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MRCPCH GUIDE Inf

Varicellazoster immunoglobulin (VZIG) is recommended for individuals who are at increased


risk of severe varicella and who have no antibodies to varicellazoster virus and who have
significant exposure to chickenpox or herpes zoster. Those at increased risk include neonates
of women who develop chickenpox in the period 7 days before to 7 days after delivery, women
exposed at any stage of pregnancy, and the immunosuppressed including those who have
received corticosteroids in the previous 3 months at the following dose equivalents of
prednisolone; 2mg/kg/day for at least 1 week, or 1mg/kg/day for 1 month.

Universal BCG immunisation of teenagers has recently been removed from the immunisation
schedule, with a targeted strategy now recommended to immunise groups at increased risk in
infancy or adulthood. Pneumococcal conjugate vaccine was recommended for children under 5
years with chronic lung, renal, liver and cardiac conditions, diabetes, immunosuppresion /
immunocompromised, cochlear implants, CSF shunts and previous invasive pneumococcal disease.
Conjugate vaccine produces a better immune response than polysaccharide vaccine in young
children and has now been included in the routine vaccination schedule. MMR is indicated for
post-exposure prophylaxis within 3 days of exposure to measles as the antibody response to the
vaccine is faster than the response to natural infection. Individuals at high risk of severe illness
should receive human normal immunoglobulin. Varicella vaccine is not currently recommended in
the UK for universal childhood immunisation, but it is recommended for non-immune close
contacts of immunocompromised patients and non-immune health care workers. Palivizumab is
recommended for specific groups at risk of severe RSV disease, although these individuals
represent a very small fraction of the health burden of RSV. Currently use in children under 2 years
with chronic lung disease requiring oxygen is recommended, but use in those with chronic lung
disease not requiring oxygen requires more evidence.

Group B streptococcus (GBS, Streptococcus agalactiae) is the commonest cause of severe early
onset (within 7 days of birth) infection in new born infants. About 25% of mothers in the UK are
carriers, and the incidence of proven neonatal disease is about 0.7/1000 live births. Universal
screening and intrapartum intravenous antibiotic prophylaxis is practised in the United States
and has resulted in a decrease in the incidence of early onset neonatal infection with GBS, but
has not clearly demonstrated a decrease in neonatal deaths and there are concerns about
antibiotic resistance and other organisms replacing GBS infection. GBS is one of the most
common causes of early onset neonatal meningitis, but recent studies show that the incidence
appears to be declining, probably as a result of antibiotic prophylaxis policies. Blood cultures
are probably negative in more than half of cases of probable GBS infection, due to antibiotic
prophylaxis or insufficient samples of blood. Late onset GBS infection (after 1 week of age) is
well described and accounts for about one-third of all cases.


Diseases notifiable by law differ between the three areas of England & Wales, Northern Ireland
and Scotland. Generally speaking the diseases against which routine immunisation is
recommended, are notifiable with the exception of Haemophilus influenzae. Others include
serious imported infections: typhoid, cholera, malaria and viral haemorrhagic fever. It is
important that clinicians think about whether an infectious disease is notifiable, as it is the
responsibility of the clinician looking after the patient to submit the notification.

Syphilis is undergoing a resurgence at present, so paediatricians need to be aware of how to
deal with neonates born to mothers with positive serology. Positive non-treponemal tests such
as RPR can be caused by a number of conditions other than syphilis eg EBV, TB, SLE. False
positive treponeme specific tests (such as TPPA) can occur with other spirochaetal diseases
such as Yaws. In this case it is very unlikely that the results represent a false positive,
especially as the girl has signs consistent with secondary syphilis, but they should be repeated
to confirm. Treatment in pregnancy should be given at least one month before delivery and
parenteral penicillin is the treatment of choice. Symptomatic congenital syphilis at birth is
unusual, and it is more common for the infant to become unwell during the first three months
of life with failure to thrive, rashes and desquamation, nasal discharge and
hepatosplenomegaly. In this case it would be advisable to treat the infant with a 10-14 day
course of intravenous penicillin.

Herpes simplex virus can cause overwhelming infection in the neonate. The risk of infection in
the newborn is around 5% if the mother has active recurrent infection, but up to 50% if it is a
primary infection. Clinically it can be difficult to distinguish primary from recurrent episodes in
the mother as primary episodes may be asymptomatic. Empirical aciclovir treatment may be
justified for infants born to mothers with primary episodes, but for secondary episodes most
experts advise waiting for the results of swabs and specimens submitted for viral culture or PCR
(nasopharynx, rectum, mouth, stool and urine). Disease in the newborn occurs within four
weeks of birth, and even low-risk infants with no HSV detected from swabs / stool/ urine,
should be observed for the appearance of any rash, seizures or sepsis-like illness.

Peritonsillar abscess (quinsy) typically causes an asymmetrical appaearance of the tonsils
with displacement of the uvula away from the affected side. Lemieres disease is
retropharyngeal abscess caused by fusobacterium necrophorum, with thrombosis of the
internal jugular vein and metastatic abscesses. Streptococcal throat infection is a possibility in
this case but the fact that the spleen is palpable, the palatal petechiae and the failure to
respond to antibiotics makes this less likely. Diphtheria is rare in the UK and classically a grey-
white membrane develops which is firmly adherent to the throat. The most damaging effects
are due to an exotoxin acting on local tissues, motor nerves and myocardium.

Cutaneous Leishmaniasis
Leishmaniasis is caused by an intracellular protozoal organism, transmitted by the bite of
sandflies. In cutaneous leishmaniasis there is usually a papule which develops into a nodule before
ulcerating. It will frequently resolve by itself after months or even years. Most cutaneous
leishmaniasis is acquired is South America, Afghanistan, Iran, Syria and Saudia Arabia. It is
important to evaluate New World cases thoroughly because some species cause cutaneous
lesions which are later followed by destructive mucosal lesions (mucocutaneous leishmaniasis).
Tinea
Tinea capitis can present in six different patterns.
1. Extensive scaling in circular patches of hair loss.
2. Black dots where hair follicles have broken off.
3. Kerion a boggy inflammatory swelling.
4. Diffuse dandruff like scaling.
5. Moth-eaten patchy hair loss.
6. Widespread pustules often with cervical lymphadenopathy.
Treatment should be systemic with griseofulvin and terbinafine.

Diseases associated with EBV include:
Stevens Johnson syndrome
Hepatitis
Herpes
Infectious mononucleosis (glandular fever)
Alice in Wonderland syndrome
Non-Hodgkin's lymphoma, including Burkitt's lymphoma and primary cerebral lymphoma
Hodgkin's disease
Post-transplant lymphoproliferative disorder
nasopharyngeal cancer
Herpangina

MMR is the best protection against these viruses. There is no credible link with bowel disease
or autism. It is contraindicated in those with suppressed immunity. According to the WHO,
measles vaccine is not given to HIV positive children with severe immunosuppression (i.e. CD4
<15%). However the majority of children under age 15 months with HIV do not (yet) have
sufficient immunosuppression to mean that measles vaccine is unsafe, and it is particularly
important to follow national guidelines in immunising these children, on time, to protect them
against wild measles. Like wild measles, measles vaccine virus may rarely cause a fatal giant
cell pneumonitis, but only in individuals with profound immunosuppression. MMR is useful in
measles outbreaks, but it is less helpful in providing individual protection in mumps or rubella
epidemics since the antibody response is too slow to provide protection for those already
exposed. The contraindications include those who are allergic to gelatine or neomycin.
The contraindications to MMR are :
Untreated malignant disease or altered cell-mediated immunity
Another live vaccine within 3 weeks
Allergies to gelatine or neomycin
Acute febrile illness
Pregnancy within 1 month
Within 3 months of an immunoglobulin injection

Palivizumab is an intramuscular injection to prevent serious lower respiratory tract infection
caused by respiratory syncitial virus (RSV) given in chronic lung disease and haemodynamically
significant congenital heart disease infants. The injections are monthly for 5 months during the
winter RSV season and it reduces hospitalisations and oxygen requirement in protected
children.

Rabies vaccination consists of pre-exposure immunisation to those at risk (3 injections, with
booster doses). Post exposure treatment for fully protected individuals is just 2 more doses of
immunisation, but for unprotected individuals is also rabies immunoglobulin. Most children are
unprotected. Cholera immunisation is no longer recommended. Yellow fever immunisation is
recommended under 9 months of age if the risk of yellow fever is unavoidable. Malaria
prophylaxis with chloroquine or mefloquine is not appropriate for those with a history of
epilepsy. Hepatitis A vaccine is the preferred prophylaxis and is likely to be effective even if
given shortly before exposure.
Leishmaniasis is caused by a number of species of leishmania including L. donovani and is
present in Africa, the middle East, Arabia, China, India and South America. Humans are the
main hosts and it is spread by the sandfly. Massive splenomegaly is an early sign in visceral
leishmaniasis where dermal nodulesmay present later. Conventional treatments for visceral and
mucosal disease have used the antimony-based drugs stibogluconate and meglumine but there
are problems with availability, toxicity and resistance to these agents. Success has been
reported more recently with amphotericin preparations and with miltefosine, and these are
increasingly being used as first-line therapy.

The main causes of acute watery diarrhoea are rotavirus, calciviruses, E. coli, Salmonella,
Campylobacter, Shigellae, giardia, Cholera and Cryptosporidium. E. coli 0157:H7 (the
commonest serotype of the 'enterohaemorrhagic' strains of E. coli) can cause haemolytic
uraemic syndrome typically following an episode of bloody diarrhoea. Shigella, Salmonella and
Campylobacter may also cause bloody diarrhoea. Although the presence of toxin-producing
Clostridium difficile may be associated with pseudomembranous colitis and the presence of
blood in the stools. C. difficile is more usually found with watery, non-bloody diarrhoea
following antibiotic use. Cryptococcus neoformans , a fungal pathogen responsible for
meningitis and invasive illness in immunocompromised individuals does not cause diarrhoea.

Lymphogranuloma venereum is a sexually transmitted disease that primarily infects the
lymphatics and is caused by serovars L1, L2, and L3 of Chlamydia trachomatis. Onchocerciasis
causes blindness; it is caused by the nematode, Onchocerca volvulus, but black flies are vectors
of O volvulus. Yellow fever is a viral illness which is spread by the bite of a mosquito.
Trypanosomiasis is carried by the tsetse fly.

Typhoid is associated with slow onset of fever, headache, constipation, diarrhoea in second
week, abdominal pain, hepatomegaly, Rose spots, gram negative septicaemia and delirium.
Haemorrhage is common in children. The rash appears day 7-10 and consists of discrete
erythematous, popular lesions (1-5mm) appearing in crops on chest and abdomen. 10% of
children may have severe intestinal haemorrhage
Palivizumab is an effective monoclonal antibody, not a vaccine for prophylaxis against RSV. The
highest incidence is in the first year of life, 80% of children having had the disease by 1 year.
Ribavirin is not effective as prophylaxis or treatment although the monoclonal antibody
palivizumab does offer some protection. T he cough usually lasts for up to 6 weeks and many of
the children dying with RSV will have large left to right shunts due to congenital heart disease.
Cholera toxin stimulates the adenyl cyclase AMP pathway.

Mainly occurring in children in south-east A sia, it occurs after 3-4 days of fever due to the
flavivirus, especially in the hot season when the mosquitoes are most numerous. The vector is
Aedes Aegyptii with an incubation period of only 2-7 days. There is an increase in haematocrit,
Disseminated intravascular coagulation, capillary leak with ascites and pleural effusion,
complement activation, release of vasoactive mediators. There is leucopenia and
thrombocytopenia. Fatality is up to 10%.

A loading dose of quinine should not be given if the patient has received quinine, mefloquine or
quinidine in the previous 24 hours. IV quinine should be given first. Hypoglycaemia is a side
effect of therapy andmay be a cause of failure to respond. In a comatose patient, a lumbar
puncture should be performed to exclude co-existing bacterial infection. In heavy infections
(>10% red cells infected), exchange transfusion is indicated to reduce the infective load.
Initially IV quinine should be started, then oral dose should be given

HBsAg is present from 1-6 months after exposure and is always present in serum (togther with
anti-core IgM antibody) when symptoms appear. Antibody to HBs by contrast does not appear
until complete recovery 3-4 months after illness. The presence of HBeAg implies high
infectivity; it is usually present for 1.5-3 months after the acute illness. The persistence of
HBsAg for >6 months defines carrier status. Antibodies to both HBcAg (anti-HBc) imply previous
infection, whereas those to HBsAg alone imply vaccination. HBV can be detected by PCR in
acute infection, but use of these assays is restricted to determination of the need for and
resonse to therapy.

Intrapartum, not transplacental is the commonest route of vertical transmission; the risk of
perinatal acquisition of HIV infection is 25%.The disease progresses rapidly in approximately
10-20% of children who are infected, and they die of AIDS by age 4 years, whereas 80-90%
survive to a mean age of 9-10 years. A higher incidence of neoplasia is noted including B cell
lymphoproliferative diseases, including non-Hodgkin lymphoma, Burkitt lymphoma, and smooth
muscle tumours, have been identified. A variety of skin conditions, including exaggerated
eczema, psoriasis, drug eruptions (including morbilliform eruptions and Stevens-Johnson
syndrome), intense reactions to arthropod bites, alopecia, and trichomegaly, have been
reported in children who are HIV positive.

Brucellosis is an infectious disease caused by the Brucella bacteria , which
induces inconstant fevers, sweating, weakness, anorexia, headaches,
depression and muscular and bodily pain. The disease's sequelae are highly
variable and may include granulomatous hepatitis, arthritis, spondylitis,
anaemia, leukopenia, thrombocytopenia, meningitis, uveitis, optic neuritis and
endocarditis.
Toxoplasmosis is caused by the parasite Toxoplasma gondii. It causes infections that can be
either acute or chronic. 60% if those who become infected will be asymptomatic. Most of the
remaining 40 percent experience mild, flu-like symptoms (characterised by fever,
lymphadenopathy, malaise, myalgias, and a maculopapular skin rash that spares the palms and
the soles), low-grade fever, and fatigue that resolve without intervention in a few weeks.
Lymphadenopathy is the most common finding. Once exposed, re-infection does not occur in
healthy individuals. However, in immunocompromised individuals, such as those with HIV/AIDS,
symptoms can be severe, life threatening, and recurring. T. gondii infection of a fetus or
newborn can also cause severe neurological impairment, blindness, mental retardation, and
death. When a fetus acquires the infection through its mother, this is called congenital
toxoplasmosis. The classic clinical triad of retinochoroiditis, cerebral calcifications, and
convulsions defines congenital toxoplasmosis. Other findings include hydrocephalus,
microcephaly, organomegaly, jaundice, rash, fever, and psychomotor retardation.
Where only P. vivax malaria exists, prophylaxis should be chloroquine or proguanil (Paludrine).
Where P. falciparum exists and is sensitive to chloroquine, this should be used. Where
chloroquine-resistant P. falciparum exists, chemoprophylaxis should be by mefloquine although
this is not advised for young children, for whom chloroquine plus proguanil should be used.
Both chloroquine and mefloquine are unsuitable for malaria prophylaxis in individuals with a
history of epilepsy. In areas without chloroquine resistance proguanil is recommended; in areas
with chloroquine resistance, doxycycline or Malarone may be considered.
Doxycycline is contra-indicated during pregnancy.
Humoral responses to HIV can be measured by various antibody assays. Antibodies to core (p24)
and envelope (gp120) proteins can be detected 6 weeks to 3 months following infection. In the
adult, a positive antibody test is a sensitive and specific indicator of HIV infection. The
presence of transplacentally acquired maternal HIV antibody in a newborn limits the usefulness
of antibody testing as a criterion for infection. Maternal antibodies clear at around 12-18
months of age.
Some children with clinical features of HIV infection but no HIV antibody response because of B
cell dysfunction.
Abnormalities in B cell function usually precede T cell abnormality
With the exception of BCG, it is probably safe to give live vaccines to HIV-positive individuals,
with or without symptoms of the disease. Because oral polio vaccine virus may be excreted for
prolonged periods from individuals with immune dysfunction, the clinician may choose to use
inactivated polio vaccine especially if there positive individuals.

Children at risk of pneumococcal disease include:

Child under 5 years with a history of invasive pneumococcal disease;
Asplenia or splenic dysfunction (including homozygous sickle cell disease and coeliac disease
which could lead to splenic dysfunction);
Chronic respiratory disease (includes asthma only if treated with continuous or frequent use of
a systemic corticosteroid);
Chronic heart disease;
Chronic renal disease;
Chronic liver disease;
Diabetes mellitus;
Immune deficiency because of disease (e.g. HIV infection) or treatment (including prolonged
systemic corticosteroid treatment);
Presence of cochlear implant;
Presence of CSF shunt or other condition where leakage of cerebrospinal fluid could occur.
Vaccination was targeted to these groups prior to the introduction of universal pneumococcal
vaccination in the UK in late 2006.
The conjugate vaccine covers the seven most common serotypes responsible for invasive
pneumococcal disease in the developed world. Since 2006 it has been given routinely to infants
in the UK in three doses, two in the first year of life with a booster dose at age 13 months. It is
recommended that children in the above risk groups are also subsequently given the plain
polysaccharide vaccine after the age of 2 years. This vaccine contains polysaccharide antigens
from 23 serotypes of pneumococcus which cause the majority (>95%) of episodes of invasive
disease. The plain polysaccharide vaccine is not immunogenic in children below two years of
age.

It is currently recommended that all children over 6 months who are at risk of severe disease
from influenza virus receive the vaccine each autumn. It is reformulated each year based on
WHO recommendations of the most likely strains to cause disease in the coming winter. The
following are considered at risk
Chronic respiratory disease, including asthma requiring frequent courses of steroids;
Chronic heart disease including heart failure and haemodynamically significant congenital heart
disease;
Chronic liver disease;
diabetes mellitus;
Immunodeficiency or immunosuppression (including asplenia or splenic dysfunction, and
prolonged corticosteroid treatment);
HIV infection (regardless of immune status)
The recommendations also include individuals with chronic renal disease and diabetes,
although there is little evidence that children with these conditions are at increased risk of
severe complications from influenza.
The standard vaccine is not a live product, therefore it is safe to use in immunocompromised
individuals - indeed they are more vulnerable to severe disease without it. Children with HIV
can safely receive it irrespective of CD4 count and disease status. The vaccine is developed
from virus grown in embryonated hens eggs. It is contraindicated in those who have a history
of anaphylactic reaction to egg, as well as those with neomycin allergy.

Leukocyte adhesion deficiency is a very rare defect in molecules such as LFA1 required for
cells such as neutrophils to migrate out of blood vessels. It is associated with delayed
separation of the cord, very poor wound healing, recurrent infections and vasculitic skin
lesions.
IgG subclass deficiencies have varied manifestations involving recurrent sinopulmonary
infections.

Common variable immune deficiency describes individuals with a B-cell defect, sometimes
associated with a T-cell defect. They suffer sinopulmonary bacterial infections, may develop
bronchiectasis, and some are vulnerable to opportunistic infection.
This boy has chronic granulomatous disease. The majority of cases are inherited in X-linked
recessive fashion, although it can be autosomally inherited as well. Defective respiratory burst
in phagocytic cells means they are unable to kill catalase-positive organisms that they ingest.
Catalase-negative organisms are vulnerable to hydrogen peroxide killing, and do not rely on the
respiratory burst. Common organisms include staphylococci, burkholderia, nocardia, as well as
the fungus aspergillus. Skin infections, pneumonia and deep abscesses occur. Colitis is also
seen, and granulomata can cause obstruction of nasal passages, GI or urinary tract. The
investigation used to diagnose this condition is the nitroblue tetrazolium test. A drop of whole
blood is placed on a microscope slide coated with an activating agent, such as
lipopolysaccharide or phorbol ester. Phagocytes adhering to the slide are activated and develop
blue inclusions upon incubation with NBT.
Twice weekly full blood counts are the only way to diagnose cyclical neutropenia. This is
caused by a defect in the gene for neutrophil elastase. Neutrophil counts cycle on a 2-3
weekly basis, and when low give rise to fever, mouth ulcers and bacterial infections, which can
be life threatening. Treatment is with G-CSF. This boy does not have any periodicity to his
infections.
Leukocyte adhesion molecule deficiency is a very rare defect in molecules such as LFA1
required for cells such as neutrophils to migrate out of blood vessels, hence white cell counts
can be very high. To test for it, the expression of these molecules is looked for on the surface
of leukocytes. It is associated with delayed separation of the cord, very poor wound healing,
recurrent infections and vasculitic skin lesions. Patients cannot form abscesses as neutrophils
cannot leave blood vessels. The treatment is bone marrow transplant
T-cell proliferation assays test whether T-cells are able to respond to an appropriate stimulus
and clonally expand. Phytohemaglutinin is often used. The CD3 count is a measure of T-cell
numbers (quantity); proliferation assays are measures of T-cell quality. A T-cell proliferation
assays will be impaired in cellular immune deficiencies, such as Di George syndrome, Wiskott-
Aldrich syndrome or combined immune deficiency.
A raised serum IgE level is associated with many disorders, including atopy. IgE levels of
several thousand may suggest hyper IgE syndrome (Job syndrome). It is autosomally dominantly
inherited, and causes dermatitis, recurrent infections, often with staphylococci, typically skin
infections and pneumonia which may lead to pneumatocoeles. The normal skin and facies
make less likely in the patient in the question.

Extract from RCPCH Immunisation of the immunocompromised paper
Significant contact with an individual with chickenpox (play or direct contact for more than
15 minutes, on ward or in household), during the infectious period from 2 days prior to onset
of rash, until crusting of all vesicles, or with herpes zoster (direct contact with exposed lesions
only) requires one of the following prophylactic treatments in varicella antibody negative
patients:
Either
Aciclovir is widely prescribed as a prophylactic agent in this setting. However, there is
relatively little supportive clinical literature.
High dose oral aciclovir from 7 21 days following the initial contact.
Aciclovir dose:
Under 2 years age 200 mg four times daily
2-6 years age 400 mg four times daily
Over 6 years age 800 mg four times daily
Or
If less than 72 hours from contact, give intramuscular zoster immunoglobulin (ZIG) (may
attenuate infection if administered up to 10 days post exposure) or (especially if
thrombocytopenic) IVIg. The protection lasts approximately 4 weeks.
ZIG dose:
Under 5 years age 250 mg
5-10 years age 500 mg
Over 10 years age 750 mg
IVIg (standard dose) 0.4g/kg

Wiskott-Aldrich syndrome is an X-linked condition caused by mutation in the WASP gene, with a
range of clinical severity. It is characterised by the triad of thrombocytopenia, eczema and
immunodeficiency, often with reduced T-lymphocyte counts. Bruising, bleeding and petechiae
are all common, but infective complications predominate with increasing age. Definitive
management is with bone marrow transplant.
Di George syndrome results from abnormal embryological development of the 3
rd
and 4
th

pharyngeal pouches. Most cases are sporadic and associated with microdeletion at 22q11. The
severity of the immunodeficiency is very variable and caused by failure of thymic development
(sometimes seen to be absent on a chest radiograph). The immunodeficiency may be
associated with hypocalcaemia (due to hypoparathyroidism), congenital heart defects and
abnormal facies (low-set ears, hypertelorism, micrognathia and short philtrum). It is not
associated with thrombocytopenia.
Severe combined immune deficiency (SCID) is caused by a range of genetic defects transmitted
in autosomal or x-linked recessive fashion. They all result in T-lymphopenia, but the presence
of B-cells depends on type. Where present, B cells do not function normally. The typical
infant has failure to thrive with chronic diarrhoea in the first few months of life, with atypical,
severe or recurrent infections. Although definitive treatment is with bone marrow transplant,
there are clinical trials of gene therapy underway for certain types of SCID. In some cases of
SCID there is an eczematous rash. SCID does not cause thrombocytopenia.
Bernard-Soulier syndrome is an autosomal recessive disorder. The blood film shows giant
platelets. It clinically manifests as a mild bleeding disorder, and is not associated with any
immunodeficiency. (It is Very, very rare - 1 in million)
Hyper-IgE syndrome (also known as Job syndrome) is characterised by eczema and recurrent
staphylococcal infections. Staphylococcal pneumonias can result in pneumatocoeles and
chronic lung disease. Infection with other bacteria or candida also occurs. Serum IgE levels
are usually extremely elevated with levels up to 40,000 U/L or more. Treatment consists of
anti-staphylococcal prophylaxis. The platelet count is normal.

Antibodies are produced in glandular fever which are able to agglutinate red blood cells
of other species, such as sheep (Paul-Bunnell test) or horses (Monospot test). This is the
basis of the heterophile antibody test. This may not be positive in the first week of
illness, especially in younger children.

CSF pneumococcal PCR
Streptococcus pneumoniae and Neisseria meningitides are the two common causes of
pyogenic meningitis in the UK, since universal vaccination against Haemophilus
influenzae group B was introduced. A 7-valent conjugate pneumococcal vaccine was
added to the routine immunisation schedule in 2006 but infants and children will
remain susceptible to non-vaccine serotypes. The universal Group C meningococcus
conjugate vaccine does not provide protection against Group B disease, the other
common serotype in the UK. The presence of gram-positive cocci (in chains) is strongly
suggestive of pneumococcal meningitis. Meningococci appear as gram-negative
diplococci. Although no organisms may be seen on gram stain if partially treated with
antibiotics, both can be detected at this stage by rapid antigen tests of the CSF
(although sensitivity of test low), or more reliably by PCR. Blood culture is unlikely to
be positive as there will be some antibiotic present in the blood still. Pneumococcal
meningitis is associated with a strong inflammatory response often causing a high CRP,
and a high CSF protein. Complications such as cranial nerve palsies or subdural
collections are not uncommon with pneumococcal meningitis. The long-term
neurodevelopmental prognosis is worse with pneumococcal compared to meningococcal
meningitis. Both pneumococcus and meningococcus may cause septicaemia in the
absence of significant meningitis. Meningoccal sepsis is characterised by a non-
blanching rash leading to purpura fulminans. It heralds a rapid decline with multi-
organ failure with the need for intensive care support


Enterovirus serology
Enteroviruses (e.g. echovirus, Coxsackie virus) are the commonest cause of viral
meningitis in a mumps immune population, accounting for >90% of cases of aseptic
meningitis. Viral meningitis is usually clinically milder than bacterial meningitis, and
associated with a lymphocyte-predominant CSF. Neutrophils may predominate
however in the first few days. The CSF glucose is usually normal. Herpes simplex virus
usually causes a meningo-encephalitis with significant neurological disturbance
manifest as change in consciousness/behaviour or focal seizures. There is often evidence
of temporal lobe involvement on CT scanning or EEG. Diagnosis can be made by PCR
of CSF. West Nile virus can cause meningo-encephalitis, but is not found in the UK.
Ziehl-Neelsen stain of CSF
Tuberculous meningitis most commonly affects young children, and results from a
microtubercle rupturing into the sub-arachnoid space. It usually presents insidiously,
with vomiting, low-grade fever and increasing drowsiness. Patients with reduced
consciousness should have a CT scan to look for evidence of raised intracranial pressure
prior to lumbar puncture. There may be hydrocephalus, enhancement of the brain stem
with contrast, or focal tuberculomas. The CSF is predominantly lymphocytic with low
glucose and high protein. The diagnosis can be confirmed by the presence of acid-
alcohol fast bacilli on a Ziehl-Neelsen stain of the CSF. However ZN stains now mostly
superceded by auramine staining for acid fast bacilli in developed countries and
detection on initial microscopy is unusual. The organisms should also be cultured for
sensitivity testing to guide therapy. Treatment should include 4 drugs: isoniazid and
rifampicin for 12 months with ethambutol and pyrazinamide for at least 2 months.
Steroids are often used to reduce inflammation concurrently with antimicrobials.

Organism Disease Vector Reservoir
Plasmodium
spp.
Malaria
Anopheles
mosquito
-
Dengue
virus
Dengue
fever
Aedes
mosquito
-
Yellow
fever virus
Yellow
fever
Aedes
mosquito
-
West Nile
virus
West Nile
encephalitis
Culex
mosquito
Birds
Borrelia
burgdorferei
Lyme
disease
Ixodes
tick
Deer
(plus
other
mammals
and
birds)
Yersinia
pestis
Plague
Oriental
rat flea
Urban
rat
(Ratus
ratus)
Rickettsia
rickettsii
Rocky
mountain
spotted
fever
Tick
Various
including
dogs

Congenital cytomegalovirus
Primary infection in a pregnant mother poses the greatest risk to the foetus. This can
result in intra-auterine growth restriction, premature delivery or stillbirth. Affected
infants may be asymptomatic, or may have a range of features including jaundice,
hepatosplenomegaly, thrombocytopenia with petechiae/purpura, encephalitis,
microcephaly, chorioretinitis, cerebral calcification. Sensori-neural deafness and
learning disability are significant long-term complications. Diagnosis is made by
identifying the virus in a sample from the baby within the first three weeks of life. After
this period, a positive result may be indicative of neonatal infection. CMV can be
detected in the urine, blood or csf, using either culture and immunological detection, or
a PCR-based approach. There is evidence ganciclovir therapy in affected infants may
reduce deafness
Congenital herpes simplex
The greatest risk is to a baby born through a birth canal which has active primary
herpetic lesions. Lesions due to reactivation pose less risk, as the infant will have
passively received IgG antibodies across the placenta. Affected infants display one of
three manifestations: ii) encephalitis Infants with SEM disease should receive two weeks
of intravenous aciclovir. Infants with CNS or systemic disease should receive three
weeks therapy.

Congenital varicella
Infection in early pregnancy can lead to the foetal varicella syndrome. This results in
low-birth weight infants with a range of congenital abnormalities including cicatricial
skin lesions (pale yellow dermatomal scars), limb hypoplasia, microcephaly,
chorioretinitis, corneal clouding, optic atrophy, and results in learning disability in the
child. Suspected in utero diagnosis can be confirmed by PCR on an amniocentesis or
chorionic villus biopsy sample. Non-immune pregnant women who come into contact
with chicken-pox should receive varicella-zoster immune globulin, but not varicella
vaccine. If she develops chicken-pox she should receive aciclovir. Infection nearer the
time of delivery poses the risk of severe chickenpox in the neonate. If the rash appears
in the mother from five days prior to delivery up to two days afterwards, the concern is
that the infant will become infected without the protection of any maternal antibody,
resulting in very severe disease. Babies born to mothers developing chickenpox within a
week before or after delivery are therefore given VZIG. Should symptoms develop they
also receive aciclovir.
In areas where diphtheria is relatively common it should be suspected in any child with
exudate in the throat. If the exudate is thick and discoloured the child should be given
antitoxin. Clinical diagnosis is much more difficult where diphtheria is rare. The
differential diagnosis includes infectious mononucleosis, streptococcal or viral tonsillitis,
peritonsillar abscess, oral thrush, and leukaemia and other blood dyscrasias. The bull-
neck of malignant diphtheria may be mistaken for mumps. In adults, secondary syphilis
can sometimes cause a glairy (resembling egg-white) exudate on the tonsils, and may be
accompanied by rash and laryngitis.
Outbreaks of paramyxovirus infection (mumps in this case) are occasionally seen
amongst students. In fact, there has been a recent increase in the number of cases of
mumps cases in the late teenage years, as a result of individuals who may have missed
the mumps vaccination before the introduction of MMR. The number of cases seen in
this age group may increase further if MMR (measles, mumps, rubella) vaccination
continues to fall out of favour. Mumps is spread via respiratory contact and patients are
contagious from 48 h before, to 9 days after parotid swelling.
There is a prodromal period characterised by low-grade fever, malaise, anorexia and
headache. This is followed by parotid swelling and tenderness, which is usually the first
sign of overt infection. It is unilateral in 25% of cases.
CNS involvement may lead to meningitis in 110% of cases. Encephalitis is very rare,
but may be seen early, or late in the second week after the onset of parotitis as a
postinfectious demyelinating process. Other CNS complications include cerebellar
ataxia, transverse myelitis and GuillainBarr syndrome. Epididymo-orchitis occurs in
3038% of postpubertal males who suffer mumps. Oophoritis may occur in 5% of
postpubertal women suffering from the condition. Deafness is usually transient, but
unilateral permanent high-tone hearing loss may occur in around 1 in 20,000 cases.
Treatment is generally of a supportive nature with fluids and analgesics, and the
majority of patients recover with no long-term consequences.
Campylobacter enteritis is the most common bacterial infection of the gut found in
industrialised countries. Some 55,000 laboratory isolations per annum are currently
reported in the United Kingdom, representing an annual incidence of 100/100,000, but
the true incidence is likely to be at least ten times this figure. In developed countries
campylobacter enteritis affects people of all ages, especially young adults. However, in
developing countries it is almost entirely confined to children below the age of 23 years,
after which they are immune through repeated exposure to infection.
Normal cooking destroys campylobacters, but the consumption of raw or barbecued
meats, especially poultry, carries a distinct risk of infection. Broiler chickens are the
most prolific source of campylobacters. Retailed chickens are almost universally
contaminated (frozen ones less so than fresh ones), so self-infection when handling them
in the kitchen, or cross-contamination to other foods, readily occurs if good hygiene is
not observed.
A lesion with central scarring is suggestive of lupus vulgaris. This is the commonest
manifestation of cutaneous tuberculosis.
Ringworm (Tinea corporis) of the body usually presents with slightly itchy,
asymmetrical scaly patches that show central clearing and an advanced scaly raised
edge. Occasionally vesicles or pustules may be seen in the edge. Granuloma annulare is
a dermatosis predominantly of children and young adults. It is characterised by clusters
of small dermal papules that often form into rings or part of a ring. As they heal, the
centre becomes dusky and altered in texture. Borderline leprosy (BB) presents with
numerous skin lesions that may form macules, papules and plaques. The annular-
rimmed lesion with a punched-out hypopigmented anaesthetic centre is characteristic.
There is widespread nerve involvement and limb deformity. Cutaneous leishmaniasis
presents as a single or multiple painless nodules that enlarge and ulcerate with a
characteristic erythematous raised border. An overlying crust may develop.

Important Gram-positive cocci include staphylococci, streptococci and enterococci.
Staphylococci typically form clumps and clusters in culture, whereas streptococci
characteristically grow in chains of variable length. Staphylococcus aureus is coagulase
positive, unlike S. epidermidis. Enterobacter spp. are Gram-negative coliforms not to be
confused with the Gram-positive enterococci, such as E. faecalis and E. faecium.

Listeria species are non-sporing , facultatively anaerobic, Gram-positive bacilli that are
ubiquitous in the environment and distributed world-wide. Listeria monocytogenes is the
major pathogen. Enrichment and selective methods are now well established for the
isolation of listeria from food or the environment; immunoassays and nucleic acid-
amplification techniques have also been used. Several typing methods are used to trace
food sources, distinguish relapses from re-infections and investigate outbreaks. The
ability to multi ply at temperatures of 040C and tolerate preserving agents makes
listeria of particular concern if present in refrigerated foods that are consumed without
further cooking.

This patient has a dermatophyte infection. The three main genera
responsible are Trichophyton, Microsporumand Epidermophyton. They
can be identified by their colonial appearance and microscopic
morphology:
Dermatophyte Microconidia
Trichophyton Abundant
Microsporum
Single
(multicellular)
Epidermophyton None
Candidiasis presents with several pustules and numerous small
satellite lesions that have a typical frayed peeling edge on rupture.


Nasopharyngeal carcinoma
This tumour is restricted to the postnasal space where it arises from squamous
epithelial cells. Although the tumour is seen rarely throughout the world, it has a
remarkably high incidence in southern Chinese and in the Inuit and related circum-
Arctic races. In high-incidence areas, nasopharyngeal carcinoma is the most common
cancer in men and the second most common in women. The tumour usually occurs in
middle or old age, but in North Africa it has bimodal age peaks: one involving young
people up to 20 years of age and a second much later in life. Irrespective of geographical
region, nasopharyngeal carcinoma cells always carry the EBV genome.
Nasopharyngeal carcinoma causes nasal obstruction, discharge or bleeding, deafness,
tinnitus or earache, headache and ocular paresis from tumour spread to involve cranial
nerves. Patients may present with either a single symptom caused locally by the tumour
or with several symptoms, while about one-third complain only of cervical lymph-node
enlargement due to metastatic spread from an occult primary tumour.
Direct spread from the primary tumour may involve the soft tissues, bone, parotid
gland, buccal cavity and oropharynx. The neoplasm may extend into the nasal fossas,
the paranasal sinuses or the orbit, and can invade the Eustachian canal or the
parapharyngeal space where cranial nerves IX, X, XI and XII can be involved. Invasion
of the skull or cranial foramina may damage cranial nerves II, IV, V and VI. Lymphatic
spread causes enlarged cervical lymph nodes and subsequently extends to the
supraclavicular glands. Blood-borne metastases most frequently occur in the bones,
liver and lungs, but may be found in any organ.
Untreated nasopharyngeal carcinoma progresses inexorably to death.

In patients with suspected extracutaneous Lyme borreliosis, serological testing is
essential to support the diagnosis. Patients with extracutaneous Lyme borreliosis almost
always have diagnostic serum antibodies to Borrelia burgdorferi, except for some
patients with early VIIth nerve palsy or occasional patients in whom antibodies to
Borrelia burgdorferi are only present in cerebrospinal fluid.
A two-step approach to serological diagnosis has recently been proposed in the United
States (and is being studied in Europe) to increase the specificity of a positive test. A
positive or equivocal first-stage test (usually an enzyme-linked immunosorbent assay
(ELISA) or indirect immunofluorescence assay (IFA)) is followed on the same serum
sample by a second-stage test (immunoblot). Two-step testing, however, is not indicated
for those with little or no clinical evidence of Lyme borreliosis because of a low positive-
predictive value. Since IgM and IgG antibodies to Borrelia burgdorferi may persist in
the serum for years after clinical recovery, serology has no role in measuring the
response to treatment.
The culture of Borrelia burgdorferi is a highly insensitive diagnostic technique for
patients with extracutaneous Lyme borreliosis, presumably because of the
inaccessibility of tissues that contain the organism.

Yellow fever is caused by a flavivirus, and can vary in severity from a mild illness to the
severe classical form seen here. It is confined to Africa and South America between the
latitudes of 15N and 15S. It is transmitted in South and Central America by the
Haemagogus mosquito species. There is an incubation period of 36 days.
In the classical illness the patients then present with a severe flu-like illness with pyrexia
up to 40 C; there may be associated epigastric pain and vomiting. Relative bradycardia
(Fagets sign) is present from the second day of the illness. There is then a recovery
phase and the patient feels well for several days. After this time, severe fever develops
once again, the patients become jaundiced, with hepatomegaly, evidence of severe
bruising, bleeding from the gums, haematemesis and melaena. Liver biopsy at late
presentation shows mid-zone necrosis, with eosinophilic degranulation of hepatocytes.
Supportive therapy only is possible, and mortality is unfortunately up to 40%.
Pseudomembranous colitis has been reported to follow the use of every antimicrobial in
common medical practice, but its association with lincomycin, clindamycin, ampicillin,
amoxicillin, and cephalosporins is strongest. It occasionally occurs in individuals with
no history of antimicrobial treatment or as a complication of chronic colonic
obstruction, carcinoma, leukaemia, or uraemia.

People of West African origin are strikingly resistant to Plasmodium vivax infection.
This correlates with the extreme rarity of the Duffy blood-group antigen alleles FYA
and FYB encoding Fya and Fyb, which are receptors for penetration of the red cell by
the merozoites.

Lyme disease is an infection caused by the spirochaete Borrelia burgdorferi, which is
transmitted by contact with ticks of the genus Ixodes. Erythema chronicum migrans is
usually the first symptom along with malaise, arthralgia and lymphadenopathy. Up to
60% of patients develop chronic oligoarthritis. Radiculoneuritis is another feature in
around 15%, often involving the cranial nerves. A lymphocytic meningitis is a
recognised complication. Carditis is rare (< 10%) especially with European strains of
the disease compared with those found in North America. Heart block and arrhythmias
may occur.
HIV:
The use of a two-nucleoside analogue drug regime (double therapy), compared with a
protease inhibitor with two nucleoside drug analogues (triple therapy), is associated
with a 50% decrease in the risk of death over 1 year
False
Triple therapy is likely to decrease the likelihood of resistance compared with double
therapy
True
Zidovudine and either another nucleoside analogue or a protease inhibitor, compared
with using zidovudine alone, significantly reduces the risk of AIDS-defining illness in
groups followed up between 1 and 3 years
True
The risk of infection is at least 25 times greater in people with othersexually
transmitted diseases
True
Presumptive mass treatment for infection in people with other sexually transmitted
diseases has decreased the incidence of retroviral infection in a 20-month study
False
Triple therapy is associated with a reduction of 50% in the risk of death in HIV-infected
patients and is believed to be less likely to give rise to resistance. People with sexually
transmitted diseases are at greater risk of HIV infection, but presumptive mass treatment has
not been found to decrease the incidence of infection.

Longer courses of zidovudine are more effective at reducing transmission, nevirapine being
more efficacious than zidovudine. The presence of p24 antigen or culture-positive samples
indicating viraemia is associated with a doubling of the risk of vertical transmission.
Breastfeeding is also a risk and is not recommended in developed countries. The risk in
developing countries is not as great as the risk of making up formula feeds. Three-quarters of
infants die without treatment in the first year of life.
The risk of vertical transmission varies in different countries:
Europe: 1520%
USA: 1530%
Africa: 2535%.
HIV type 2 is rarely transmitted vertically; HIV type 1 infection occurs during pregnancy, in
the intrapartum period or by breastfeeding.

Which of the following are the recommended periods for keeping infected children out
of contact with other children?
The following periods are recommended:
Chickenpox 5 days from skin eruption
Escherichia coli enteritis 2 days of negative stool samples
Fifth disease no exclusion recommended as this is such a common illness
Haemophilus influenzae infection 48 hours after treatment has commencedopical
Medicine
Hepatitis A 5 days in under 5-year-olds
Infectious mononucleosis no exclusion
Influenza A no exclusion
Lyme disease no exclusion
Measles 5 days from onset of the rash
Meningococcal disease 48 hours from the start of treatment
Mumps 5 days from the onset of parotitis
Norwalk virus 3 days from the last episode of diarrhoea
Pertussis 5 days from the start of treatment
Roseola infantum no exclusion
Rubella 5 days from onset of the rash
Scabies until treated
Scarlet fever 5 days from the start of treatment
Streptococcal pharyngitis no exclusion
Tuberculosis smear positive: 2 weeks after starting treatment; smear negative: no
exclusion.

Influenza type A causes a worse illness than type B. The incubation period is 14 days,
infected patients being contagious from the day prior to the onset of symptoms until 5 days
after the onset. Elderly patients, children and those who are immunosuppressed are at greatest
risk of being admitted (as well as of having one of the complications listed above).
AOM
Xylitol is associated with abdominal pain so is not used in children. The difference between
5- and 10-day courses are that the longer course significantly reduces treatment failure,
relapse and reinfection rates at 810 days but shows no difference at 2030 days. Immediate
treatment with antibiotics as compared with no treatment significantly reduces the number of
days of earache and ear discharge, as well as the amount of paracetamol used after 1 day;
there is, however, no difference in pain scores.

For pulmonary tuberculosis, which of the following statements are true?
A standard shortened course of 6 months of chemotherapy is associated with a higher
rate of relapse than a longer (8 to 9 month) course
False
Daily medication has a better cure rate than medication given 2 or 3 times per week
False
Courses lasting less than 6 months are associated with an increased rate of relapse
True
The completion of treatment is improved with repeated home visits and reminder
letters than with a single reminder letter and home visit
True
The cure/completion rate is greater with directly observed treatment versus self-
treatment
False

An atypical lymphocytosis is associated with EpsteinBarr virus, cytomegalovirus,
toxoplasmosis, tuberculosis, mumps and malarial infections. It may also be associated with
Burkitts lymphoma, B-cell driven lymphoma, and nasopharyngeal carcinoma in adults.
The PaulBunnell test is a circulating heterophile antibody test and may be negative in 50%
of paediatric infections. It may be non-specific in 30% in the first week and 90% in the third
week. It works by showing the lack of agglutination to both sheep and horse erythrocytes. It
may cause a false-positive Wassermann reaction due to polyclonal stimulation.

HIV
Prophylaxis for Pneumocystis carinii pneumonia should be initiated when HIV-exposed infants
are six weeks old and should be continued for at least four months, regardless of negative
virologic tests, because P. carinii pneumonia is often the initial presentation of HIV infection in
infants.
The following infections can be acquired from dogs: Rabies, Tinea (Ringworm), Scabies,
Echinococcus granulosus, Toxocara canis, Enterobiasis (pinworm, Leptospirosis, Canicola fever
(Leptospiracanicola), Leishmaniasis, Dipylidium caninum, Cutaneous larva migrans, Dirofilaria
immitis, Capnocytophaga canimorsus.
Congenital rubella causes sensorineural hearing loss, microcephaly, cataracts, chorioretinitis,
hepatosplenomegaly, rash and PDA.
Live vaccines include BCG, MMR, oral polio, yellow fever and typhoid.
Cholera usually starts with severe diarrhoea (rice water stools), but may start with mild
symptoms in the first week, serotype 01 or 0139. Chronic carriage is rare but it is endemic in
most of south America, Africa and Bangladesh. The organism survives up to 8 weeks in salt
water. Treatment is with fluid and electrolyte rehydration. 3 days treatment with tetracycline
or co-trimoxazole reduces symptoms.
Mycoplasma may cause erythema nodosum, erythema multiforme or Stevens-Johnson
syndrome. Pneumonia may occur in 3-4 yearly cycles and be associated with many
other illnesses often without many signs in the chest. Myocarditis, Haemolytic
anaemia
5% of the adult population and 20% of the elderly are carriers of C. Difficile. Asymptomatic
carriage is more common still in infants and with reported rates of carriage of 30-70% in
otherwise healthy infants. Cephalosporins, amp/amoxicillin, and clindamycin are the most
likely to cause C. difficile diarrhoea. Since many people carry the organism, the presence of
toxin alone is not enough for diagnosis, but culture has to be positive and is found in 30% of
antibiotic associated diarrhoea. If antibiotic-associated C. diff. diarrhoea is suspected, the most
important intervention is to stop the antibiotic thought to be associated with its development.
Oral metronidazole is used as first-line therapy to suppress growth and toxin production by C.
difficile. Vancomycin is usually reserved for persistent treatment failure. More important is
source-isolation of the patient with strict handwashing and hygienic measures to reduce the
risks of cross infection.
Infection is either congenital or as a result of eating undercooked beef or lamb. It may cause
cerebral necrosis and patchy calcification. If a mother is infected in early pregnancy,
teratogenic damage is maximum, and maternal IgM has little effect on the fetus.
chickenpox (varicella) infection
Diffuse encephalitis may occur in the first week and cerebellar ataxia may occur in the second
week. Pneumonitis, myocarditis, transverse myelitis, glomerulonephritis are all recognised
complications. Varicella embryopathy is seen with some first trimester infections. There are
two problems in late pregnancy - the risk of severe disease in non-immune mothers and in their
newborn infants, particularly if the baby is born within 5 days of the appearance of the rash in
the mother or if the mother develops disease within 48 hrs of delivery. Deaths in pregnant
women with varicella are approximately 5 times more likely than in non-pregnant adults and
the risk for mothers appears to be the highest around the beginning of the third trimester. The
incubation period for Varicella is typically 10-14 days.
Indications for influenza vaccination in the UK are: chronic respiratory disease, chronic heart
disease, chronic renal disease, diabetes, immunosuppression and HIV.
erythmema marginatum occurs in Kawasakis and rheumatic fever.

Which of the following is the most appropriate treatment for the contacts of a child who
is admitted with meningococcal sepsis
Treat those contacts as advised by the Consultant for Communicable Disease Control
(CCDC)
Although it is within the remit of the CCDC part of the public health department to
contact, trace and treat the necessary family members, it is good practice to liaise with them
and treat the contacts at risk. This is easier for the acute clinicians to do because the contacts
(usually family members) are often with the unwell child.