Fibiger J (1898)

Om serumbehandling af difteri [On treatment of diphtheria with serum]. Hospitalstidende 6:309-325.
At the end of the 19th century, French studies using historical controls to assess the effect of anti-diphtheritic serum were controversial. Johannes Fibiger, a Danish physician, used serum only in child patients admitted to hospital on alternate days, and confirmed that serum reduced mortality.

Key passage(s)




“The only method that could be used rationally was to treat every second patient with serum and every second as usual. The crucial importance of such a method, according to my knowledge, has, for the first time in Denmark been emphasised by Wanscher1), during his discussion on the importance of tracheotomy for diphtheritic stenosis. The method has subsequently been referred to by P. Heiberg2) as the only statistically correct one. The method was previously applied at the end of the trial by Professor Sørensen [Fibiger’s chief at Blegdam Hospital, who had tried to conduct a controlled trial a couple of years earlier. ed.]. As the method had since created practical difficulties, I proposed to Professor Sørensen that all patients admitted on one day should be given serum, but none of the patients admitted on the next day. The latter patients were to be treated as usual.

Professor Sørensen agreed to this, provided that I conducted the trial.

The trial started on 13 May 1896 and finished on the same day in 1897. All patients admitted to the hospital every other day were injected with serum, the injections starting immediately on or shortly after admission, or as soon as it was possible for the doctor on duty.

[The throats of] All patients were swabbed with silver nitrate solution or creolin solution. In addition, potassium chlorate solution or creolin were used for gargling. Those patients not treated with serum were also given a solution of hydrargyrum cynatum internally (though not the mild cases).

Repeated bacteriological examinations were carried out on all patients using throat swabs. In patients with nasopharyngeal diphtheria the nasal cavity was examined as well. In patients with laryngeal diphtheria or croup the larynx was examined. In 493 of the patients who were hospitalised for diphtheria or croup, no diphtheria bacilli were found. These patients, who suffered from follicular-, phlegmoneous-, scarlet fever-, or pseudomembraneous non-diphtheria anginas, or laryngitis, bronchopneumonia, etc., were excluded from the statistics, which thus include only diphtheria patients in whom the presence of diphtheria bacilli had been proven.

However, not all such patients were included. Some were excluded because their disease on admission to hospital was complicated with measles, scarlet fever, or erysipelas, and some of them because they were moribund or in agony on admission and died within 24 hours (17 patients). Further, three persons were excluded because they were hospitalised with diphtheria bacilli in the throat, but did not have any clinical signs of diphtheria. Furthermore, we had to exclude from our statistics a few more patients: those who refused serum treatment (3 mild cases), although they should have been injected according to the rotation; 2 other more severe cases, who, because of the wishes of the parents and the referring doctor, were injected with serum, though they came on “non-serum days”; and finally, a couple of seriously affected patients who were admitted during the final phase of the trial, who were also treated with serum against the rotation, as it was considered proven by then that the serum had a favourable effect.

Thus, the statistics comprise 484 patients with diphtheria and croup. Diphtheria bacilli were detected in all of them. Of these

239 were treated with the serum,

245 were treated without the serum.”

Translation by Peter Goetzsche


 Johannes Andreas Grib Fibiger (1867-1928)




The editors are grateful to:

Peter Goetzsche, Nordic Cochrane Centre, and Christian Gluud and Dimitrinka Nikolova, Cochrane Hepatobiliary Group, for providing biographical details and a portrait of Johannes Fibiger, and a translation of the key passage.

The Wellcome Trust for making available the portrait of Johannes Fibiger (1867-1928).


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