No 5 - 2013

Three cases of infant botulism
Measles in Jutland
Opening of Danish Vaccination Register

Three cases of infant botulism

From November 2011 to September 2012, three cases of infant botulism (IB) were detected in Denmark. All three cases were observed at Aarhus University Hospital, Skejby. Since 1995, only three more cases of IB have been reported, two in 1995 and one in 2008.
IB is caused by ingestion of Clostridium botulinum spores. In the intestine of infants (< 1 year), the spores can develop into toxin-producing bacteria after which the released botulinum toxin is absorbed through the intestinal wall. In contrast, classic food-borne botulism is caused by ingestion of preformed botulinum toxin.

C. botulinum is a spore-forming, anaerobic, gram-positive bacterium that occurs naturally across the world. Its spores are found in dirt and dust. Sources of infection of IB are therefore abundant, but ingestion of honey is a classic risk factor causing up to 20% of the diagnosed cases. In the remaining cases, the source of infection is not established.

The botulinum toxin binds to cholinergic receptors in the neuromuscular synapses and blocks the release of acetylcholine which causes neuromuscular blockade. The binding is irreversible, and the synapse is destroyed. Re-establishment of nerve conduction is conditional on the formation of new synapses, a process which takes months.

The symptoms of infants with botulism include weakness, reduced ability to suck, paralytic ileus/constipation, urine retention, drooling and so-called "weak cry" (weak or altered crying). More rarely, symmetrical cranial nerve palsy with e.g. dilated pupils and ptosis are seen. Blood pressure fluctuation and hypothermia may occur due to affection of the parasympathetic nervous system. Respiratory insufficiency may develop, and artificial respiratory support may be required.

Diagnosis and treatment indication are established on the basis of the clinical picture and, if possible, confirmed through microbiological analyses of faeces and blood bioassay. Faeces culture of the bacterium is the "gold standard". Furthermore, Statens Serum Institut (SSI) has recently developed a more sensitive PCR-based method for detection of the primary C. botulinum toxin genes found in faeces, i.e. A, B and E. Detection of botulinum toxins in serum and neutralisation bioassays should also be performed. All of the above-mentioned analyses can be ordered from the SSI Clinical Microbiology Reference Laboratory.

Treatment is initiated on relevant clinical suspicion. Treatment consists of symptomatic treatment, laxatives for bowel paralysis and administration of botulism antitoxins which bind to the free toxins, neutralising these and thereby blocking disease progression and hence shortening the duration of the condition. Treatment with antitoxins should be initiated as soon as possible, and is more effective in the early phase of IB (up to 7-10 days after symptom onset) while the disease is still progressing.

Two commercial botulism antitoxin drugs are currently marketed. One is a human-derived drug from the US specifically made for the treatment of IB and comprising antitoxins of types A and B (BabyBIG®, which can be ordered from the SSI following authorisation from the Danish Health and Medicines Authority. The second is a sheep-derived drug kept on stock at the SSI (botulism antitoxin types A-F). Antibiotics are not indicated for IB treatment and some antibiotics are contraindicated (e.g. aminoglycosides) because they may potentiate neuromuscular blockade.

Case 1

A five-month-old child is admitted with weakness and reduced ability to suck and swallow. The child presents as afebrile with muscular weakness, weak deep reflexes, near-absence of facial expressions and weak crying. On suspicion of encephalitis, a lumbar puncture is performed and the child is started on antibiotic treatment. Subsequently, increasing hypotonia with a lack of spontaneous movement of the extremities is observed. The child is transferred to the ICU following dysphagia leading to aspiration with reduced oxygen saturation, but with no need for additional respiratory support. The child has marked dysphagia and is tube-fed. The child develops bilateral ptosis and has dilated pupils, signs of urinary retention requiring a bladder catheter and constipation, also requiring treatment.

Botulism is suspected shortly after admission and treatment with human-derived antitoxin is given within the first week. Clinical improvement is seen as from the fifth day of admission, primarily as incipient spontaneous motor function and improved ability to swallow. Bladder paresis persists far beyond this stage. The child had been sucking on parsley which is established as a possible source of infection.

The child is discharged after one month and before recovering completely from the neurological symptoms. The diagnosis is confirmed through injection of serum from the child into mice. C. botulinum is detected by faeces culture, and PCR testing yields toxin genotypes A and B.

Case 2

A five-month-old infant is admitted due to weakness and reduced ability to suck. The child presents as afebrile, generally hypotonic with ptosis and weak crying. The infant is admitted, primarily on suspicion of CNS infection, and aminoglycoside treatment (among others) is initiated. The disease course is characterized by worsening hypotonia, lacking deep reflexes, dilation of pupils, urinary retention, constipation and fluctuating blood pressure. Subsequently, the child develops respiratory insufficiency and is transferred to the ICU for artificial respiratory support. Treatment with human-derived antitoxin is initiated within the first week.

After three weeks on artificial respiratory support, the child is transferred to the department once again, but only to develop toxic megacolon with general malaise, vomiting and bleeding from the rectum. The child is treated with oral vancomycin on suspicion of Clostridium botulinum and improves after a few days. The child is discharged after two months of admission. No obvious sources of infection were determined.

IB is confirmed through injection of serum from the child into mice. C. botulinum is detected by faeces culture, and PCR testing yields C. botulinum toxin genotypes A and B.

Case 3

A five-week-old child is admitted with reduced ability to suck and reduced spontaneous motor function and weak crying. The child presents as afebrile with modest spontaneous movements, lacking eye contact and universally reduced tonus. On suspicion of CNS infection lumbar puncture is performed, and aminoglycoside treatment is initiated.
Few hours later, the child develops respiratory insufficiency and is therefore transferred to the ICU where the child is ultimately treated under artificial respiratory support. The child becomes increasingly hypotonic with weak to lacking deep reflexes, dilation of pupils, signs of urinary retention and constipation. Treatment with human-derived antitoxin is initiated within the first week, and the child then slowly starts to improve.

Artificial respiratory support is maintained for a total of three weeks and the child is discharged following a normal neurological examination after one month of admission. There was no specific suspicion of source of infection.
In this case, IB was not confirmed by injection of serum into mice, but PCR in faeces established toxin genotype B. C. botulinum was detected by faeces culture.


Infant botulism is probably an underdiagnosed condition. Infants should not be given foods that may have been contaminated by dirt or dust. On suspicion of IB, the Clinical Microbiology Reference Laboratory at the SSI may be contacted for relevant diagnostics. The diagnosis is made by microbiological analysis of faeces and blood bioassay. If stool samples are unavailable due to paralytic ileus, a rectal swab may be made or a rectal irrigation solution may be used to obtain a sample.

On clinical suspicion of botulism, the case shall be reported by phone to the Medical Officers of Health. The physician on guard at the Department of Infectious Disease Epidemiology can be reached at phone: 41317404 if treatment with botulism antitoxin is being considered.

(T. Pedersen, A. K. Hansen, T. B. Henriksen, Paediatric Department A, Aarhus University Hospital, Skejby, B. H. Jensen, A. K. Jensen, A. Kjerulf, Clinical Microbiology Reference Laboratory)

Measles in Jutland

Mid January 2013 saw a laboratory-confirmed measles case in Jutland. The patient, who was unvaccinated, had been travelling in Europe at the turn of the year. It is therefore presumed that the patient was infected abroad.

Physicians are encouraged to pay particular attention to the diagnosis in children and younger adults who present with measles symptoms. It is important that persons who are suspected of having measles, avoid being in waiting rooms with other patients, as measles is extremely infectious.

Vaccination against measles is covered by the MMR vaccine which is offered to all children via the Childhood Vaccination Programme. The vaccine may also be given to adults who have not previously been vaccinated. These, however, pay for the vaccine themselves as the temporary offer of free MMR vaccination of young adults ended as per 31/12 2012. In case of definite exposure of non-immune persons, MMR vaccination may be given within three days, or immunoglobulin injection within six days to prevent or lessen the effects of the disease.

(Department of Infectious Disease Epidemiology)

Opening of Danish Vaccination Register

The Danish Vaccination Register (DVR) is an electronic service which gives health professionals and citizens access to a joint vaccination card containing an overview of any administered and planned vaccinations.
Access to the DVR for citizens as well as health professionals is expected to be launched via and as from 1 February 2013.

Login requires either a digital employee signature or a NemID. In the longer term, it is the intention to integrate the DVR into local medical practice systems.

The DVR holds information on all childhood vaccinations and any other vaccinations settled with the National Danish Health Insurance (Sygesikringen) as from 1996. There is about three months of latency from a vaccination is administered until it appears in the DVR. The DVR also holds information on vaccines prescribed to persons and dispensed from pharmacies as from 2006.

The DVR does not hold information on vaccinations given at emergency rooms or hospitals nor travel vaccinations, unless these were given by prescription.
Health professionals as well as citizens can add vaccinations to the vaccination card.

Parents have access to their children's vaccinations provided parental rights were recorded with the Danish Civil Registration System after 27 May 2004, or when the custody of older children was settled by the state administration and recorded in the Civil Registration System. Parents’ access to their child's data ends when the child turns 15 years old. Children aged 15 years or older can access the DVR themselves using their NemID.

The DVR is expected to bring service improvements for health professionals and citizens alike; and in the long term, the Register will improve our capacity to monitor the efficacy of vaccines to the benefit of future vaccination programmes.

For more information on the DVR (in Danish), click here. Further Informations on DDV

(T.G. Krause, Department of Infectious Disease Epidemiology)

Link to previous issues of EPI-NEWS

30 January 2013