In response to infection, your immune system springs into action. White blood cells , antibodies , and other mechanisms go to work to rid your body of the foreign invader. Indeed, many of the symptoms that make a person suffer during an infection—fever, malaise, headache, rash—result from the activities of the immune system trying to eliminate the infection from the body. Pathogenic microbes challenge the immune system in many ways.
Viruses make us sick by killing cells or disrupting cell function. Many bacteria make us sick in the same way that viruses do, but they also have other strategies at their disposal. Sometimes bacteria multiply so rapidly they crowd out host tissues and disrupt normal function. Sometimes they kill cells and tissues outright. The protozoa that cause malaria , which are members of the genus Plasmodium, have complex life cycles.
Sporozoites, the stage of the parasite that infects new hosts, develop in the salivary glands of Anopheles mosquitos. Pathogens with low virulence would more likely result in mild signs and symptoms of disease, such as low-grade fever, headache, or muscle aches. Some individuals might even be asymptomatic. An example of a highly virulent microorganism is Bacillus anthracis , the pathogen responsible for anthrax.
The most serious form of anthrax is inhalation anthrax. After B. An active infection develops and the bacteria release potent toxins that cause edema fluid buildup in tissues , hypoxia a condition preventing oxygen from reaching tissues , and necrosis cell death and inflammation. Signs and symptoms of inhalation anthrax include high fever, difficulty breathing, vomiting and coughing up blood, and severe chest pains suggestive of a heart attack.
With inhalation anthrax, the toxins and bacteria enter the bloodstream, which can lead to multi-organ failure and death of the patient. If a gene or genes involved in pathogenesis is inactivated, the bacteria become less virulent or nonpathogenic. Figure 2. A graph like this is used to determine LD 50 by plotting pathogen concentration against the percent of infected test animals that have died.
Virulence of a pathogen can be quantified using controlled experiments with laboratory animals. Two important indicators of virulence are the median infectious dose ID 50 and the median lethal dose LD 50 , both of which are typically determined experimentally using animal models. To calculate these values, each group of animals is inoculated with one of a range of known numbers of pathogen cells or virions.
In graphs like the one shown in Figure 2, the percentage of animals that have been infected for ID 50 or killed for LD 50 is plotted against the concentration of pathogen inoculated. Figure 2 represents data graphed from a hypothetical experiment measuring the LD 50 of a pathogen.
Interpretation of the data from this graph indicates that the LD 50 of the pathogen for the test animals is 10 4 pathogen cells or virions depending upon the pathogen studied. Table 2 lists selected foodborne pathogens and their ID 50 values in humans as determined from epidemiologic data and studies on human volunteers. Keep in mind that these are median values. The actual infective dose for an individual can vary widely, depending on factors such as route of entry; the age, health, and immune status of the host; and environmental and pathogen-specific factors such as susceptibility to the acidic pH of the stomach.
For example, just a single cell of Salmonella enterica serotype Typhimurium can result in an active infection. In contrast, S. Pathogens can be classified as either primary pathogens or opportunistic pathogens.
Individuals susceptible to opportunistic infections include the very young, the elderly, women who are pregnant, patients undergoing chemotherapy, people with immunodeficiencies such as acquired immunodeficiency syndrome [AIDS] , patients who are recovering from surgery, and those who have had a breach of protective barriers such as a severe wound or burn. An example of a primary pathogen is enterohemorrhagic E.
This toxin inhibits protein synthesis, leading to severe and bloody diarrhea, inflammation, and renal failure, even in patients with healthy immune systems.
Staphylococcus epidermidis , on the other hand, is an opportunistic pathogen that is among the most frequent causes of nosocomial disease. However, in hospitals, it can also grow in biofilms that form on catheters, implants, or other devices that are inserted into the body during surgical procedures.
Once inside the body, S. Other members of the normal microbiota can also cause opportunistic infections under certain conditions. This often occurs when microbes that reside harmlessly in one body location end up in a different body system, where they cause disease.
For example, E. This is the leading cause of urinary tract infections among women. Members of the normal microbiota may also cause disease when a shift in the environment of the body leads to overgrowth of a particular microorganism. For example, the yeast Candida is part of the normal microbiota of the skin, mouth, intestine, and vagina, but its population is kept in check by other organisms of the microbiota.
If an individual is taking antibacterial medications, however, bacteria that would normally inhibit the growth of Candida can be killed off, leading to a sudden growth in the population of Candida , which is not affected by antibacterial medications because it is a fungus.
An overgrowth of Candida can manifest as oral thrush growth on mouth, throat, and tongue , a vaginal yeast infection , or cutaneous candidiasis. Other scenarios can also provide opportunities for Candida infections. Untreated diabetes can result in a high concentration of glucose in the saliva, which provides an optimal environment for the growth of Candida, resulting in thrush. Vaginal yeast infections can result from decreases in estrogen levels during the menstruation or menopause.
The amount of glycogen available to lactobacilli in the vagina is controlled by levels of estrogen; when estrogen levels are low, lactobacilli produce less lactic acid. The resultant increase in vaginal pH allows overgrowth of Candida in the vagina.
To cause disease, a pathogen must successfully achieve four steps or stages of pathogenesis : exposure contact , adhesion colonization , invasion, and infection. In many cases, the cycle is completed when the pathogen exits the host and is transmitted to a new host. An encounter with a potential pathogen is known as exposure or contact. The food we eat and the objects we handle are all ways that we can come into contact with potential pathogens.
Yet, not all contacts result in infection and disease. For a pathogen to cause disease, it needs to be able to gain access into host tissue. An anatomic site through which pathogens can pass into host tissue is called a portal of entry. These are locations where the host cells are in direct contact with the external environment. Major portals of entry are identified in Figure 3 and include the skin, mucous membranes, and parenteral routes. Figure 3. Shown are different portals of entry where pathogens can gain access into the body.
With the exception of the placenta, many of these locations are directly exposed to the external environment. Mucosal surfaces are the most important portals of entry for microbes; these include the mucous membranes of the respiratory tract, the gastrointestinal tract, and the genitourinary tract.
Although most mucosal surfaces are in the interior of the body, some are contiguous with the external skin at various body openings, including the eyes, nose, mouth, urethra, and anus. Most pathogens are suited to a particular portal of entry. The respiratory and gastrointestinal tracts are particularly vulnerable portals of entry because particles that include microorganisms are constantly inhaled or ingested, respectively. Pathogens can also enter through a breach in the protective barriers of the skin and mucous membranes.
Pathogens that enter the body in this way are said to enter by the parenteral route. For example, the skin is a good natural barrier to pathogens, but breaks in the skin e. In pregnant women, the placenta normally prevents microorganisms from passing from the mother to the fetus. However, a few pathogens are capable of crossing the blood-placental barrier. The gram-positive bacterium Listeria monocytogenes , which causes the foodborne disease listeriosis, is one example that poses a serious risk to the fetus and can sometimes lead to spontaneous abortion.
Other pathogens that can pass the placental barrier to infect the fetus are known collectively by the acronym TORCH Table 3. Transmission of infectious diseases from mother to baby is also a concern at the time of birth when the baby passes through the birth canal. Babies whose mothers have active chlamydia or gonorrhea infections may be exposed to the causative pathogens in the vagina, which can result in eye infections that lead to blindness. Fifth disease erythema infectiosum Treponema pallidum bacterium.
Upon learning that Pankaj became sick the day after the party, the physician orders a blood test to check for pathogens associated with foodborne diseases. There he is to receive additional intravenous antibiotic therapy and fluids. Following the initial exposure, the pathogen adheres at the portal of entry. The term adhesion refers to the capability of pathogenic microbes to attach to the cells of the body using adhesion factors , and different pathogens use various mechanisms to adhere to the cells of host tissues.
Another situation where a resistance gene does not reach fixation arises when the protective variant is deleterious when homozygous, as in sickle cell anaemia. We might also speculate that the evolutionary potential and high genetic diversity of most pathogens limits our ability to detect protective variants in the human genome, particularly so if these were only effective against a subset of lineages within a pathogenic species.
In addition to the few variants protective against specific pathogens, we also know of genomic regions involved in immunity against a wide spectrum of pathogens, such as interleukin genes or the major histocompatibility complex MHC system.
The very high genetic diversity of the MHC is believed to have been shaped by exposure to different pathogen species [ 18 ]. Also, following the recent development of techniques to sequence ancient DNA, it has been suggested that immunity genes such as those encoding toll-like receptors have been acquired following hybridization with archaic humans and are over-represented in the current gene pool of anatomically modern humans relative to genes not involved in immunity [ 19 , 20 ].
Infectious diseases had a massive impact on our history, leading to the rise and fall of civilizations, both through the toll they took on human life but also through economic and societal collapse following epidemics. Thucydides reports in his History of the Peloponnesian War , written in the 5 th century BC, how the plague of Athens devastated the city-state of Athens in ancient Greece during the second year of the Peloponnesian War BC when it was on the cusp of victory against Sparta, ending the golden age of Pericles and Athenian predominance in the ancient world.
The eventual fall of the Roman Empire was also largely down to another epidemic, the Justinian plague in — CE, which precluded the Emperor Justinian recovering lost territories in the western part of the empire [ 21 ].
Infectious disease played an equally important role in past human migrations. Conversely, one of the possible reasons Europeans managed to colonize Africa was that they used quinine, an antimalarial drug derived from the bark of the cinchona tree [ 23 ]. History has been shaped not only by pathogens infecting humans, but also those affecting domestic animals and crops. For example, it has been suggested that the Islamic conquest of the 7 th and 8 th centuries did not extend to Sub-Saharan Africa because the horses and camels of the Islamic armies were dying from trypanosma spread by tsetse flies [ 24 ].
Conversely, pathogens were at other times the drivers of large migration. Around one million Irish people died and another million migrated to the US to escape the famine caused by Phytophthora infestans destroying potato harvests between and [ 25 ].
At least in the developed world, the leading causes of human mortality are no longer infectious diseases but instead age-associated disorders such as cancer, heart disease and diabetes. Numerous countries have undergone an epidemiological transition, starting some years ago in some developed countries and less than 80 years ago for developing countries. Diseases that once devastated human populations, such as smallpox, are now eradicated.
Others, such as the plague or leprosy, are largely under control with the exception of a few hotspots. The current situation is, however, one of new challenges. Globalization and increased mobility, particularly air travel, have facilitated the transmission of diseases not just locally but between continents. The recent outbreak of Zika in the Americas, for example, has been attributed in part to an increase in air travel from infected areas into Brazilian airports, extending both the incidence and geographic range of the virus [ 26 ].
The outbreak of severe acute respiratory syndrome SARS and recurrent Ebola crises in Central Africa highlight the ability of new and existing diseases rapidly to become significant international health threats.
In addition, our ability to combat infectious diseases is also challenged by the widespread emergence of pathogen drug resistance. The global antimicrobial resistance AMR crisis is increasingly limiting our resources to combat disease through antimicrobial therapy. Thus, in spite of the global health narrative supporting a decline in the number of deaths caused by infectious disease, the complexity of our interactions with disease-causing agents are as significant now as through history.
Infectious diseases continue to be a major cause of mortality globally, responsible for between a quarter to a third of all deaths and nearly half of all deaths in people under the age of 45, with most of these in principle avoidable.
Microbiology by numbers. Nat Rev Microbiol. Revised estimates for the number of human and bacteria cells in the body. PLoS Biol. Google Scholar. The role of damselflies Odonata: Ztgoptera as paratenic hosts in the transmission of Halipegus eccentricus Digenea: Hemioridae to Anurans.
J Parasitol. Article PubMed Google Scholar. Red squirrels in the British Isles are infected with leprosy bacilli. A single natural nucleotide mutation alters bacterial pathogen host tropism. Nat Genet. Yersinia pestis, the cause of plague, is a recently emerged clone of Yersinia pseudotuberculosis. Insight into the evolution and origin of leprosy bacilli from the genome sequence of Mycobacterium lepromatosis.
Achtman M, Wagner M. Microbial diversity and the genetic nature of microbial species. Immunobiology and pathogenesis of viral hepatitis. Annu Rev Pathol. The influenza pandemic: insights for the 21st century. J Infect Dis. Infectious diseases of humans. Dynamics and control. Oxford: Oxford University Press; Myxoma virus and the leporipox viruses: an evolutionary paradigm.
Emerging fungal threats to animal, plant and ecosystem health. Age of the association between Helicobacter pylori and man. PLoS Pathog. Article Google Scholar. Myths and misconceptions: the origin and evolution of Mycobacterium tuberculosis. Hill AVS.
Evolution, revolution and heresy in the genetics of infectious disease susceptibility. Pathogen-driven selection and worldwide HLA class I diversity. Curr Biol. Genomic signatures of selective pressures and introgression from archaic hominins at human innate immunity genes. Am J Hum Genet. Introgression of Neandertal- and Denisovan-like haplotypes contributes to adaptive variation in human Toll-like receptors.
Nat Geosci. Insights from paleomicrobiology into the indigenous peoples of pre-colonial America - a review. Mem Inst Oswaldo Cruz. Webb Jr JLA. Malaria in Africa. History Compass. William CS. The historical spread of Trypanosoma evansi surra in camels: a factor in the weakening of Islam? In: Emery E, editor. London: RN Books; Turner RS. After the famine: plant pathology, Phytophthora infestans, and the late blight of potatoes, — Historical Studies Phys Biol Sci.
0コメント