Postgrad Med J: first published as 10.1136/pgmj.38.437.140 on 1 March 1962. Downloaded from

POSTGRAD. MED. J. (I962), 38, 140

CLINICAL TYPES OF AS SEEN IN AN EPIDEMIC

GUILHERME RODRIGUES-DA-SILVA, M.D. (Salvador) JUAN J. IANGULO, M.D. (Havana) Fellow in Epidemiologist S. Ivo RABELLO, M.D. (Recife) Fellow in Epidemiology Instituto , Sao Paulo, Brazil

THE clinical picture of smallpox has been the by variola or , and in all instances subject of numerous publications, some of which the previous exposure to these had deserve special mention like the fundamental occurred too long a time before for justifying the work of Ricketts and Byles (I9I0) and the studies present, positive complement fixation; (c) labora- of Marsden (1948) and of Dixon (I948). Dixon's tory confirmation of diagnosis was made in i6 out report is outstanding because of the improved of the 53 cases in the epidemic; (d) in 48 cases classification of clinical types proposed. The diagnosis was established through standard clinical potentialities of this classification in smallpox and epidemiological criteria, while in the five cases studies became apparent during a sharply limited not seen the epidemiological data strongly sug- epidemic occurring in a semi-isolated borough of gested a variolous xetiology; (e) no case was ob- Sao Paulo City and they are remarked in the served among the rather numerous household present paper. contacts who had suffered from smallpox in the past, not even a variola sine eruptione; (f) theby copyright. Clinical Material majority of cases had suffered from . Collection of clinical data was aimed at classi- fication of the symptomatology according to the Observations on Clinical Types types proposed by Dixon (1948). Twenty cases The distribution of the cases studied among were seen while still sick and followed up, I2 of clinical types of smallpox is presented in Table i. whom had been admitted to the Isolation Hospital The 48 cases examined were classified as: Type i, ' Emilio Ribas '. Twenty-eight additional cases 'purpura variolosa '; type 4, 'benign confluent'; were examined soon after disappearance of the type 6, 'discrete'; type 7, ' mild'; type 8,

. From these patients fairly reliable data ' abortive'; and type 9, ' variola sine eruptione '. http://pmj.bmj.com/ on symptomatology could retrospectively be ob- Type 2, ' malignant confluent '; type 3, ' ma- tained which were checked by cross-questioning, lignant semi-confluent ', and type 5, 'benign physical examination and inquiries among their semi-confluent ' were not observed. Type 6, ' dis- relatives. The remainder of the 53 cases com- crete ', was the predominant clinical type-68.7% posing the epidemic were not seen and they are of the cases. not included in this report. In an attempt to Type 9, 'variola sine eruptione' cases, were support clinical diagnosis vwth etiological (labora- classified as such when they showed a syndrome tory) and epidemiological data, skin identical with that of the prodromal period of on September 30, 2021 by guest. Protected material from eight cases was obtained for virus undoubted cases; its duration was similar and its isolation (Downie and Dumbell, 1947), blood was onset occurred after the same time interval. collected for titration (Lederle Labora- Finally, diagnosis of four cases of variola sine tories Division, 1954) from ten cases and 37 con- eruptione was confirmed by serological tests whose tacts, and information on previous smallpox, significance was increased by a strongly suggestive chickenpox and was obtained from vaccinal history. All four cases showed a i : 64 each case. titre in the complement fixation test while the Identification of the responsible for last vaccination had been made more than i, 20, the epidemic could be established beyond any 20 and 40 years before, respectively. Symp- reasonable doubt through the following evidence: tomatology of type 9 cases was apparently not (a) Only variola virus was isolated and identified milder than that of the prodromal period in in skin lesion specimens and all the latter were patients with exanthem and the duration of the positive; (b) the antibody response of cases and corresponding periods was essentially the same. of household contacts indicated a recent infection The age distribution of clinical types is also Postgrad Med J: first published as 10.1136/pgmj.38.437.140 on 1 March 1962. Downloaded from March I962 RODRIGUES-DA-SILVA AND OTHERS: Clinical Types of Smallpox 141

TABLE I DISTRIBUTION OF 48 SMALLPOX CASES AMONG CLINICAL TYPES Total Age-group (Years) Clinical Types* No. % I 4 6 7 8 9

0- 7 ...... 2 21 1 2 1 27 56.3 8-i5 ...... I 7 I 2 II 22.9 16+ ...... I 5 I 3 10 20.8 Total Number ...... 3 33 I 4 6 48 % 2.1 6.3 68.7 2.1 8.3 i I2.5 100.0 *According to Dixon's classification (Dixon, 1948) found in Table i. Type 6, 'discrete' smallpox, the palms, where they were rather numerous predominated in the pre-school age-group, 0-7 although very small. On the other hand, the years, while the more benign clinical types 8 and 9 lower half of the body exhibited a pock-exanthem were more frequent among individuals 8 or more with no purpuric lesion. A centrifugal distribution years of age. This fact apparently contradicts of pocks was apparent and these were the known higher severity of infection among better defined on the legs and feet. Pocks were older age-groups. However, the vaccinal history velvety, rather flat, clear, and apparently did not explains this finding since most school-age and become pustules. The exanthem on the lower adult cases had a previous vaccination while most half of the body was rather profuse although con- of the pre-school cases were not vaccinated. fluence of pocks was only noticed in a few places. Pocks were rare on the soles of the feet. The by copyright. TABLE 2 onset and disappearance of the purpuric DISTRIBUTION OF CLINICAL TYPES IN RELATION TO coincided with the pock-exanthem. Diagnosis of * this striking case was confirmed by isolation and Years after identification of variola virus from two specimens, Clinical Without successful vaccination each consisting of pooled content of several Typet Vaccinationt vesicles. Besides, the patient had never had 5+ I-5 0-I smallpox or vaccination 'take' and two cases

- . occurred in the same household before hers and

one case thereafter. The illness began with http://pmj.bmj.com/ 4 3 and headache to which were added chills 6 I and intense , all lasting three days and dis- 30 2 appearing at the onset of the exanthem. The 7I latter was manifest first on the abdomen and face; it then appeared on the legs and later on the rest of the body. Intense toxwemia and mental symp- 9 3 3 toms like clouding of consciousness and anxiety were observed in this case who, incidentally, on September 30, 2021 by guest. Protected * The vaccinal history of five cases was unknown. t After Dixon's (1948) classification. recovered with no other than a t Including those unsuccessfully vaccinated. palpebral cellulitis. During convalescence there was intense desquamation, leaving pinkish areas The only patient showing type i, purpura which contrasted with the normal colour of the variolosa, was a 30-year-old Negro woman. This patient's skin. Bleeding time, time, case exhibited a striking characteristic. The upper Rumpel-Leede (Hess) test and platelet count were half of the body showed numerous large purpuric negative for haemorrhagic diatheses, but these spots of irregular shape and well differentiated examinations were, unfortunately, made after dis- contour. Large areas of skin-sloughing up to appearance of the exanthem. 12 x 8 cm. in size were observed on the face, The epidemic was characterized by a well- shoulders, chest, abdomen, back and buttocks. marked predominance of benign clinical types, in On the upper half of the body pocks were only such a way that 38 out of the 42 cases whose seen on the face, chest and palms, but these exanthem was classified could be identified as lesions were ill-defined and very scanty except in cases of the so-called or variola minor Postgrad Med J: first published as 10.1136/pgmj.38.437.140 on 1 March 1962. Downloaded from

I42 POSTGRADUATE MEDICAL JOURNAL March I962z

(Tables I and 2). This is the usual pattern of hibited alastrim-like eruptions. Three other babies smallpox epidemics in the state of Sao Paulo and, presented a severe clinical picture while their apparently, in the rest of Brazil. Clinicians with mothers showed mild syndromes. long experience in smallpox have noticed that (c) The epidemiological data disclosed a chain several decades ago admissions to the Isolation of contagion stemming from the two introducers Hospital 'Emilio Ribas' of Sao Paulo City in- of infection in the borough and giving rise to cluded a strikingly larger proportion of severe widely varying clinical pictures. Incidentally, cases (Pereira-Barreto). none of the introducers showed a picture of variola major. Comment (d) The case of type i, purpura variolosa, who Dixon's classification permits standardizing clinically was a typical case of variola major clinical features which in turn allows a quanti- (variola vera), belonged to an intra-household tative comparison between epidemics as well as outbreak where three cases preceded and another between individual cases. Incidentally, com- one followed hers. None of these contact cases parison of the clinical type of an infecting case was of variola major, particularly that apparently with that of his infected contacts has a direct infected by her. The latter contact exhibited a bearing on a much discussed subject, namely, the type 8, ' abortive' variola. relationships between smallpox and the so-called (e) The relationship of variola sine eruptione to alastrim. The clinical findings made in the previous vaccination (Table 2). In this regard, present study as well as the epidemiological and four of these six cases had their diagnoses con- laboratory data do not support the pretended firmed by laboratory evidence. separation of alastrim and smallpox as two different (f) The relationship between vaccination and diseases (Jorge, 1924; Marsden, 1948). Quite on 'mild' and 'abortive' eruptions (types 7 and 8). the contrary, the evidence obtained supports, One out of the ii cases exhibiting type 7, 8 or 9 without being conclusive, the contrary thesis, that was unvaccinated, while 34 of the 37 cases show- is, the identity of alastrim and 'true' smallpox. ing types I, or 6 were unvaccinated (Table 2).

4 by copyright. The controversy on this point has lasted several A very similar relationship between vaccination decades and, apparently, has not been settled. and clinical type was noticed by Dixon (1948). The remarks on the significance of the data col- Incidentally, many of Dixon's cases were typical lected in the present study were derived from the of variola major and the epidemic cannot be con- following facts and arguments: sidered as an outbreak of alastrim. (a) Dixon's classification of clinical types, unlike (g) The behaviour, on isolation and serial the classifications found in textbooks and treatises, passaging on the chick embryo chorioallantois, of represents a logical arrangement where a gradation the virus strain recovered from the case of pur- in intensity is ably presented. This classification pura variolosa was not different from the behaviour was the resultant of a rather large body of accurate of the strains isolated from cases clinically belong- http://pmj.bmj.com/ field observations and its reproducibility has been ing to the so-called alastrim nor has a difference confirmed in the clinical and epidemiological been noticed when working with other strains in experience of the present authors who have this laboratory. observed hundreds of smallpox cases in hospitals and in the field. Observations on Individual Signs and (b) A gradation in the severity of syndromes Symptoms and isolated manifestations was evident in the The cases studied exhibited a definitely biphasic whole series of cases in the sharply limited epi- clinical picture in which the first phase consisted on September 30, 2021 by guest. Protected demic studied. This gradation was particularly of systemic manifestations while the second phase evident in the intra-household outbreaks observed corresponded to an exanthem. Table 3 sum- during the study of cases and which actually com- marizes the characteristics of the prodromic period posed the epidemic. In most households, several in 46 patients showing, at the same time, the cases occurred at intervals, suggesting contagion frequency of each individual sign or symptom. from one index case, and these secondary cases Sudden onset was noted in 930% ofcases. Headache, showed differences in the severity of their clinical chills and/or fever composed the initial symp- pictures which at times were strikingly marked, tomatology in most patients. Fever was noted in not only among themselves but also in relation to all cases during the prodromal period and it was the index case. In this regard, Dixon's comparison usually preceded by chills, while the temperature of the clinical type of I3 mothers with the type rise was rapid, reaching suddenly 390 or 40° C. of their infants under i year of age deserves (I02°-I04 F.). Fever was of the continuous type, mention. While three mothers showed clinical had a duration of three days (three days + o.5) types proper of variola major, their babies ex- and usually disappeared on the first day of the Postgrad Med J: first published as 10.1136/pgmj.38.437.140 on 1 March 1962. Downloaded from

March I962 RODRIGUES-DA-SILVA AND OTHERS: Clinical Types of Smallpox exanthem. Prostration, headache, anorexia, back TABLE 4 pains, general , chills and vomiting were MAIN CLINICAL CHARACTERISTICS OF THE EXANTHEM IN the other more common symptoms and signs 42 SMALLPOX CASES 0/ during the prodromal period (Table 3). Symp- ,o toms related to the digestive system, such as PLACE OF APPEARANCE OF EXANTHEM nausea, vomiting, diffuse abdominal pain and Face ...... 95.2 diarrhcea, were observed among patients not older Trunk ...... 2.4- Legs ...... 2.4 than 8 years, except for one, a 38-year-old case. BODY DISTRIBUTION Centrifugal ...... 78.6 Indefinite ...... 21.4 TABLE 3 REGIONAL MONOMORPHISM .. .. 97.6 PREVALENCE OF COMPOSING THE PRESENCE OF POCKS IN PALMS AND SOLES PRODROMIC PERIOD AMONG 46 CASES OF SMALLPOX* Palmar pocks ...... 95-2 Plantar pocks ...... 85.7 MODE OF ONSET PUSTULATION FEVER Sudden ...... 93-4 Present I...... 1.9 Absent ...... 88. i Gradual ...... 6.6 INITIAL SYMPTOMS AND SIGNS DURATION OF EXANTHEM: Headache ...... 71.1 Mean i8.5 days; s.d. 3.5 Chills ...... 5 I. I *Six of the 48 patients examinated exhibited no Fever ...... 35.5 eruption. General malaise ...... 17.7 Pain in the back ...... 4.4 Prostration ...... 4.4 cases pocks were found in the palms, while plantar Vomiting 2...... 2 pocks were not observed in six patients. The Generalized myalgia ...... 2.2 mean duration of the exanthem, from onset to SYMPTOMATOLOGY total shedding of crusts, was I8.5 days ± 3.5. Fever ...... 100.0 Prostration ...... 95-7 The pustulation fever, uncommon in alastrim

Headache ...... 84.8 cases, occurred in only five cases (i2%), from the by copyright. Anorexia ...... 67.4 third to the fifth day. It is possible, however, that Pain in the back ...... 58.7 this was not the true frequency since many cases General malaise ...... 56.5 were nursed at was not Chills ...... 50.0 home where temperature Vomiting ...... 41.3 efficiently recorded. Severe toximia accompany- Nausea ...... 26. I ing the. eruption, typical of variola major, was Generalized myalgia ...... I.6 noticed only in the case of purpura variolosa. Sore throat I...... 5.2 Diffuse abdominal pain ...... 9 Mortality was nil, all patients recovering, in- Cough ...... 4.3 cluding the case of purpura variolosa. The only Diarrheea ...... 4.3 complication observed was palpebral cellulitis Clouding of consciousness .. .. I.2 resulting from secondary infection which appeared http://pmj.bmj.com/ DURATION .. Mean 3.o days; s.d. 0.5 in the latter case. No antibiotic was employed in * Data from two other cases were incomplete. the cases studied. Treatment consisted of symp- tomatic and local measures protective The onset of the exanthem coincided with of skin lesions. disappearance of systemic manifestations in all cases. Table 4 summarizes the main character- Summary istics of the exanthemic phase in 42 cases. In the Dixon's classification of the clinical types of majority of patients the exanthem first appeared smallpox was employed in the study of a sharply on September 30, 2021 by guest. Protected on the face. In five cases observed since onset of limited epidemic occurring in a semi-isolated the prodromic period, it was possible to follow borough of Sao Paulo City. Observations are the classical course of macule, papule, crust and made on the advantages of this classification in . In the first day of the rash macules and smallpox studies since it allows comparison, on a papules were observed, and from the second day quantitative basis, between epidemics as well as on vesicles became apparent. The latter lasted between individual cases. The identity of alastrim three or four days and then pus was apparent. and smallpox is discussed in the light of the Duration of pustules was approximately two weeks clinical and epidemiological findings, particularly when crusts ensued. Regional monomorphism of the relationship between vaccination and clinical skin lesions was observed in all but one case. type and the comparison between the clinical type Umbilication of pustules was rarely observed. of the infecting case and that of his infected The body distribution of the exanthem was contacts. The prevalence of relevant signs and definitely centrifugal in 79% of the 42 cases whose symptoms of smallpox in the study group is exanthem was classified. In all but two of these presented. Postgrad Med J: first published as 10.1136/pgmj.38.437.140 on 1 March 1962. Downloaded from

I44 POSTGRADUATE MEDICAL JOURNAL March I962

REFERENCES DIXON, C. W. (1948): Smallpox in Tripolitania, 1946; Epidemiological and Clinical Study of 500 Cases, including Trials of Penicillin Treatment, J. Hyg. (Lond.), 46, 35I. DOWNIE, A. W., and DUMBELL, K. R. (1947): Isolation and Cultivation of Variola Virus on Chorio-allantois of Chick Embryos, Y. Path. Bact., 69, I89. JORGE, R. (1924): Alastrim and Variola, Lancet, ii, I3I7; ii, I366. Lederle Laboratories Division, A.C.C. (1954): ' Rickettsial and Viral Antigens ', Leaflet IO M-IO-54, New York. MARSDEN, J. P. (1948): Variola Minor, Bull. Hyg. (Lond.), 23, 735. PEREIRA-BARRETO, L.: personal communication. RICKETTS, T. F., and BYLES, J. B. (I9IO): 'The Diagnosis of Smallpox', New York: Funk and Wagnalls. by copyright. http://pmj.bmj.com/ on September 30, 2021 by guest. Protected