Medical microbiology is a subdivision of microbiology that concerns the study of pathogenesis and epidemiology of microorganisms that can infect and cause disease symptoms in human beings. This subject specialization evolved to complement medical science with its hands-on applications as diagnostic and therapeutic guidance in disease management. The clinical facet of the field emphasizes on detecting the occurrence of microbial infections and its spread in individuals, the prognosis of the disease, and protocols for treatment. This individualistic concept derived from clinical microbiology must be elaborated to public health as most of the time the infectious diseases do not remain confined in one or few subjects, rather can spread, persist and affect a large number of people over time. This is true for all infectious diseases irrespective of the ailments being sporadic, endemic, epidemic, or pandemic. A cornerstone to this public health is the second facet of medical microbiology known as epidemiology. The word “Epidemiology”, is derived from Greek ‘epi’, meaning ‘upon, among’, ‘demos’, meaning ‘people, district’, and ‘logos’, meaning ‘study. Therefore epidemiology is the study of where-about of a disease and is considered to be the basic science of preventive medicine. An epidemiologist moves ahead of the biology of understanding the disease processes, and also relies on social sciences to elucidate proximate and distal causes, engineering for assessment of exposure to the disease and statistics to utilize the data/observation to reach apt inferences. This is because, for the prevention of infectious disease, it is crucial to understand the causative agents, risk factors, and circumstances that lead to a specific disease, and even simple interventions may break the chain of transmission. Clinical microbiology and epidemiology operate in cooperative and interdependent ways to determine the dynamics of infection and also accurate tracking of etiological agents.
Ignaz Semmelweis was the first to demonstrate the significance of epidemiology who by careful analysis of statistical data alone inferred about the mode of transmission of streptococcal puerperal fever. He also formulated handwashing to be a way out to prevent transmission decades before the discovery of the causal agent itself (Streptococcus pyogenes). Since then, each organism can be assigned with its profile of vital statistics contributing significantly to morbidity and mortality of human beings globally. Some agents are transmitted by air or water, some by food, and others by insects or other animals; many are en route from one person to another. Some agents occur globally, and others are limited in specific geographic locations or ecologic niche. Knowledge regarding the mode of transmission of the causal organism in the target population is crucial to understanding the disease. Considering the advent of new diseases, it is also essential to determine whether the etiological agent is truly novel or derivatized from previously existing ones. Unraveling mysterious outbreaks or identification of new epidemiologic patterns have often led to the path of isolating new agents.
Epidemiologists concentrate their study on population groups rather than on individuals. It can cohort studies where subjects are selected based on their exposure status, i.e., the study participants should be at risk of the outcome under investigation as the study initiates and will be followed through time to assess their later outcome status. Infectious disease epidemiology also considers the interaction between individuals within the population group in two ways-
(i) case-series study involving the qualitative study of the outcome in a single patient/ small group of patients with comparable diagnosis/ a statistical factor to cause illness with periods when they are unexposed. Considering a single patient or patients with a similar diagnosis, no inference can be drawn about the general population of patients. However, the identification of a unique feature of disease/ patient history may lead to the proposition of a new hypothesis regarding the natural history of the disease or possible causal factors.
(ii) case-control study which is a retrospective study of subjects who are disease positive (case) w.r.t. group of disease negative people (control) within the same population.
The Changing Picture of Infectious Disease Epidemiology
More than forty new pathogens have been identified in the last three decades, some of which are of global importance. Causative agents for infectious diseases are specific, but they may change over time. The best illustration of an etiological agent to undergo modifications that enable them to reinfect subjects that have already been infected and immune is the Influenza virus owing to antigenic shift and antigenic drift in surface antigens (H and/or N).
In recent times all over the world, there has been an increase in the number of people who are at high risk for infectious disease. Improvement in health –care and increased life expectancy in developed countries have led to an increase in the number of people who are aged and /or immune-deficient (cancer survivors, transplant patients, or people on immunosuppressive drugs for long-term autoimmune diseases) predisposed to infectious diseases and developing life-threatening complications. In populations that were originally at low risk, adoption of altered lifestyles has increased opportunities for disease transmission. Intravascular drug injections, air travel, consumption of raw fish, ethnic foods expanded the area of distribution of a variety of infectious agents.
Infectious disease epidemiology is aimed at curtailing the influence of pathogens on public health. As both pathogens and their hosts have evolved, knowledge of evolutionary biology is pertinent to decipher the nature of their interactions for fitness, as well as to understand the history of pathogen transmission. Mathematical models can be used to study the effects of different selective markers (measurable biological and behavioral risk factors), whereas molecular data can be used to define different strains and their genetic variations. Recent progressions, particularly in the rapid determination of sequence data, have increased the propensity of evolutionary biology towards clinical microbiology.
Molecular strain typing
The practical science of infectious disease epidemiology involves the authentication of infectious etiologies through repeated isolation of a specific microorganism from patients with a given disease or syndrome as well as from animals, vectors, and environmental sources to identify reservoirs and modes of transmission. To prescribe effective therapy often it is essential to identify species of infecting microorganisms through phenotypic and genotypic characterization. Phenotypic methods like biotyping of biochemical profiles, phage typing, and serological typing help to characterize the products of gene expression to differentiate strains. But they are inadequate to provide enough unrelated parameters for proper reflection of genotype. Also, phenotypic methods tend to give variable results as many gene expressions are affected by spontaneous mutations, environmental conditions, or reversible phenotypic changes; therefore, they have been replaced by genotypic methods that rely on the analysis of the genetic structure of an organism. Highly sensitive and specific molecular techniques have recently been adopted to facilitate epidemiologic studies through the detection and characterization of the genetic variability of infectious agents (bacteria, fungi, protozoa, viruses). It necessitates the selection of molecular method(s) that can discriminate genetic variants at different hierarchical levels namely, above the level of species, between species, between intraspecific variants, etc. coupled with the selection of a region of nucleic acid suitable for interrogation. For bacterial fingerprinting RFLP-PFGE, RFLP+ probe & ribotyping have been the most commonly used. RAPD and karyotyping have been used for fingerprinting fungi while MLEE, RAPD, and PCR-RFLP have been used for parasitic protozoa. Except for whole-genome sequencing, the other molecular methods analyze only a small portion of the organisms’ genetic complement. For this reason, only whole-genome sequencing would provide the unequivocal data required to distinguish isolates exhibiting similar patterns despite being unrelated epidemiologically.
Omics and epidemiology
Application of omics to infectious disease epidemiology breaks free the study beyond single organisms. Next-generation sequencing technologies like the 454 Pyrosequencing (Roche, Branford, CT) and massively parallel sequencing by synthesis (Illumina, San Diego, CA) allow the characterization of the structure and functionality of microbial communities based on genetic sequence based on the sequence of the ribosomal genes ( rDNA ). Rapid sequencing technologies provide adequate data to characterize the microbial communities living on and in the human body, how they vary over periods, respond to treatment, and interact with pathogens. The Human Microbiome Project is an on-going effort funded by the National Institutes of Health to provide these parameters. Taxonomy based on the ribosomal gene sequence gives rise to operational taxonomic units (OTUs) or phylotypes that enable identification and characterization of minute variations in candidate species in a microbial community in terms of species richness, evenness, and diversity.
In the pretext of COVID-19 pandemic, interrogating epidemiology of viral and other infectious diseases has gained the utmost priority through the study of the complex relationships among hosts and infectious agents to reduce a load of pathogenicity on the public health sector globally. Epidemiologists are concerned with virus spread or transmission, with or without the disease. Viral epidemiologists try to envisage the potential for the development of epidemics, with the ultimate aim to define the kinds of interventions that could contain a virus outbreak. To model virus transmission, epidemiologists must try to consider a variety of attributes involving both host and virus. Similar objectives and modeling are applicable for any other type of infectious disease transmission too. Factors that can impact microbial transmission and spread of infection include: a) prevalence of the causal agent within the population, b) mode of transmission of the agent, c) duration of the infection, d) proportion of susceptible and resistant individuals in the population, e) population density, f) modes of travel or associations, g) lifestyle and h) climate and/or season. Once all the parameters are taken into account a disease model can be envisioned that will complement the clinical findings to formulate appropriate disease management protocol for infectious diseases.
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