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Gastroenteritis and Food Poisoningnd 43
• Liver abscess – metronidazole 500 mg three times daily for 7–10
days. A large tense abscess may require percutaneous drainage
under ultrasound guidance. As a pyogenic abscess may be difficult to
distinguish from, broad- spectrum antibiotic therapy is often used until
the diagnosis is confirmed.
Shigellosis (bacillary dysentery)
Shigellosis is an acute self-limiting intestinal infection which occurs worldwide but is more common in tropical countries and in areas of poor hygiene.
Transmission is by the faecal–oral route. The four Shigella species (S. dysen-
teriae, S. flexneri, S. boydii and S. sonnei) invade and damage the intestinal
mucosa (Table 2.6). Some strains of S. dysenteriae secrete a cytotoxin which
results in diarrhoea. Differential diagnosis is from other causes of bloody
diarrhoea. Sigmoidoscopic appearances may be the same as those in inflammatory bowel disease. Ciprofloxacin is the treatment of choice although there
is increasing resistance worldwide.
Cholera
Cholera is caused by the Gram-negative bacillus Vibrio cholerae (Tables 2.7
and 2.9). Infection is common in tropical and subtropical countries in areas
of poor hygiene. Infection is by the faecal–oral route and while contaminated
water plays a major role in the dissemination of cholera, contaminated
foodstuffs and contact carriers may contribute in epidemics.
nd
nd
Pathophysiology and clinical features
Following attachment to and colonization of the small intestinal epithelium, V.
cholerae produces its major virulence factor, cholera toxin. The toxin binds to
its enterocyte surface receptor, causing a cascade of events which leads to
chloride ion and water secretion with inhibition of sodium and chloride absorption. This produces massive secretion of isotonic fluid into the intestinal lumen.
Cholera toxin also increases serotonin release from enterochromaffin cells in
the gut, which contributes to the secretory activity and diarrhoea. The incubation period varies from a few hours to 6 days. The majority of patients have a
mild illness, but in severe cases there is abrupt onset of profuse painless diarrhoea, followed by vomiting. As the illness progresses, the typical ‘rice water’
stool, flecked with mucus, may be seen. This may lead to massive fluid loss
and, if not replaced, features of hypovolaemic shock.
Management
Management is aimed at aggressive volume replacement and, with appropriate and effective rehydration therapy, mortality may be decreased to
less than 1%. Oral fluids are usually sufficient but intravenous fluids are
given in severe cases. Oral rehydration solutions (ORS) are based on the
44 Infectious diseases
observation that glucose (and other carbohydrates) enhance sodium and
water absorption in the small intestine, even in the presence of secretory
loss due to toxins. The WHO and UNICEF recommend the use of reducedosmolarity ORS. Cereal-based electrolyte solutions have been found to be
as effective as sugar/salt ORS and actually reduce stool volume, as well
as rehydrating. Antibiotics (e.g. azithromycin, doxycycline) may shorten
the duration and severity of diarrhoea but should be given only to patients
with severe dehydration.
Prevention and control
Good hygiene and sanitation are the most effective measures for the reduction of infection. Oral live attenuated and killed vaccine are recommended in
potential or actual outbreak situations.
Giardiasis
Giardia intestinalis is a flagellated protozoan that is found worldwide,
causing a small intestinal disease, with diarrhoea and malabsorption.
Prevalence is high in many developing countries and it is the most common
parasitic infection in travellers returning to the UK.
Clinical features
The clinical features are the result of damage to the small intestine. The
changes in architecture are usually mild partial villous atrophy; subtotal villous atrophy is rare. The mechanism by which the parasite causes alteration
in mucosal architecture and produces diarrhoea and intestinal malabsorption
is unknown. Many individuals excreting Giardia cysts have no symptoms.
Others will report diarrhoea (often watery in the early stage of the illness),
nausea, anorexia, and abdominal discomfort and bloating. In most cases,
symptoms resolve after a few days, but in some they persist. Stools may
then become paler, with the characteristic features of steatorrhoea. If the illness is prolonged, weight loss occurs and can be marked. Chronic giardiasis,
frequently seen in developing countries, can result in growth retardation in
children.
Investigations
Treatment is often given based on clinical suspicion. If necessary, the diagnosis is made by finding cysts on stool examination (but negative stool does
not exclude the diagnosis) or parasites in duodenal aspirates or biopsies.
Management
Metronidazole 2 g as a single dose daily for 3 days will cure most infections;
some patients need two or three courses. Alternative drugs include tinidazole
and mepacrine.
Sexually Transmitted Infections 45
HELMINTHIC INFECTIONS
The helminths or worms that infect humans are of three classes (Table 2.8).
In the UK, only three species are commonly encountered: Enterobius
vermicularis, Ascaris lumbricoides and Taenia saginata. Other species occur
in tropical and subtropical countries and may be imported into the UK. A
raised blood eosinophil count (eosinophilia) occurs at some stage in nearly
all helminth infections.
SEXUALLY TRANSMITTED INFECTIONS
Sexually transmitted infections (STIs) are among the most common illnesses
in the world and remain endemic in all societies. The WHO estimates that
more than 1 million people acquire an STI every day. The highest prevalence
of STIs is in young people, men who have sex with men (MSM), and black and
ethnic minority populations. STIs are associated with high-risk sexual behaviour, frequent partner change and inconsistent use of condoms. Increased
travel, recreational drug use and alcohol are also implicated.
Asymptomatic STIs are common and multiple infections frequently
coexist. Sexual health checks offer public health, as well as individual,
benefits because treatment of asymptomatic infections reduces the period
of infectivity, prevents long-term complications and minimizes onward
transmission. Tests for all STIs are indicated in any patient with a known STI or
in those who have been in contact with an STI. All patients should be tested for
chlamydia, gonorrhoea (including samples from extra-genital sites if indicated
by the sexual history), syphilis and HIV.
Gonorrhoea
The causative organism, Neisseria gonorrhoeae (gonococcus), is a Gramnegative intracellular diplococcus which infects epithelium, particularly of the
urogenital tract, rectum, pharynx and conjunctivae. Infection is via mucous
membranes by direct contact.
Clinical features
The incubation period ranges from 2 to 14 days. In men the symptoms are
purulent urethral discharge and dysuria. In MSM, proctitis may produce
anal pain, discharge and itch. Women may be asymptomatic or complain
of vaginal discharge, dysuria, lower abdominal pain and intermenstrual
bleeding. Pharyngeal infection is asymptomatic in >90%. Complications
include epididymo-orchitis and prostatitis in men, while women may experience salpingitis, Bartholin’s abscess, pelvic inflammatory disease and
perihepatitis. Haematogenous spread causes disseminated infection with
46 Infectious diseases
rash and arthritis (p. 280). Infants born to infected mothers may develop
ocular infections (ophthalmia neonatorum).
Diagnosis
Testing is carried out for symptomatic patients, contacts of those infected and in
those with risk factors. In men, a first catch urine (FCU) and in women vaginal
or endocervical swabs are taken for nucleic acid amplification tests (NAAT). This
technique is highly sensitive but can give false-positive results. Rectal and pharyngeal swabs should be sent for culture and sensitivity testing. A positive NAAT
must be followed up by samples for culture to allow sensitivity testing to be carried out. In disseminated disease, blood/synovial fluid cultures should be taken.
Management
Antibiotic-resistant strains of N. gonorrhoeae are increasing and so cultures
should be taken prior to treatment. Single-dose 1 g ceftriaxone intramuscularly is recommended when treatment is commenced prior to knowing
antibiotic sensitivity. If susceptibility is known in advance of treatment, ciprofloxacin 500 mg single dose should be used. Longer courses of antibiotics
are required for complicated infections (e.g. pelvic inflammatory disease,
eipididymo-orchitis). Abstinence from sex for at least 7 days, or until treatment has been completed, should be advised. All sexual contacts should be
notified, tested, and treated if positive.
Chlamydia urethritis
Urogenital C. trachomatis is the most common curable STI in the UK. The
majority of infections are asymptomatic and can therefore remain untreated.
Pelvic inflammatory disease (PID), the main complication of chlamydia, can
result in tubal infertility, ectopic pregnancy and chronic pelvic pain, causing
significant morbidity.
In men, infection can cause an anterior urethritis with a mucopurulent
urethral discharge and dysuria. The infection can ascend along the vas
deferens, leading to epididymo-orchitis. In women, symptoms may include
increased vaginal discharge, dysuria, postcoital or intermenstrual bleeding,
and lower abdominal pain. Ascending infection into the uterus and fallopian
tubes causes PID. In pregnancy, infection is associated with preterm
birth, postpartum infection, and neonatal mucopurulent conjunctivitis and
pneumonia due to vertical transmission during vaginal delivery. In MSM, rectal
infection can occur, leading to proctitis. The diagnosis is made by NAAT from
vulvo-vaginal swabs in women and FCU or rectal swabs in men. Treatment for
uncomplicated urogenital infection is with doxycycline for 7 days or singledose azithromycin 1 g. Test of cure is not usually necessary. Abstinence from
sex for at least 7 days, or until treatment is completed, should be advised.
Sexual contacts must be traced, notified and treated, as many infections are
asymptomatic.
Sexually Transmitted Infections 47
Genital ulcers
The infective causes of genital ulceration in the UK include syphilis, herpes
simplex and herpes zoster. Non-infective causes are Behçet’s disease
(p. 307), toxic epidermal necrolysis (p. 788), Stevens–Johnson syndrome
(p.788), carcinoma and trauma.
Syphilis
Syphilis is a multisystem and multistage disease. The causative organism,
Treponema pallidum, is a motile spirochaete which enters the new host
through breaches in squamous or columnar epithelium either by direct contact or vertical transmission.
Early stages
Primary infection
After an incubation period of 10–90 days a papule (usually anogenital)
develops at the site of inoculation often with regional lymphadenopathy. This
ulcerates to become a painless, firm chancre, which heals spontaneously
within 2–3 weeks.
Secondary infection
In 25% of patients, 4–10 weeks after the appearance of the primary lesion,
constitutional symptoms appear with fever, sore throat and arthralgia. There
may be generalized lymphadenopathy, widespread skin rash (except the face,
but may affect palms and soles), superficial ulcers in the mouth and on the
genitalia (snail-track ulcers) and condylomata lata (warty perianal lesions).
Many systems may be affected (hepatitis, glomerulonephritis, arthritis, meningitis, uveitis). In most patients, symptoms subside within 3–12 weeks and
the disease enters an asymptomatic, latent phase.
Late stages
Tertiary syphilis
This occurs after a latent period of 2 years or more. The characteristic lesion
is a gumma (granulomatous, sometimes ulcerating lesion) occurring in the
skin, bones, liver and testes. Cardiac syphilis and neurosyphilis are discussed
on page 706.
Congenital syphilis
Two-thirds of cases are asymptomatic at birth, but 2–6 weeks after birth
there is nasal discharge, skin and mucous membrane lesions and failure to
thrive. Signs of late syphilis (see above) appear after 2 years of age, when
there are also characteristic bone (‘sabre tibia’) and teeth abnormalities
48 Infectious diseases
(Hutchinson’s teeth) as a result of earlier damage. Screening programmes
are undertaken in pregnant women in the UK.
Diagnosis
A full sexual history including all partners over many weeks to decades is
necessary depending on the stage of infection at presentation. T. pallidum
cannot be cultured but may be identified by dark-ground microscopy of
secretions from a primary chancre or condylomata lata. Most laboratories,
however, use a treponemal enzyme immunoassay (EIA) to detect IgG and IgM
as a screening test. If this is positive, a further treponemal test and a nontreponemal test are performed.
Treponemal tests. T. pallidum haemagglutination (TPHA) and T. pallidum
particle agglutination (TPPA) assays are highly specific for treponemal
disease but usually remain positive for life, even after treatment, so are
unable to differentiate between a previous infection that has been treated
and a subsequent infection.
Non-treponemal tests. The Venereal Disease Research Laboratory
(VDRL) and rapid plasma reagin (RPR) tests become positive within
3–4 weeks of the primary infection. They are quantifiable tests that can be
used to monitor treatment response and evidence of re-infection. They are
not specific to syphilis and false-positive results occur, particularly in other
infections and autoimmune diseases.
Monitoring serological effect of treatment is carried out by quantitative
RPR/VDRL.
Management
• Primary, secondary and early latent syphilis – intramuscular benzathine
penicillin G 2.4 million units (MU) as a single dose. Doxycycline can be
used in the case of penicillin allergy.
• Late latent, cardiovascular and gummatous disease – extend early-stage
treatment weekly for 3 weeks.
• Neurosyphilis – procaine penicillin 1.8–2.4 MU intramuscularly once daily
plus probenecid 500 mg four times daily for 14 days.
The Jarisch–Herxheimer reaction, characterized by malaise, fever and
headache, occurs most commonly in early syphilis and resolves within
24 hours.
HUMAN IMMUODEFICIENCY VIRUS
Acquired immunodeficiency syndrome (AIDS) was first reported in 1981
when clusters of opportunistic infections were identified in drug users
and gay men with no obvious history of immunosuppression. In 1983, the
causative organism, the retrovirus HIV, was discovered and since then HIV
has become a major global public health problem. In 2018, it was estimated
Human Immuodeficiency Virus 49
that 37.9 million people were living with HIV and 770,000 people died of
HIV-related illnesses. Antiretroviral therapy (ART) has dramatically reduced
mortality for those who are able to access care, transforming HIV from a
universally fatal infection into a long-term, manageable condition, with a
consequent rise in global prevalence. In the UK, it was estimated in 2018 that
103,800 people were living with HIV, with approximately 7% of those with HIV
being unaware of their diagnosis. Late diagnosis is the most common cause
of HIV-related morbidity and mortality in the UK. Reducing late diagnosis
and undiagnosed HIV through wider testing, particularly in those patients
presenting with clinical conditions that are associated with HIV, is critical to
both individual and public health.
With effective ART, increasing numbers of people with HIV are living
with long-term, sustained viral suppression. In countries where ART is
consistently accessible, non-communicable conditions, rather than AIDSdefining illnesses, are now the major health problems for people with HIV.
Leading causes of hospital admission of people with HIV include respiratory
illness, psychiatric conditions, and cardiovascular, renal and neurological
disorders. The prevention, identification and treatment of comorbidities are
now central to HIV care.
Routes of acquisition
Transmission is by:
• Sexual intercourse (vaginal and anal). Worldwide, heterosexual
intercourse accounts for the vast majority of infections. In the UK,
diagnoses in MSM still account for over half of the infections per annum,
with black African heterosexuals the next most commonly diagnosed
group. Coexistent STIs, especially those causing genital ulceration,
enhance transmission.
• Mother to child. Transmission can occur in utero, although the majority of
infections take place perinatally or via breast milk.
• Contaminated blood, blood products and organ donations. The risk is
now minimal in developed countries since the introduction of screening
blood products in 1985.
• Contaminated needles. This is a major route of transmission of HIV
among intravenous drug addicts who share needles and syringes.
Healthcare workers have a risk of approximately 0.3% following a single
needle-stick injury with known HIV-infected blood but post-exposure
prophylaxis is available.
HIV infection is not spread by ordinary social or household contact.
Pathogenesis of HIV infection
There are two types, HIV-1 and HIV-2. HIV-2 is mainly confined to West
Africa, runs a more indolent course than HIV-1 and may not respond to many
of the drugs used in HIV-1. The virus consists of an outer envelope and an
inner core. The core contains RNA and the enzyme reverse transcriptase,
50 Infectious diseases
66
latency
infection
which allows viral RNA to be transcribed into DNA and then incorporated into
the host cell genome (i.e. a retrovirus). The rapid emergence of viral quasispecies (closely related but genetically distinct variants) is due to the high
mutation rate of reverse transcriptase and the high rate of viral turnover. This
genetic diversification has implications for the evolution of viral variants with
resistance to antiviral drugs.
HIV surface glycoprotein gp120 binds to the CD4 molecule on host
lymphocytes and other cells bearing the CD4 receptor. The interaction
between CD4 and HIV surface glycoprotein together with host chemokine
co-receptors CCR5 and CXCR4 is responsible for HIV entry into cells
and release of viral RNA. There is a progressive and severe depletion of
infected CD4 helper lymphocytes, which results in host susceptibility to
infections with intracellular bacteria and mycobacteria. The coexisting
antibody abnormalities predispose to infections with capsulated bacteria, e.g.
Streptococcus pneumoniae and Haemophilus influenzae. The clinical illness
associated with HIV infection is due to this immune dysfunction, and also to
a direct effect of HIV on certain tissues.
Natural history of HIV infection
The typical pattern of HIV infection is shown in Fig. 2.1. Throughout the
course of HIV infection, viral load and immunodeficiency progress steadily,
despite the absence of observed disease during the latency period.
Antibody to gp120
CD4 cells
(HIV specific)
Viral load
12345
Weeks
Primary
Fig. 2.1 Schematic representation of the course of human immunodeficiency
virus (HIV) infection. The effect of antiretroviral therapy is also s h o w n .
6 weeks–10 years
(average)
Clinical
12 years
(average)
Antiretroviral
12
Weeks
therapy
Human Immuodeficiency Virus 51
HIV infection is divided into the following stages:
• Primary HIV infection or seroconversion. Illness occurs in most individuals
2–4 weeks after infection. Symptoms are non-specific and include fever,
maculopapular rash, myalgia, headache/aseptic meningitis. The illness
lasts up to 3 weeks and recovery is usually complete.
• Clinical latency. Most are asymptomatic. A subgroup of patients have
persistent generalized lymphadenopathy defined as lymphadenopathy
(>1 cm) at two or more extra-inguinal sites for more than 3 months
in the absence of causes other than HIV infection. There may be
splenomegaly.
• Early symptomatic HIV infection. A rise in viral load occurs with a fall in
CD4 count and development of symptoms and signs due to direct HIV
effects and immunosuppression. Non-HIV-related malignancies are more
common.
• Significant immunosuppression. Opportunistic infections and specific
malignancies may develop. AIDS is a term used to describe these
potentially life-threatening infections and cancers. In most patients the
CD4 count will be below 200 and often much lower (Table 2.10).
Clinical features
The spectrum of illnesses associated with HIV infection is broad and is
the result of direct HIV infection (Table 2.11), infections associated with
immunodeficiency (p. 58), co-infections (e.g. hepatitis B and C) (pp. 149–156)
and side effects of the drugs used to treat the condition.
Diagnosis
Informed consent and testing for HIV infection is within the competence of
any health professional. UK national guidelines for HIV testing are intended
to facilitate an increase in testing and prevent late diagnosis (Table 2.12).
Testing should be offered to those with signs and symptoms of acute or
chronic infection and those with risk exposure (i.e. MSM, intravenous drug
users), but it should also be incorporated into the routine care of healthy
individuals. HIV testing should be considered in any demographic of patient.
All pregnant women are offered testing to prevent vertical transmission in
the UK.
• Combination immunoassays detecting HIV-1 and HIV-2 antibodies and
the HIV P24 antigen are used for initial screening and, when positive,
confirmatory testing is undertaken. These assays have improved
identification of early infection by reducing the ‘window period’
where antibodies may not be detected, but this is still an important
consideration and repeat testing may be required.
• Plasma HIV RNA levels are very high in early infection and may be
used when the above approach is indeterminate to confirm early
infection.
52 Infectious diseases
Table 2.10 AIDS-defining conditions*
Candidiasis of bronchi, trachea or lungs
Candidiasis, oesophageal
Cervical carcinoma, invasive
Coccidioidomycosis, disseminated or extrapulmonary
Cryptococcosis, extrapulmonary
Cryptosporidiosis, chronic intestinal (1 month duration)
CMV disease (other than liver, spleen or nodes)
CMV retinitis (with loss of vision)
Encephalopathy (HIV-related)
Herpes simplex, chronic ulcers (1 month duration); or bronchitis, pneumonitis
or oesophagitis
Histoplasmosis, disseminated or extrapulmonary
Isosporiasis; chronic intestinal (1 month duration)
Kaposi’s sarcoma
Lymphoma, Burkitt’s
Lymphoma, immunoblastic (or equivalent term)
Lymphoma (primary) of brain
Mycobacterium avium-intracellulare complex or M. kansasii, disseminated or
extrapulmonary
Mycobacterium tuberculosis, any site
Mycobacterium, other species or unidentified species, disseminated or
extrapulmonary
Pneumocystis jiroveci (formerly P. carinii) pneumonia
Pneumonia, recurrent
Progressive multifocal leucoencephalopathy
Salmonella septicaemia, recurrent
Toxoplasmosis of brain
Wasting syndrome, due to HIV
*USA definition also includes those with a CD4 count <200 cells/mm3.
• Rapid point-of-care and home testing kits are now available but positive
results need to be confirmed in a laboratory setting.
• Viral genotype analysis is undertaken for all newly diagnosed patients
with HIV along with resistance testing.
• All newly diagnosed patients should also have routine bloods, testing
for co-infection with hepatitis B and C, syphilis serology and a sexual
health screen, screening for antibody detection for a variety of vaccinepreventable infections and, if aged over 50 years, estimation of
cardiovascular risk and fracture risk.