Scarlet fever

• 1. Introduction

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  Scarlet fever, an infection caused by the bacterium Streptococcus pyogenes, was a killer of children. Around 1900, in several places, about one in four of those who caught it died. Today the same illness is usually a short, treatable episode. Yet its name still carries an old dread. Why does a throat infection sometimes paint the whole body red? How did a disease this dangerous lose so much of its force before modern medicine could explain it? And why do health agencies keep reporting its return?

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• 2. The Strawberry Tongue

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  A fever above 39 degrees Celsius, which is 102.2 degrees Fahrenheit, often announces the illness. A sore throat and general tiredness come with it. The tonsils redden and swell, and the roof of the mouth may be dotted with small red spots.

  The tongue gives the disease its most famous sign. For the first two days it wears a whitish coat, with swollen red bumps poking through. Doctors call this the white strawberry tongue. After four to five days the coat sheds, and the tongue turns the red of a ripe berry.

  The rash usually follows the sore throat by a day or two, though it can arrive earlier or up to a week later. It begins as small flat spots on the neck or trunk, then becomes tiny bumps that travel to the arms and legs. To the fingertips it feels like sandpaper. The cheeks look flushed, with a pale ring around the mouth, while the palms and soles are spared. Pressing on the red skin makes it turn pale.

  On brown or black skin the redness can be hard to see. There, the sandpaper texture and larger bumps may be the better clues. Children under five can look quite different. Toddlers may only have a stuffy nose and a mild fever, and infants may simply be irritable and eat less.

  When the rash fades, in about a week, the skin begins to peel. The peeling starts on the face and moves downward, and it can last for weeks on the fingers and toes. Sometimes it is the only proof that scarlet fever ever happened.

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• 3. A Toxin Borrowed From a Virus

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  Only about one in ten children with strep throat goes on to develop the rash, and the reason lies in a poison. Certain strains of the bacterium make streptococcal pyrogenic exotoxins, which damage tiny blood vessels in the skin. Four of them, labelled A, B, C and F, have been identified.

  The bacterium cannot make the best-studied toxin, speA, on its own. It needs a borrowed tool. A virus that infects bacteria, a bacteriophage called T12, slips its genes into the bacterial chromosome, specifically into a gene for a serine tRNA. Those viral genes carry the recipe for speA. Other streptococcal phages may carry it too.

  The gene was cloned and sequenced in 1986. It is 753 base pairs long and codes for a protein of 29.244 kilodaltons. The finished protein, once a 30-amino-acid leader is removed, weighs 25.787 kilodaltons. Its tail resembles toxins made by Staphylococcus aureus.

  These toxins are called superantigens, because they set off an outsized reaction in the immune system. Antibodies made against one toxin protect only against that one. Since there are 12 different pyrogenic exotoxins, a person can be struck again by a strain that makes a different set.

  The viral trick is still at work. Research published in October 2020 found that a North-East Asian lineage of the bacterium, known as emm12, had gained three new genes from viruses. Those genes produce superantigens aimed at white blood cells, and they made the strain more virulent.

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• 4. When the Body Turns on Itself

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  Two to six weeks after a streptococcal throat infection, acute rheumatic fever can appear. The immune system, trained to attack the bacterium, starts attacking the body's own tissues too. Scientists call the cause molecular mimicry. Doctors diagnose the fever with the Jones criteria, which include arthritis, inflammation of the heart, neurological problems and skin findings.

  The heart is the most serious target. The resulting rheumatic heart disease usually damages the mitral valve and can narrow it. Australia treats the link as a particular worry, because these diseases are common in Aboriginal and Torres Strait Islander communities.

  The kidneys can be hit sooner. One to two weeks after a strep throat, poststreptococcal glomerulonephritis may bring high blood pressure, swelling, and blood and protein in the urine. Unlike rheumatic fever, it can also follow a skin infection such as impetigo.

  A third complication is reactive arthritis, which can start within 10 days and affect many different joints. Rheumatic fever, by contrast, tends to strike larger joints like the knees.

  There is a second family of problems, the suppurative complications. They are rare, and they come from the bacteria spreading directly or through lymph and blood. Examples include abscesses near the tonsils, mastoiditis, endocarditis, pneumonia and meningitis.

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• 5. Many Names for One Fever

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  Around 400 BC, Hippocrates described a patient with red skin and fever. Historians cannot say whether he saw this disease. The first clear description in medical writing came in 1553, in a book called De Tumoribus praeter Naturam by the Sicilian physician Giovanni Filippo Ingrassia. He called the illness rossalia and took care to separate it from measles.

  Johann Weyer met it again during an epidemic in lower Germany between 1564 and 1565, and named it scarlatina anginosa. In 1578 Joannes Coyttarus of Poitiers published a book in Paris with an unmistakable account. Daniel Sennert of Wittenberg had already described the classic peeling in 1572. He was also the first to note the swollen joints, fluid retention and abdominal fluid that can accompany it.

  The English physician Thomas Sydenham wrote down the word scarlatina in 1675, and it stuck. In 1827 Richard Bright was the first to see that the kidneys can be involved.

  Naming trouble did not end there. In the 1890s Clement Dukes and Nil Filatov each described a rash illness they took for a form of rubella. Dukes later called it a separate disease, known as Dukes' disease, Filatov's disease or fourth disease. In 1979 Keith Powell showed it was a form of scarlet fever caused by a staphylococcal toxin.

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• 6. Hunting the Culprit

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  In 1874 the surgeon Theodor Billroth linked chains of round bacteria to skin infections, and he coined the name Streptococcus. Friedrich Fehleisen first grew the organism in culture in 1883, from lesions of erysipelas. A year later Friedrich Julius Rosenbach settled on the name Streptococcus pyogenes.

  In 1884 Friedrich Loeffler found streptococci in the throats of scarlet fever patients. The finding stayed controversial, because many people carrying the bacteria in their throats never developed the disease. George and Gladys Dick, working with Alphonse Dochez, confirmed the link in the early 1900s. Rebecca Lancefield's grouping scheme of the 1920s finally tied the illness to group A streptococci.

  The Dicks then proved that a toxin was responsible. Liquid that had been filtered to remove every bacterium could still produce the red skin reaction.

  From that insight came the Dick test in 1924. A small injection of diluted streptococci went into the skin. A reaction at the site, visible after four hours and clearer by 24, marked a person as susceptible. No reaction meant immunity. The test was hailed as a major breakthrough and made the Dicks famous, even earning them a Nobel Prize nomination.

  The link to viruses came from a separate thread. Frederick Twort found bacteriophages in 1915, but his work was overlooked. Felix d'Herelle rediscovered them in 1917. In 1926 Ioan Cantacuzino and Bonciu tied them to scarlet fever.

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• 7. Serum, Antitoxin and Penicillin

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  Beginning in 1900, children with scarlet fever were treated with serum drawn from horses' blood, and deaths fell significantly. An antitoxin followed in 1924. The Dicks also developed a vaccine that year, but it was dropped in the 1940s once penicillin arrived. A separate vaccine that combined diphtheria and scarlet fever protection proved ineffective and was gone by the end of the Second World War.

  The 1922 epidemic shows what the disease could still do before those tools spread. Agathe Whitehead was among its victims.

  Today the first choice is penicillin V by mouth for 10 days. Children who cannot swallow tablets can take liquid amoxicillin, which works equally well. A single injection of benzathine penicillin G is another option. For people allergic to that drug family, doctors reach for a first-generation cephalosporin, or clindamycin or erythromycin if the allergy is severe.

  Timing matters. If antibiotics begin within nine days, rheumatic fever becomes very unlikely. A child stops being contagious 24 hours after the first dose. The peeling still happens, and antibiotics have not been shown to prevent kidney inflammation.

  The tonsils once took the blame. Surgeons removed them for recurrent strep throat, but the practice is no longer advised, because the bacteria can infect a person with no tonsils at all.

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• 8. A Comeback in the Data

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  In 2011 a strain in Hong Kong resisted macrolide antibiotics such as erythromycin while still yielding to penicillin. It was linked to at least two deaths, the first from the disease there in over a decade. Professor Yuen Kwok-yung of Hong Kong University's microbiology department reported that about 60% of circulating strains were resistant. Earlier rates had run at 10-30%, and he linked the rise to overuse of macrolides.

  England saw its own surge. Between 2013 and 2016, cases rose from 8.2 to 33.2 per 100,000 people, and hospital admissions climbed by 97%. Laboratory reports of the bacterium rose 68% between 2014 and 2018. Rises were also reported in Wales, South Korea, Vietnam and China, and after pandemic restrictions eased in 2020. Doctors still do not agree on why.

  In late December 2022 the United States Centers for Disease Control and Prevention sent out a health alert about more invasive group A strep in children. The disease itself is not reported there. The World Health Organization noted increases in England and other European countries, and cases were also reported in France and Ireland.

  The disease strikes boys and girls equally and peaks in winter and spring. Its toll had already been falling before antibiotics existed. Researchers have pointed to better housing, better control measures, or a milder bacterium. A safe vaccine against the 180 to 200 types of the bacteria has been sought for over 20 years, and none existed as of 2020.

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