**3. Results**

#### *3.1. Study Group*

This study took place 58 years after the outbreak. Thirty people contacted the authors. Of these, 27 had personally experienced the outbreak and met inclusion criteria for the study group. Two responders provided information about friends who had developed Royal Free disease, and one told us about developing ME subsequent to the outbreak. Nineteen participants who provided a phone number were interviewed by phone. Participants' data are given in Table 1.


#### *3.2. Descriptions of the Outbreak*

The study group confirmed that the outbreak started in July of 1955 and lasted several months. Importantly, staff in all five hospitals of the Royal Free Group were affected. People from the local community outside the hospital with symptoms of the disease were also seen in the casualty (Accident and Emergency) departments of the Royal Free and other London hospitals. The main Royal Free hospital in Gray's Inn Road was closed to new admissions for three months due to a lack of healthy staff. Affected hospital staff were isolated at the Liverpool Road branch of the hospital, or were sent home. The epidemic was covered widely in national newspapers. The disease affected men and women, and both young and older, junior and senior staff. Very few existing hospital inpatients were affected. Most of those affected were nurses. Two study participants described secondary cases following close contact with a patient. The incubation period was "4–5 days" in one and "a few days" in the other. No secondary cases were reported following immediate visual exposure to a patient.

#### *3.3. Descriptions of the Illness*

Six study group participants developed the disease. Their experiences are compiled in Table 2.


**Table 2.** Patients who developed Royal Free disease.

\* The electromyogram (EMG) showed changes that were associated with Royal Free disease.

> The study group described a biphasic illness. Initially, there were prodromal symptoms and signs (see Table 2). Tender enlarged posterior cervical glands were a defining diagnostic feature. Initial symptoms persisted into the second phase of the illness. A few days after illness onset, diverse muscular and neurological manifestations developed in many patients. Muscular pain and tenderness occurred in the neck, back, and/or limbs. Reported neurological manifestations included ptosis, difficulty with focusing eyes, hemiparesis, mono-paresis, weakness of hand muscles, foot drop, various sensory losses, and hyperesthesia. Other reported symptoms included difficulty urinating, anorexia, nausea, and vomiting. Hyperventilation was not reported. Patients often delayed seeking medical care until several days after illness onset. Symptom severity ranged from mild to very severe. Myalgia was sometimes extreme, causing patients to cry with pain. A putative diagnosis of abortive Royal Free disease was proposed for patients with mild symptoms who lacked physical signs. The study group also reported that there were some patients lacking physical signs, who were thought to be neurotic or to have exaggerated their symptoms.

> Many patients were diagnosed clinically without blood testing, but in patients who were tested, leukopenia, or lymphocytes typical of viral diseases were found. Leucocytes, characteristic of glandular fever (infectious mononucleosis) were not found. Paul Bunnell tests were negative except in a patient diagnosed with glandular fever. Cerebro-spinal fluid testing did not show changes typical of poliomyelitis. Electromyograms (EMGs) (carried out in some patients) showed unspecified findings regarded as characteristic of the disease. Possible causal pathogens were sought but none identified.

> Treatment was symptomatic. Severe muscle pain sometimes required the strongest analgesics. Complete bed rest while symptoms lasted (except for walking to the toilet) was insisted on, followed by slow mobilization. Convalescence was advised for the same period of time as the duration of symptoms because an early return to work could precipitate a relapse. Patients were hospitalized for two weeks and upwards. A few very severely ill

patients, some with paralyzses, were hospitalized for over six months and were widely investigated for many bizarre symptoms.

The time for recovery varied from a few days in those with the possible abortive disease to several weeks or months in others. Prolonged time to recovery also occurred in patients isolated at home. Some affected staff were only able to return to work part-time, and in several individuals, an unusual fatigue persisted for up to two to three years. Some patients appeared to recover but later relapsed. One patient committed suicide. Patients with persisting paralysis were transferred to a rehabilitation unit. A number of patients remained disabled and were unable to return to their previous occupations. We received a report of one patient in whom ME/CFS symptoms persisted long term.

Initially, a glandular fever (infectious mononucleosis)-like illness was diagnosed, but this was rejected because diverse neurological signs occurred and Paul Bunnell tests were negative. A poliomyelitis diagnosis was also rejected because muscle weakness clearly differed from the paralysis seen in poliomyelitis and lumbar puncture testing was inconclusive. The question of hysteria was raised as some patients were thought to be neurotic. However, since a large number of patients were seriously ill with significant physical signs, the study group indicated that most hospital staff believed that the outbreak was an infectious illness.

#### *3.4. Long Term Health Effects Attributed to the Illness*

We were told of five people who developed a persisting paralysis. They included one person each with ptosis, weakness of one hand, foot drop, wasting of hypothenar muscles of both hands, and severe weakness of one leg that required arthrodesis of the knee and ankle.
