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We observed an increase in notifications of puerperal group A Streptococcus (GAS) infections in July and August 2018 throughout the Netherlands without evidence for common sources. General practitioners reported a simultaneous increase in impetigo. We hypothesised that the outbreak of puerperal GAS infections resulted from increased exposure via impetigo in the community. We conducted a case–control study to assess peripartum exposure to possible, non-invasive GAS infections using an online questionnaire. Confirmed cases were recruited through public health services while probable cases and controls were recruited through social media. We calculated odds ratios (OR) and 95% confidence intervals (95% CI) with logistic regression analysis. We enrolled 22 confirmed and 23 probable cases, and 2,400 controls. Contact with persons with impetigo were reported by 8% of cases and 2% of controls (OR: 3.26, 95% CI: 0.98–10.88) and contact with possible GAS infections (impetigo, pharyngitis or scarlet fever) by 28% and 9%, respectively (OR: 4.12, 95% CI: 1.95–8.68). In multivariable analysis, contact with possible GAS infections remained an independent risk factor (aOR: 4.28, 95% CI: 2.02–9.09). We found an increased risk of puerperal fever after community contact with possible non-invasive GAS infections. Further study of this association is warranted.

Several medical conditions can cause children to present with fever and a maculopapular rash Although some presentations are benign, others may be medical emergencies, which warrant a prompt diagnosis. We review some of the more common causes of fever and maculopapular dermatitirs, rash including infectious processes (roseola; rubeola; rubella; parvovirus B19; hand, foot, and mouth disease; scarlet fever; meningococcemia; Epstein-Barr virus infection), hypersensitivity reactions (exanthematous drug reactions), and vasculitis syndromes (Kawasaki disease). We have included a diagnostic algorithm to facilitate rapid identification of the etiology of the rash and fever. Those conditions that can occur in children but are seen predominantly in adults are discussed in the contribution "Rash with maculopapules and fever in adults" in this issue.

We used multivirulence locus sequence typing to analyze 68 Yersinia pseudotuberculosis isolates from patients in Russia during 1973-2014, including 41 isolates from patients with Far East scarlet-like fever. Four genotypes were found responsible, with 1 being especially prevalent. Evolutionary analysis suggests that epidemiologic advantages could cause this genotype's dominance.

Essential facts Scarlet fever is characterised by a rash that usually accompanies a sore throat and flushed cheeks. It is mainly a childhood illness. While this contagious disease rarely poses a danger to life today, outbreaks in the past led to many deaths.

A child with a febrile exanthema is a complex medical problem involving diagnostic challenges, epidemiological threats and a great concern for the parents and any physician, should be prepared to deal with it. Many of the classical ones (measles, rubella, chickenpox) have now a decreased incidence due to a high vaccine coverage, which makes even harder for the physician to establish an early diagnosis. To the untrained eye most of them are difficult to differentiate. Their prompt recognition is necessary in order to manage them adequately and to prevent spreading of the disease.

Febrile seizures (FS) are the most common type of convulsive events in children. FS are suggested to result from a combination of genetic and environmental factors. However, the pathophysiologic mechanisms underlying FS remain unclear. Using an animal model of experimental FS, it was demonstrated that hyperthermia causes respiratory alkalosis with consequent brain alkalosis and seizures. Here we examine the acid-base status of children who were admitted to the hospital for FS. Children who were admitted because of gastroenteritis (GE), a condition known to promote acidosis, were examined to investigate a possible protective effect of acidosis against FS.We enrolled 433 age-matched children with similar levels of fever from two groups presented to the emergency department. One group was admitted for FS (n = 213) and the other for GE (n = 220). In the FS group, the etiology of fever was respiratory tract infection (74.2%), otitis media (7%), GE (7%), tonsillitis (4.2%), scarlet fever (2.3%) chickenpox (1.4%), urinary tract infection (1.4%), postvaccination reaction (0.9%), or unidentified (1.4%). In all patients, capillary pH and blood Pco(2) were measured immediately on admission to the hospital.Respiratory alkalosis was found in children with FS (pH 7.46 ± 0.04, [mean ± standard deviation] Pco(2) 29.5 ± 5.5 mmHg), whereas a metabolic acidosis was seen in all children admitted for GE (pH 7.31 ± 0.03, Pco(2) 37.7 ± 4.3 mmHg; p0.001 for both parameters). No FS were observed in the latter group. A subgroup (n = 15; 7%) of the patients with FS had GE and, notably, their blood pH was more alkaline (pH 7.44 ± 0.04) than in the GE-admitted group. During the enrollment period, eight of the patients were admitted on separate occasions because of FS or GE. Consistent with the view that generation of FS requires a genetic susceptibility in addition to acute seizure triggering factors, each of these patients had an alkalotic blood pH when admitted because of FS, whereas they had an acidotic pH (and no FS) when admitted because of GE (pH 7.47 ± 0.05 vs. pH 7.33 ± 0.03, p0.005).The results show that FS are associated with a systemic respiratory alkalosis, irrespective of the severity of the underlying infection as indicated by the level of fever. The lack of FS in GE patients is attributable to low pH, which also explains the fact that children with a susceptibility to FS do not have seizures when they have GE-induced fever that is associated with acidosis. The present demonstration of a close link between FS and respiratory alkalosis may pave the way for further clinical studies and attempts to design novel therapies for the treatment of FS by controlling the systemic acid-base status.

Group A streptococcal strains were isolated from the throats of 46 children suffering from scarlet fever. For detection of erythrogenic toxins (ETs), the culture supernatants were concentrated 100 times by ethanol precipitation and solubilisation in acetate buffer. ELISA was used to identify ETA and double immunodiffusion to identify ETB and ETC. The presence of the ETA gene was detected by a specific DNA probe. ETA (alone or in combination with ETB and/or ETC) was found in 51.9% of the strains, ETB (alone or in combination with ETA and/or ETC) in 76.9% and ETC (in combination with ETA and ETB) in 28.9%. Only 5.8% of strains did not produce any detectable ET. In SDS-PAGE, supernatants of ETB-producing strains showed a pronounced band in either the region of the proteinase zymogen or the active proteinase. There was no correlation between the type of erythrogenic toxin and the serological M or T type of the producing strain. The mitogenic potency of culture supernatants did not differ significantly irrespective of the toxin type(s) present. Culture supernatants of strains without a detectable amount of the known ETs were highly mitogenic, indicating the production of other streptococcal mitogens. A correlation with clinical symptoms was determined with regard to exanthema and fever. Strains producing two or three toxins caused a more intense exanthema. Patient temperature was higher (greater than or equal to 38 degrees C) when the infecting strain produced ETB. The toxin-producing patterns of the strains of this study were compared with those isolated during the last epidemic outbreak of scarlet fever in East Germany.

The differential diagnosis of a fever and rash presenting in a pediatric patient is quite extensive. This article is not all-inclusive but is meant to aid in the diagnosis to differentiate serious, life-threatening eruptions from more benign common rashes.

Scarlet fever was diagnosed in a girl with high fever, a sore throat and exanthema marginatum.

We report a 3-year-old boy with varicella complicated by cellulitis and scarlet fever. He developed a typical rash of scarlet fever following the onset of varicella. Streptococcus pyogenes was isolated from the ulcers due to varicella. The present case suggests that scarlet fever may rarely develop following varicella and should be considered in children with complicated varicella.

A 25-year-old female meeting all six criteria for Kawasaki disease is reported. A total of 22 reported cases of adult Kawasaki disease, including the present case, are reviewed. In adult Kawasaki disease, arthralgia, gastrointestinal complications and hepatic dysfunction are seen more frequently than in childhood cases. Cardiac complications are rarely seen in adult Kawasaki disease. Two cases have been positive for anti-nuclear antibody (ANA). The present patient had increased levels of serum IgE and was positive for ANA, suggesting involvement of an immune mechanism. Adult Kawasaki disease is rare but appears to be on the increase; internists treating adults must be aware of this disease.

The role played by lymphocytes in the pyretic response to scarlet fever toxin (ET) was studied in vivo using antilymphocyte serum (ALS). Two i.v. injections of ALS inhibited the pyretic response to a subsequent ET injection in rabbits. The course of endotoxin fever remained uninfluenced by ALS. Antipolymorphonuclear serum had no effect on the pyretic response to either of the toxins. Pretreatment with ALS also inhibited the skin reaction after i.d. injection of ET. These findings are further evidence a mediating role of lymphocytes in the biological effects of ET, among other things in the release of endogenous pyrogen.

In normal rabbits and mice, one i.v. injection of scarlet fever toxin (ET) (30 000 STD per kg of rabbit weight or 20-g mouse) elicited a similar biphasic change in carbon clearance rate - early depression followed by a stimulating phase - as has been described for Gram-negative endotoxins. Prolonged depression without a subsequent stimulation phase was obtained in mice by raising the ET dose. The reasons of the discrepancy between these findings and those of Hanna and Watson (1965b) are discussed. Pyrogenic tolerance to ET is not accompanied by accelerated carbon clearance and is not impaired by RES blockade. A possible mechanism of ET tolerance is suggested.

What may be a new disease has been afflicting infants and young children in Japan since 1960. It is an acute, febrile, mucocutaneous condition accompanied by swelling of cervical lymph nodes (tentatively called mucocutaneous lymph node syndrome [MLNS]). It may be misdiagnosed as scarlet fever, the Stevens-Johnson syndrome, or infantile periarteritis nodosa. The disease is now known to be widely occurring all over Japan with an increasing incidence each year. More than 6,000 cases have been reported as of 1973. One to two percent of the patients reported have died suddenly of cardiac failure. All the autopsies showed infantile periarteritis nodosa-like arteritis accompanied by coronary thrombosis and aneurysm. Some of the surviving cases have been shown to have similar changes. These findings lead us to believe that this clinical picture is a new clinical entity. Recently, rickettsia-like bodies were found by electron microscopy in biopsy specimens from the skin and lymph nodes of the patients. The bodies were isolated by yolk sac culture and their pathogenicity is now under investigation.

The factors present in streptococcal lesion extracts (SLE) which enhanced the lethal and tissue-damaging properties of Gram-negative bacterial endotoxins and streptolysin O were identified with the scarlet fever group of toxins. Toxic manifestations attributed to this group of toxins included lethality, cardiotoxic and other tissue damage, enhancement of toxicity, and pyrogenicity. Of these, the measurement of febrile response in American Dutch rabbits was the most useful parameter of toxicity. In rabbits, repeated daily intravenous injections of 0.125 Lf of a purified erythrogenic toxin immunizes specifically against the pyrogenic activity; this technique was used to type the toxins and to distinguish them from exogenous and endogenous pyrogens; non-specific pyrogens, such as streptococcal endotoxin, were not found in SLE. All types of the Lancefield Group A streptococci tested produced one or or more immunologically distinct toxins in vivo in contrast to Groups B and C which did not produce them; toxins A and B, previously distinguished by neutralization of rash-inducing activity in the skin, were produced in vivo. The A toxin was the most common, as indicated by its presence in extracts prepared with Types 28, 12, 17, and 10 (NY-5); B toxin was found in 10 (NY-5) and 19. A new toxin, designated C, was obtained from a Type 18. In American Dutch rabbits, purified toxin at a concentration of 15 Lf (900,000 STD) neither gave a Dick test nor prepared the skin for the local Shwartzman reaction; by this route, however, in contrast to classical endotoxins, they enhance the lethal and tissue-damaging properties of sublethal doses of these and other toxins. These properties of the immunologic distinct exotoxins as demonstrated in American Dutch rabbits suggest by analogy their importance in the pathogenesis of streptococcal disease in man. Evidence that might implicate them in sequelae, in addition to scarlet fever, is discussed.

The clinical effect of a new penicillin (azidocillin—the potassium salt of 6-d-alpha-azidophenylacetamido-penicillanic acid) was compared with that of penicillin V in a double-blind study on 183 patients with scarlet fever. No decisive difference as to the advantage of either of these preparations could be noticed in this material, which represented a mild form of the disease. Azidocillin eradicated Haemophilus influenzae in a few cases with concomitant infection with this organism, whereas penicillin V did not prevent the emergence of H. influenzae during treatment. There was a distinct relation between upper respiratory tract disease after leaving the hospital and the presence of β-haemolytic streptococci among cases treated with penicillin V, whereas no such correlation was found among those given the new penicillin. Neither in this material of 97 cases nor in a preliminary pilot series, which comprised a further 79 cases, were any side-effects or complications observed which could be ascribed ...