    Culture of micro-organisms
·    Desease reservoir
·    Disease control
·    Disease eradication
·    Disease outbreak
·    Disease vector
·    Drug resistance
·    Germ
·    Horizontal transmission
·    Host
·    Immunization
·    Incubation
·    Infection
·    Isolation
·    Latency
·    Microbial sensitivity
·    Micro-organism
·    Natural history
·    Parasite
·    Prevention: 1ry, 2ry, 3ry
·    Reservoir host
·    Sexually transmitted disease
·    Superinfection
·    Tachyphyllaxis
·    Trans-infection
·    Transmission
·    Vaccination
·    Vector
·    Vertical transmission
·    Virus



UNIT OUTLINE:

7.1.1 EPIDEMIOLOGICAL CHARACTERIZATION
A. Definitions
B. Communicable Disease Model
C. Rates & Proportions
D. Epidemiology
E. Trends of Incidence

7.1.2 THE AGENT: MICRO-ORGANISM
A. Complex Interactions
B. Classification of Microorganisms
C. Description of Major Groups of Microorganisms
D. Transmission
E.  Environment-Related Factors

7.1.3 THE HOST
A. Humans Hosts:
B. Susceptibility:
C. Spread of Infection
D. Host Response

7.1.4 THE DISEASE
A. Clinical Severity
B. Clinical Manifestations
C. Natural History
D. Epidemicity
E. Epidemiological Models

7.1.5 CONTROL and PREVENTION OF COMMUNICABLE DISEASE
A. Control Strategy
B. Primary Prevention
C. Secondary Prevention
D. Tertiary Prevention
E. Control of Disease Outbreak
F. Breaking the Transmission Cycle by Type of Disease


7.1.1 EPIDEMIOLOGICAL CHARACTERIZATION
A. DEFINITIONS
Infectious disease is disease transferred from person to person by micro-organisms. Infectious disease results from the action of the infectious agent or its products. The terms communicable disease and infectious disease are synonymous. Infection is the process of lodging, growing, and multiplication of micro-organism in host’s body. Invasion is mere presence of micro-organism in body of host without necessarily multiplying. Infestation is  . Infectivity is the ability of the infective agent to lodge and grow in the host. Pathogenicity is the ability of the organism to cause disease and is measured as the proportion of the number of infected poersons with clinical disease to the total number of infected person. Virulence is the ability to cause severe disease. The measles and varicella zoster viruses are very pathogenic but not virulent. HIV is very virulent since all those affected eventually die. Pathogenicity is affected by invasiveness, toxigenicity, and hypersensitivity. Some organisms like shigella invade tissues. Others like Cl. Botulinum produce toxins. Mycobacterium tuberculosis causes hypersensitivity or allergic reactions in the host. An epidemic is said to occur when the epidemic threshold is breached. The term epidemic is used to refer to a wide-spread disease whereas the term outbreak is used to refer to localized disease.
B. COMMUNICABLE DISEASE MODEL
THE TRIAD
The communicable disease model comprises of the three minimum factors needed for occurrence and spread of disease: the agent, the host, and the environment.  The environment, physical or biological, may inhibit or promote disease transmission. Disease transmission occurs when a susceptible host and a pathogenic agent exist in an environment conducive to disease transmission.                                                

GASTRIC INFECTION – PEPTIC ULCER
Peptic ulceration is a problem in both developed and less developed countries. The disease is a result of interplay of genetic and environmental factors. Death from PU complications rises with age. H. pylori infection and use of non-steroidal anti-inflammatory drugs are factors determining severity of the disease. Smoking increases the risk of PU. There is no evidence for the role of diet or stress in PU. H. pylori infection is found in association with PU. Its eradication leads to subsiding of PU symptoms. PU infection is acquired in childhood due to poor sanitation. Most of those infected do not develop the ulcer. The risk of H.pylori infection is falling in Europe and America.

INTESTINAL INFECTION
Intestinal infections present as watery diarrhoea, bloody diarhoea (dysentery), or chronic diarrhoea with or without steatorrhoea. Watery diarrhoea is self limiting and resolves within 5-7 days. It requires only fluid and electrolyte replacement. Dysentery and chronic diarrhoea require specific treatment. The prevalence of intestinal infections is higher in less developed countries because of poor sanitation, water shortage, poor hygiene, and crowding. Intestinal infections still accounts for substantial morbidity in developed countries. Intestinal infection in the US is on the increase. Most intestinal infections are self limiting and a very small proportion is notified. Children bear the heaviest burden of intestinal infections.

The following are factors in intestinal infection: travel, immunodeficiency, institutional living, dat care, reduced gastric acid secretion, extremes of age, swimming, eating raw fish, eating partially cooked eggs, and eating myonnaise. Intestinal infections are transmitted by the feco-oral route. Humans are the major reservoirs of intestinal infections. Salmonella spp and Cl. Jejuni are exceptions because they have animal reservoirs. The majority of bacterial enteropathogens have seasonality. Cholera occurs more in the rainy season. Parasites occur more in winter because their cysts can survive better in the cold climate. Ritavirus infection is more common in the winter. Intestinal infections are prevented by interrupting the fecal-oral transmission route. Thus is achieved by using clean potable water, safe fecal disposal, personal hygiene, and food hygiene. Propyhllatic antibiotics can be used at half the therapeutic dose. Vaccination can be carried out for cholera, salmonella spp. and shigella spp. The evidence for probiotics in prevention is not definitive.

C. RATES & PROPORTIONS
The primary attack rate is defined as the number of new cases of disease expressed as a proportion of the total susceptible population. The secondary attack rate is defined as the number of additional cases of disease among contacts of the primary or index cases within the maximum incubation period expressed as proportion of the  total number of susceptible contacts. The case fatality ratio is number of fatal outcomes expressed as a proportion of the total number of cases with symptomatic illness.

D. EPIDEMIOLOGY
Correct and complete incidence and prevalence on communicable diseases is not available for many diseases. This is due to incomplete reporting and non-detection of sub-clinical cases.

E. TRENDS OF INCIDENCE
Most morbidity & mortality in the world is due to microbials. Most of this mortality and morbidity is in the less developed countries of Asia, Africa, and Latin America. Infection patterns differ according to level of economic development. Less developed countries have higher incidence and prevalence of infectious diseases than the developed countries. Most less developed countries are experiencing a falling incidence of infection and mortality due to socio-economic improvement, specific and non-specific primary prevention (sanitation and immunisation).  In both LDC and industrialised countries, old diseases like small poxes are being controlled. Some old ones like TB and syphilis are re-emerging. New diseases related to lifestyle like HIV and other STDs are appearing and are increasing.

7.1.2 THE AGENT: MICRO-ORGANISM
A. COMPLEX INTERACTIONS
The interaction between human tissues and microorganisms is very complex. The most successful parasites do not destroy their human hosts. The profile of disease-causing microorganisms is changing. New agents are being discovered. Some old agents are being eradicated. New pathogenic effects are being discovered for old known agents. Some agents are undergoing changes in pathogenicity. Organisms like the influenza virus can avoid host immune defences because of their frequent antigenic shift. Many microorganisms like N. gonorrhea have developed resistance to antibiotics.

B. CLASSIFICATION OF MICROORGANISMS
There are several approaches to classification of microorganisms: cellular complexity, method of transmission, ability to cause disease, and method of interaction with humans. According to cellular complexity microorganisms can be classified as pro-karyotes, eucaryotes, and viruses. Prokaryotes comprise bacteria, rickettsiae, and chlamydia. Eucaryotes comprise fungi, protozoa, and helminths. Viruses are chemical entities with only rudimentary functions of life. Microorganisms can be classified according to the method of transmission. There are several methods of transmission: feco-oral, soil contact, water contact, skin contact, air transmission, contact with body fluids, and arthropod-borne transmission. Examples of organisms transmitted by the feco-oral metjhods are ameba, giardia, shigella, vibrio cholera, salmonella spp, hepatitis virus A&E, polio virus, and tapeworms. Examples of microorganisms transmitted by the soil are trichuris, ascaris, hookworms, strongyloides, and tetanus. Examples of microorganisms transmitted by water contact are schistosomiasis and guinea worm. Examples of microorganisms transmitted by contact with infectious skin rashes are chickenpox and smallpox. Examples of organisms transmitted by inhalation are measles, pertussis, diphtheria, and tuberculosis. The following microorganisms are transmitted by contact with infected body fluids: trachoma, syphilis, gonorrhoea, and HIV. Arthropod vectors transmit the dengue virus and the malarial protozoan. Microorganisms can be classified according to their ability to cause disease. The following parameters are used: infectivity, virulence, pathogenicity, toxigenicity, and the infective dose. Microorganisms can be classified according to their mode of interaction with the human host as saprophytic, parasitic, and symbiotic. Saprophytes live on dead organic matter. Parasites are dependent on the human host either as harmless commensals or as pathogenic parasites. Obligate parasites cannot exist outside their host. Non-obligate parasites are able to pursue an independent existence of they cannot find a host. Symbiotic relations involve mutualism and are mutually beneficial. Normal flora is bacteria in the body described as opportunist pathiogens. They are found in the mouth, URT, GIT, urethra, vagina, and the conjuctiva. They are beneficial to the body by preventing colonisation by pathogens as well as vitamin K synthesis. Normal flora can become opportunistic infections when they are in unusual sites or in conditions of reduced immunity.

C. DESCRIPTION OF MAJOR GROUPS OF  MICROORGANISMS
VIRUSES
Viruses are obligate intracellular parasites. They take over and use the cell's metabolism for their own replication. They are most vulnerable during transmission to and from the host. Viral infections are recognized by detection of viral antigens or antibodies to viral antigens. Among the commonly used serological techniques are: neutralization, hemagglutination inhibition, complement fixation, fluorescent antibody, radioimmunoassay, and ELISA. Small amounts of viruses can also be detected by cell culture.

BACTERIA
Normal healthy individuals have a lot of bacteria most of which are harmless normal flora that prevents colonization by pathogenic bacteria. Bacteria may produce pathogenicity by direct action on the tissues, producing toxins, proteases, and cytolysins. Bacteria adhere to specific sites on the cell and initiate damage of the cell wall and gain entrance to the interior of the cell. Enterotoxins act on intestinal villi to cause diarrhoea. Toxins produced by vibrio cholerae, clostridium, tetanus, diphtheria, and anthrax bacteria have various effects on body tissues. Bacteria can be destroyed in the blood stream before entering cells by humoral or cell-mediated immune defence mechanisms. Adherence to the cell wall may be blocked by antibodires. Bacteria have developed methods of avoiding desrruction both outside and inside the cell. Encapsulation provides protection against physical elements. Antibiotic resistance mediated by plasmids and other mechanisms protects against antibiotic effects. Diagnosis of bacterial infections is based on cultivation & identification, gram staining & microscopy, biochemical reactions, use of specific antibodies, and DNA hybridization.

FUNGI
Fungal infections are comparatively less common than viral, bacterial, protozoal, or helminthic infections. Fungal infection is usually by direct contact with the soil or inhalation from the air. Person to person transmission of fungal infections is rare, the exception being dermatophytoses. The route of transmission determines the form of disease. Cutaneous and muco-cutaneous infection follows direct contact with the soil. Pulmonary disease is due to air inhalation. Fungal infections are usually localized. Systemic infections are rare but could occur and in a severe form in cases of malignancy and other causes of immune deficiency. Fungi can cause disease on ingestion in food. Examples of fungal poisons, mycotoxins, are amanita phalloides, a type of mushroom, aflatoxins and aspergillus flavus. Diagnosis of fungal infection is difficult and is based on clinical or histological examination.

PROTOZOA
Protozoa are single-celled eucaryotic organisms widely distributed in the world in both parasitic and free-living forms. Protozoa have developed ways of avoiding host immune defences but are prudent enough not to destroy the host on whom they depend. This explains the high prevalence of protozoal infections but low morbidity levels. The following are protozoal species that are epidemiologically most important: plasmodium, toxoplasma, and pneumocytes. Plasmodia cause malaria that is the most important protozoal disease in terms of mortality and morbidity. P. falciparum causes more mortality and morbidity and is more important epidemiologically than the 3 other plasmodial species: P.ovale, P. vivax, and P. malariae. Red blood cells with HB-S, HB-F, or G6PD deficiency have natural resistance to malarial infection.  T.gondi is another protozoal infection with a high prevalence with little clinical disease. P. carinii is wide-spread and has become important epidemiologically because it is an opportunistic infection complicating HIV/AIDS.

HELMINTHS
There are 3 types of helminths: flat worms also caled cestodes, flukes also called trematodes, and roundworms also called nematodes. Helminths are widely distributed in the world but most species are in the tropics. Helminths can reside in human hosts for years producing eggs or larvae. They however cannot complete their life cycle in the human host. They have to live in the soil or other hosts for part of the lifecycle. Helminths are transmitted by vertebrate or invertebrate vectors. Helminths that migrate in the blood stream or that invade tissues can elicit an immune response. Those that infest the intestines elicit no immune response. The most important helminths from the epidemiological perspective are: schistosomiasis, hookworm, stringyloides, echinococcus, tenia, and toxicara. Schistosomiasis is of major worldwide epidemiological importance. Hookworm by causing chronic blood loss is responsible for a lot of malnutrition. S.stercoralis can live freely but also as a human parasite being able to live asymptomatically in the human body for 30 years or more. Strongyloides commonly causes intestinal disease; pulomnary disease occurs but is rare. It is associated with severe morbidity and mortality in immune-compromised persons. The larval stages of the following helminths are of epidemiological importance: echinococcus granulosus causing hydatid disease, echinococcus multiocularis causing hydatid disease, tenia solium causing cysticercosis, and toxacara canis causing visceral larva migrans.

D. TRANSMISSION
SURVIVAL
During part of its lifecycle, the microorganism passes from one human host to another. It can also pass from the outside environment to the human host and vice versa. In a group of diseases called zoonoses, transmission is from animal to the human host. It is most vulnerable to destruction during the stage of transmission to the host. Microorganisms can survive adverse conditions and be transmitted by living in reservoirs, persistence in spores, latency, and growing in the vector or an intermediate host. Resrvoirs can be humans, animals, or the soil..  Clostridia are bacteria that can survive long periods in the soil in an encapsulated form. EBV and CMV are examples of microorganisms that survive for a long time in a latent form.

RESERVOIRS
Some microorganisms survive in reservoirs until they can infect humans. These reservoirs are intermediate animal hosts required to complete the lifecycle. Reservoirs that do not get diseased are more dangerous for humans because eradication is more difficult. Diseases without reservoirs are easier to eradicate. This explains the eradication of small pox because it has no natural resrvoir. There are about 150 zoonoses. Direct zoonoses require only one animal reservoir for example rabies, brucellosis, and trichnosis. Cyclozoonozes like the tapeworm require at least 2 vertebrate species to complete the life cycle. Metazoonoses like the schistosoma helminth and the yellow fever virus require an intermediate invertebrate host. Saprozoonoses like coccidiomycosis require an inanimate intermediary in addition to an animal reservoir.

VECTORS
Vectors are organisms that tranfer the microorganisms. The transmission may be mechanical (eg flies and cockroaches) or hematophangous (eg ticks, lice, fleas, mites). Hematophagous transmission involves growth and replication in the vector. Replication within the host increases the number of infective microorganisms and thus enhances the infection potential.

ROUTES OF TRANSMISSION, SOURCES OF INFECTION and PORTALS OF ENTRY and EXIT
Transmission is described as common vehicle spread for example by water, air of food or as serial transmission when it is human to human, human to animal to human, or human to the environment to human. Transmission may be direct or indirect. Indirect transmission may be vehicle-borne eg by fomites, vector-borne (mechanical and biological) or airborne (droplets or dust). Infection can be exogenous or endogenous. Exogenous infection is from outside the body of the host. It can be from humans, transient or chronic carriers, or the environment. Endogenous infection is from within the body of the host. The phenomenon of auto-infection found in strongyloides and E.coli are examples of auto-infection. Disease transmission may be horizontal or vertical; the horizontal being more common. Horizontal transmission is from one human to another. Vertical transmission is intra-uterine from the mother to the fetus. The natural portals of entry into human are the respiratory tract (common cold, influenza, measles, TB, whooping cough), the urogenital tract (gonorrhoea, syphilis, herpes, HIV), the alimentary tract (amebic dysentery, shigellosis, polio, and cholera), the mucous membranes, the skin, the placenta (rubella, syphilis, and HBV), and the parenteral portal (intravenious and sexual). The skin is a good natural barrier to infection but can be penetrated by insects, ticks, needles, and traumatic injuries. The chain of infection starts with the pathogen in the reservoir (case, carrier, animal). It goes out from a portal of exit and is transmitted to the portal of entry. It enters the new host where it is established to cause disease. 

HORIZONTAL TRANSMISSION
Horizontal transmission may be direct or incirect. Direct horizontal transmission causes immediate infection and occur in 4 forms: direct contact with the skin by biting or touch (eg hookworm), inoculation of the micro-organism (eg STD), ingestion of the micro-organism in food, drink, or contact with fomites (eg E.coli), and aerial/droplet spread (eg measles). Indirect horizonal transmission may be airborne, vehicle-borne, or vector-borne. The involvement of an intermediate host or vector causes delayed disease. Air-borne infections are carried as microbial erosols for example TB, influenza, histoplasmosis, and legionellosis. Vehicle borne transmission is by contaminated materials or objects (fomites) for example toys, handkerchiefs, soiled clothes, beddings, food service utensils, surgical instruments, water, blood, milk, organs and tissues. The vectors may be arthropods (such as mosquitoes, fleas, flies, lice, and ticks), zoonoses, plants, or other vehicles. They transmit organisms either mechanically or biologically. Dysentary and polio are examples of mechanical transmission. Biological transmission is more common than mechanical transmission. Arthropods transmit microorganisms from one animal to another with humans being only accidental hosts like in plague. Mosquitoes transmit yellow fever, dengue, and malaria. Flies transmit African trypanosomiasis, onchocerciasis, loaiasis, and leishmaniasis. Ticks transmit rock mountain spotted fever, relapsing fever, and Lyme disease. Fleas transmit plague, and murine tyohus. Lice transmit epidemic typhus and trench fever. Kissing bugs transmit Chagga’s disesse. Zoonoses are diseases of whose reservoirs are vertebrates animals and are transmitted to humans by accident for example plague, rabies, rocky mountain spotted fever. Antrhoponooses are diseases whose reservoirs are human for example measles. Plants can be vectors of disease when they are contaminated by micro-organisms and are eaten raw.

VERTICAL TRANSMISSION
The vertical route of disease transmission is trans-placental transmission in utero. It is thought but not yet decisively proved that the following organisms can be transmitted vertically: ?CMV, ?toxoplasma, ?rubella, ?HSV, ?syphilis, ?TB, ?VZ.

MATHEMATICAL MODELS OF DISEASE TRANSMISSION
We can predict microbial transmission using mathematica models that have been developed from empirical observations. The factors of transmission probability are: the infected host, the susceptible host, contact, and the parasite. The basic reproductive number, R0, is the number of contacts per unit time x transmission probability per unit time x duration of infectiousness. An approximate formula for the basic reproductive number is R0 = 1 + L/A where L = average lifespan of an individual in the population and A = average age at infection. The serial interval or generation time is the time between two generations of infection.

E.  ENVIRONMENT-RELATED FACTORS
The concept of the communicable disease triangle simplifies discussion of communicable disease. The triangle consists of the agent, the host, and the disease. They interact among one another. Elements of the environment that affect disease transmission are: climate (temperature, rain, wind patterns), vegetation (swamps, forest, and desert), water sanitation, air pollution, excreta disposal, housing, occupation (farm, factory). Poor sanitation and crowding increase the transmission of microorganisms. Breeding places near homes, forest reservoirs, and soil help the survival of organisms and their vectors.

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