Principles of Infectious Diseases

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Principles of Infectious Diseases: Transmission, Diagnosis, Prevention,
and Control
Jean Maguire van Seventer, Boston University School of Public Health, Boston, MA, USA
Natasha S Hochberg, Boston University School of Medicine, Boston, MA, USA
Ó 2017 Elsevier Inc. All rights reserved.

Introduction interferon gamma release assay – but with a lack of symptoms


(e.g., cough or night sweats) or signs (e.g., rales on auscultation
An infectious disease can be defined as an illness due to a path- of the chest) of disease. This is in contrast to active pulmonary
ogen or its toxic product, which arises through transmission TB (disease), which is accompanied by disease symptoms
from an infected person, an infected animal, or a contaminated and signs.
inanimate object to a susceptible host. Infectious diseases are Recovery from infection can be either complete (elimina-
responsible for an immense global burden of disease that tion of the agent) or incomplete. Incomplete recovery can result
impacts public health systems and economies worldwide, in both chronic infections and latent infections. Chronic infections
disproportionately affecting vulnerable populations. In 2013, are characterized by the continued detectable presence of an
infectious diseases resulted in over 45 million years lost due infectious agent. In contrast, latent infections are distinguished
to disability and over 9 million deaths (Naghavi et al., 2015). by an agent which can remain quiescent in host cells and can
Lower respiratory tract infections, diarrheal diseases, HIV/ later undergo reactivation. For example, varicella zoster virus,
AIDS, malaria, and tuberculosis (TB) are among the top causes the agent causing chicken pox, may reactivate many years after
of overall global mortality (Vos et al., 2015). Infectious diseases a primary infection to cause shingles. From a public health
also include emerging infectious diseases; diseases that have newly standpoint, latent infections are significant in that they repre-
appeared (e.g., Middle East Respiratory Syndrome) or have sent silent reservoirs of infectious agent for future transmission.
existed but are rapidly increasing in incidence or geographic
range (e.g., extensively drug-resistant tuberculosis (XDR TB)
Determinants of Infectious Disease
and Zika virus (Morse, 1995). Infectious disease control and
prevention relies on a thorough understanding of the factors When a potential host is exposed to an infectious agent, the
determining transmission. This article summarizes some of outcome of that exposure is dependent upon the dynamic rela-
the fundamental principles of infectious disease transmission tionship between agent determinants of infectivity, pathogenicity,
while highlighting many of the agent, host, and environmental and virulence, and intrinsic host determinants of susceptibility to
determinants of these diseases that are of particular import to infection and to disease (Figure 2(b)). Environmental factors,
public health professionals. both physical and social behavioral, are extrinsic determinants
of host vulnerability to exposure.

The Epidemiological Triad: Agent–Host–Environment

A classic model of infectious disease causation, the epidemio-


logical triad (Snieszko, 1974), envisions that an infectious
disease results from a combination of agent (pathogen), host,
and environmental factors (Figure 1). Infectious agents may
be living parasites (helminths or protozoa), fungi, or bacteria, Agent Host
or nonliving viruses or prions. Environmental factors deter-
mine if a host will become exposed to one of these agents,
and subsequent interactions between the agent and host will
Disease
determine the exposure outcome. Agent and host interactions
occur in a cascade of stages that include infection, disease,
and recovery or death (Figure 2(a)). Following exposure, the
first step is often colonization, the adherence and initial multipli-
cation of a disease agent at a portal of entry such as the skin or
the mucous membranes of the respiratory, digestive, or urogen-
ital tract. Colonization, for example, with methicillin-resistant Environment
Staphylococcus aureus in the nasal mucosa, does not cause
disease in itself. For disease to occur, a pathogen must infect
(invade and establish within) host tissues. Infection will always
cause some disruption within a host, but it does not always Figure 1 The epidemiological triad model of infectious disease causa-
result in disease. Disease indicates a level of disruption and tion. The triad consists of an agent (pathogen), a susceptible host, and
damage to a host that results in subjective symptoms and objec- an environment (physical, social, behavioral, cultural, political, and
tive signs of illness. For example, latent TB infection is only economic factors) that brings the agent and host together, causing
infection – evidenced by a positive tuberculin skin test or infection and disease to occur in the host.

22 International Encyclopedia of Public Health, 2nd edition, Volume 6 http://dx.doi.org/10.1016/B978-0-12-803678-5.00516-6


Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control 23

by the attack rate, the number of exposed individuals who


develop disease (as it may be difficult to determine if someone
has been infected if they do not have outward manifestations
of disease). Virulence is often measured by the case fatality rate
or proportion of diseased individuals who die from the
disease.

Host Factors
The outcome of exposure to an infectious agent depends, in
part, upon multiple host factors that determine individual
susceptibility to infection and disease. Susceptibility refers to
the ability of an exposed individual (or group of individuals)
to resist infection or limit disease as a result of their biological
makeup. Factors influencing susceptibility include both innate,
genetic factors and acquired factors such as the specific immu-
nity that develops following exposure or vaccination. The
malaria resistance afforded carriers of the sickle cell trait exem-
plifies how genetics can influence susceptibility to infectious
disease (Aidoo et al., 2002). Susceptibility is also affected by
extremes of age, stress, pregnancy, nutritional status, and
underlying diseases. These latter factors can impact immunity
to infection, as illustrated by immunologically naïve infant
populations, aging populations experiencing immune senes-
cence, and immunocompromised HIV/AIDS patients.
Mechanical and chemical surface barriers such as the skin,
the flushing action of tears, and the trapping action of mucus
are the first host obstacles to infection. For example, wound
infection and secondary sepsis are serious complications of
severe burns which remove the skin barrier to microbial entry.
Lysozyme, secreted in saliva, tears, milk, sweat, and mucus, and
gastric acid have bactericidal properties, and vaginal acid is
microbicidal for many agents of sexually transmitted infections
(STIs). Microbiome-resident bacteria (a.k.a. commensal bacteria,
Figure 2 Potential outcomes of host exposure to an infectious agent.
(a) Following an exposure, the agent and host interact in a cascade of
normal flora) can also confer host protection by using available
stages the can result in infection, disease, and recovery or death. (b) nutrients and space to prevent pathogenic bacteria from taking
Progression from one stage to the next is dependent upon both agent up residence.
properties of infectivity, pathogenicity, and virulence, and host suscepti- The innate and adaptive immune responses are critical compo-
bility to infection and disease, which is in large part due to both protec- nents of the host response to infectious agents (Table 1). Each
tive and adverse effects of the host immune response. Credit: of these responses is carried out by cells of a distinct hemato-
Modification of original by Barbara Mahon, MD, MPH. poietic stem cell lineage: the myeloid lineage gives rise to innate
immune cells (e.g., neutrophils, macrophages, dendritic cells)
and the lymphoid lineage gives rise to adaptive immune cells
Agent Factors (e.g., T cells, B cells). The innate immune response is an imme-
Infectivity is the likelihood that an agent will infect a host, diate, nonspecific response to broad groups of pathogens. By
given that the host is exposed to the agent. Pathogenicity refers contrast, the adaptive immune response is initially generated
to the ability of an agent to cause disease, given infection, and over a period of 3–4 days, it recognizes specific pathogens,
virulence is the likelihood of causing severe disease among and it consists of two main branches: (1) T cell-mediated
those with disease. Virulence reflects structural and/or immunity (a.k.a. cell-mediated immunity) and (2) B cell-
biochemical properties of an infectious agent. Notably, the mediated immunity (a.k.a. humoral or antibody-mediated
virulence of some infectious agents is due to the production immunity). The innate and adaptive responses also differ in
of toxins (endotoxins and/or exotoxins) such as the cholera toxin
that induces a profuse watery diarrhea. Some exotoxins cause Table 1 Comparison of innate and adaptive immunity
disease independent of infection, as for example, the staphylo-
coccal enterotoxins that can cause foodborne diseases. Agent Innate Immune Response Adaptive Immune Response
characteristics can be measured in various ways. Infectivity is
Immediate response; initiated Gradual response; initially generated
often quantified in terms of the infectious dose 50 (ID50), the
within seconds over 3–4 days (primary response)
amount of agent required to infect 50% of a specified host
population. ID50 varies widely, from 10 organisms for Shigella Targets groups of pathogens Targets-specific pathogens
dysenteriae to 106–1011 for Vibrio cholerae (Gama et al., 2012; No memory Memory
FDA, 2012). Infectivity and pathogenicity can be measured
24 Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control

that the latter has memory, whereas the former does not. As following an earthquake, environmental disruption can
a consequence of adaptive immune memory, if an infectious increase the risk of exposure to Clostridium tetani and result in
agent makes a second attempt to infect a host, pathogen- host traumatic injuries that provide portals of entry for the
specific memory T cells, memory B cells, and antibodies will bacterium. Environmental factors promoting vulnerability can
mount a secondary immune response that is much more rapid also lead to an increase in susceptibility to infection by inducing
and intense than the initial, primary response and, thus, better physiological changes in an individual. For example, a child
able to inhibit infection and disease. Immune memory is the living in a resource-poor setting and vulnerable to malnutrition
basis for the use of vaccines that are given in an attempt to stim- may be at increased risk of infection due to malnutrition-
ulate an individual’s adaptive immune system to generate induced immunosuppression. Table 2 provides examples of
pathogen-specific immune memory. Of note, in some cases some of the many environmental factors that can facilitate the
the response of the immune system to an infectious agent emergence and/or spread of specific infectious diseases.
can contribute to disease progress. For example, immunopa-
thology is thought to be responsible for the severe acute disease
that can occur following infection with a dengue virus that is Transmission Basics
serotypically distinct from that causing initial dengue infection
(Screaton et al., 2015). A unique characteristic of many infectious diseases is that expo-
An immune host is someone protected against a specific path- sure to certain infectious agents can have consequences for
ogen (because of previous infection or vaccination) such that other individuals, because an infected person can act as a source
subsequent infection will not take place or, if infection does of exposure. Some pathogens (e.g., STI agents) are directly
occur, the severity of disease is diminished. The duration and transmitted to other people, while others (e.g., vectorborne
efficacy of immunity following immunization by natural infec- disease (VBD) agents) are transmitted indirectly.
tion or vaccination varies depending upon the infecting agent, From a public health standpoint, it is useful to define stages
quality of the vaccine, type of vaccine (i.e., live or inactivated of an infectious disease with respect to both clinical disease and
virus, subunit, etc.), and ability of the host to generate an potential for transmission (Figure 3). With respect to disease,
immune response. For example, a single yellow fever vaccina- the incubation period is defined as the time from exposure to
tion appears to confer lifelong immunity, whereas immune an infectious agent until the time of first signs or symptoms
protection against tetanus requires repeat vaccination every of disease. The incubation period is followed by the period of
10 years (Staples et al., 2015; Broder et al., 2006). In malaria- clinical illness which is the duration between first and last
endemic areas, natural immunity to malaria usually develops disease signs or symptoms. With respect to transmission of
by 5 years of age and, while protective from severe disease and an infectious agent, the latent (preinfectious) period is the dura-
death, it is incomplete and short-lived (Langhorne et al., 2008). tion of time between exposure to an agent and the onset of
Functionally, there are two basic types of immunization, infectiousness. It is followed by the infectious period (a.k.a. period
active and passive. Active immunization refers to the generation of communicability) which is the time period when an infected
of immune protection by a host’s own immune response. In person can transmit an infectious agent to other individuals.
contrast, passive immunization is conferred by transfer of In parasitic infections, the latent and infectious periods are
immune effectors, most commonly antibody (a.k.a. immuno- commonly referred to as the prepatent period and patent period,
globulin, antisera), from a donor animal or human. For example, respectively.
after exposure to a dog bite, an individual who seeks medical The duration of disease stages is unique for each type of
care will receive both active and passive postexposure immune infection and it can vary widely for a given type of infection
prophylaxis consisting of rabies vaccine (to induce the host depending upon agent, host, and environmental factors that
immune response) and rabies immune globulin (to provide affect, for example, dose of the inoculated agent, route of expo-
immediate passive protection against rabies). An example of sure, host susceptibility, and agent infectivity and virulence.
natural passive immunization is the transfer of immunity Knowledge of the timing of disease stages is of key importance
from mother to infant during breastfeeding. in the design of appropriate control and prevention strategies
Vaccination does not always result in active immunization; to prevent the spread of an infectious disease. For example,
failure of vaccination can be due to either host or vaccine efforts to control the recent Ebola West Africa outbreak through
issues. Individuals who are immunosuppressed as, for contact tracing and quarantine were based on knowledge that the
example, a result of HIV infection, malnutrition, immunosup- infectious period for Ebola does not begin until the start of the
pressive therapy, or immune senescence might not mount period of clinical illness, which occurs up to 21 days following
a sufficient response after vaccination so as to be adequately exposure (Figure 3(a); Pandey et al., 2014).
immunized (protected). Similarly, vaccination with an inade- A carrier is, by definition, an infectious individual who is not
quate amount of vaccine or a vaccine of poor quality (e.g., showing clinical evidence of disease and, thus, might unknow-
due to break in cold chain delivery) might prevent even a healthy ingly facilitate the spread of an infectious agent through a pop-
individual from becoming immunized. ulation. Incubatory carriers exist when the incubation period
overlaps with the infectious period, as can occur in some cases
Environmental Factors of chicken pox (Figure 3(b)). Convalescent carriers occur when
Environmental determinants of vulnerability to infectious the period of infectiousness extends beyond the period of clin-
diseases include physical, social, behavioral, cultural, political, ical illness (Figure 3(c)). Carriers of this type can be a signifi-
and economic factors. In some cases, environmental influences cant issue in promoting the spread of certain enteric
increase risk of exposure to an infectious agent. For example, infections, such as those caused by the bacterium, V. cholerae.
Table 2 Environmental factors facilitating emergence and/or spread of specific infectious diseases

Environmental factor facilitating transmission Mechanism Disease References

Climate/weather EI Niño- persistent, above-normal rainfall Increased vegetation promoting increase in rodent reservoir Hantavirus pulmonary syndrome Engelthaler et al. (1999)
EI Niño-persistent, above-normal rainfall Expansion of vertically infected mosquitoes and secondary vectors Rift Valley fever Anyamba et al. (2010)
Flooding Promotes exposure to contaminated rat urine and water Leptospirosis, cholera Cann et al. (2013)

Natural disaster Tsunami, earthquake Environmental disruption promoting exposure Tetanus Afshar et al. (2011)
Tornado Environmental disruption promoting exposure Cutaneous mucormycosis Neblett Fanfair et al. (2012)

Infrastructure Engineering infrastructure Defective plumbing promoting viral dispersal SARS Yu et el. (2004)
Water treatment plant Inadequate microbial barriers Cryptosporidiosis Widerstrom et al. (2014)
Engineered water systems Reservoir and distribution Legionellosis Ashbolt (2015)

Development/change Water resource development and management Dams, irrigation schemes, mining expanding intermediate Schistosomiasis Steinmann et al. (2006)
in land use host habitat

Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control


Water resource development and management Dams, irrigation schemes expanding vector habitat Malaria Keiser et al. (2005)
Water resource development and management Expansion of irrigated rice farming creating vector breeding sites Japanese encephalitis Erlanger et al. (2009)
Forest fragmentation Loss of biodiversity expanding natural reservoir Lyme Granter et al. (2014)
Deforestation Creation of vector breeding sites Malaria Yasuoka and Levins (2007)
Deforestation Driving contact with reservoir host Hendra Plowright et al. (2011)

Technology and Medical technology Inappropriate use of antibiotics driving genetic change Antibiotic-resistant infections Goossens et al. (2005)
industry
Medical technology Transfusion of contaminated blood Chagas Angheben et al. (2015)
Food processing Undercooked hamburger E. coli O157:H7 outbreak Bell et al. (1994)
Globilization of food industry Transport contaminated seed from Egypt to Germany and France E. coli O104:H4 outbreak EFSA (2011)
Food storage Improper storage of maize Acute aflatoxicosis Azziz-Baumgartner et al. (2005)
Crop introduction Maize cultivation promoting vector abundance Malaria Kebede et al. (2005)
Animal husbandry Small-scale poultry farming facilitating animal-to-human H5N1 avian influenza Halpin (2005)
virus transfer

Travel and commerce Visiting friends and family Import of virus Chikungunya Rezza et al. (2007)
Recreational Exposure while rafting, kayaking Schistosomiasis Morgan et al. (2010)
Commercial Import of infected animals Monkeypox CDC (2003a)
Commercial Contamination ice cream premix during tanker trailer transport Salmonellosis Hennessyet al. (1996)

Politics Government response Denial of viral etiology epidemic HIV/AIDS Simelela et al. (2015)

Economics Low income Lack of protection against vector Dengue Brunkard et al. (2007)
Resource-poor environment Inadequate WASH promoting transmission Trachoma Taylor et al. (2014)
Poor urban environment Poor WASH promoting vector expansion Lymphatic filariasis Simonsen and Mwakitalu (2013)

War and conflict Displaced persons camps Inadequate WASH Cholera CDC (1996)
Displaced persons camps Inadequate WASH Cutaneous leishmaniasis Alawieh et al. (2014)

Social/behavioral Injection drug use Sharing contaminated injection equipment Hepatitis C Nelson et al. (2011)
Sexual practices High-risk sexual behavior among truckers HIV-1 infection Rakwar et al. (1999)
Cultural practices Unsafe burial practices Ebola Hewlett and Amola (2003)
Consumptive behaviors Consumption of raw or undercooked marine fish or squid Anisakidosis Hochberg and Hamer (2010)
Forest encroachment, bushmeat hunting Exposure to infected bush animals Ebola Pourrut et al. (2005)

25
Live-animal markets Close contact facilitating animal virus jumping species to humans SARS Peiris et al. (2004)

WASH, water, sanitation, and hygiene; E. coli, Escherichia coli; SARS, severe acute respiratory syndrome.
26 Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control

Figure 3 Stages of infectious disease. The stages of an infectious disease can be identified with relation to signs and symptoms of illness in the
host (incubating and clinically ill), and the host’s ability to transmit the infectious agent (latent and infectious). The red bar indicates when an indi-
vidual is infectious but asymptomatic. The relationship between stages is an important determinant of carrier states and, thus, the ease of spread of
an infectious disease through a population. (a) Patients infected with Ebola virus do not become infectious until they show signs of disease. (b) In
some cases, varicella (chicken pox)-infected individuals can act as incubatory carriers and become infectious before the onset of symptoms (e.g.,
rash). (c) Some patients with Vibrio cholerae infection remain infectious as convalescent carriers after recovery. (d) Salmonella Typhi infection can
result in an apparently healthy carrier that never shows signs or symptoms of disease.

Healthy carriers, infected individuals that remain asymptomatic of endemicity are well defined and used as parameters for
but are capable of transmitting an infectious agent, occur identifying disease risk and implementing control activities.
commonly with many infectious diseases (e.g., meningococcal Malaria endemicity is quantified based upon rates of palpable
meningitis and typhoid fever) and are also significant chal- enlarged spleens in a defined (usually pediatric) age group:
lenges to disease control (Figure 3(d)). holoendemic >75%, hyperendemic 51–75%, mesoendemic
11–50%, and hypoendemic <10% (Hay et al., 2008). An
epidemic refers to an, often acute, increase in disease cases above
Dynamics of Infectious Diseases within Populations the baseline level. An epidemic may reflect an escalation in the
occurrence of an endemic disease or the appearance of a disease
A variety of terms are used to describe the occurrence of an that did not previously exist in a population. The term outbreak
infectious disease within a specific geographic area or popula- is often used synonymously with epidemic but can occasion-
tion. Sporadic diseases occur occasionally and unpredictably, ally refer to an epidemic occurring in a more limited geograph-
while endemic diseases occur with predictable regularity. Levels ical area; for example, a foodborne illness associated with
of endemicity can be classified as holoendemic, hyperendemic, a group gathering. By contrast, a pandemic is an epidemic that
mesoendemic, or hypoendemic depending upon whether a disease has spread over a large geographic region, encompassing
occurs with, respectively, extreme, high, moderate, or low multiple countries or continents, or extending worldwide.
frequency. For some infectious diseases, such as malaria, levels Influenza commonly occurs as a seasonal epidemic, but
Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control 27

periodically it gives rise to a global pandemic, as was the case Infectious Disease Diagnosis
with 2009 H1N1 influenza.
Two fundamental measures of disease frequency are preva- Proper diagnosis of infectious illnesses is essential for both
lence and incidence. Prevalence is an indicator of the number appropriate treatment of patients and carrying out prevention
of existing cases in a population as it describes the proportion and control surveillance activities. Two important properties
of individuals who have a particular disease, measured either that should be considered for any diagnostic test utilized are
at a given point in time (point prevalence) or during a specified sensitivity and specificity. Sensitivity refers to the ability of the
time period (period prevalence). In contrast, incidence (a.k.a. test to correctly identify individuals infected with an agent
incidence rate) is a measurement of the rate at which new cases (‘positive in disease’). A test that is very sensitive is more likely
of a disease occur (or are detected) in a population over a given to pick up individuals with the disease (and possibly some
time period. Usually measured as a proportion (number without the disease); a very sensitive test will have few false
infected/number exposed), attack rates are often calculated negatives. Specificity is the ability of the test to correctly identify
during an outbreak. In some circumstances, a secondary attack individuals not infected by a particular agent (‘negative in
rate is calculated to quantify the spread of disease to susceptible health’); high specificity implies few false positives. Often,
exposed persons from an index case (the case first introducing screening tests are highly sensitive (to capture any possible
an agent into a setting) in a circumscribed population, such cases), and confirmatory tests are more specific (to rule out
as in a household or hospital. During the 2003 SARS epidemic, false-positive screening tests).
secondary attack rates in Toronto hospitals were high but Broadly, laboratory diagnosis of infectious diseases is based
varied from 25% to 40% depending upon the hospital ward on tests that either directly identify an infectious agent or
(CDC, 2003b). provide evidence that infection has occurred by documenting
The basic reproductive number (basic reproductive ratio; R0) is agent-specific immunity in the host (Figure 5). Identification
a measure of the potential for an infectious disease to spread of an infecting agent involves either direct examination of
through an immunologically naïve population. It is defined host specimens (e.g., blood, tissue, urine) or environmental
as the average number of secondary cases generated by a single, specimens, or examination following agent culture and isola-
infectious case in a completely susceptible population. In tion from such specimens. The main categories of analyses
reality, for most infectious diseases entering into a community, used in pathogen identification can be classified as phenotypic,
some proportion of the population is usually immune (and revealing properties of the intact agent, nucleic acid-based, deter-
nonsusceptible) due to previous infection and/or immuniza- mining agent nucleic acid (DNA or RNA) characteristics and
tion. Thus, a more accurate reflection of the potential for composition, and immunologic, detecting microbial antigen or
community disease spread is the effective reproductive number evidence of immune response to an agent (Figure 5). Direct
(R) which measures the average number of new infections phenotypic analyses include both macroscopic and/or micro-
due to a single infection. In general, for an epidemic to occur scopic examination of specimens to determine agent
in a population, R must be >1 so that the number of cases morphology and staining properties. Cultured material con-
continues to increase. taining large quantities of agent can undergo analyses to deter-
Herd immunity (a.k.a. community immunity) refers to mine characteristics, such as biochemical enzymatic activity
population-level resistance to an infectious disease that occurs (enzymatic profile) and antimicrobial sensitivity, and to perform
when there are enough immune individuals to block the chain phage typing, a technique which differentiates bacterial strains
of infection/transmission. As a result of herd immunity, suscep- according to the infectivity of strain-specific bacterial viruses
tible individuals who are not immune themselves are indirectly (a.k.a. bacteriophages). Nucleic acid–based tests often make
protected from infection (Figure 4). Vaccine hesitancy, the use of the polymerase chain reaction (PCR) to amplify agent
choice of individuals or their caregivers to delay or decline DNA or complementary DNA (cDNA) synthesized from
vaccination, can lead to overall lower levels of herd immunity. messenger RNA (mRNA). The ability of pathogen-specific
Outbreaks of measles in the United States, including a large PCR primers to generate an amplification product can confirm
2014 measles outbreak at an amusement park in California, or rule out involvement of a specific pathogen. Sequencing of
highlight the phenomena of vaccine refusal and associated amplified DNA fragments can also assist with pathogen identi-
increased risk for vaccine-preventable diseases among both fication. Restriction fragment analysis, as by pulse-field gel electro-
nonvaccinated and fully vaccinated (but not fully protected) phoresis of restriction enzyme-digested genomic DNA isolated
individuals (Phadke et al., 2016). from cultured material, can yield distinct ‘DNA fingerprints’
An important public health consequence of herd immunity that can be used for comparing the identities of bacteria. The
is that immunization coverage does not need to be 100% for CDC PulseNet surveillance program uses DNA fingerprinting
immunization programs to be successful. The equation as the basis for detecting and defining foodborne disease
R ¼ R0(1  x) (where x equals the immune portion of the pop- outbreaks that can sometimes be quite widely dispersed
ulation) indicates the level of immunization required to (CDC, 2013). Most recently, next-generation sequencing tech-
prevent the spread of an infectious disease through a popula- nologies have made whole-genome sequencing a realistic subtyp-
tion. The proportion that needs to be immunized depends ing method for use in foodborne outbreak investigation and
on the pathogen (Table 3). When the proportion immunized surveillance (Deng et al., 2016). The objective of immunologic
(x) reaches a level such that R < 1, a chain of infection cannot analysis of specimens is to reveal evidence of an agent through
be sustained. Thus, Ro and R can be used to calculate the target detection of its antigenic components with agent-specific anti-
immunization coverage needed for the success of vaccination bodies. Serotyping refers to the grouping of variants of species of
programs. bacteria or viruses based on shared surface antigens that are
28 Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control

Figure 4 Herd immunity occurs when one is protected from infection by immunization occurring in the community. Using influenza as an example,
the top box shows a population with a few infected individuals (shown in red) and the rest healthy but unimmunized (shown in blue); influenza
spreads easily through the population. The middle box depicts the same population but with a small number who are immunized (shown in yellow);
those who are immunized do not become infected, but a large proportion of the population becomes infected. In the bottom box, a large proportion
of the population is immunized; this prevents significant transmission, including to those who are unimmunized. Source: National Institute of Allergy
and Infectious Diseases (NIAID).
Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control 29

Table 3 Herd immunity thresholds for selected infectious identified using immunologic methodologies such as enzyme-
diseases linked immunosorbent assay (ELISA) and Western blotting.
Immunologic assays are also used to look for evidence that
Herd immunity
an agent-specific immune response has occurred in an exposed
Disease Ro threshold (%)
or potentially exposed individual. Serologic tests detect
Diphtheria 6–7 83–86 pathogen-specific B cell–secreted antibodies in serum or other
Ebola (West Africa) 1.5–2.5a 33–60 body fluids. Some serologic assays simply detect the ability of
Measles 12–18 92–94 host antibodies to bind to killed pathogen or components of
Mumps 4–7 75–86 pathogen (e.g., ELISA). Others rely on the ability of antibodies
Polio 5–7 80–86 to actually neutralize the activity of live microbes; as, for
Rubella 6–7 83–85
example, the plaque reduction neutralization test which deter-
Smallpox 5–7 80–85
mines the ability of serum antibodies to neutralize virus. Anti-
a
Althaus (2014). body titer measures the amount of a specific antibody present in
Source: Modification of table from CDC, WHO, 2001. Course: “Smallpox: serum or other fluid, expressed as the greatest dilution of serum
Disease, Prevention, and Intervention” [Online]. The Centers for Disease
Control and Prevention and the World Health Organization. Available:
that still gives a positive test in whatever assay is being
http://www.emergency.cdc.gov/agent/smallpox/training/overview/ employed. Intradermal tests for identification of T cell–medi-
(accessed and retrieved 28.04.16.) unless otherwise indicated. ated immediate type (Type I) hypersensitivity or delayed type

Analysis of host or environmental specimen


to directly identify infectious agent

Morphology
Direct Phenotypic
Staining

PCR amplification DNA/RNA


Agent-specific primers
Nucleic acid-based Random primers
Sequencing
Gene probes
Antigen detection
Immunologic Immune staining agents/tissues
ELISA

Culture Biochemical
Phenotypic Antimicrobial sensitivity
Phage typing

Restriction fragment analysis


Nucleic acid-based PFGE
Gene probes

Antigen detection
Immunologic Serotyping
ELISA
Western blotting

Analysis of host to identify


host immune response to infectious agent

Serology- antibody detection


ELISA
Immunologic Plaque reduction neutralization test
Cell-mediated responsiveness
Hypersensitivity testing

Figure 5 Methods of infectious disease diagnosis. Laboratory methods for infectious disease diagnosis focus on either analyzing host specimens
or environmental samples for an agent (upper section), or analyzing the host for evidence of immunity to an agent (lower section). Closed solid
bullets, category of test; open bullets, examples of tests. PCR, polymerase chain reaction; ELISA, enzyme-linked immunosorbent assay; PFGE,
pulsed-field gel electrophoresis.
30 Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control

(Type IV) hypersensitivity responses to microbial antigen can


be used to diagnose or support the diagnosis of some bacterial,
fungal, and parasitic infections, such as, the Mantoux (tuber-
culin) test for TB.

Infectious Disease Control and Prevention

Based on the classic model of Leavell and Clark (1965), infec-


tious disease prevention activities can be categorized as primary,
secondary, or tertiary. Primary prevention occurs at the predis-
ease phase and aims to protect populations, so that infection
and disease never occur. For example, measles immunization
campaigns aim to decrease susceptibility following exposure. Figure 6 The chain of infection (a.k.a. chain of transmission). One
The goal of secondary prevention is to halt the progress of an way to visualize the transmission of an infectious agent though a pop-
infection during its early, often asymptomatic stages so as to ulation is through the interconnectedness of six elements linked in
prevent disease development or limit its severity; steps impor- a chain. Public health control and prevention efforts focus on breaking
tant for not only improving the prognosis of individual cases one or more links of the chain in order to stop disease spread.
but also preventing infectious agent transmission. For example,
chain starts with the infectious agent residing and multiplying
interventions for secondary prevention of hepatitis C in injec-
in some natural reservoir; a human, animal, or part of the envi-
tion drug user populations include early diagnosis and treat-
ronment such as soil or water that supports the existence of the
ment by active surveillance and screening (Miller and Dillon,
infectious agent in nature. The infectious agent leaves the reser-
2015). Tertiary prevention focuses on diseased individuals with
voir via a portal of exit and, using some mode of transmission,
the objective of limiting impact through, for example, interven-
moves to reach a portal of entry into a susceptible host. A thorough
tions that decrease disease progression, increase functionality,
understanding of the chain of infection is crucial for the preven-
and maximize quality of life. Broadly, public health efforts to
tion and control of any infectious disease, as breaking a link
control infectious diseases focus on primary and secondary
anywhere along the chain will stop transmission of the infec-
prevention activities that reduce the potential for exposure to
tious agent. Often more than one intervention can be effective
an infectious agent and increase host resistance to infection.
in controlling a disease, and the approach selected will depend
The objective of these activities can extend beyond disease
on multiple factors such as economics and ease with which an
control, as defined by the 1997 Dahlem Workshop on the Erad-
intervention can be executed in a given setting. It is important
ication of Infectious Diseases, to reach objectives of elimination
to realize that the potential for rapid and far-reaching move-
and eradication (Dowdle, 1998; Box 1).
ment of infectious agents that has accompanied globalization
As noted earlier, the causation and spread of an infectious
means that coordination of intervention activities within and
disease is determined by the interplay between agent, host,
between nations is required for optimal prevention and control
and environmental factors. For any infectious disease, this
of certain diseases.
interplay requires a specific linked sequence of events termed
the chain of infection or chain of transmission (Figure 6). The
The Infectious Agent and Its Reservoir
The cause of any infectious disease is the infectious agent. As dis-
Box 1 Hierarchy of public health efforts targeting infec- cussed earlier, many types of agents exist, and each can be char-
tious diseases acterized by its traits of infectivity, pathogenicity, and virulence.
A reservoir is often, but not always, the source from which the
The 1997 Dahlem Workshop on the Eradication of Infectious Diseases
defined a continuum of outcomes due to public health interventions target-
agent is transferred to a susceptible host. For example, bats
ing infectious diseases: “1) control, the reduction of disease incidence, are both the reservoir for Marburg virus and a source of infec-
prevalence, morbidity or mortality to a locally acceptable level as a result tion for humans and bush animals including African gorillas.
of deliberate efforts; continued intervention measures are required to main- However, because morbidity and mortality due to Marburg
tain the reduction (e.g. diarrheal diseases), 2) elimination of disease, infection is significant among these bush animals, they cannot
reduction to zero of the incidence of a specified disease in a defined act as a reservoir to sustain the virus in nature (they die too
geographical area as a result of deliberate efforts; continued intervention quickly), although they can act as a source to transmit Marburg
measures are required (e.g. neonatal tetanus), 3) elimination of infec- to humans.
tions, reduction to zero of the incidence of infection caused by a specific Infectious agents can exist in more than one type of reservoir. The
agent in a defined geographical area as a result of deliberate efforts;
number and types of reservoirs are important determinants of
continued measures to prevent re-establishment of transmission are
required (e.g. measles, poliomyelitis),4) eradication, permanent reduction
how easily an infectious disease can be prevented, controlled,
to zero of the worldwide incidence of infection caused by a specific agent and, in some cases, eliminated or eradicated. Animal, particu-
as a result of deliberate efforts; intervention measures are no longer needed larly wild animal, reservoirs, and environmental reservoirs in
(e.g. smallpox), and 5) extinction, the specific infectious agent no longer nature can be difficult to manage and, thus, can pose significant
exists in nature or in the laboratory (e.g. none)” (Dowdle, 1998). challenges to public health control efforts. In contrast, infec-
tious agents that only occur in human reservoirs are among
Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control 31

those most easily targeted, as illustrated by the success of communicable diseases, such as Ebola, can require isolation of
smallpox eradication. infected individuals to minimize the risk of transmission. As
Humans are the reservoir for many common infectious part of the global effort to eradicate dracunculiasis, several
diseases including STIs (e.g., HIV, syphilis) and respiratory endemic countries have established case containment centers
diseases (e.g., influenza). Humans also serve as a reservoir, to provide treatment and support to patients with emerging
although not always a primary reservoir, for many neglected trop- Guinea worms to keep them from contaminating water sources
ical diseases (NTDs) as, for example, dracunculiasis (a.k.a. Guinea and, thereby, exposing others (Hochberg et al., 2008). Contact
worm). From a public health standpoint, an important feature of tracing and quarantine are other activities employed in the
human reservoirs is that they might not show signs of illness control of infections originating from a human reservoir or
and, thus, can potentially act as unrecognized carriers of disease source. During the West Africa Ebola outbreak, key control
within communities. The classic example of a human reservoir is efforts focused on the tracing and daily follow-up of healthy
the cook Mary Mallon (Typhoid Mary); an asymptomatic individuals who had come in contact with Ebola patients and
chronic carrier of Salmonella enterica serovar Typhi who was were potentially infected with the virus (Pandey et al., 2014).
linked to at least 53 cases of typhoid fever (Soper, 1939). One Health emphasizes the importance of surveillance and
Animals are a reservoir for many human infectious diseases. monitoring for zoonotic pathogens in animal populations. For
Zoonosis is the term used to describe any infectious disease that some diseases (e.g., Rift Valley fever) epizootics (analogous to
is naturally transmissible from animals to humans. These epidemics, but in animal populations) can actually serve as
diseases make up approximately 60% of all infectious diseases, sentinel events for forecasting impending human epidemics.
and an estimated 75% of recently emerging infectious diseases Once animal reservoirs (and sources) of infection are identi-
(Burke et al., 2012). Zoonotic reservoirs and sources of human fied, approaches to prevention and control include reservoir
disease agents include both domestic (companion and produc- elimination and prevention of reservoir infection. Zoonotic
tion) animals (e.g., dogs and cows) and wildlife. Control and diseases exist in nature in predictably regular, enzootic cycles
prevention of zoonotic diseases requires the concerted efforts and/or epizootic cycles and are transmitted to humans via
of professionals of multiple disciplines and is the basis for distinct pathways. The focus of prevention and control activi-
what has become known as the One Health approach (Gibbs, ties for these diseases reflects the extent to which a zoonotic
2014). This approach emphasizes the interconnectedness of pathogen has evolved to become established in human popu-
human health, animal health, and the environment and recog- lations (Wolfe et al., 2007). For some zoonotic diseases (e.g.
nizes the necessity of multidisciplinary collaboration in order anthrax, Nipah, rabies), primary transmission always occurs
to prevent and respond to public health threats. from animals, with humans acting as incidental (dead end)
Inanimate matter in the environment, such as soil and water, hosts; control of these diseases thus concentrates on preventing
can also act as a reservoir of human infectious disease agents. animal-to-animal and, ultimately, animal-to-human transmis-
The causative agents of tetanus and botulism (Clostridium tetani sion. Currently, most human cases of avian influenza are the
and C. botulinum) are examples of environmental pathogens result of human infection from birds; human-to-human trans-
that can survive for years within soil and still remain infectious mission is extremely rare. Thus, reservoir elimination by culling
to humans. Legionella pneumophila, the etiologic agent of Legion- infected poultry flocks is a recommended measure for control-
naires’ disease, is part of the natural flora of freshwater rivers, ling avian influenza in birds and preventing sporadic infection
streams, and other bodies. However, the pathogen particularly of humans (CDC, 2015). Other zoonotic diseases demonstrate
thrives in engineered aquatic reservoirs such as cooling towers, varying degrees of secondary human-to-human transmission
fountains, and central air conditioning systems, which provide following primary transmission (a.k.a. spillover) from animals.
conditions that promote bacterial multiplication and are Both rates of spillover and the ability to sustain human-to-
frequently linked to outbreaks. Soil and water are also sources human transmission can vary widely between zoonoses and,
of infection for several protozoa and helminth species which, in consequence, control strategies can also be quite different.
when excreted by a human reservoir host, can often survive For example, outbreaks of Ebola arise following an initial
for weeks to months. Outbreaks of both cryptosporidiosis and bush animal-to-human transmission event, and subsequent
giardiasis commonly occur during summer months as a result human-to-human transmission is often limited (Feldmann
of contact with contaminated recreational water. Soil containing and Geisbert, 2011). In contrast, the four dengue viruses origi-
roundworm (Ascaris lumbricoides) eggs is an important source of nally emerged from a sylvatic cycle between non-human
soil-transmitted helminth infections in children. primates and mosquitoes, and are now sustained by a contin-
uous human-mosquito-human cycle of transmission with
Targeting the Agent and Reservoir outbreaks occurring as a result of infected individuals entering
Early steps in preventing exposure to an infectious agent include into naïve populations (Vasilakis et al., 2011). Thus, while
interventions to control or eliminate the agent within its reser- Ebola outbreak prevention efforts would include limiting
voir, to neutralize or destroy the reservoir, and/or to stop the contact with bush animals, such efforts would not be useful
agent from exiting its reservoir. Central to these interventions for prevention of dengue outbreaks. HIV is an example of
are surveillance activities that routinely identify disease agents a virus that emerged from an ancestral animal virus, simian
within reservoirs. When humans are the reservoir, or source, immunodeficiency virus, but has evolved so that it is now
of an infectious agent, early and rapid diagnosis and treatment HIV is an example of a virus that emerged from an ancestral
are key to decreasing the duration of infection and risk of trans- animal virus, simian immunodeficiency virus, but has evolved
mission. Both active surveillance and passive surveillance are used so that it is now only transmitted human to human (Faria et al.,
to detect infected cases and carriers. Some readily 2014).
32 Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control

Portal of Exit prolonged periods of time. The infectious droplets traverse


a space of generally less than 1 m to come in contact with the
Infectious agents exit human and animal reservoirs and sources
skin or mucosa of a susceptible host. Many febrile childhood
via one of several routes which often reflect the primary loca-
diseases, including the common cold, are transferred this way.
tion of disease; respiratory disease agents (e.g., influenza virus)
Diseases spread by direct contact and droplet transmission
usually exit within respiratory secretions, whereas gastrointes-
require close proximity of infected and susceptible individuals
tinal disease agents (e.g., rotavirus, Cryptosporidium spp.)
and, thus, commonly occur in settings such as households,
commonly exit in feces. Other portals of exits include sites
schools, institutions of incarceration, and refugee/displaced
from which urine, blood, breast milk, and semen leave the
person camps. Infectious agents spread exclusively in this
host.
manner are often unable to survive for long periods outside
For some infectious diseases, infection can naturally occur
of a host; direct transmission helps to ensure transfer of a large
as a result of contact with more than one type of bodily fluid,
infective dose.
each of which uses a different portal of exit. While infection
Direct contact to an agent in the environment is a means of
with the SARS virus most frequently occurred via contact with
exposure to infectious agents maintained in environmental
respiratory secretions, a large community outbreak was caused
reservoirs. Diseases commonly transmitted in this manner
by the spread of virus in a plume of diarrhea (Yu et al., 2004).
include those in which the infectious agent enters a susceptible
Control interventions targeting portals of exit and entry are dis-
host via inhalation (e.g., histoplasmosis) or through breaks in
cussed below.
the skin following a traumatic event (e.g., tetanus).
Animal bites are another way in which some infectious
Modes of Transmission agents are directly transferred, through broken skin. This is
the most common means of infection with rabies virus.
There are a variety of ways in which infectious agents move Transplacental (a.k.a. congenital, vertical) and perinatal trans-
from a natural reservoir to a susceptible host, and several missions occur during pregnancy and delivery or breastfeeding,
different classification schemes are used. The scheme below respectively. Classic examples include mother-to-child trans-
categorizes transmission as direct transmission, if the infective mission of the protozoa Toxoplasma gondii during pregnancy,
form of the agent is transferred directly from a reservoir to an HIV during pregnancy, delivery, or breastfeeding, and Zika
infected host, and indirect transmission, if transfer takes place virus during pregnancy (Rasmussen et al., 2016).
via a live or inanimate intermediary (Box 2).
Targeting Directly Transmitted Infectious Diseases
Modes of Direct Transmission Case finding and contact tracing are public health prevention
and control activities aimed at stopping the spread of infectious
Direct physical contact between the skin or mucosa of an infected diseases transmitted by either direct contact or direct spread of
person and that of a susceptible individual allows direct trans- droplets. Once identified, further activities to limit transmis-
fer of infectious agents. This is a mode of transmission for most sion to susceptible individuals can involve definitive diagnosis,
STIs and many other infectious agents, such as bacterial and treatment, and, possibly, isolation of active cases and carriers,
viral conjunctivitis (a.k.a. pink eye) and Ebola virus disease. and observation, possible quarantine, or prophylactic vaccina-
Direct droplet transmission occurs after sneezing, coughing, or tion or treatment of contacts. Patient education is an important
talking projects a spray of agent-containing droplets that are feature of any communicable infectious disease control effort.
too large to remain airborne over large distances or for Environmental changes, such as decreasing overcrowded areas
and increasing ventilation, can also contribute to limiting the
spread of some infectious diseases, particularly respiratory
Box 2 Modes of transmission of infectious agents diseases.
Central to prevention of transplacental and perinatal infec-
Modes of Direct Transmission (infective form of agent transferred directly
tious disease transmission is avoidance of maternal infection
from reservoir or host):
and provision of early diagnosis and treatment of infected
1. Direct contact
women prior to or during pregnancy. For example, public
2. Direct spread of droplets
health efforts targeting congenital toxoplasmosis focus on
3. Direct exposure to an infectious agent in the environment
preventing pregnant women from consuming undercooked
4. Bite
meat or contacting cat feces that may be contaminated.
5. Transplacental/perinatal
Current WHO guidelines for prevention of mother-to-child
Modes of Indirect Transmission (infective form of agent transferred indi- HIV transmission recommend that HIV-infected pregnant
rectly from reservoir or infected host): and breastfeeding women should be maintained on
1. Biological antiretrovirals (WHO, 2013).
l Biological vector

l Intermediate host
Modes of Indirect Transmission
2. Mechanical
l Mechanical vector There are three main categories of indirect transmission: bio-
l Vehicle logical, mechanical, and airborne. Box 3 provides definitions
3. Airborne of the different types of hosts, vectors, and vehicles involved
in the life cycle of agents that are transmitted indirectly.
Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control 33

transmission are shigellosis (transmission of Shigella spp. on


Box 3 Hosts, vectors, and vehicles involved in the life cycle the appendages of flies) and plague (transmission of Yersinia
of infectious agents transmitted indirectly pestis by fleas). Many diarrheal diseases are transmitted by the
Definitive host: A host in which a parasite reproduces sexually. Humans are fecal-oral route with food and water often acting as vehicles
definitive hosts for roundworms. By strict definition, mosquitoes are the (Figure 7). Other types of vehicles for infectious disease agents
definitive host of malaria as they are the organism in which sexual reproduc- are biologic products (e.g., blood, organs for transplant) and
tion of the agent protozoa, Plasmodium spp., occurs. fomites (inanimate objects such as needles, surgical instru-
Reservoir host: A host that serves to sustain an infectious pathogen as ments, door handles, and bedding). Transfusion-related proto-
a potential source of infection for transmission to humans. Note that a reser- zoal infection resulting in Chagas disease has been of
voir host will not succumb to infection. Lowland gorillas and chimpanzees increasing concern to the US blood banks that have instituted
can be infected by Ebola virus, but they are not a reservoir host as they
screening measures (CDC, 2007).
suffer devastating losses from infection. Bats are a suspected reservoir
Airborne transmission involves aerosolized suspensions of
for Ebola virus.
Intermediate host: A host in which larval or intermediate stages of an residue (less than five microns in size, from evaporated aerosol
infectious agent develop but sexual reproduction does not take place. An droplets) or particles containing agents that can be transported
intermediate host does not directly transfer an agent to the definitive over time and long distance and still remain infective. TB is
host. Snails are an intermediate host in the lifecycle of Schistosoma spp. a classic example of an infectious disease often spread by
Dead-end host: A host from which infectious agents cannot be trans- airborne transmission.
mitted to other susceptible hosts. Humans are a dead-end host for West
Nile virus which normally circulates between mosquitoes and certain avian Targeting Indirectly Transmitted Infectious Diseases
species. VBDs comprise approximately 17% of the global burden of
Vector: A generic term for a living organism (e.g., biological vector or
infectious diseases (Townson et al., 2005). For some diseases
intermediate host) involved in the indirect transmission of an infectious agent
(e.g., dengue, Zika, Chagas), chemoprophylaxis and immuno-
from a reservoir or infected host to a susceptible host.
Biological vector: A vector (often arthropod) in which an infectious prophylaxis are not prevention and control options, leaving
organism must develop or multiply before the vector can transmit the vector control as the primary means of preventing disease trans-
organism to a susceptible host. Aedes spp. mosquitoes are a biological mission. Integrated vector management is defined by the WHO as,
vector for dengue, chikungunya, and Zika. “a rational decision-making process to optimize the use of
Mechanical vector: A vector (often arthropod) that transmits an infec- resources for vector control” (WHO, 2012). There are four
tious organism from one host to another but is not essential to the life cycle major categories of IVM vector control strategies: biological,
of the organism. The house fly is a mechanical vector in the diarrheal chemical, environmental, and mechanical. IVM interventions
disease shigellosis as it carries feces contaminated with the Shigella spp. are chosen from these categories based upon available
bacterium to a susceptible person.
resources, local patterns of disease transmission, and ecology
Vehicles: Inanimate objects that serve as an intermediate in the indirect
of local disease vectors. Two key elements of IVM are collabo-
transmission of a pathogen from a reservoir or infected host to a susceptible
host. These include food, water, and fomites such as doorknobs, surgical ration within the health sector and with other sectors
instruments, and used needles. (e.g., agriculture, engineering) to plan and carry out vector
control activities, and community engagement to promote
program sustainability. Another core element is the integrated
approach which often permits concurrent targeting of multiple
Biological transmission occurs when multiplication and/or VBDs, as some diseases are transmitted by a single, common
development of a pathogenic agent within a vector (e.g., biolog- vector, and some vector control interventions can target several
ical vector or intermediate host) is required for the agent to different vectors. In addition, combining interventions serves
become infectious to humans. The time that is necessary for not only to reduce reliance on any single intervention, but
these events to occur is known as the extrinsic incubation period; also to reduce the selection pressure for insecticide and drug
in contrast to the intrinsic incubation period which is the time resistance. Table 4, adapted from the 2012 WHO Handbook
required for an exposed human host to become infectious. for IVM, illustrates some of the many types of IVM activities
Indirect transmission by mosquito vectors is the primary and provides examples of VBDs that might be controlled by
mode of transmission of a large number of viruses such interventions (WHO, 2012).
(arthropod-borne viruses or arboviruses) of public health Diarrheal diseases primarily result from oral contact with
concern (e.g., West Nile, Zika). A number of NTDs are also water, food, or other vehicles contaminated with pathogenic
transmitted by biological vectors including lymphatic filariasis agents originating from human or animal feces. Most (88%)
(a.k.a. elephantiasis) by mosquitoes. Ticks are biological of diarrhea-associated deaths are attributable to unsafe drinking
vectors for many bacterial etiological agents (e.g., Lyme disease water, inadequate sanitation, and insufficient hygiene (Black
and ehrlichiosis), and the parasitic agent causing babesiosis. et al., 2003; Prüss-Üstün et al., 2008). Interruption of fecal–
The infectious agent of the helminthic NTDs, schistosomiasis, oral transmission through provision of safe water and adequate
and dracunculiasis are transmitted indirectly via intermediate sanitation, and promotion of personal and domestic hygiene
freshwater snail and copepod hosts, respectively. are fundamental to diarrhea prevention and control. Fecal–
Mechanical transmission does not require pathogen multipli- oral transmission of a diarrheal agent can occur via one of
cation or development within a living organism. It occurs when several routes. In 1958, Wagner and Lanoix developed a model
an infectious agent is physically transferred by a live entity of major transmission depicted in what has become known as
(mechanical vector) or inanimate object (vehicle) to a susceptible the ‘F-diagram,’ based on steps within the fecal–oral flow of
host. Classic examples of diseases spread by mechanical vector transmission starting with the letter ‘F’: fluids (drinking water),
34 Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control

Figure 7 The ‘F-diagram’ illustrates major direct and indirect pathways of fecal–oral pathogen transmission and depicts the roles of water,
sanitation, and hygiene interventions in providing barriers to transmission. Primary barriers prevent contact with feces, and secondary barriers
prevent ingestion of feces. Source: Water, Engineering and Development Centre (WEDC), Loughborough University.

fingers, flies, fields (crops and soil), floods (representative of pathogens. Safe excreta disposal and handling act as primary
surface water in general), and food (Wagner and Lanoix, 1958; barriers to transmission by preventing fecal pathogens
Figure 7). Other F’s that can be considered include facilities from entering the environment. Once the environment has
(e.g., settings where transmission is likely to occur such as become contaminated with pathogen-containing feces,
daycare centers) and fornication. The F-diagram is useful for secondary and tertiary barriers to transmission include water
depicting where water, sanitation, and hygiene (WASH) treatment, safe transport and storage of water, provision of
interventions act as barriers in the fecal–oral flow of diarrheal sewage systems to control flooding, fly control, and good
Table 4 Methods used to control vectorborne diseases examples of various types of IVM activities and some of the VBDs they might control and prevent

Chagas Japanese Lymphatic

Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control


Category Method disease Dengue Trypanosomiasis encephalitis Leishmaniasis filariasis Malaria Onchocerciasis Schistosomiasis Trachoma

Environmental Source reduction þ þ þ þ


Habitat manipulation þ þ þ
Irrigation management and þ þ þ þ
design
Proximity of livestock þ þ þ
Waste management þ þ
Mechanical House improvement þ þ þ þ
Removal trapping þ þ þ
Polystyrene beads þ
Biological Natural enemy conservation þ þ þ þ
Biological larvicides þ þ þ þ þ
Fungi
Botanicals þ þ
Chemical Insecticide-treated bednets þ þ þ þ þ
Indoor residual spraying þ þ þ
Insecticidal treatment of habitat þ þ þ þ þ
Insecticide-treated targets þ
Biorational methodsa þ þ
Chemical repellants þ þ þ
a
For example, pheromones to trap pests or disrupt mating.
Source: Modification of table from WHO, 2012. Handbook for Integrated Vector Management. WHO Press, France.

35
36 Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control

personal and domestic hygiene (e.g., food hygiene) practices Targeting Portals of Exit and Entry
(requiring adequate water quantity) (Figure 7). As with IVM, Standard infection control practices target portals of exit (and
the control of diarrheal diseases increases with integration of entry) of infectious agents from human reservoirs and sources.
control measures to achieve multiple barriers to fecal–oral CDC guidelines suggest two levels of precautions to stop trans-
transmission. mission of infectious agents: Standard Precautions and
The basic approach to preventing transmission of an transmission-based precautions (Siegel et al., 2007). Standard
infectious agent from a contaminated vehicle is to prevent Precautions prevent transmission of infectious agents that can
contamination of, decontaminate, or eliminate the vehicle. be acquired by contact with blood, body fluids, nonintact
Food is a common vehicle for infectious agents, and it can skin, and mucous membranes. They can be used to prevent
potentially become contaminated at any step along the transmission in both health-care and non-health-care settings,
food production chain of production, processing, distribution, regardless of whether infection is suspected or confirmed.
and preparation. Production refers to the growing of plants Hand hygiene is a major component of these precautions, along
for harvest and raising animals for food. An example of with use of personal protective equipment (PPE). Common PPE
contamination at this step includes the use of fecally include gloves, gowns, face protection (e.g., eye-protecting
contaminated water for crop irrigation. Processing refers to face shields), and respiratory protection using N95 masks to
steps such as the chopping, grinding, or pasteurizing of prevent inhalation of airborne infectious particles (e.g., from
food to convert it into a consumer product; if the external Mycobacterium tuberculosis). Of note, depending on the circum-
surface of a melon is contaminated, chopping it into pieces stance, PPE can be used to prevent dispersal of infectious agents
for sale can result in contamination of the fruit. Distribution, from their source by providing a barrier to the portal of exit, or
in which food is transferred from the place where it was to protect a susceptible individual by placing a barrier to
produced and/or processed to the consumer, can result in a portal of entry. Respiratory hygiene/cough etiquette is used to
contamination if, for example, the transportation vehicle is prevent spread of infection by respiratory droplets. Main
not clean. Finally, preparation is the step in which food is elements of respiratory hygiene/cough etiquette include
made ready to eat; not cleaning a cutting board after cutting covering the nose and mouth area with one’s elbow during
raw chicken can result in microbial pathogen cross- coughing or sneezing or using a surgical mask to limit dissem-
contamination of other food items. Food hygiene is the ination of infectious respiratory secretions, and hand hygiene
term used to describe the conditions and activities employed after contact with respiratory secretions. Other components of
to prevent or limit microbial contamination of food in order standard precautions include needle stick and sharp injury
to ensure food safety. Decontamination includes sterilization, prevention, safe injection practices, cleaning and disinfection
the destruction of all microbial agents, and disinfection, the of potentially contaminated equipment and other objects,
destruction of specific agents. and safe waste management.
Control of airborne diseases focuses on regulating environ-
mental airflow and air quality to minimize contact with infec-
The Susceptible Host
tious droplet nuclei. In health-care settings, negative pressure
isolation rooms and exhaust vents can be used to manipulate A susceptible host is an individual who is at risk of infection
airflow. Recirculating, potentially infectious air can undergo and disease following exposure to an infectious agent. As dis-
high-efficiency particulate air (HEPA) filtration and/or be cussed previously, there are many determinants of host suscep-
mixed with ‘clean’ (noncontaminated) air to remove or dilute tibility, including both innate factors determined by the genetic
the concentration of infectious particle to below the infectious makeup of the host and, acquired factors such as agent-specific
dose. Health-care workers should use N95 masks. On commer- immunity and malnutrition.
cial aircraft, airborne pathogen transmission is minimized by
methods including regulating airflow to prevent widespread Targeting the Susceptible Host
dispersal of airborne microbes throughout the cabin, HEPA Important prevention and control interventions that target the
filtering recirculating air, and mixing recirculating air with fresh susceptible host include both those that address determinants
air (considered sterile) (Dowdall et al., 2010). of susceptibility in the host (e.g., immunoprophylaxis, provi-
sion of adequate nutrition, treatment of underlying diseases)
and those that target an infecting agent (e.g., chemoprophy-
Portal of Entry
laxis). Immunoprophylaxis encompasses both active immuni-
The portal of entry refers to the site at which the infectious zation by vaccination and passive immunization through
agent enters a susceptible host and gains access to host tissues. provision of pathogen-specific immunoglobulin.
Many portals of entry are the same as portals of exit and Malnutrition is a strong risk factor for morbidity and
include the gastrointestinal, genitourinary, and respiratory mortality due to diarrheal disease, and a vicious cycle exists
tracts, as well as compromised skin and mucous membrane between infectious diarrheal disease leading to malnutrition
surfaces. Some infectious agents can naturally enter a suscep- and impaired immune function which, in turn, promotes
tible host by more than one portal. For example, the three increased susceptibility to infection (Keusch et al., 2006).
forms of human anthrax can be distinguished according to Consequently, breastfeeding and safe complementary feeding
the route of agent entry: cutaneous anthrax due to entry play crucial roles in protecting infants and young children
through the skin, gastrointestinal anthrax resulting from from infectious diseases, particularly in resource-poor
ingestion of spores, and pulmonary anthrax following inhala- settings. Micronutrients are required for normal immune
tion of spores. function, and vitamin A and zinc supplementations have
Principles of Infectious Diseases: Transmission, Diagnosis, Prevention, and Control 37

been shown to decrease some types of infections in children


Tetanus; Tuberculosis Epidemiology; Typhoid Fever; Viral
deficient in these micronutrients (Mayo-Wilson et al., 2014;
Infections, an Overview with a Focus on Prevention of
Imdad et al., 2010).
Transmission; Waterborne Diseases.
In certain circumstances, chemoprophylaxis is employed to
protect a susceptible host in anticipation of, or following expo-
sure to an infectious agent. Antimalarial drugs are routinely
used in combination with personal protective measures to
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