A new approach to febrile infants

Cite this article as:
Henry Goldstein. A new approach to febrile infants, Don't Forget the Bubbles, 2016. Available at:
https://doi.org/10.31440/DFTB.9565

The fortnight has seen two hot off the press articles by a group from the Basque Country. They are challenging the existing paradigm in the investigation and management of febrile infants with their “Step by step” approach. The approach questions the relative supremacy of the Rochester criteria as a basis for investigating and managing infants under 90 days with fevers and controversially considers managing a subset of “low risk” infants on the outpatient basis without lumbar puncture or antibiotics.

“Step by Step” – the new kid on the block – aims to risk stratify this group to both reduce the number of unnecessary investigations and treatments in this group as well as predict those patients at risk of serious bacterial infections (SBI). The Step by Step approach was first suggested by the same group in 2014. The algorithm is thus;

step by step algorithm

There are clear parameters for each of the components of the algorithm. To be considered “low risk” an infant with fever without source must be:

  • Well appearing
  • Aged >21 days
  • No leukocytes in urine
  • Procalcitonin <0.5 ng/mL
  • Absolute Neutrophil Count <10,000/mm3
  • CRP < 20 mg/L

 

Firstly, the larger of the two papers is a validation study for the “step by step” method. The algorithm was applied retrospectively to 2185 infants presenting to 11 European Paediatric emergency departments over a 24 month period, with the aim of comparing the Step by step algorithm to the Rochester Criteria and Lab-score.

Gomez B, Mintegi S, Bressan S, et al. Validation of the “Step-by-Step” Approach in the Management of Young Febrile Infants. Pediatrics. 2016;138(2):e20154381

 

Population: A prospective study of 2185 infants aged <90 days presenting with a fever without source.

Intervention: Risk stratification via the “Step by step” approach to identify the level of risk for invasive bacterial infection.

Comparator: Rochester criteria and Lab-score for same.

Outcome: For Step by Step an overall Sensitivity of 92% and NPV 99.3%, vs Rochester 81.6% and 98.3% for IBI or non-IBI in the “low risk” group. This compares favourably v Rochester. 

Patients were excluded if there was any of 1) a clear source of fever on history & examination, 2) no fever at arrival and subjective/tactile ‘fever’ identified by the parents , 3) absence of 1+ of the mandatory ancillary tests, or 4) parents refused participation.

The authors define fever without source, serious bacterial infections, invasive bacterial infections, occult bacteraemia, sepsis and possible bacterial infections individually. Of note, all growths of Staphylococcus epidermidis, Propionibacterium acnes, Streptococcus viridans, or Diphtheroides were considered contaminants.

The real meat of this algorithm is in the number of patients identified in the “low risk” group with any significant, treatable infection. In this validation study, ~45% of infants made it to the “low risk” group, and of these 991, there were 7 invasive bacterial infections (IBI) and 4 Non-invasive bacterial infections (Non-IBI).

The paper presents findings separately between IBI & Non-IBI. The multiple definitions of bacterial infections seem very reasonable in theory, but in practice we’re probably concerned about “missing” a serious bacterial infection. Hence, I’ve reworked the calculations analysing IBI and Non-IBI together. Practically, this means that the Negative Predictive Value of “low risk” is 97.8%, with a miss rate of 11 per 1000. Here’s my working, based on the data provided in figure 3.

validation of step by Step

The other article from the same group published this week put the “step by step” approach into practice over a 7 year period at a single paediatric emergency department in the Basque Country. Infants in the “low risk” group were offered the no LP, no antibiotics and up to 24hours observation (with a view to discharge); there was planned follow-up and support for representation.

Mintegi S, Gomez B, Martinez-Virumbrales L, et al. Outpatient management of selected young febrile infants without antibiotics. Arch Dis Child. 2016 Jul 28. pii: archdischild-2016-310600. doi: 10.1136/archdischild-2016-310600. [Epub ahead of print]

 

Population: A dataset of 1472 infants of fever without source is presented, however the analysis focuses on 767 at “low risk” of SBI as per the step by step criteria.

Intervention: This subgroup of patients were managed without lumbar puncture, antibiotics, 48hr admission.

Comparator: There was no control group for the trial

Outcome: 2 of 586 infants had a serious bacterial infection. 29 of 586 had a UTI (culture positive, leuks negative) and 51 returned for review due to persistent fever or irritability. 

Additionally, assessment was done by a Paeds trained attending or resident. Safety mechanisms for the low risk group included a follow-up phone call or primary care practitioner review; 10 patients were entirely lost to follow-up. There were no differences in rates of return in patients observed for <6hrs or >6hrs in the short stay unit.

Within the “low risk” group, as per the step by step algorithm, a significant number received CSF examination (for persistent fever, irritability or poor feeding), or deteriorated. None of these infants had SBIs, although almost half receiving lumbar puncture had viral meningitis.

The study is an impressive example of putting your money where your mouth is, and an excellent example of a theoretical construct applied in the real world. I suspect it probably overstates the success of the no LP, no antibiotics, outpatient management group. Using the initial patients in the “low risk” group as an intention to (not) treat analysis from the 767 “low risk” as per the “Step by step” group gives a miss rate of 52 SBI per 1000;

trial of step by step

The authors also state … in our series, no infant was finally diagnosed with bacterial meningitis and no infant had a clinical deterioration compatible with bacterial meningitis.

The title of the paper focusses on those infants as “low risk” who are do not receive a lumbar puncture and are then managed as outpatients without antibiotics. A reasonable point of focus, but in the context of the group’s overall goal – rolling out the step by step as a tool for risk stratification – I think they have identified the algorithm’s weaknesses.

Commentary:

This is an exciting development. There is more nuance than meets the eye in a febrile infant and whilst our current Australian standard of care is a “full septic screen”, the potential to reduce iatrogenic complications and overtreatment in this population whilst keeping these patients safe has some promise.

As the authors of these studies note, the actual rate of SBI in this population is low, but we likely also overestimate the risk of SBI; deVos-Kerkhof and colleagues attempt to illustrate this in their 2015 European Journal of Paediatrics article.

What are we actually comparing?

The stakes for a “rule out” algorithm – rather than a “rule-in” algorithm – are high. Considering that standard practice in this group is about reducing the risk, and I suspect an individual tendency to default to the safest option, the numbers and pragmatics of the algorithm would have to be breathtakingly good to modify practice.

I think the comparison against the Rochester criteria is ultimately flawed; the numbers need to stand alone with respect to having an acceptable miss rate. Additionally, the epidemiology of bacterial infections, vaccination and population health as a whole has changed markedly since the Rochester criteria was published in 1985.

It’s also worth noting that the “step by step” approach also attempts to reach towards an earlier age; previous criteria have treated and investigate all infants <28 days, whereas the “step by step” approach only takes this approach with infants <21 days.

The nuances of infection

Both studies describe a number of infants with urinary tract infections (UTI) (and normal leukocyte counts) with a significant pure bacterial growth; these patients are managed as “low risk” via the algorithm. In practice, it would be not uncommon for an infant with a “fever without source” to receive their UTI diagnosis during admission, with subsequent management for same. Most other studies I’ve seen in this area consider a UTI as a serious bacterial infection.

With respect to other infections, 44 of the 91 infants in the second paper had viral meningitis. Although not amenable to antibiotic treatment, there’s no mention of the rate of Herpes simplex encephalitis. More so, in many departments the initiation of acyclovir goes hand in hand with antibiotics in the management of this population until the HSV CSF PCR shows no virus. Additionally, symptoms and signs of viremia may warrant inpatient management or observation, and it’s my impression that “step by step” is vulnerable in this area.

Finally on this, I think it is relevant to bundle the SBI into a single outcome at the “low risk” stage. The IBI vs Non-IBI dichotomy is, I think, useful and relevant for unwell and very unwell infants (“high risk”), as it may be predictive of other metrics including outcomes, place of management and other clinical trajectories. Additionally, at the intermediate and high risk strata, the ratio of IBI:Non-IBI will likely be different to the low risk group. Alternatively, with a planned management of no treatment with antibiotics and discharge, I have sought to conceive all missed SBIs as just that.

Which test is best?

 It would be interesting to see an analysis for the independence of each of the variables in this sample. Without a comprehensive review of the literature for each of the constituent parts of the step by step approach, I can’t honestly say that “no one test” can predict the likelihood of a serious bacterial infection in infants, although it’s what I’ve been taught for a long time. I welcome any robust evidence that contradicts this dogma.

On that front, although procalcitonin isn’t yet widely ordered in Australian laboratories, there is a growing weight of evidence that there it has some utility in this area. A paper from JAMA Paediatrics earlier this year suggests PCT is equivocal to CRP for SBI but more accurate for IBI.

Certainly, “Step by step” shows promise – the Rochester criteria and other American predecessors have had a profound influence on paediatric practice since their inception. There remains significant ground to cover to find the a safe medium of both an acceptable level of risk for missed SBI and the likelihood of over-treatment in this population.

 

References

Mintegi S, Bressan S, Gomez B et al. Accuracy of a sequential approach to identify young febrile infants at lowrisk for invasive bacterial infection. Emerg Med J. 2014 Oct;31(e1):e19-24. doi: 10.1136/emermed-2013-202449. Epub 2013 Jul 14.

Gomez B, Mintegi S, Bressan S, et al. Validation of the “Step-by-Step” Approach in the Management of Young Febrile Infants. Pediatrics. 2016;138(2):e20154381

Mintegi S, Gomez B, Martinez-Virumbrales L, et al. Outpatient management of selected young febrile infants without antibiotics. Arch Dis Child. 2016 Jul 28. pii: archdischild-2016-310600. doi: 10.1136/archdischild-2016-310600. [Epub ahead of print]

Dagan R, Powell KR, Hall CB, Menegus MA. Identification of infants unlikely to have serious bacterial infection although hospitalized for suspected sepsis. J Pediatr. 1985 Dec;107(6):855-60.

deVos-Kerkhof E, Roland D, de Bekker-Grob E, et al. Clinicians’ overestimation of febrile child risk assessment. Eur J Pediatr. 2016 Apr;175(4):563-72. doi: 10.1007/s00431-015-2667-5. Epub 2015 Dec 4.

Key trials in developing countries – 2015-2016

Cite this article as:
Andrew Tagg. Key trials in developing countries – 2015-2016, Don't Forget the Bubbles, 2016. Available at:
https://doi.org/10.31440/DFTB.7460

Here is a recently published booklet which summarises much of the latest research on child health in developing countries. It consists of evidence derived from all the randomised trials published over the last year.

Professor Trevor Duke, Intensivist at the Royal Children’s Hospital in Melbourne has put together this excellent summary of some of the key findings, and has kindly allowed us to share it with our DFTB readers.

This year there were 187 publications from randomised or controlled trials. We have high-lighted just a few of the trials.  It is well worth perusing the booklet, if only to realise how lucky those of us are that practice in the developed world when it comes to resources.

Pneumonia

Pneumonia is a leading cause of mortality in children under 5 years old worldwide.

In a trial of over 1000 Indian children with clinical signs of pneumonia with tachypneoa, and chest indrawing out-patient treatment with oral amoxicillin was similar, in regard to treatment failure, as in-hospital treatment, at 7 days.

In a trial of hospitalized children with community acquired pneumonia in Thailand, switching to oral antibiotics within 24 hours of cessation of fever and symptom improvement, was as effective as conventional intravenous therapy.

Use of bubble-CPAP in children with severe pneumonia in Bangladesh was associated with lower risk of death than standard oxygen therapy.

Inotropes

In the setting of fluid refractory shock, in Brazil, early peripheral adrenaline was associated with decreased mortality when compared with dobutamine.

Diarrhoeal illness

A single dose of oral ondansetron reduced the risk of treatment failure with oral rehydration solution and reduced the need for IV therapy in India.

Whilst medical interventions do work, cultural interventions are more useful.

In a large meta-analysis of over 14,000 cases in low and middle income countries hand-washing promotion reduced community diarrhoea rates by about 30%.

Improving water quality in communities in Ghana by drilling bores reduced diarrhoea prevalence in children by 11%. This is in contrast to efforts in rural India to improve sanitation and reduce open defecation which were only partially successful in reducing faecal bacterial loads and cases of diarrhoea.

Neonates

When treating hyperbilirubinemia in term and late-preterm neonates in Nigeria, filtered sunlight was effective in controlling bilirubin levels on 93% of days, and conventional phototherapy was effective in 90% of days. It appeared safe with temperatures higher than 38.0°C occurringin 5% of infants receiving filtered sunlight and in 1% of those receiving conventional phototherapy.

Like most studies in low and middle income countries sample sizes are small and so it is hard to generalize but among preterm Indian neonates with a patent ductus arteriosus, enteral paracetamol was as effective as intravenous indomethacin in closing the PDA: 100% (36/36) versus 94.6% (35/37) respectively.

This is the 14th edition of this booklet.  Previous editions, which summarise 2182 trial publications from 2002-2015 are available at www.ichrc.org.

Probiotics in review

Cite this article as:
Henry Goldstein. Probiotics in review, Don't Forget the Bubbles, 2016. Available at:
https://doi.org/10.31440/DFTB.9304

Like almost every other human entering a pharmacy in the ten last years, I was offered some probiotics when I collected a prescription recently. On my walk back to the car I mused about the evidence behind the shop assistants attempted up-sale. I reminded myself of the use of probiotics to prevent necrotising enterocolitis, and was starting to think of some other indications. Some days later, this review by Hania Szajewska in the Archives of Disease in Childhood popped up; here’s a precis of an excellent paper:

Szajewska, H.What are the indications for using probiotics in children? Arch Dis Child. Published Online First: 7 September 2015

Probiotics are “live microorganisms that, when administered in adequate amounts, confer a health benefit on that host.” The most common strains used therapeutically are the lactobacillus strains L. reamnosus GG (LGG) and L. reuteri DSM 17938 as well as bifidobacterium and saccharomyces. There are also some novel probiotics in development.

Probiotic preparations differ to standard medications as the dose, viability and even agent (organism) are harder to control. There is significant industry influence and, in my opinion, therapeutic development has likely suffered at the expense of populist marketing. Research into probiotics is strain specific; with that comes the challenges of extrapolating the findings to any over-the-counter product. Specifically, probiotics are not regulated as drugs, hence significant concerns exist with respect to labelling and quality.

In this paper, Szajewska reviews the evidence for a number of paediatric indications for probiotics. I’ve simplified and summarised the findings here;

What do we think works?

Necrotising enterocolitis – Multiple RCTs and a Cochrane review, mostly using L. reuteri DSM 17938 show a reduction in NEC in preterm infants. Additionally, there was a reduced time to full feeds, reduced admission length and reduced rates of late-onset sepsis.

Antibiotic associated diarrhoea – Szajewska references her own meta analysis – albeit primarily an adult population – which identified a NNT of 13 for antibiotic associated diarrhoea; the database is predominantly adults. Most effective probiotic agents for this indication are saccharomyces boulardii and LGG.

Infantile colicL. reuteri DSM 17938 was assessed in 4 RCTs; their combined results showed that the use of reduced crying times in breastfed infants with infantile colic. In one analysis (3 trials), L. reuteri DSM 17938 vs placebo reduced crying times at 21 days of life by an average of 43 minutes/day. Probiotics appear more helpful in breastfed by comparison to formula fed infants.

Functional abdominal pain – A meta analysis of LGG for a range of abdominal pain-related functional gastrointestinal disorders (FGDs) showed that LGG was significantly better than placebo in this population, with a NNT = 7. Szajewska doesn’t appear to have much faith in these results with respect to FGDs as a whole, but notes that patients with Irritable bowel syndrome showed the most benefit (NNT = 4).

Acute gastroenteritis – ESPGHAN (the European Society for Paediatric Gastroenterology, Hepatology & Nutrition) recommend consideration of probiotics (LGG > S. boulardii > L. reuteri DSM 17938) for children with acute gastroenteritis, in addition to hydration therapy.

What might work?

Nosocomial infection – The review considers a number of nosocomial infections, and briefly mentions the importance of rotavirus immunisation, where available. A handful of trials showed that probiotics (LGG) vs placebo had no significant differences for risk of post-admission diarrhoea in children under 2 years old; the results contradict some earlier trials in this area, which showed promise.

Prevention of allergy – This is controversial – two studies published by opposing peak bodies disagree. This includes maternal probiotics to reduce long-term outcomes.

H.Pylori – May improve eradication rate, but limited evidence in children.

IBD – Some evidence for inducing remission of Ulcerative colitis; insufficient evidence in Crohn’s disease. 

What doesn’t work?


Functional constipation – no evidence of benefit; not recommended via ESPGHAN 

Within the review, two positive studies jumped out at me, so I went back to the primary literature for a deeper dive.

Firstly, I was fascinated by the idea of preventing infections in daycare centres – Szajewska’s overall verdict was that there was not currently sufficient evidence, but that LGG and L. reuteri DSM 17938 may have some effect on community-acquired infections. Particularly, the review describes this study;

Gutierrez-Castrellon, P., Lopez-Velazquez, G., Diaz-Garcia, L. et al. Diarrhea in Preschool Children and Lactobacillus reuteri: A Randomized Controlled Trial. Pediatrics Mar 2014, peds.2013-0652; DOI: 10.1542/peds.2013-0652

P: 336 children born at term aged 6-36 months attending a daycare in Mexico
I: 5 drops L. reuteri DSM 17938 for 12 weeks
C: placebo drops
O: The primary outcome was the number of days with diarrhoea per child, which was defined as days when 3 or more loose or watery stools were passed within a 24-hour period with or without vomiting, both during the intervention and for 12 weeks afterwards.

  • About ¼ of families offered enrolment decline; which means we should question the (?social) acceptability of the intervention in this population.
  • Semi blinded – one of the authors was overseeing the block-randomisation.
  • Interesting exclusion criteria including birth weight < 2500 g, chronic disease, failure to thrive, allergy or atopic disease, recent (previous 4 weeks) exposure to probiotics, prebiotics, or antibiotics, or were participating in other clinical trials.
  • A reasonably well defined list of secondary outcomes.
  • Parents were educated about stool descriptors using the Bristol stool scale, and upon a loose motion had to contact the study centre, and then report for assessment. I wonder if this call-presentation process lent itself to underreporting (in both groups.)
  • All four primary outcomes: Number of diarrhea episodes, Episodes of diarrhea per child, Mean duration of diarrhea episodes and Days with diarrhea per child were significantly better in the treatment arm, both during the intervention and afterwards. With p values ranging from 0.03 to 0.01.


Secondly, the idea that probiotics could reduce infantile colic seemed immensely appealing; it’s an area that has had a myriad of debunked therapies over the last several millenia. T

Indrio F.,Di Mauro A., Riezzo G., et al..Prophylactic use of a probiotic in the prevention of colic, regurgitation, and functional constipation: a randomized clinical trial. JAMA Pediatr. 2014 Mar;168(3):228-33.

P: 589 term infants aged less than one week, in 9 centres across Italy.
I: 5 drops of L reuteri DSM 17938 (1×10^8 cfu) for 90 days
C: placebo
O: Primary outcomes were daily crying time, regurgitation, and constipation during the first 3 months of life. Cost-benefit analysis of the probiotic supplementation.

  • Infants receiving antibiotics in the first week of life were excluded; (in Australian maternity units, this would account for a significant number.)
  • Trial was independently randomized and double blinded.
  • Around ⅙ patients were lost to follow-up; a significant number were withdrawn from the treatment arm for protocol violations by the investigator.
  • Parents recorded data in a structured diary and sought advice as required via usual channels.
  • At both one and 3 months of life, the infants in the treatment arm cried for significantly shorter periods of time and stooled more frequently. At three months, there were fewer episodes of regurgitation in the treatment arm.
  • Although this is a single study, there are a number along similar lines; Szajewska’ paper mentions 4 in total. The results are most striking in this paper, hence my curiosity.

The organism of the hour, L. reuteri DSM 17938 was first cultured from breast milk of a Peruvian mother; it is patented by BioGaia whom provided the study drug and placebo for both trials above.

Conclusions


There’s a growing body of evidence for the potential benefits of probiotics in a number of paediatric conditions.

There is a bias in this review (and pretty much all of academic medicine) towards positive trials. That being said, I haven’t given the details of every study mentioned; Szajewska’s review does so nicely and I also recommend a read of the primary literature.

Most importantly, communicating with parents about the uncertainties about over-the-counter probiotics with respect to labelling, quality, dose and organism remain central to this discussion.

Key points:

  • Probiotics are “live microorgnaisms that, when administered in adequate amounts, confer a health benefit on that host.”
  • There are many vested interests & popular marketing with issues around labelling and quality in this area.
  • Research is strain specific.
  • Main strains researched are; Lactobacillus reuteri DSM 17938, Lactobacillus reamnosus GG (LGG), Bifidobacterium and Saccharomyces
  • Presently, benefit has been demonstrated in NEC, Antibiotic associated diarrhoea, infantile colic, functional abdominal pain and acute gastroenteritis.

References:

Szajewska, H.What are the indications for using probiotics in children? Arch Dis Child archdischild-2015-308656 Published Online First: 7 September 2015

Gutierrez-Castrellon, P., Lopez-Velazquez, G., Diaz-Garcia, L. et al. Diarrhea in Preschool Children and Lactobacillus reuteri: A Randomized Controlled Trial. 

Whoop, Whoop, Hooray

Cite this article as:
Andrew Tagg. Whoop, Whoop, Hooray, Don't Forget the Bubbles, 2016. Available at:
https://doi.org/10.31440/DFTB.8344

Henry Goldstein wrote an excellent article on pertussis a few years ago.  With some interesting new data coming to press with regard to risk factors for complications of the disease we thought it might be worthwhile doing some spaced repetition.

“My childhood was full of deep sorrow – colic, whooping cough, dread of ghosts, hell, Satan, and a deity in the sky who was angry when I ate too much plum cake” – George Eliot

Although cases have been described as far back as the Middle Ages it wasn’t until 1906 when the organism, Bordetella pertussis, was isolated by Bordet and Gengou. Up to 16 million cases develop worldwide every year with the majority of cases being in the developing world. Australia reported around 10,000 cases in 2009. Data from 2013 suggests it caused at least 61,000 death worldwide though this is likely to be a gross underestimate. Pertussis is one of the leading causes of vaccine preventable deaths worldwide.

Incubation

B. pertussis is highly infectious with the majority of exposed household contacts becoming infected to various degrees. The incubation period is usually quoted as 4-21 days with the average being 7-10 days.

Prodrome

Before the harsh coughing begins there is often a couple of weeks of symptoms that could easily be mistaken for a viral upper respiratory tract infection. Children may have a runny nose and a very mild tickly cough. This is the catarrhal phase. The classic ‘whoop’ might not be hard until week three or four of the illness.

Clinical course

The classical presentation is of a patient that has paroxysms of coughing that terminates in an audible inspiratory ‘whoop’. Like most classical presentations we learn about in medicine this presentation is rarer than we think. Children may also present with a protracted cough, or forceful post-tussive vomiting. Parents often seek advice as their children have had a couple of courses of antibiotics with no improvement in cough. It’s not know as the ‘one hundred day cough’ for nothing.

People with pertussis (adults and children alike) are infectious from the beginning of the catarrhal stage through to the third week after the onset of the paroxysmal stage of coughing. They cease being infectious five days after a course of antibiotics.

Diagnosis

Other than a suspicious clinical picture, formal diagnosis is best made by performing PCR for Bordetella on a nasopharyngeal swab. Once the initial three weeks have past though, it becomes increasing difficult to culture and it may be necessary to use rising IgA titres to make the diagnosis though this does not affect management.

Treatment

A number of treatments have been posited including vitamin C injections.

“In 66 [of 81] cases… [we saw] reduction of lip cyanosis in coughing attacks…[disappearance of] attacks with breathing difficulty, vomiting and recurrence … also the number of cough attacks diminished. Patients became lively, had good appetite and the convalescence progressed very satisfactorily.” – Concerning the Vitamin C Therapy of Pertussis [Whooping Cough]: Otani, Klinische Wochenschrift, December 1936

Coughs last, on average, 16 days. A Cochrane review found no specific benefit of steroids, bronchodilators or immunoglobulins for the treatment of the cough. Over the counter remedies are unlikely to help and may potentially cause harm.  To hear more listen to this great rant from Dr Anthony Crocco. The only thing that may help (a little) is honey.  Take a listen to Ken Milne’s podcast SGEM #26 – Honey, Honey for more on this subject.

What about antibiotics? Well (in adults) they are recommended in the initial catarrhal phase to help reduce duration of infectivity but they don’t seem to have much effect after the disease has been hanging around for three weeks. Because of this they are not recommended beyond this time period.

If they are needed then macrolides such as erythromycin, azithromycin or clarithromycin are recommended. Azithromycin should be used in children less than one month of age as erythromycin use has been linked to an increased incidence of hypertrophic pyloric stenosis.

Complications

Pertussis is far from benign in unvaccinated infants. According to the CDC, in children under 1 that are not fully vaccinated:-

  • 1 in 4 (23%) get pneumonia
  • 1 in 100 (1.1%) will have convulsions
  • 3 out of 5 (61%) will have apneoic episodes
  • 1 in 300 (0.3%) will develop encephalopathy
  • 1 in 100 (1%) will die

In Winter’s retrospective analysis of US pertussis deaths in infants under 120 days old mortality was linked with:

  • Significantly low birth weight
  • Younger gestational age
  • Younger age at onset
  • Higher WBC and higher lymphocyte count

In those less severely affected it may still cause sub-conjuctival haemorrhages, rib fractures and loss of bladder control.

Post-exposure prophylaxis

So who should get antibiotics if exposed to a confirmed case of pertussis? Most guidelines recommend that the following groups of people receive antibiotic prophylaxis.  It’s not really to treat the illness but rather to halt the spread.

  • Pregnant mothers in the last month of gestation (WHY)
  • Members of a household that has an  infant that is not fully vaccinated
  • Healthcare workers and babies potentially exposed and in a newborn nursery environment

To be fully vaccinated the child must have three effective doses of pertussis vaccine given at least four weeks apart.

Prevention

Whilst childhood immunisation does prevent the majority of cases, individual immunity does appear to decrease with time so there has been an upswing in the number of older children and teenagers affected. Pertussis is a notifiable disease and over 70% of cases that are notified are in patients over the age of 15.

The current Australian immunisation schedule has pertussis vaccine being given as a part of the combined Diptheria, Tetanus, acellular Pertussis (DTaP) vaccine at two, four and six months of age. Other countries may have an alternative schedule. The child then receives a pre-school booster at 4 years old. Because of the waning immunity they should also receive a dose in their teenage years. An individual’s immunity to pertussis may well have disappeared by the time they reach adulthood so new parents, or grandparents living in a house with a newborn should be offered a booster.

 

HT to Tim Horeczko (@EMtogether) for the heads up regarding the latest data

 

References

Royal Children’s Hospital, Melbourne guidelines on Pertussis can be found here

Cherry JD. Historical review of pertussis and the classical vaccine. Journal of Infectious Diseases. 1996 Nov 1;174(Supplement 3):S259-63. full text here

Pertussis (Whooping cough) complications. (2015). Retrieved April 13, 2016, from https://www.cdc.gov/pertussis/about/complications.html

GBD 2013 Mortality and Causes of Death Collaborators. “Global, Regional, and National Age-Sex Specific All-Cause and Cause-Specific Mortality for 240 Causes of Death, 1990-2013: A Systematic Analysis for the Global Burden of Disease Study 2013.” Lancet 385.9963 (2015): 117–171. PMC. Web. 14 Apr. 2016.

Forsyth K, Plotkin S, Tan T, von König CH. Strategies to decrease pertussis transmission to infants. Pediatrics. 2015 Jun 1;135(6):e1475-82.

Hay AD, Wilson A, Fahey T, Peters TJ. The duration of acute cough in pre-school children presenting to primary care: a prospective cohort study. Family Practice. 2003 Dec 1;20(6):696-705

Winter K, Zipprich J, Harriman K, Murray EL, Gornbein J, Hammer SJ, Yeganeh N, Adachi K, Cherry JD. Risk factors associated with infant deaths from pertussis: a case-control study. Clinical Infectious Diseases. 2015 Oct 1;61(7):1099-106.

 

Passing the TORCH

Cite this article as:
Andrew Tagg. Passing the TORCH, Don't Forget the Bubbles, 2016. Available at:
https://doi.org/10.31440/DFTB.8541

6 year old Ella has been sent home from school as she has been itching all day.  When her mum, Val, picked her up she noticed a few spots and thought she better get them checked out.  You see the classical rash of chickenpox and reassure of the relatively benign nature of the illness and discourage her from holding any ‘chickenpox parties’.  As you explain that it would be wise to keep her away from babies, the immunocompromised and pregnant women, Val pauses, looks up at you and says, “I’m 15 weeks pregnant!”.

How long is a piece of string? – antibiotic treatment duration in paediatrics

Cite this article as:
Ben Lawton. How long is a piece of string? – antibiotic treatment duration in paediatrics, Don't Forget the Bubbles, 2016. Available at:
https://doi.org/10.31440/DFTB.9011

 

It’s 2am on your fourth night shift in a row. Johnny is 2 years old and has osteomyelitis of his toe. He looks pretty well and doesn’t like sitting still for cannulas. Poor Johnny has marks on both hands and both elbows from recent IVs that have not gone the distance and now you have just been paged to say he has managed to remove another one. He has been being treated for 5 days and you are wondering if he really needs this IV re-siting.

Parechovirus

Cite this article as:
Annabel Smith. Parechovirus, Don't Forget the Bubbles, 2016. Available at:
https://doi.org/10.31440/DFTB.8851

A 2-week old baby, Isabelle, is rushed into the emergency department by her frantic parents. She is tachycardic to 220bpm, febrile to 39.5°C, with a widespread, blanching red rash. She is screaming and looks very unwell. She is rushed into a resus bay and the septic workup begins…

 

 

 Bottom line

  • Particularly during the warmer months, parechovirus is an important differential diagnosis in the septic neonate or young infant
  • All neonates and most young infants will still need a full septic workup pending culture and PCR results
  • Treatment is supportive and no vaccination is available at this stage

 

History, virology, and overview

Parechovirus was first described in the United States in 1956. Parechoviruses were originally known as echoviruses and thought to be a type of enterovirus. In the 1990s, molecular virology and genotyping advanced sufficiently to note some distinct differences between enteroviruses and the so-called echoviruses, and the latter were reclassified to the current term – parechovirus. They remain related to enteroviruses, within the family Picornaviridae (small RNA viruses).

Parechoviruses have now been detected worldwide, with the first cases in Australia reported in 2013.

Human parechovirus (HPeV) causes a spectrum of disease from asymptomatic infection to severe, potentially life-threatening illness, predominantly in very young infants.

Parechovirus causes a seasonal illness, which typically peaks over summer in warm climates, but occurs year-round in tropical regions.

 

How is it transmitted?

Transmission is by person to person via contact with respiratory secretions or faeces from an infected individual.

Viral shedding occurs from the pharynx at 3-4 weeks,  and in the faeces at 5-6 weeks.

 

What is the incubation period?

2 to 14 days.

 

What are the symptoms?

The classical presentation is a sepsis-like illness in a very young infant, with additional features of;

  • Severe irritability, in apparent pain
  • Erythematous/maculopapular rash (can be quite pronounced)
  • Diarrhoea/loose stools
  • Marked tachycardia
    • Likely due to myocarditis, though typically normal echocardiogram and full recovery
  • Tachypnoea
  • Abdominal distension
  • Encephalitis
    • Usually, normal CSF counts but white matter changes can be seen on MRI in a small number of affected infants
  • Myoclonic jerks
  • Hepatitis +/- coagulopathy

 

Parechovirus

Source: https://www.thechronicle.com.au/news/rare-disease-almost-kills-2-newborns-qld-health-al/2889313/

How should I investigate?

All neonates and most young infants warrant standard full septic workup (bloods, urine, CSF) and commencement of empiric antibiotics on presentation

Bloods including white cell count and inflammatory markers, along with CSF and urine studies, are often normal

Parechovirus PCRs should be sent, with the gold standard sample being stool, but can also be ordered on CSF, throat swab/NPA, and blood (the 2015 NSW Health alert regarding parechovirus requested for stool and CSF to be sent preferentially).

NB: HPeV is NOT detected on the standard enterovirus PCR

 

What is the treatment?

Most babies will be given empiric antibiotics as per sepsis guidelines until cultures/PCR results available. Some will require respiratory and/or circulatory support.

 

How long do they take to recover?

The acute illness lasts 4-7 days followed by defervescence and rapid recovery. Most infants recovery fully, even from very severe illness requiring intensive care admission.

 

Are there potential complications?

Meningoencephalitis with seizures (rare), abdominal complications (volvulus, intussusception, and bowel ischaemia have been reported).

However, a 2015 Australian study (Khatami et al) which reviewed 118 children with parechovirus across 5 NSW hospitals found no significant complications, despite a high proportion of PICU admissions and the fact that a small group of children had MRIs performed showing white matter changes and diffusion restriction.

Long term sequelae unclear at this stage but likely rare.

 

Prevention/Public Health

  • Parechovirus is not a notifiable condition
  • Young babies should routinely be protected and kept away from persons with any infective symptoms
  • Strict hand hygiene and cleaning of surfaces may reduce transmission

 

Selected references

NSW Health Human Parechovirus Factsheet

McMullan B. Enterovirus and parechovirus infections in Children. Presentation slides.

Khatami A, McMullan BJ, Webber M, Stewart P, Francis S et al. Sepsis-like Disease in Infants Due to Human Parechovirus Type 3 During an Outbreak in Australia. Clin Infect Dis. (2015) 60 (2): 228-236.

NSW Health Human Parechovirus: Information for NSW EDs & Paediatricians (2015)

Measles – A brief historical & clinical review

Cite this article as:
Henry Goldstein. Measles – A brief historical & clinical review, Don't Forget the Bubbles, 2015. Available at:
https://doi.org/10.31440/DFTB.7413

Bella, 11m, is brought to your emergency department by her parents. She’s had 3 days of cough with fears over 40oC, conjunctivitis and just today has developed a bright red rash along her hairline.

Although you’ve never seen a case before, you suspect measles.

Bottom Line:

  • Measles is one of the classic febrile exanthematous illnesses.
  • Although rare in the developed world, thanks to a good vaccination program & a historically well understood disease process, is still a major cause of childhood mortality worldwide.
  • Measles outbreaks occur sporadically in areas with close contact and lower rates of vaccination.
  • Measles may be the cause of fever & rash in a recently returned traveller from an endemic area.
  • It is very contagious and there may be a need for large-scale post-exposure prophylaxis after a confirmed case.
  • Children under five and immunocompromised patients are the most vulnerable to measles and complications thereof.

“It would be unfortunate if the classic sign of Koplik spots passed into history without a good facsimile of their appearance and a historical record of their description. As the use of measles vaccine grows more frequent and world-wide, future generations of physicians may not often see this important prodromal sign of measles. Already, many young North American physicians answer in the negative when asked ig they have ever actually seen these spots.” – Brem 1972

Measles is caused by a paramyxoviridae. It was considered the ‘first’ in the classical list of childhood febrile exanthems (along with Scarlet fever, rubella, ‘fifth disease’ et al), and was first described by the Persian physician ar-Razi (Razes) in 910 AD, in his “Treatise on the Small Pox and Measles”.

Measles was traditionally a disease of the city, with smaller outbreaks in rural or regional communities often more severe. There was a long held tradition of describing measles as ‘mild’ or ‘mortal’- some outbreaks, notably the 1875 Fiji Measles outbreak have had death rates in excess of 30%.

Since the introduction of a measles vaccine in 1963, the rates in the developed world have plummeted, approaching zero. Unfortunately, in the developing world, measles still kills about 400 people a day, mostly children.

Measles occurs in several phases:

Incubation

 After infection, the virus spreads to local lymphatics and then disseminates via the haematology route to other lymph nodes and the spleen (viremia #1). Incubation averages around 13 days (6-19 days). This is usually an asymptomatic period, however upper respiratory symptoms, fever and rash are occasionally described.

Prodrome

 The usual onset of symptoms accompanied by a second viremia. Symptoms include a fever (up to 40oC) and malaise, then a cough, conductivity and coryza symptoms. Respiratory symptoms may occur, but this two to three day prodrome generally precedes any rash, at which symptoms increase in severity.

Also around this time the pathognomic feature of measles, Koplik spots, can be seen. Koplik himself described them as “one of the most, if not the most, reliable sign of the invasion of measles”. In addition to preceding the exanthem, Koplik spots are said to appear prior to maximum infectivity. Interestingly, Koplik’s original paper quotes Osler’s description of the spots, but implies it is insufficient and, along with Henoch’s description is overly focussed on the pharynx.

“On the buccal mucous membrane and the inside of the lips, we invariably see a distinct eruption. It consists of small, irregular spots, of a bright red color. In the centre of each spot, there is noted, in strong daylight, a minute bluish white speck.” … “[I]t will be seen that the buccal eruption is of greatest diagnostic value at the outset of the disease, before the appearance of the skin eruption and at the outset and height of the skin eruption.” – Koplik, 1896

Koplik Spots

Exanthem

 Described as morbiliform, the measles rash typically begins at the hairline & face and spreads cephalocaudally to involve the neck, trunk then extremities. The palms and soles are spared. The rash blanches initially, but can include petechiae and occasionally appears hemorrhagic. Severity of the illness generally correlates with the rash coverage and confluence. It fades in the same direction. This phase of Measles also entails a fever which peaks on day two of rash, as well as lymphadenopathy (which may be generalised), pharyngitis, non purulent conjunctivitis and occasionally splenomegaly. After three days, the rash darkens, and may desquamate. By this time there has usually been a clinical improvement. The rash typically lasts for a total of seven days. 

The period of contagiousness is taken from the appearance of the rash. It is thought to be from (day minus five) to (day plus four) of the onset of rash.

Recovery

 Further fever after the fourth day is suggestive of a secondary infection or additional complication. The cough may persist for several weeks. 

“But,” Bella’s parents say, “she’s immunised as per the Australian schedule!”

As per the Australian Immunisation schedule, the first dose of measles vaccine is given at 12 months. Seroconversion rates are described as 95% after the first vaccine, increasing to approximately 99% after a second vaccine. Irrespective of her immunisation status, Bella is not yet currently immune to measles, relying instead on herd immunity. This is also important for children whose immune status precludes immunisation with MMR, as it is a live attenuated vaccine. These patients include children on high-dose steroids, those with HIV (and a CD4+ count <15%), those receiving chemo- or radiation-therapy.

The Australian Immunisation Handbook specifically mentions that, if given <12 months of age, there is still a need for two doses >12 months, as persistent maternal antibodies to measles (up to 11 months) may interfere with active immunisation.

Complications

Complications of measles are more common in children, especially <5 years. About 1 in 5 children with measles will have at least one complication.

Acute otitis media occurs in 10%.

Lower respiratory tract infection occurs in 6% of measles cases; pneumonia is the most common cause of death.

1 in 1000 children will have a measles encephalitis, with a high mortality rate (greater than 10%). Survivors have neurologic sequelae.

Measles-associated immune suppression, particularly in the developing world, confers an increased risk of mortality for three years post-infection.

Subacute sclerosing pan encephalitis occurs in about 1/10,000 cases of measles, manifesting as a progressive, eventually fatal, deterioration including ataxia and seizures, typically seven years after infection.

Differential diagnoses

What else could it be?

Having just described a petechial rash in a febrile child, we need to consider bacterial sepsis. Also recall the childhood febrile exanthems:

Exanthem 2 – Group A Streptococcus

Exanthem 3 – Rubella

Exanthem 4 – likely enterovirus

Exanthem 5 – B19 parvovirus

Exanthem 6 – Roseola infantum (HHV6)

Also, mycoplasma pneumonia (the great mimic!), EBV, adenovirus or other viruses should be considered, and it is reasonable to entertain the possibility of Kawasaki disease, Henoch-Schonlein purpura or other vasculitides too.

It’s particularly worth noting that a significant number of measles cases are contracted from measles endemic areas. That is, for cases in the developed world, it is (as always) essential to elicit a travel history. Likewise, consider measles as a differential diagnosis for the suspected Ebola patient in your isolation room (!).

Do we need to do any tests?

 Measles IgM serology is not an unreasonable test if measles is high up your list of differentials. Additionally, the measles virus can be found in blood, throat swabs or urine via PCR. Although they might not change management, the results will give public health some leads and some diagnostic clarity for the patient and their family.

If you’ve done a FBC and LFTs, you might see a leukopenia, a lymphopenia, and mildly raised transaminases.

Infectivity:

We’ve mentioned several times above the period for which measles is contagious. Most notably, measles can survive for up to 2 hours in air, but is rapidly inactivated by heat, light, and extremes of pH. It is reasonable to assume that each case will have associated a number of contacts. Measles is likely to be a notifiable disease in your jurisdiction; and the Public Health Unit may refer contacts for post-exposure prophylaxis, thus:

Post-exposure prophylaxis:

Immunocompromised patients or those patients <9 months should receive a dose of ‘Normal Human Immunoglobulin’ (NHIG). Patients over 9 months who have yet to receive their first does of MMR vaccine should receive a vaccine, as should those over 12 months if they’re yet to receive a second MMR vaccine, provided their first dose was greater than four weeks previously. Pregnant patients should be offered NHIG.

References:

Brem, J. Koplik Spots for the Record: An Illustrated Historical Note CLIN PEDIATR March 1972 11: 161-163,

Dobson, M. Disease. Oxford: BCS Publishing (2007) pp140-6.

Baxby, Derrick (July 1997). “Classic Paper: The diagnosis of the invasion of measles from a study of the exanthema as it appears on the buccal mucous membrane”. Reviews in Medical Virology 7 (2): 71–74.

Koplik, H.: The diagnosis of the invasion of measles from a study of the exanthema as it appears on the buccal mucous membrane. Arch. Pediat. 13: 918, 1896.

Kliegman R. (Ed.) Measles. Nelson essentials of pediatrics. Philadelphia, PA: Saunders/Elsevier. (2013)

Tasker, RC (Ed.) Exanthema 1; measles. Oxford Handbook of Paediatrics. Oxford: Oxford University Press. (2008) pp684

The Australian Immunisation Handbook 10th Edition (2013) via: www.immunise.health.gov.au

Measles – World Health Ogranisation. https://www.who.int/topics/measles/en/

Measles images via Center for Control of Disease – Public Health Image Library. https://phil.cdc.gov/phil/details.asp?pid=3168 & https://phil.cdc.gov/phil/details.asp?pid=3167 (Public domain)

Williams on Emerging Viral Infections

Cite this article as:
Davis, T. Williams on Emerging Viral Infections, Don't Forget the Bubbles, 2015. Available at:
https://dontforgetthebubbles.com/apls-pac-williams/

The DFTB team are really excited to announce an upcoming video series…We have teamed up with APLS to share the videos from their Paediatric Acute Care Conferences. These videos have never been open access before, so if you weren’t able to attend the conferences, then now’s your chance to catch up.

Community needlestick injury in children

Cite this article as:
Henry Goldstein. Community needlestick injury in children, Don't Forget the Bubbles, 2014. Available at:
https://doi.org/10.31440/DFTB.5241

Alfie, 6, is playing at local playground under Mum’s watchful eye. He goes down the slide and jumps off, landing on his hands and feet. He starts to cry and shows his Mum a syringe lying in the bark and a needlestick injury of his left hand. Mum is distraught when she brings Alfie into your department. What next?

Bottom Line:

  • Needlestick injuries in the community are a source of great concern for parents.
  • There is one reported case of seroconversion of Hepatitis B in children.
  • The actual chance of viral transmission is very low.
  • Ensure your patient is immunised!
  • High risk patients should be discussed with your local infectious disease team for consideration of post-exposure prophylaxis.
  • Educate children not to handles needles – 2/3 CANSI’s are from intentional handling!

There is a risk of transmission of Hepatitis B, Hepatits C or HIV from a community-acquired needlestick injury (CANSI). Although the risk is very low, this is a source of significant concern to parents. Several studies lasting from several months to nearly two decades in length have looked at the epidemiology of CANSIs. These studies, undertaken in Melbourne, Montreal, Birmingham and Perth broadly agree that;

~65% CANSIs occur in boys

Mean age is around 6-8 years

In two-thirds of CANSIs, the syringe or needle was intentionally handled by the child

The most common site of injury was the hand

About a quarter of wounds bled

In the Melbourne study CANSIs often occurred in public places in parks (30%), in the street (18%), in carparks (5%) and at the beach (6%). In Montreal, CANSIs occurred predominantly in the street (30%) and in parks (24%). Whilst the obvious difference  is the lack of beaches in downtown Montreal, it’s also worth noting that a number of CANSIs must also occur in private residences.

So, what’s the risk?

Each of the papers described the baseline prevalence of HBV, HCV & HIV in their population, as well as the same prevalence within the IVDU community. None of the papers reviewed (total patients 416) reported any cases of seroconversion to Hep B, Hep C or HIV. There is a single case report of seroconversion to Hepatitis B after a CANSI in a child, reported in Barcelona in 1997. In 1999, Bowden et al, proposed conversion rates in the Victorian population to be around 6-30% for HepB, 0-7% for HepC and 0.4% HIV.

 

Although the risk is largely theoretical, factors that are considered to be high risk for acquired infection are:

  • known needle source user
  • needle user known to be infected
  • a deliberate assault
  • a large-volume injection
  • wide bore, hollow needle
  • blood in or on syringe
  • deep wound (vs superficial)

These children should be discussed with your local infectious diseases team for consideration of HIV post-exposure prophylaxis, after their initial management.

What is the initial management?

Wash the wound with soap and water.

Ensure the syringe/needle has been safely disposed

History of note:

  • Time, date and location of CANSI
  • Type of exposure?
  • What did the needle look like?
  • What kind of needle was it?
  • Is the child immunised? (specific details of each)
  • Were there other children around that may have an unreported CANSI?
  • Is this a high-risk exposure, as outlined above?

Take blood for HepB Surface antibody (HepB AbS) in a serum gel tube to store.

 

Consider tetanus vaccine +/- tetanus immunoglobulin.

Not required if immunised against tetanus in last five years.

If unimmunised, for immunoglobulin and vaccine.

Otherwise, if previously immunised, for booster dose.

 

Hepatitis B vaccination +/- Hep B immunoglobulin

If unimmunised, give first dose of vaccine and HepB Ig within 72 hours of exposure (in different limbs!)

If immunised, check titre & give booster.

 

Luckily, Alfie is immunised for both Hepatitis B and Tetanus. After a thorough wash of his hand, and some relatively obliging blood tests, he’s ready for home. His Mum asks if he needs any other medicine to reduce the risk of  “catching one of those viruses you mentioned.”

Post-exposure prophylaxis : Hepatits B immunoglobulin

There is a larger argument that there are risks associated with Hepatitis B immunoglobulin, including that of acquired infection, which must be weighted against the potential benefits of preventing a seroconversion when this may be highly unlikely in the first instance.

In the UK, Hep B immunoglobulin is only recommended in patients with exposure to known Hepatitis B source, although there is some leeway depending on the clinical circumstances. The Auckland District Health Board (ADHB), in NZ states “Administration of hepatitis immune globulin (HBIG) is not indicated if the child has completed a standard three-dose regimen of hepatitis B vaccination.” RCH Melbourne advises to offer HBIG to all unimmunised children with CANSI. There remains controversy in this component of management.

Hence, if the decision is made to treat, give HBIG within 72hrs.

(In Australia, Hep B Immunoglobulin is provided by the Red Cross Blood Service.)

Give the HBIG in a different limb to the Hep B booster you’ve just administered!

Dosing:

<30kg – give 100 iu IM injection

>30kg – give 400 iu IM injection

 

Post-exposure prophylaxis: HIV

The papers reviewed had no reports of viral transmission of HIV from a CANSI. All mentioned antiretroviral therapy as potential post-exposure prophylaxis for HIV exposure. There were no clear guidelines on which children should be offered HIV-PEP; the ‘high-risk’ patients identified in the list above were more likely to receive prophylaxis. In the Montreal study, of the 210 patients who presented thereafter, an offer of prophylaxis to 87 patients (41.4%) was documented, and 82 (94.3%) of these patients accepted. Prophylaxis was zidovudine and lamivudine for 28 days in 74 patients (90.2%), additionally eight patients were also prescribed a protease inhibitor (nelfinavir, indinavir or ritonavir). Papenburg and colleagues go on to describe the rates of adverse effects from these medications. Consideration of HIV:PEP should be discussed with the local infectious diseases team.

 

Follow up & counselling

Although the risk of seroconversion is low, it’s important not to underestimate the stress a needlestick will place on the child and family. Provide reassurance that the risk of viral transmission from a CANSI is very low. Don’t forget some written information about completing a catch-up course of immunisation. Contact your local paediatric infectious disease team; they may be happy to provide additional follow-up or counselling. That being said, always consider the prevalence of the blood-borne viruses where you work! The majority of DFTB readers are working in the Australasian, United Kingdom & North American settings; within and without these areas, the prevalence of Hep B, C & HIV can vary considerably.

 

It’s also worth noting that the studies mentioned probably underestimate the rate of CANSIs; not all children with a needlestick injury will tell their parents, and likewise, not all parents whose child reports a needlestick injury will present for care.

Finally, there’s clearly a huge public health component of this issue. Papenburg et al. identified that in nearly two-thirds of cases, the child actively handled the needle; it’s important to teach children to avoid any discarded syringes or needles and to tell an adult.

 

References:

Russell FM.  Nash MC. A prospective study of children with community-acquired needlestick injuries in Melbourne.  Journal of Paediatrics & Child Health.  38(3):322-3, 2002 Jun. https://onlinelibrary.wiley.com/doi/10.1046/j.1440-1754.2002.t01-2-00859.x/abstract

Papenburg J.  Blais D.  Moore D.  Al-Hosni M.  Laferriere C.  Tapiero B.  Quach C. Pediatric injuries from needles discarded in the community: epidemiology and risk of seroconversion.  Pediatrics.  122(2):e487-92, 2008 Aug. https://www.academia.edu/942640/Pediatric_injuries_from_needles_discarded_in_the_community_epidemiology_and_risk_of_seroconversion

Celenza, A. et al. Audit of emergency department assessment and management of patients presenting with community-acquired needle stick injuries. Australian Health Review, 2011, 35, 57–62. https://www.ncbi.nlm.nih.gov/pubmed/21367332

Garc ́ıa-Algar O, Vall O. Hepatitis B virus infection from a needle stick. Pediatr Infect Dis J. 1997;16(11):1099 https://journals.lww.com/pidj/Citation/1997/11000/Hepatitis_B_Virus_Infection_From_A_Needle_Stick.27.aspx

Makwana N.  Riordan FA. Prospective study of community needlestick injuries.  Archives of Disease in Childhood.  90(5):523-4, 2005 May. https://adc.bmj.com/content/90/5/523.short

Bowden S, Druce J, Kelly H. Stability of blood-borne viruses in the environment and risk of infection. Victorian Infect. Dis. Bull. 1999; 2: 71–2. https://docs.health.vic.gov.au/docs/doc/D785EE77B8899CD1CA2578C4000219EA/$FILE/vidbv2i4.pdf

Starship Children’s Hospital, Auckland, NZ – Clinical Guidelines (Needlestick Injuries) https://www.adhb.govt.nz/starshipclinicalguidelines/Needlestick%20Injuries.htm

Decle, P. Post-Exposure Prophylaxis (PEP) guidelines for children and adolescents exposed to blood-borne viruses 06/08/2011 https://www.chiva.org.uk/professionals/health/guidelines/pep/young-pep-ref.html

Royal Children’s Hospital, Melbourne, Clinical Practice Guidelines – Needlestick Injury https://www.rch.org.au/clinicalguide/guideline_index/Needle_Stick_Injury/

Updated 5/11/2017: Corrected initial investigations from HepB Surface Antigen to Antibody. See comments below.

Infantile botulism

Cite this article as:
Tessa Davis. Infantile botulism, Don't Forget the Bubbles, 2014. Available at:
https://doi.org/10.31440/DFTB.5172

Milla is a 4-month-old girl, brought into ED by her parents.  She’s been quieter than normal for the last couple of days and today seems really weak and not sucking on the breast anymore.  On examination, she has poor head control and marked hypotonia.  They also mention a history of constipation for the last few days. Has she been eating honey?

Bottom Line

  • Infants (under 1-year-old) can get botulism from ingesting spores in honey or dust.  Older children would have to actually ingest the toxin
  • Symptoms are constipation and weakness
  • Prognosis is excellent
  • BabyBIG can shorten the length of hospital stay
  • Recommend against giving honey to under 1-year-olds (breastfeeding mothers eating honey is fine)

 

What is it?

Botulism is caused by Clostridium botulinum – it is a gram-positive, spore-forming anaerobe. It produces botulinum toxin which is extremely potent and harmful. There are 4 types that cause the disease in humans: A, B, E, and F.

It can come from foods e.g. honey or poorly prepared meat (50% are type A), or from wounds (80% are type A). Often babies with infantile botulism have had honey ingestion. Many cases have no known cause, though, and are thought to be due to inhalation of spores from dust.

Exclusive breastfeeding is in fact a risk factor (possibly due to the nature of the flora which allows more spore germination).

 

Why is it ‘infantile’?

In people over 1-year-old, ingestion of Clostridium botulinum spores doesn’t cause problems, because the spores cannot germinate in the gut (i.e. you would actually have to ingest the toxin).

In those under 1 year old, however, the spores can germinate in the gut and consequently produce the actual toxin. This is because of infants’ relative lack of gastric acid, immature immunity, and reduction in the normal flora.

It usually occurs in 2-4 months of age but some patients are older.

 

How does it present?

Constipation is often the first sign, along with a dry mouth. Then facial palsy can occur.

Following this, there is a worsening weakness with poor suck, poor head control, hypotonia, hyporeflexia, and a weak cry.

 

How is it diagnosed?

Stool culture needs to be obtained and cultured for the toxin. In view of constipation, patients may need a saline washout to get a stool sample.

Specific assays can be used to test for the toxin. This is done in California – they inject the toxin into mice and if the mice die of respiratory arrest within 24 hours then the patient is toxin positive.  This has also been used to specify the type of C botulinum.

Patients usually do also undergo nerve conduction studies, EMG and brain MRI to exclude other causes.

 

What’s the management?

Ventilatory support is needed due to respiratory weakness and loss of gag reflex.

Antitoxin (botulism immunoglobulin – BabyBIG) can shorten the course of the disease, if given in the early stages.

N.B. Avoid giving aminoglycosides as this can worsen neuromuscular function.  Antibiotics are also thought to worsen the disease by increasing the release of toxin.

 

Is the toxin effective?

Well, the toxin is certainly not cheap at around $50,000 for the treatment of a 5kg baby.

The largest infantile botulism study was by Los Angeles Children’s Hospital ICU (2012) looked at all their infantile botulism patients over a 30 year period

  • 52 patients with botulism who received no toxin; and 15 who received BIG-IV
  • Outcomes were the length of stay, length of ICU stay and length of mechanical ventilation

 The use of BIG-IV significantly reduces the length of ICU stay, length of mechanical ventilation and length of hospital stay. It should be given within 10 days of onset of symptoms.

 

What’s the prognosis?

The prognosis is excellent. In the study mentioned above, all patients (both groups) survived to discharge and none had any serious sequelae.

Complications are essentially secondary to being in the hospital.

 

Selected references

Pediatric botulism, Medscape.

Underwood K, Rubin S, Deakers T, Newth C. Infant botulism: a 30-year experience spanning the introduction of botulism immune globulin intravenous in the intensive care unit at Children’s Hospital Los Angeles. Pediatrics. 2007;120:e1380.

Cox N, Hinkle, R. Infant botulism. American Family Physician. 2002;65(7):1388-1393.

Ramroop S. Williams B, Vora S, Moshal K. Infant botulism and botulism immune globulin in the UK: a case series of four infants. Archives of Disease in Childhood. 2012;97:459-460.