UK: Scarlet Fever On The Ascendant (Again)

Group A streptococcal infections: update on seasonal activity, 2014 to 2015

Ref: HPR 9(5)

 

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In 2014 the UK saw a huge increase in the number of Scarlet Fever cases (blue line in chart above), after a decade of declining or flat numbers.  We looked at that rising tide of cases last March in UK : Sharp Rise In Scarlet Fever Cases In 2014, but the peak in cases didn’t occur until April.

 

Before the year ended, more than 14,000 Scarlet fever cases were diagnosed in the UK, the highest number since the 1960s.

 

Once again this year  Scarlet Fever notifications are up, averaging more than 200 cases a week for the past 6 weeks (n=1265).  As the chart above shows (red line), the number of cases is running nearly double that of last year, with the expected peak of the season still weeks (or months) away.

 

Scarlet Fever primarily affects children under the age of 12. It is highly contagious, there is no vaccine, but antibiotics are generally effective when treated early.

 

Scarlet fever (Group A Streptococcus or GAS) is caused by the bacterium Streptococcus pyogenes - which like viruses, can evolve over time – sometimes resulting in increased virulence, greater transmissibility, and/or antibiotic resistance. 

 

Strains are identified by changes in their M-protein gene sequence (emm types) – which often determines virulence - and within these types new variants can emerge.

 

Although less common, a more serious yet related illness is called iGAS (invasive Group A Strep), which indicates infection of the bloodstream, deep tissues, or lungs, and may result in severe (and frequently fatal) cases of necrotizing fasciitis and streptococcal toxic shock syndrome.

 

In 2011 and 2012 we followed an unusual erythromycin resistant (but still sensitive to Penicillin & other 1st generation cephalosporins) scarlet fever outbreak in Hong Kong (see Hong Kong: Scarlet Fever In 2012), which resulted in a small number of pediatric fatalities. 

 

Last November a Nature Genetics journal article attributed Hong Kong’s severe outbreak to the emergence of a new emm12 variant (see Emergence of scarlet fever Streptococcus pyogenes emm12 clones in Hong Kong is associated with toxin acquisition and multidrug resistance).

 

On Friday the UK’s PHE released the following statement about this year’s increased activity:

 

 

Scarlet fever notifications continue to increase

From: Public Health England

First published: 13 February 2015

Latest PHE report shows a high number of scarlet fever notifications across England, with 1265 new cases reported in the first 6 weeks of 2015.

Steep increases in scarlet fever activity are being seen across the country, with over 300 cases reported last week (2 to 9 February 2015).

Increases in scarlet fever are normal at this time of year as we approach high season between March and April. However, the numbers of cases currently being reported are above what is typical for this time of the year. Whilst this might reflect heightened awareness and improved diagnosis and/or notification practices, the high number of cases currently being notified are of concern. Last year in England, over 14,000 cases of scarlet fever were notified, the highest total since the late 1960s.

Dr Theresa Lamagni, PHE’s head of streptococcal infection surveillance, said:

As we enter into high season for scarlet fever, we ask GPs and other frontline medical staff to be mindful of the current high levels of scarlet fever activity when assessing patients. Prompt notification of cases to local health protection teams is critical to enable local monitoring and rapid response to outbreaks. Schools and nurseries should similarly be mindful of the current elevated levels of scarlet fever and promptly inform local health protection teams at an early stage if they become aware of cases, especially if more than 1 child is affected. 

(Continue . . . )

In March of 2014, during last year’s dramatic spike in cases, the Eurosurveillance Journal ran a Rapid Communications Report that described the UK outbreak, and discussed possible causes for the recent increase in cases.

 

Eurosurveillance, Volume 19, Issue 12, 27 March 2014

Rapid communications

Increase in scarlet fever notifications in the United Kingdom, 2013/2014

R Guy¹, C Williams², N Irvine³, A Reynolds⁴, J Coelho¹, V Saliba¹, D Thomas², L Doherty³, V Chalker¹, B von Wissmann⁴, M Chand¹, A Efstratiou¹, M Ramsay¹, T Lamagni ()¹

<SNIP>

Discussion

Scarlet fever incidence has shown a remarkable increase this season. Previous analysis of scarlet fever notifications in England over the last century suggest cyclical patterns of incidence, with resurgences occurring on average every four years [3]. The last peak year for scarlet fever was 2008/09, with incidence of invasive disease tending to mirror those of superficial manifestations of GAS infection in many but not all years [4]. While the enhanced media coverage and public health alerts may have increased case ascertainment during this season, the escalation prior to this suggests a genuine increase in disease incidence. The reasons behind this increase are unclear but may be attributable to a natural cycle in disease incidence.

It remains possible that the increase or part of the increase is attributable to changes in virulence of circulating strains or increased incidence in particular risk groups. An exceptional increase in scarlet fever incidence in Hong Kong during 2011 and 2012 was attributed to the introduction of a new emm12 strain [5]. Continued vigilance for the emergence of a novel strain or changes in pattern of clinical disease is essential.

At present, antimicrobial susceptibility results are not indicating any change in antibiotic susceptibility [6]. Analysis of isolates originating from normally sterile sites, which were submitted to the national reference laboratory, has not identified any unusual types circulating, although a slight increase in the proportion of due to emm3 is currently being observed. Strains harbouring this emm type were implicated in the UK rise in incidence in scarlet fever and iGAS infection during 2008/09 [7], and also implicated in population increases in iGAS infection incidence in Ireland in 2013 [8]. While the current rise in emm3 is slight, it raises some concern given its association with a higher case fatality rate than other emm types [9;10]. Rapid assessment of changes in case fatality rate will assist in monitoring any such changes during the current season.

As a result of the current rise in scarlet fever notifications, clinicians, microbiologists and health protection specialists across Europe should continue to be mindful of potential increases in invasive disease and maintain a high index of suspicion in relevant patients, as early recognition and prompt initiation of specific and supportive therapy for patients with iGAS infection can be life-saving. Alerts have been issued by local health protection staff to frontline medical staff in the UK. An unusual pattern of outbreaks of scarlet fever has also been noted in Belgium during this season (K Loens, personal communication, March 2014). Comparison of strains across the two countries would be beneficial in understanding the current situation in the UK. 

 

I’ll update this story later in the spring, as the size of this year’s outbreak becomes more apparent.

UK PHE: Revisiting Influenza Antiviral Recommendations

Credit UK PHE

 

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Last spring the Cochrane group made headlines (again) for their less-than-sparkling review of the influenza antiviral drug oseltamivir (Tamiflu ®), which cast doubts on its efficacy and on the wisdom of governments around the world stockpiling the drug. (see Revisiting Tamiflu Efficacy (Again)).  

The Cochrane Summary is available at:

Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children

Editorial Group: Cochrane Acute Respiratory Infections Group

Published Online: 10 APR 2014

These results were then picked up by tabloid (and other) media sources, tortured to within an inch of its life, and then splashed across the media as `proof’ that the governments of the world were nothing but shills for Big Pharma (see Ministers blew £650MILLION on useless anti-flu drugs.).

Much of this ire has been garnered through Roche’s long-standing resistance to releasing all of the testing data on their antiviral drug, and that has led to critical editorials in the BMJ, and frequent excoriation in the British press.

 

As a result, many people have come away with the erroneous impression that these drugs are worthless – or worse.   And that could dissuade some from seeking early medical treatment during this year’s flu season, costing lives in the process. 

While research purists may applaud their methods, the problem that I (and many others) have with this analysis is that the Cochrane group set the bar much too high as to what studies they would consider, excluding many observational studies. 

 

They also were looking at the effects of Tamiflu on healthy children and adults – those least likely to see benefits from taking antivirals.

 

Despite its critics, there are studies that show that Tamiflu can significantly reduce morbidity and mortality associated with influenza – particularly with severe infection, or those with comorbidities. Some we’ve looked at in the past include:

 

• In 2010 we saw an observational study that appeared in JAMA (see Study: Antivirals Saved Lives Of Pregnant Women) that strongly suggested that Tamiflu was life saving for some patients with pandemic flu.
• And again in 2010, in BMJ: Efficacy of Oseltamivir In Mild H1N1, we saw a study which suggested that the administration of oseltamivir may have significantly reduced the incidence of pneumonia among otherwise healthy pandemic H1N1 patients.
• In December of 2012, in Study: The Benefits Of Antiviral Therapy During the 2009 Pandemic we looked at a meta-analysis of 90 observational studies that appeared in the  Journal of Infectious Diseases that spanned nearly 35,000 patients, 85% of whom has laboratory confirmed H1N1.

Their main finding was antiviral therapy - principally oseltamivir - initiated within 48 hours of onset, reduced the likelihood of severe outcomes, namely admission to a critical care unit or death, by 49 to 65%.

• Last March in The Lancet: Effectiveness Of NAI Antivirals In Reducing Mortality In Hospitalized H1N1pdm09 Cases we looked at yet another observational study conducted by researchers at The University of Nottingham – that reviewed more than 29,000 hospitalized H1N1pdm cases across 38 countries between 2009 and 2011, and found that the administration of NAI antivirals was associated with a 19% reduction in mortality compared to receiving no NAI treatment at all.
• And last summer, in  CID Journal: Under Utilization Of Antivirals For At Risk Flu Patients, we saw a study showing that antiviral drugs are underused for at-risk patients, while antibiotics (which don’t work against viral infections) are overused.

 

While it is true that antivirals are of limited value for those who are healthy, and suffering from uncomplicated seasonal influenza, the preponderance of evidence shows significant benefits from the early administration in cases of severe infection, co-morbidities, or infection with novel influenza strains.

One of the most dramatic avian flu studies (see Study: Antiviral Therapy For H5N1) looked at the outcomes of H5N1 patients who either received, or did not receive, antiviral treatment. The research appears in the IDSA’s Journal of Infectious Diseases.

 

The bottom line is essentially out of 308 cases studied, the overall survival rate was a dismal 43.5%. But . . . of those who received at least one dose of Tamiflu . . .  60% survived . . .  as opposed to only 24% who received no antivirals.

 

Last April we saw the The CDC Responds To The Cochrane Tamiflu Study, where they provided their rationale for continuing to recommend its use. You can visit the CDC’s current advice on antiviral administration (which is unchanged) at this site:

 

Recommendations of the Advisory Committee on Immunization Practices (ACIP): Information for Health Care Professionals

The information on this page should be considered current for the 2014-2015 influenza season for clinical practice regarding the use of influenza antiviral medications. Also see the current summary of recommendations available at Influenza Antiviral Medications: Summary for Clinicians and a list of related references at Antiviral Guide References.

 

Today the UK’s Public Health England has released the following recommendations, which also restates their position on the use of antivirals: Influenza: treatment and prophylaxis using anti-viral agents  4 November 2014. 

In addition to their recommendations, you’ll also find a push-back against the Cochrane study.

Update following the 2014 Cochrane Review Public Health England (PHE) has produced a summary of the current guidance and evidence and a position statement on the use of antivirals for the treatment and prophylaxis of influenza. (2). The PHE summary and position statement has been published following the 2014 Cochrane Review on the efficacy of antivirals (3). The findings of the 2014 Cochrane review were not substantially different to the previous (2010 and 2012) reviews. Overall the 2014 review adds to the evidence base for the treatment of influenza in some settings, however the conclusions made are limited due to the variation in outcomes, patient groups, and settings studied.

The key messages from the summary are:

• there is evidence that antivirals can reduce the risk of death in patients hospitalised with influenza
• in the light of this evidence, it is important that doctors treating severely unwell patients continue to prescribe these drugs where appropriate
• PHE continues to support the early use of antivirals for patients with proven or suspected seasonal influenza who are in high risk groups, or who are considerably unwell (even if not in a high risk group)

This position is consistent with that taken by the World Health Organisation (WHO) and other national public health organisations such as the USA’s Centers for Disease Control and Prevention (CDC). Although there is no evidence to support any change to the recommended use of neuraminidase inhibitor, media reporting around the Cochrane Review 2014 publication suggested that antivirals are not effective for influenza. This may impact the prescribing of these important drugs. It is essential that physicians treating severely unwell patients in any setting are not deterred from prescribing what may be lifesaving drugs as a result of confusion over efficacy in this situation; this is especially true for patients hospitalised with proven or suspected influenza.

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