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stool samples. Immunity develops to natural infection. Monovalent and
multivalent vaccines have been licensed in many countries and have now
demonstrated efcacy in large trials in Africa and the Americas.
Hepatitis viruses (A–E)
See Chapter 24
Other viruses
Adenoviruses are frequently identied from stool culture and implicated
as a cause of diarrhoea in children. They have also been linked to cases
of intussusception.
Respiratory viral infections
Fig. 13.16 Electron micrograph of molluscum contagiosum, a poxvirus. Courtesy
of Prof. Goura Kudesia, Northern General Hospital, Shefeld.
Cowpox
Humans in contact with infected cows develop large vesicles, usually on
the hands or arms and associated with fever and regional lymphadenitis.
The reservoir is thought to be wild rodents.
Vaccinia virus
This laboratory strain is used as the smallpox vaccine. Widespread
vaccination is no longer recommended due to the likelihood of local
spread from the vaccination site (potentially life-threatening in those with
eczema (eczema vaccinatum) or immune deciency) and of encephalitis.
However, vaccination may still be recommended for key medical staff.
Other poxviruses: orf and molluscum contagiosum
See page 1091 and Figure 13.16
Gastrointestinal viral infections
Norovirus
Norovirus is the most common UK cause of infectious gastroenteritis and causes outbreaks in hospital wards, cruise ships and military camps. Food handlers may transmit this virus, which is relatively
resistant to decontamination procedures. The incubation period is
24–48 hours. High attack rates and prominent vomiting are characteristic. Diagnosis may be achieved by antigen or DNA detection (PCR) in
stool samples, although the characteristic clinical and epidemiological
features mean that microbiological conrmation is not always necessary. The virus is highly infectious and cases should be isolated and
environmental surfaces cleaned with detergents and disinfected with
bleach.
Astrovirus
Astroviruses cause diarrhoea in small children and occasionally in immunocompromised adults.
Rotavirus
Rotaviruses infect enterocytes and are a major cause of diarrhoeal illness
in young children worldwide. Winter epidemics are common in high-income countries, particularly in nurseries. Adults in close contact with
cases may develop disease. The incubation period is 48 hours and
patients present with watery diarrhoea, vomiting, fever and abdominal
pain. Dehydration is prominent. Diagnosis is aided by commercially
available enzyme immunoassay kits, which require fresh or refrigerated
These infections are described further on page 512.
Adenoviruses, rhinoviruses and enteroviruses (coxsackieviruses
and echoviruses) often produce non-specic upper respiratory tract
symptoms but may cause viral pneumonia. Parainuenza and respiratory syncytial viruses cause upper respiratory tract disease, croup and
bronchiolitis in small children and pneumonia in the immunocompromised. Respiratory syncytial virus also causes pneumonia in nursing
home residents and may be associated with nosocomial pneumonia.
Metapneumovirus and bocavirus cause upper and occasionally lower
respiratory tract infection, especially in immunosuppressed individuals.
Coronaviruses
Coronaviruses are single-strand positive-sense RNA viruses that cause
widespread infection in animals and humans.
Coronaviruses HCoV-229E, HCoV-NL63, HCoVH-KU1 and
HCoV-OC43 have a worldwide distribution. They usually cause mild
upper respiratory tract infection, but occasionally more serious respiratory infection at extremes of age or in immunocompromised hosts.
Three coronaviruses have emerged in recent years that cause more
serious infections. These are SARS-CoV (severe acute respiratory syndrome coronavirus), MERS-CoV (Middle East respiratory syndrome
coronavirus) and SARS-CoV-2 (the cause of coronavirus disease 2019;
COVID-19). These coronaviruses have emerged as zoonoses from bats
and potentially intermediate hosts. The intermediate hosts for SARS-CoV
and MERS-CoV include palm civets and camels respectively, but the
identity of the intermediate host(s) for SARS-CoV-2 remains elusive.
It has been suggested that both SARS-CoV and SARS-CoV-2 may
have been spread to humans through contact with wild animals in wild
food markets.
Pathogenesis
The coronaviruses contain non-structural proteins including RNApolymerases and proteases and structural proteins including the envelope,
spike (S) glycoprotein and nucleocapsid protein. RNA replication occurs in
double membrane vesicles originating from the endoplasmic reticulum and is
incorporated into virions which are released from infected cells. The coronaviruses infect a range of cells, including respiratory and gastrointestinal epithelial cells. Initial interactions involve the S glycoprotein, which binds to the
surface receptor. For SARS, SARS-CoV-2 and HCoV-NL63 the receptor is
the human angiotensin-converting enzyme 2 (hACE2). Infection with SARSCoV-2 results in reduced expression of hACE2, a protein that normally plays
important anti-inammatory roles in the lung, and it is thought that reduced
expression may contribute to pathogenesis. In SARS-CoV-2 infection the
S glycoprotein requires priming by the human serine protease TMPRSS2
to allow optimal engagement with its receptor, hACE2. For MERS-CoV
the receptor is the dipeptidyl peptidase 4 (DPP4). The receptor-binding
domain of the S glycoprotein undergoes mutation to allow adaptation during cross-species transmission from bats to other species, including man.
Coronaviruses induce suboptimal early interferon responses,
in part thought to be because the RNA is shielded from pattern
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recognition receptors, since it is contained in the double membrane vesicles. Furthermore, several coronaviruses contain a nucleocapsid protein that suppresses interferon production. However, despite suppression
of interferon in some cells, other cells such as macrophages and dendritic
cells do produce interferon, and excessive production of interferon and other
pro-inammatory cytokines by these cells is associated with failure to clear
virus and poor outcomes. Antiviral immunity requires production of neutralising antibody and effective CD4
antiviral responses, however, also appear to cause tissue injury. In SARSCoV and SARS-CoV-2 infection pulmonary complications typically emerge
after 1–2 weeks and are thought to result from dysregulation of innate and
adaptive immune responses. For SARS-CoV-2 it is suggested that suboptimal innate immune responses and recruitment of pro-inammatory CCR2
monocytes contribute to inammation, while apoptotic cell death of CD8
T-cells is prominent. Disease is more severe in older individuals and it is
thought this may correlate with suboptimal T-cell responses and enhanced
pro-inammatory responses with ageing. Skewing of immune responses
away from early protective interferon responses and suboptimal antiviral immunity may lead to dysregulated immune responses and prolonged
inammatory responses that lead to tissue injury in multiple organs. For
SARS-CoV-2, activation of the clotting cascade in association with marked
inammation appears to be a distinct feature. Microthrombi occur around
the body and both venous thromboembolism and arterial clots in the heart
and brain may be prominent features.
+
and CD8
+
T-cell responses. These same
SARS coronavirus (SARS-CoV)
SARS-CoV emerged as a major respiratory pathogen during an outbreak
of SARS in 2002–2003, in which there were approximately 8000 cases.
The virus originated in Guangdong, China, and spread to several other
countries, with secondary transmission reported in Canada (Toronto),
Hong Kong, Taiwan, Singapore and Vietnam during the outbreak. SARS
presented as a u-like illness with non-specic symptoms, including
fever, malaise, myalgia, headache, diarrhoea and shivering. In severe
cases these progressed to pneumonia, requiring intensive care admission. The case fatality rate was approximately 11%.
According to the World Health Organization, SARS infection has been
recorded only four times since the global epidemic, three times from laboratory accidents and once in southern China from an unknown source.
Middle East respiratory syndrome coronavirus
(MERS-CoV)
In 2012, a novel coronavirus, distantly related to SARS-CoV, caused several
deaths connected with pneumonia in patients originating from the Middle
East. The Middle East respiratory syndrome coronavirus (MERS-CoV)
appears to be a zoonosis, involving transmission from bats to camels and
then to humans. Over 20 countries have reported cases, although most
cases have a history of travel to Saudi Arabia or other countries in the Arabian
Peninsula. By 2020 there had been over 2500 reported cases. MERS-CoV
remains an important but still geographically restricted coronavirus.
Clinical features
The incubation period in person-to-person transmission is 2–14 (average
5) days. Any age may be infected but the patients over 50 with medical comorbidities are particularly susceptible to severe disease. Initial
symptoms are fever, chills, headache, myalgia, dry cough and dyspnoea.
Abdominal pain and diarrhoea may be prominent. The mean period from
symptom onset to hospitalisation is 4 days, and 5 days to intensive care
unit admission. Illness is complicated by rapid development of respiratory
failure and features of ARDS and multi-organ failure. Mortality is 35%.
Diagnosis and management
Laboratory features include lymphopenia, thrombocytopenia and raised
lactate dehydrogenase (LDH). Diagnosis is conrmed by detection of
virus RNA (PCR) in serum, nasopharyngeal or other respiratory samples. Antibody detection may also be useful. Treatment is supportive.
Strict infection control measures should be implemented for anyone with
fever, severe respiratory illness and epidemiological risk factors. Patients
should be managed in an airborne infection isolation room with contact
and airborne infection control measures, including personal protective
equipment for health-care workers.
SARS-CoV-2
SARS-CoV-2 was rst identied in December 2019 in Wuhan, China,
where it caused an outbreak that spread rapidly to other parts of China
and then the rest of the world. The virus is believed to have been transmitted to humans via horseshoe bats (Rhinolophus sinicus) and poten-
+
tially other intermediate hosts, to whom individuals may have been
+
exposed at wild food markets.
SARS-CoV-2 appears to be more easily transmissible than SARS-CoV
and MERS-CoV. Consequently, early efforts to contain the virus were
unsuccessful and it spread rapidly. The earliest secondary outbreaks were
identied in Iran, Italy and Spain, but most of the world was affected within
a few weeks (Fig. 13.17). The World Health Organization declared COVID-
19 to be a global pandemic in March 2020, just 3 months after it was
rst identied in China. By late 2020 new variants had emerged carrying
several amino acid substitutions. As the virus mutates variants of interest
and variants of concern have been identied to aid public health measures
to monitor transmission and research. The nomenclature of new variants
developed alongside the pandemic. The variants were initially assigned
‘Pango’ lineage codes (letters and numbers) or identied with designations
associated with clade (GISAID or Nexstrain), although as these were difcult for the public to use the variants tended to be referred to according to
the geographic location where they were rst identied, e.g. B1.1.7 (‘Kent’,
United Kingdom), B1.351 (South Africa) and P.1 (Brazil). In May 2021, to
both simplify the nomenclature and avoid the pejorative connotations of
geographic associations, the WHO started to assign Greek characters
to the variants, and these strains were named Alpha (e.g. B1.1.7), Beta
(e.g. B1.351), Gamma (e.g. P.1) and Delta (e.g. B1.617.2). The Greek letter names are designed to facilitate discussion in non-scientic audiences
and do not replace the scientic names. The variants have higher R numbers than the native virus and are more transmissible due to mutations in
the receptor-binding domain of the S protein, such as the replacement
of asparagine with tyrosine at amino acid position 501 (N501Y). B1.1.7
(Alpha) was found to cause increased mortality compared to previous
SARS-CoV-2 strains in several studies. Mutation may also modify interactions with antibody, as suggested for the E484K mutation (where a glutamic acid residue is replaced by lysine) found in the Beta and Gamma
variants. The highly transmissible B1.617.2 (Delta) variant emerged in
December 2020 causing a ‘2nd wave’ in India before spreading across the
world. The pattern was repeated in November 2021 with the B.1.1.529
(Omicron) variant, rst reported in South Africa. However, Omicron tended
to cause disease of less severity than earlier variants, presumably because
of a combination of altered virulence factors and herd immunity from vaccination and natural infection.
As well as exhibiting differences in transmissibility, symptomatology and case-fatality, infection by the variants is prevented to different
extents by the separate COVID-19 vaccines available. For example, the
Delta variant was found to have a greater propensity to infect individuals who had received only single doses of vaccines, most of which are
designed to be given as a two-dose ‘course’; and the Omicron variant
had a propensity to infect people who were fully vaccinated but had not
had ‘booster’ doses. SARS-CoV-2 is therefore very much a ‘moving
target’ with respect to disease prevention strategies.
Responses to control the pandemic
The rapid emergence and exponential increase in COVID-19 case
numbers as the pandemic developed raised signicant challenges to
the control of its transmission in both health-care settings and the
wider community. Particular infection prevention and control (IPC)
challenges raised by the pandemic included the rapid depletion of
personal protective equipment (PPE), the lag between the spread of
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January 2020
A
February 2020
Number of confirmed
cases by area
1–2
3–20
31–100
>100
Country, area or territory
with cases
Fig. 13.17 Global spread of COVID-19 in 2020.
of COVID-19 from late January with an epicentre in China to foci
in Asia and Europe in late February, with more widespread cases
shown in July 2020. Redrawn with permission from WHO
B
Number of
confirmed
cases by
area
1–2
3–10
11–100
101–500
501–5000
<5000
Country, area or territory
with cases
March 2020
Number of
confirmed cases
1–10
11–100
101–1000
1001–5 000
5001–10 000
10001–30 000
<30000
Country, area or territory
with cases
1–100
101–1000
1001– 10 000
10001–100 000
>100000
No cases reported
in the last 7 days
No reported cases
13.36 Infection prevention and control strategies used for COVID-19 in the health-care setting*
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‘Standard’ precautions
Transmission-based precautions
Isolation, cohorting and quarantining
Screening
Visitor restriction
Contact tracing
*Infection prevention and control measures vary with time, in different countries and according to resource availability.
infection and the acquisition of evidence required to inform IPC precautions to control its spread, the requirement by health-care providers to implement frequent changes in IPC guidance in response to the
availability of PPE, and huge uctuations in case numbers as the periodic introduction and relaxation of population-based control measures
brought about ‘waves’ of infection, which had the potential to repeatedly overwhelm the ability of health services to function effectively.
Infection prevention and control in health-care settings
SARS-CoV-2 is acquired predominantly from the oropharyngeal and
respiratory secretions of infected patients. Respiratory transmission has
traditionally been categorized into ‘airborne’ (or ‘aerosol’) and ‘droplet’
spread, which are distinguished by the size of respiratory particles in
which viable organisms are carried, with a cut-off size of 5 μm. The theo-
retical basis for the distinction is that particles of 5–10 μm diameter (‘respiratory droplets’) tend to fall out of the air soon after being produced.
They are therefore unlikely to travel more than 1 m or so from the source
patient and are transmitted mainly by settling on mucous membranes
(direct transmission) or by being transported to mucous membranes via
fomites (indirect transmission). Conversely, particles of <5 μm (‘droplet
nuclei’) can remain suspended in the air for prolonged periods of time
and can therefore travel longer distances and be taken into air passages
by inhalation. In reality, both the size of respiratory particles produced
by an infected person and the distance they can travel is likely to fall on
a spectrum. The range of particle sizes will be affected by factors such
as the speed of the passage of air across the infected person’s respiratory tract mucous membranes, the volume and character of secretions
being produced and the extent to which droplets are converted to droplet nuclei by evaporation; and the duration of airborne suspension and
distance travelled will be inuenced by environmental factors such as
temperature, humidity and prevailing air currents. Therefore, the distinction between airborne/aerosol and droplet transmission is not absolute,
and different precautions may be required for the same infection in different circumstances.
SARS-CoV-2 is believed to be predominantly transmitted by droplet
spread in most circumstances (e.g. when an infected patient is breathing
rapidly or coughing) but can be transmitted by the airborne route when
the patient is subjected to an ‘aerosol-generating procedure’ (AGP).
AGPs include (but are not limited to) tracheal intubation, manual ventilation, non-invasive ventilation and the use of certain high ow oxygenation
treaments. For this reason, in the UK (at the time of writing) ‘droplet’
Hand hygiene
Use of personal protective equipment (PPE), e.g. masks, gloves, aprons, gowns and eye protection, according to the
clinical circumstances
Spillage, sharps, laundry and clinical waste management
Environmental cleaning and disinfection
A combination of airborne, contact and droplet precautions (see Box 6.9) with airborne precautions often reserved for
situations in which aerosol-generating procedures (AGPs) are carried out
Different precautions may be applied depending on the level of patient risk (e.g. conrmed vs. suspected COVID-19)
Isolation or cohorting to minimise the risk of onward transmission (cohorting should be reserved for conrmed cases, or
it carries the risk of uninfected patients being exposed to infected patients)
Quarantining patients prior to elective procedures
Quarantining staff who test positive for SARS-CoV-2
Admission screening to identify asymptomatic infected patients
Interval screening of inpatients to identify and prevent health care-acquired COVID-19
Pre-procedure screening for patients having elective procedures
Staff screening to identify asymptomatic infected staff
To minimise the possibility of uninfected patients being infected by visitors, and vice versa
Detection (and subsequent isolation) of uninfected patients who have been exposed to infected patients (e.g. in a bay/
hospital ward) and staff
precautions are considered adequate for the management of patients
with COVID-19 (and other infections transmitted in a similar manner,
such as inuenza) in most circumstances, but ‘airborne’ precautions are
used when an infected (or suspected) patient is subjected to an AGP.
Unfortunately, the evidence-base for the distinction between airborne
and droplet transmission in any given circumstance is weak and subject
to repeated interpretation, so precautions used for COVID-19 tend to
vary with time and geographical location.
The control of COVID-19 in health-care settings therefore requires a
combination of measures, as shown in Box 13.36
Public health measures
A major strategy for limiting spread of SARS-CoV-2 has been the introduction of physical distancing measures, the most extreme of which have
been termed ‘lockdowns’. The components and restrictiveness of lockdowns vary between countries, but they have typically included: the closure
of schools, workplaces, non-essential shops, sporting and entertainment
venues; a move to remote (i.e. computer- based) working where possible;
banning mass gatherings; curfews; stay-at-home orders; and other local,
national and international travel restrictions. Not all countries have employed
lockdowns. Physical distancing measures are designed to slow the spread
of the virus and limit the burden of serious illness on overstretched health
services, rather than to eradicate the virus. However, in some countries
where they were employed early (e.g. New Zealand), they resulted in complete, although temporary, eradication of virus in the community.
Other important measures in limiting virus spread are ensuring high
levels of case identication, ramping up testing to identify cases, ensuring public health follow-up of potential cases and enforcing quarantine
measures for cases, contacts and travellers from high-incidence countries. The combination of such strategies has been termed ‘test, trace
and isolate’ (TTI). Countries have tended to increase TTI measures as
they have eased lockdowns, in an attempt to prevent rebound increases
in cases and the need for subsequent lockdowns, which are economically damaging. Novel approaches to TTI have been developed, including
the use of mobile phone apps, CCTV footage and tracking of a contact’s digital signature, depending on jurisdiction and legal constraints.
Surveillance sampling of all adults combined with advice to stay at home
have been implemented as measures against emerging variant viruses.
Social distancing strategies employed when lockdown is not considered necessary have included keeping people physically separate
(a target of ≥2 metres has been used in the UK), promoting frequent
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hand hygiene and enforcing the use of face coverings in places where
close contact is likely.
Vulnerable adults, including older and immunocompromised people,
have been advised to limit social interactions, a strategy termed ‘shielding’ in the UK.
Clinical features
The incubation period for COVID-19 is 5-6 days on average but can range
from 2-14 days. Many infections, probably between 80% and 90%, are
asymptomatic. Where patients do experience symptoms, these are very
variable and depend on the vaccination status of the patient and the
SARS-CoV-2 variant with which they are infected.
In unvaccinated patients and with variants predominating in the rst
year of the pandemic, typical symptoms include high fever, persistent
cough, shortness of breath and loss of taste or smell. Myalgia, fatigue,
dizziness or headache are also frequent, as are chest pain, vomiting
and diarrhoea. Vomiting and diarrhoea may be prominent features
and may precede fever, and gastrointestinal symptoms are often also
prominent in children. Confusion or delirium occur, particularly in older
people. Variant strains seen in the UK are associated with a greater
range of symptoms, for example cough, sore throat, fatigue, myalgia and headaches appear more common, whereas loss of smell or
taste are less common, than with the original virus. Variant B1.617.2
(Delta) became the dominant variant in many countries by summer
2021, and commonly presented with coryzal symptoms, myalgia and
headache, with cough and loss of taste or smell being a less common
presentation.
Before the introduction of vaccination, approximately 15% of symptomatic patients would develop severe symptoms and 5% critical
illness. Physical examination of such patients may reveal tachycardia,
hypotension, cyanosis, hypoxia or bilateral crackles in the lung elds.
Bronchial breath sounds and focal consolidation may suggest bacterial superinfection. Skin lesions are common and include maculopapular
lesions, vesicles, pustules and urticarial lesions. Chilblain-like lesions with
oedema or haemorrhage under the skin are also described. The differential diagnosis with a predominant respiratory presentation will include
community-acquired pneumonia, inuenza and other severe respiratory
virus infections, including MERS-CoV.
If complications occur they usually develop in the second week. These
are most commonly due to acute respiratory distress syndrome (ARDS).
Bacterial pneumonia complicates a minority of infections and sepsis may
occur. Superinfections occur, in particular in those with critical illness,
including fungal infection due to Aspergillus, for which prolonged intubation is a risk factor. In India especially, mucormycosis (p. 345) emerged
as a specic complication, especially in patients with pre-existing diabetes mellitus who were treated with steroids. Disseminated intravascular
coagulation is seen in the majority of those who do not survive and is
associated with severe disease and multi-organ failure. Venous thromboembolism occurs in 20%–30% of critically ill patients but may occur
in any patients.
Microthrombi can form in the lung and some have proposed the
term ‘microvascular COVID-19 lung vessels obstructive thromboinammatory syndrome’ (MicroCLOTS) to distinguish this syndrome
from conventional pulmonary embolism. Acute myocardial injury is
reported in 5%–31% and acute coronary syndromes, myocarditis
or arrhythmia occur. Acute kidney injury is common in hospitalised
patients and up to a third of those requiring mechanical ventilation
may require renal dialysis. Neurological complications are diverse and
include cerebrovascular disease, cerebral venous thrombosis, meningitis, encephalitis, seizures, impaired consciousness, ataxia, neuropathies and Guillain-Barré syndrome. Rhabdomyolysis and secondary
bacterial infections can occur. Hypothyroidism can be a long-term
complication.
A striking characteristic of SARS-CoV-2 is its varying severity in different age groups. In broad terms the severity of infection ranges from
mild or asymptomatic in children (in whom a fatal outcome is exceedingly rare) to severe and life-threatening in older adults. A specic but
13.37 Features of COVID-19 in older age and frailty
Pathogenesis: reduced expression of hACE2 may predispose to more severe
respiratory presentation
Immunity: increased inammatory responses in general and reduced antiviral
responses may reduce viral clearance and increase complications
Clinical features: atypical presentations with confusion, delirium and falls
Complications: increased complication rates
Mortality: case fatality rate doubled in those > 65 years and increases with age
Investigations: lack of data on PCR sensitivity in older age
Treatment: may be less likely to be admitted to intensive care
Preventative strategies: more likely to be asked to ‘shield’ (minimise social
interaction), with consequences for general well-being. Older adults are
associated with lower vaccine responses in other diseases
rare manifestation in children is the ‘paediatric inammatory multisystem
syndrome: temporally associated with SARS-CoV-2’ (PIMS-TS), also
referred to as multisystem inammatory syndrome in children (MIS-C).
This severe complication consists of fever, abdominal symptoms, rash,
conjunctivitis and markers of a high inammatory response. Myocardial
dysfunction, shock and respiratory failure are common complications,
and some children meet a clinical denition of Kawasaki disease with
features such as coronary artery dilatation or vascular aneurysms. This
syndrome appears distinct from Kawasaki disease, however, since it
involves an older age group with more marked elevation of inammatory
biomarkers, and is associated with COVID-19. There is also a variant of
MIS in adults.
The true case fatality rate for SARS-CoV-2 infection is not known
because the apparent incidence of disease is inuenced by many different factors. These factors include sampling strategies (i.e. testing a
larger number of asymptomatic individuals will reduce the apparent mortality); the denition of a COVID-19-associated death (which varies with
both time and jurisdiction); the period of follow-up or extent to which late
deaths are attributed to COVID-19; the stage of the pandemic at which
sampling was carried out (as mortality has fallen with the introduction of
specic treatments); and the proportion of vaccinated vs. unvaccinated
cases (as mortality is much lower in patients infected post-vaccination).
However, at the time of writing there have been 4.6 million deaths and
222 million conrmed cases (2.1% overall mortality). The case fatality rate
is therefore lower than for SARS-CoV and MERS-CoV, which have 11%
and 34% mortality, respectively. Where death occurs, it is most often in
the third week due to respiratory failure.
Virus is shed in respiratory secretions for approximately 17–24
days. Infection rates appear higher in urban or socially deprived areas.
Mortality is higher with male gender, age and frailty (Box 13.37) and
medical comorbidity (e.g. diabetes, heart disease, hypertension,
chronic lung disease). In the UK mortality is higher in people with
African Caribbean and South Asian origin, compared to individuals who
have primarily European ancestry. A genome-wide association study
linked severity to blood group A as opposed to blood group O, as well
as a gene cluster in chromosome 3 that includes several chemokine
receptors. The role of immunocompromise on COVID-19 is still being
established. Immunocompomised patients may have atypical presentations and prolonged viral shedding, but may be less susceptible
to severe COVID-19 if they are on anti-inammatory treatments that
modify COVID-19 pathogenesis. Early data suggested that patients
immunosuppressed due to cancer or organ transplant recipients may
present with more severe disease, while those receiving biologics do
not. Increased age and medical comorbidity are associated with severe
disease and mortality, and care homes have experienced outbreaks
with high mortality.
‘Long COVID’ is a term that has been used to describe both prolonged
COVID-19 and a post-COVID-19 syndrome that may involve almost
any body system. In the UK, the National Institute for Health and Care
Excellence (NICE) has dened acute COVID-19 as ‘signs and symptoms
of COVID-19 for up to 4 weeks’, ongoing symptomatic COVID-19 as
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‘signs and symptoms of COVID-19 from 4 to 12 weeks’ and the postCOVID-19 syndrome as ‘signs and symptoms that develop during or
after an infection consistent with COVID-19, continue for more than
12 weeks and are not explained by an alternative diagnosis’. ‘Long
COVID’ would encompass the latter two scenarios. The World Health
Organization has developed a denition for ‘post COVID-19 condition’
that species a symptom duration of at least two months, with symptoms
being either a continuation of the initial infection or new symptoms after
initial recovery. This too would accord with the popular understanding of
‘long COVID’. Whatever denition is used, the most common unifying
feature of long COVID/the post-COVID syndrome is fatigue, which can
be prolonged and extreme. Other common presentations have included
multisystem inammatory symptoms, persistent fevers and evidence of
organ dysfunction affecting almost any organ, but particularly the heart
and lungs. Persistent headache, memory problems, insomnia and mental health symptoms such as depression are frequently reported, as are
loss of taste and smell, deafness and tinnitus, arthralgia, skin rashes and
paraesthaesias. In reality, the post-COVID syndrome is likely to be a conation of different conditions, not all of which are specic to COVID-19
(e.g. COVID-19 itself, the sequelae of complications of COVID-19 and the
various causes of ICU acquired weakness, p. 215). Optimal management
strategies for long COVID have not yet been established.
Investigations
Laboratory abnormalities can include an increased neutrophil to lymphocyte ratio; elevated ALT, D-dimer and inammatory markers, including
C-reactive protein (CRP) and ferritin; hypoalbuminaemia and lymphopenia. However, these ndings are non-specic and of very little help in
distinguishing COVID-19 from other infections. Procalcitonin (PCT) may
be elevated and may raise suspicion of secondary bacterial infection,
though there is currently insufcient evidence to recommend its routine
use or on which to base decisions on whom to give antimicrobials on
this test. Acute kidney injury is common in severe disease. Hypokalaemia
and hypocalcaemia are common. Hyperglycaemia is also reported and
may be observed in patients not known to be diabetic. Hypoxia may
be accompanied by hypocapnia so that it appears inappropriately well
tolerated (‘happy hypoxia’).
Chest radiology shows bilateral predominantly basal and peripheral
inltrates, or in a minority, unilateral inltrates. CT scan of the chest
shows ‘ground glass’ abnormalities, consolidation, septal thickening or
crazy-pavement patterning (Fig. 13.18). Lesions are most often basal,
peripheral and bilateral. Pulmonary vascular enlargement, pleural or pericardial effusions may be observed in a minority. CT changes may occur
in those with negative chest radiography and negative PCR and can be
used in patients in whom COVID-19 is strongly suspected but not conrmed. In general CT is reserved for severe cases or those with other
indications for performing a CT.
Microbiological diagnosis is by nasopharyngeal or oropharyngeal
swab and reverse-transcription PCR (RT-PCR) to detect viral RNA.
Sensitivity is approximately 60%–70% and specicity is high (approximately 98%). Nasotracheal aspirates or deep sputum samples may have
greater sensitivity. Antibody detection can conrm prior exposure but
may cross-react with antibodies from other coronaviruses. Lateral ow
immunochromatography (p. 106) is also used to detect SARS-CoV-2
antigens. It is rapid (around 30 minutes) and can be used at home but is
less sensitive and specic than PCR.
Management
Treatment is supportive, with high ow oxygen and proning. Non-invasive
ventilation or mechanical ventilation are required for those with more
severe respiratory failure. Fluid resuscitation is frequently required for
hospitalised patients and antimicrobials are added if there are signs or
symptoms suggestive of secondary infection. Inotropic support may be
required for shock. Renal replacement therapy may be required for acute
kidney injury, and anticoagulation if there is evidence of venous thromboembolism. Dexamethasone improves survival and is recommended
for hospitalised patients requiring supplemental oxygen or mechanical
ventilation. Anti-interleukin (IL)-6 monoclonal antibodies (e.g. tocilizumab)
reduce mortality and reduce time to recovery in critically ill patients if
administered within 24 hours of admission to an intensive care unit. In the
UK tocilizumab is also used in patients with oxygen saturations <92%
on repeated measurement on room air with a CRP ≥75 mg/L. An initial
randomised clinical trial of the nucleotide analogue remdesivir (Chapter
6) found that it decreased the time to recovery when used within 10
days of symptom onset in patients requiring supplemental oxygen but
not mechanical ventilation. However, it has not been found to signicantly
improve survival and is not currently recommended by the WHO. Antiviral
agents are being developed with the goal of administering these early
after symptom onset to prevent the later inammatory complications.
Preliminary trial results indicate that the oral antiviral agents molnupiravir
and Paxlovid reduce hospitalisation and death if given within the rst 3-5
days of symptoms. Molnupiravir is a prodrug, which is metabolised into
a form that causes viral RNA-dependent RNA polymerase to introduce
fatal mutations into nascent RNA strands. Paxlovid is a combination of
two protease inhibitors, the investigational compound PF-07321332,
and ritonavir; PF-07321332 is targeted against SARS-CoV-2 3CL protease and ritonavir inhibits the breakdown of PF-07321332. However,
both drugs remain experimental at the time of writing, and there are
many other potential SARS-CoV-2 antiviral agents at various stages of
development. An alternative antiviral strategy is to use antibodies against
the virus. The use of single monoclonal antibodies to variable regions
of the S protein is limited by rapid emergence of viral resistance and
they have not demonstrated efcacy. In contrast, combinations of two
monoclonal antibodies (e.g. casirivimab and imdevimab (REGEN-COV)
13
Fig. 13.18 Chest computerised tomography (CT) scan of a patient with COVID-19. The images show widespread areas of consolidation in both lungs.
BA
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13.38 SARS-CoV-2 vaccines licensed or at a late stage of development*
Manufacturer Vaccine type Number of doses administered Reported efcacy Storage requirements
Oxford/AstraZeneca Viral vector, ChAdOx (chimpanze adenovirus) 2 62%–90% 4°C
Moderna mRNA 2 95%
Pzer–BioNTech mRNA 2 95%
Gamaleya (Sputnik V) Viral vector, Ad5 and Ad26 (human
2 92% 4°C
20°C
70°C
adenoviruses)
Janssen (Johnson &
Viral vector, Ad26 (human adenovirus) 1 66% 4°C
Johnson)
Novovax Protein subunit 2 95% 4°C
Sinopharm Inactivated virus 2 80% 4°C
Sinovac Inactivated virus 2 50% 4°C
Sinopharm–Wuhan Inactivated virus 2 70% 4°C
Bharat Biotech Inactivated virus 2 80% 4°C
*This list was accurate at the time of writing (mid-2021). However, because of the rapid speed of vaccine development this is not a complete list of available SARS-CoV-2 vaccines.
or bamlanivimab and etesevimab) are anticipated to represent a
greater barrier to escape mutants and preserve efcacy. Initial studies
demonstrate these reduce viral load and medical visits in outpatients
and reduce hospital stay length and mortality in patients who have not
mounted a natural antibody response following vaccination. The efcacy
of monoclonal antibodies against the S protein may be challenged by the
emergence of variants with mutations such as E484K, and approaches
being developed in response include the use of ‘broadly neutralizing’
antibodies that target more conserved regions of the S protein. Trials
using convalescent serum have not shown efcacy.
Vaccination
Because of the global impact of the SARS-CoV-2 pandemic vaccine development started very soon after the virus was identied and sequenced.
Vaccines approved or in development include inactivated vaccines, RNA
and DNA vaccines, protein subunit vaccines and recombinant RNA vaccines delivered in virus vectors (Box 13.38). The SARS-CoV-2 vaccines
induce T-cell immunity in addition to neutralizing antibody but the extent
and longevity as well as the ability to block transmission are still being
assessed. In general, vaccines have been shown to be efcacious and
some have reported efcacy against variant strains after single doses,
although the efcacy of single dose vaccination is markedly reduced for
the B1.617.2 (Delta) variant. Vaccines have a more dramatic effect on
reduction of hospitalised cases than they do on reduction of overall infection but they still play a major role in reducing community transmission.
Vaccines are being developed to combat variant strains, including potentially addition of booster doses with modied RNA vaccines. Vaccines have
demonstrated safety after billions of administered doses. Side-effects have
been minimal and dwarfed by the ongoing mortality of COVID-19 in those
without vaccination. Reported severe complications have occurred at
incidences approximating 1 per million or less. At least two of the adenoviral vector COVID-19 vaccines have been linked to very rare cases of
thrombosis with thrombocytopenia (‘vaccine-induced thrombosis with
thrombocytopenia syndrome (TTS)’), a condition with some similarities to
heparin-induced thrombocytopenia (p. 948). Guillain-Barré syndrome is
also reported after the adenoviral vaccines. The RNA vaccines have been
linked to rare cases of myocarditis and pericarditis.
Vaccination programmes were rolled out at different rates in different countries. The strategy of rollout used in the UK and some other
countries was to target the highest-risk demographic groups rst (e.g.
older people and those with underlying health conditions). As infection
is less severe in patients who have been vaccinated, this strategy gradually converted COVID-19 from a severe disease with high mortality
affecting the older population to a predominantly non-severe disease
with low mortality affecting younger people. Other strategies may have
been used in different countries. The duration of immunity conferred by
vaccines and natural infection is not yet known, and booster doses are
likely to be required depending on the evidence that emerges.
The need to maintain the ‘cold chain’ from manufacture to administration is vital for any vaccine. However, it is a particular challenge the
pure RNA SARS-CoV-2 vaccines, as they need to be stored at either
−20°C or −70°C at all times. This is likely to reduce their use in low- and
middle-income countries, where the logistical infrastructure required to
maintain the cold chain is less likely to be available.
‘Vaccine hesitancy’ refers to a heterogenous process in which individuals may refuse or delay vaccination. Vaccine hesitancy has been encountered in many countries and may be more prominent in populations with
demographics that vary in different regions. This can represent a major
challenge to ensuring high levels of vaccine uptake in a population.
Other considerations
The COVID-19 pandemic has necessitated changes in the law, e.g. to
enable governments to mandate the use of masks in public, enforce
lockdowns and streamline the processes of death certication to deal
with surges in deaths. It has caused health services to become overwhelmed with acutely ill patients, with a knock-on effect of delaying the
treatment of less urgent cases. An as yet unquantied problem is the
burden of psychological illness in staff who work in patient-facing roles
with COVID-19 patients and face issues such as physical exhaustion,
burnout and post-traumatic stress disorder (PTSD).
Viral infections with neurological involvement
See also page 1175.
Japanese encephalitis virus (JEV)
This avivirus is an important cause of endemic encephalitis in Japan,
China, Russia, South-east Asia, India and Pakistan; outbreaks also
occur elsewhere. There are 10000–20000 cases reported to the WHO
annually. Pigs and aquatic birds are the reservoirs and transmission is by
Culex mosquitoes. Exposure to rice paddies is a recognised risk factor.
Clinical features
The incubation period is 4–21 days. Most infections are subclinical in
childhood and 1% or less of infections lead to encephalitis. Initial systemic illness with fever, malaise and anorexia is followed by headache,
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photophobia, vomiting and changes in brainstem function. Other neurological features include meningism, seizures, cranial nerve palsies, accid or spastic paralysis and extrapyramidal syndromes. Mortality with
neurological disease is 25%. Some 50% of survivors have neurological
sequelae.
Investigations, management and prevention
Other infectious causes of encephalitis should be excluded. There is
neutrophilia and often hyponatraemia. CSF analysis reveals lymphocytosis and elevated protein. Serological testing of serum and CSF aids
diagnosis but may cross-react with dengue and other aviviruses.
Treatment is supportive. Vaccination is recommended for travellers to
endemic areas during the monsoon. Some endemic countries include
vaccination in their childhood schedules.
Tick-borne encephalitis virus
This avivirus is endemic in an area from northern Europe (including the
UK) that extends across Siberia to China and Japan. Its incidence is
increasing, and it is transmitted from domestic or wild animals by Ixodes
ticks or sometimes by unpasteurised dairy products. The incubation
period is up to 28 days but averages 7 days. A third of cases cause
symptoms, with fever, myalgia and headache followed by an interval of
up to a month before meningitis, encephalitis or radiculitis occur. The Far
Eastern sub-type tends to be more severe. Diagnosis is by IgM ELISA
or detection of viral RNA by RT-PCR of blood or CSF. IgG serology
cross-reacts with other aviviruses. Treatment is supportive. Prevention
is by avoidance of tick bites. A vaccine is also available.
West Nile virus
This avivirus is an important cause of neurological disease throughout
Australia, India and Russia through Africa and Southern Europe and across
to North America. The disease has an avian reservoir and a Culex mosquito vector. Older people are at increased risk of neurological disease.
Clinical features
Most infections are asymptomatic. After 2–6 days’ incubation, a mild
febrile illness and arthralgia may occur. A prolonged incubation may
be seen in immunocompromised individuals. Children may develop a
maculopapular rash. Neurological disease is seen in 1% and is characterised by encephalitis, meningitis or asymmetric accid paralysis with
10% mortality.
Diagnosis and management
Diagnosis is by serology or detection of viral RNA in blood or CSF.
Serological tests may show cross-reactivity with other aviviruses,
including vaccine strains. Treatment is supportive.
infection. Serology, sometimes conrmed with PCR, establishes the
diagnosis. Treatment is supportive.
Viral infections with rheumatological involvement
Rheumatological syndromes characterise a variety of viral infections
ranging from exanthems, such as rubella and parvovirus B19, to bloodborne viruses, such as HBV and HIV-1 and the sequelae of EVD.
Chikungunya virus
Chikungunya is an alphavirus that causes fever, rash and arthropathy.
The disease occurs mainly in Africa and throughout Asia, but is becoming
commoner in other areas, including South America and the Carribbean.
Cases occur sporadically or in epidemics, with notable epidemics occurring in Réunion and Mauritius (>272 000 cases in 2005–06) and India
(1 400 000 cases in 2006). Humans and non-human primates are the
main reservoir. The vectors are Aedes mosquitoes including Ae. aegyptii
and Ae. albopictus.
The incubation period is 2–12 days. A period of fever may be followed
by an afebrile phase and then recrudescence of fever. Children may
develop a maculopapular rash. Adults are susceptible to arthritis, which
causes early morning pain and swelling, most often in the small joints.
Arthritis can persist for months and may become chronic in individuals
who are positive for human leucocyte antigen (HLA)-B27. Related alphaviruses causing similar syndromes include Sindbis virus (Scandinavia and
Africa), O’nyong-nyong virus (Central Africa), Ross River virus (Australia)
and Mayaro virus (Caribbean and South America).
Diagnosis is by serology but cross-reactivity between alphaviruses
occurs. Treatment is symptomatic. The disease may be debilitating but
is rarely fatal.
Prion diseases
Prions cause transmissible spongiform encephalopathies and are discussed in Chapter 28.
Bacterial infections
Bacterial infections of the skin, soft tissues and
bones
Most infections of the skin, soft tissues and bone are caused by either
Staph. aureus or streptococci (mainly Strep. pyogenes) (see pp. 1025
and 1090).
13
Nipah virus encephalitis
Nipah virus is a paramyxovirus in the Henipavirus genus, which caused
an epidemic of encephalitis in Malaysia and subsequently outbreaks in
Bangladesh and India. Mortality is around 30%. Diagnosis is by PCR or
serology.
Human T-cell lymphotropic virus type I
Human T-cell lymphotropic virus type I (HTLV-1) is a retrovirus that
causes chronic infection with development of adult T-cell leukaemia/
lymphoma (ATL) or HTLV-1-associated myelopathy (HAM) in a subset of those infected (see Box 25.57). It is found mainly in Japan, the
Caribbean, Central and South America, and the Seychelles. The lifetime risk of ATL in those with chronic HTLV-1 infection is estimated
at 2.5%–4%. HAM or tropical spastic paraparesis occurs in less than
5% of those with chronic infection, and presents with gait disturbance,
spasticity of the lower extremities, urinary incontinence, impotence and
sensory disturbance. Myositis and uveitis may also occur with HTLV-1
Staphylococcal infections
Staphylococci are usually found colonising the anterior nares and skin.
Some staphylococci produce coagulase, an enzyme that converts brinogen to brin in rabbit plasma, causing it to clot. Staph. aureus is coagulase-positive, and most other species are coagulase-negative.
Staph. aureus is the main cause of staphylococcal infections.
Staphylococcus intermedius is another coagulase-positive staph-
ylococcus, which causes infection following dog bites. Among
coagulase-negative organisms, Staphylococcus epidermidis is the
predominant commensal organism of the skin, and can cause severe
infections in those with central venous catheters or implanted prosthetic materials. Staphylococcus saprophyticus is part of the normal
vaginal ora and causes urinary tract infections in sexually active young
women. Staphylococcus lugdunensis, Staphylococcus schleiferi,
Staphylococcus haemolyticus and Staphylococcus caprae are also
human pathogens.
Staphylococcal blood-stream infections can disseminate widely
(Fig. 13.19). In any patient with staphylococcal bacteraemia, especially
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Respiratory
Pneumonia
Lung abscess
Empyema
Cardiac
Endocarditis
Pericarditis
Blood stream
Blood-stream
infection
Metastatic
abscesses
CNS
Meningitis
Brain abscess
(neurosurgical
infections in
particular)
Bone and joint
Osteomyelitis
Septic arthritis
Intestinal
Enterocolitis
Multisystem
Toxic shock
syndrome
Skin
Wound
infections
Boils, styes,
carbuncles,
abscesses
Fig. 13.19 Infections caused by Staphylococcus aureus (CNS = central
nervous system)
injection drug-users, the possibility of endocarditis must be considered
(see p. 462). Growth of Staph. aureus in blood cultures should not be
dismissed as a ‘contaminant’. Spreading cellulitis mandates the urgent
need for an antistaphylococcal antibiotic, such as ucloxacillin, cefazolin or a glycopeptide if MRSA is suspected. This is particularly true for
mid-facial cellulitis, which can result in cavernous sinus thrombophlebitis.
In addition, Staph. aureus can cause severe systemic disease due to
the effects of toxin produced at supercial sites in the absence of tissue
invasion by bacteria.
Skin infections
Staphylococci cause ecthyma, folliculitis, furuncles, carbuncles, bullous impetigo and the scalded skin syndrome, which are discussed in
Chapter 27. They may also be involved in necrotising infections of the
skin and subcutaneous tissues.
Wound infections
Many wound infections, which prolong post-operative care, are caused
by staphylococci (Fig. 13.20A). Prevention involves careful attention to
hand hygiene, skin preparation and aseptic technique, and the use of
topical and systemic antibiotic prophylaxis.
Treatment is by early drainage of any abscesses, removal of prosthetic materials if possible, plus adequate dosage of antistaphylococcal
antibiotics.
Cannula-related infection
Staphylococcal infection associated with cannula sepsis ( Fig. 13.20B)
and thrombophlebitis is an important and common reason for morbidity
following hospital admission. The visual infusion phlebitis (VIP) score aids
cannula evaluation (Box 13.39). Staphylococci have a predilection for
plastic, rapidly forming a biolm on cannulae, which is a source of bacteraemia. Local poultice application may relieve symptoms but cannula
removal and antibiotic treatment with ucloxacillin (or a glycopeptide) are
necessary if there is spreading infection.
Meticillin-resistant Staphylococcus aureus
Resistance to meticillin is due to a penicillin-binding protein mutation in
Staph. aureus, which confers resistance to almost all ß-lactam antibiotics.
BA
Fig. 13.20 Manifestations of skin infection with Staphylococcus aureus
13.39 How to assess an intravenous (IV) cannula using the visual
infusion phlebitis (VIP) score
Clinical features Score Assessment and
management
IV site appears healthy 0 No signs of phlebitis
Observe cannula
One of the following is evident:
Slight pain near IV site
Slight redness near IV site
Two of the following are evident:
Pain near IV site
1 Possible rst signs of
phlebitis
Observe cannula
2 Early stage of phlebitis
Resite cannula
Erythema
Swelling
ALL of the following are evident
and extensive:
Pain along path of cannula
3 Medium stage of phlebitis
Resite cannula
Consider treatment
Erythema
Induration
ALL of the following are evident
and extensive:
Pain along path of cannula
Erythema
Induration
4 Advanced stage of
phlebitis or start of
thrombophlebitis
Resite cannula
Consider treatment
Palpable venous cord
ALL of the following are evident:
Pain along path of cannula
Erythema
Induration
5 Advanced stage of
thrombophlebitis
Initiate treatment
Resite cannula
Palpable venous cord
Pyrexia
Adapted from Jackson A. Infection control: a battle in vein infusion phlebitis. Nursing Times
1997; 94:68–71.
Resistance to vancomycin/teicoplanin (glycopeptides) in either glycopeptide intermediate Staph. aureus (GISA) or, rarely, vancomycin-resistant
(VRSA) strains threatens management of serious staphylococcal infections. Meticillin-resistant Staph. aureus (MRSA) is now a major worldwide
health care-acquired pathogen, accounting for up to 40% of staphylococcal bacteraemia in high-income countries. Community-acquired
MRSA (c-MRSA) currently accounts for 50% of all MRSA infections in the
USA. These organisms have also acquired other toxins, such as Panton–
Valentine leukocidin (PVL), and can cause rapidly fatal infection in young
people. Clinicians must be aware of the potential danger of these infections
and implement appropriate locally approved infection control measures.
Treatment options for MRSA are shown in Box 6.16. Treatment should
always be based on the results of antimicrobial susceptibility testing, since
resistance to all these agents occurs. Milder MRSA infections may be
treated with clindamycin, tetracyclines or co-trimoxazole. Glycopeptides,
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linezolid and daptomycin are reserved for treatment of more severe infections. Toxin-producing MRSA infections should be treated with the addition of protein-inhibiting antibiotics (clindamycin, linezolid).
Staphylococcal toxic shock syndrome
Staphylococcal toxic shock syndrome (TSS) is a life-threatening disease
associated with infection by Staph. aureus producing a specic toxin
(toxic shock syndrome toxin 1, TSST1). Formerly seen in young women
in association with the use of highly absorbent intravaginal tampons, it
can occur with any infection involving a TSST1-producing Staph. aureus
strain. The toxin acts as a ‘super-antigen’, triggering signicant T-cell
activation and massive cytokine release.
TSS has an abrupt onset with high fever, generalised systemic upset
(myalgia, headache, sore throat and vomiting), a widespread erythematous
blanching rash resembling scarlet fever, and hypotension. It rapidly progresses over a few hours to multi-organ failure, leading to death in 10%–
20%. Recovery is accompanied at 7–10 days by desquamation (Fig. 13.21).
The diagnosis is clinical and may be conrmed in menstrual cases by
nding a retained tampon with staphylococci on Gram stain. Subsequent
culture and demonstration of toxin production are conrmatory.
Management
Treatment is with immediate and aggressive uid resuscitation and an intravenous antistaphylococcal antimicrobial, usually with the addition of a protein
synthesis inhibitor (e.g. clindamycin) to inhibit toxin production. Intravenous
immunoglobulin is occasionally added in the most severe cases. Women
who recover from tampon-associated TSS should avoid tampons for at
least 1 year and they should be advised that the condition can recur.
Streptococcal infections
Streptococci are oropharyngeal and gut commensals, which appear as
Gram-positive cocci in chains (see Fig. 6.3). They were classied by the
pattern of haemolysis they produce on blood agar (see Fig. 6.4), by their
‘Lanceeld serogroups’ (Box 13.40) but are now usually identied and
classied by matrix-assisted laser desorption/ionisation time-of-ight
(MALDI-TOF) mass spectrometry. Some streptococci (e.g. Strep. milleri
group) defy simple classication.
Strep. pyogenes (group A streptococcus, GAS) is the leading cause of
bacterial pharyngitis. Although the presence of fever, tender anterior lymphadenopathy and purulent tonsillar exudate and the absence of cough
make streptococcal pharyngitis more likely than viral infection, clinical features alone are unreliable for diagnosing streptococcal pharyngitis. GAS
are the major cause of cellulitis, erysipelas and impetigo. They also cause
the post-streptococcal syndromes of glomerulonephrits and rheumatic
fever, which are described in Chapters 14 and 16, respectively. The closely
related Streptococcus dysgalactiae subsp. equisimilis (SDSE) (formerly
groups C and G) cause cellulitis, particularly in older people, diabetic or
immunocompromised patients. Streptococcus agalactiae (group B strep-
tococci (GBS)) colonise the gut and vagina. They cause post-partum and
neonatal sepsis, as well as other deep infections (infective endocarditis,
septic arthritis, osteomyelitis etc.), especially in older people.
Streptococcal scarlet fever
Strep. pyogenes (or occasionally SDSE) causing pharyngitis, tonsillitis
or other infection may lead to scarlet fever, if the infecting strain produces a streptococcal pyrogenic exotoxin. Scarlet fever is most common
in school-age children, but can also occur in young adults who have
contact with young children. A diffuse erythematous rash occurs, which
blanches on pressure (Fig. 13.22A), classically with circumoral pallor. The
tongue, initially coated, becomes red and swollen (‘strawberry tongue’,
Fig. 13.22B). The disease lasts about 7 days, the rash disappearing in
7–10 days, followed by a ne desquamation. Residual petechial lesions
in the antecubital fossa, ‘Pastia’s sign’, can occur (Fig. 13.22C).
Treatment involves intravenous benzylpenicillin or an oral penicillin plus
symptomatic measures.
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Fig. 13.21 Full-thickness desquamation after staphylococcal toxic shock
syndrome.
13.40 Streptococcal and related infections
β-haemolytic group A (Streptococcus pyogenes)
Skin and soft tissue infection
(including erysipelas, impetigo,
necrotising fasciitis)
Streptococcal toxic shock syndrome
Puerperal sepsis
Scarlet fever
β-haemolytic streptococci group B (Strep. agalactiae)
Neonatal infections, including
meningitis
β-haemolytic streptococci groups C and G
Cellulitis
Endocarditis
α-, β- or non-haemolytic group D (Enterococcus faecalis, E. faecium)
Endocarditis
Intra-abdominal infections
α- or non-haemolytic group D (Strep. gallolyticus subsp. gallolyticus/S.
bovis biotype I)
Bacteraemia/endocarditis associated
with large bowel malignancy
α-haemolytic optochin-resistant (viridans streptococci – Strep. mitis, Strep.
sanguis, Strep. mutans, Strep. salivarius)
Sepsis in immunosuppressed Endocarditis
α-haemolytic optochin-sensitive (Strep. pneumoniae)
Pneumonia
Meningitis
Endocarditis
Otitis media
Variable haemolysis (Strep. milleri group – Strep. anginosus, Strep.
intermedius, Strep. constellatus)
Endocarditis
Intra-abdominal infections
Anaerobic streptococci (Peptostreptococcus spp.)
Sepsis in immunosuppressed Endocarditis
N.B. All streptococci can cause sepsis.
Glomerulonephritis
Rheumatic fever
Bone and joint infection
Tonsillitis
Female pelvic infections
Cellulitis
Pharyngitis
Septic arthritis
Urinary tract infection
Sepsis
Spontaneous bacterial peritonitis
Sinusitis
Urinary tract infection
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