Table 2.
Human Experiments on Viral Hepatitis in Children at Willowbrook. Results of Seven Trials Which Pointed to Existence of Two Hepatitis Viruses are Defined. The Clinical, Epidemiological and Immunological Characteristics of MS-1- and MS-2–Related Diseases are Shown.
| Trials | Date | Inoculum | Route | Subjects | Results |
|---|---|---|---|---|---|
| First Trial [F T] | Sept 23, 1964 | WSP-5 | Oral | 13 NAS [11 EI & 2 C] | H=10 of 11 EI (6 had IH). AH = 1 of 2 C IP = 30–36 d in 6, 51–58 d in 3, 125 d in1 |
| Second Trial [S T] | March 26, 1965 | WSP-5 | IM | 13 FT [10 EI & 3 C] | H = 6 out of 10 EI (4 out of 6 had SA:- Sch, Mas, Wac, Mir]. IP = 38–102 d |
| Third Trial [T T] | Nov 22, 1965 | MS-1 | IM | 14 NAS [8 EI & 6 C] | H = 7 of the 8 EI (1 had IH); IP = 31–53 d H = 6 of 6 C (I had IH); IP = 46–85 d |
| Fourth Trial [Fi T] | August 24, 1965 | MS-2 | IM | 14 NAS [9 EI & 5 C] | H = 7 of 9 EI (1 had IH); IP = 41–69 d AH = 2 of 5 C; IP = 155–231 d |
| Fifth Trial [Ft T] | Feb 17, 1966 | MS-2 (Ham) + μ-globulin |
Oral | 9 NAS [6 EI & 3 C] | AH = 5 of 6 EI; IP = 64–209 d All 3 C had no hepatitis |
| Sixth Trial [Si T] | May 27, 1966 | MS-2 (Ham & Pel) | Oral | 6 NAS | AH = 5 of 6 EI; IP = 88–108 d |
| Seventh Trial [St T] | March 28, 1966 | MS-1 | IM | 16 [8 T T & 8 Fi T] | H = 0 of 8 T T (Immunity vs. MS-1) H = 8 of 8 Fi T (no immunity vs. MS-2)) |
| MS-1 Hepatitis |
MS-2 Hepatitis |
|
|---|---|---|
| Infectious hepatitis | Serum hepatitis | |
| Incubation Period | 15–50 days | 43–180 days |
| Transmission | Oral + Parenteral | Oral + Parenteral (IP longer with oral) (Si T vs. Fi T) |
| Contact spread | High (T T) | Low |
| Transaminitis | Sharp and short lasting | Gradual and prolonged |
| Immunity | No cross immunity between MS-1 & MS-2. Homologous immunity following MS-1 & MS-2 infections. | |
| Clinical profile | Indistinguishable | |
| IH/AH | 10/19 | 6/21 |
| Bilirubin levels | 1–3 mg/dl | 1–3 mg/dl |
| Duration icterus | 1–10 d (5d) | 1–10 d (5d) |
| Weight gain | 0.9–3.6 kg (25 weeks) | 1.8–2.7 kg (30 weeks) |
| Krugman et al JAMA 1967;200:365–373. | ||
WSP-5= Willowbrook Serum Pool from 27 patients collected 3–7 days before jaundice; NAS= Newly Admitted Subjects; EI = Experimentally Infected; C=Controls; IP= Incubation Period; SA= Second Attack; H= Hepatitis; IH= Icteric Hepatitis; AH = Anicteric Hepatitis; MS-1 = Sample of subject Mir immediately prior to First Attack; MS-2 = Sample of subject Mir immediately before the Second Attack.