PAN AMERICAN SANITARY BUREAU

OFICINA SANITARIA PANAMERICANAPuBLiCATioN No. 188 * SEPTEMBER, 1942

The Wild Fire (Pemphigus Foliaceus)of Brazil

Reprinted from Boletín de laOficina Sanitaria Panamericana,

September, 1942

WASHINGTON, D. C.

U. S. A.

FUNCIONARIOSDE LA

OPICINA SANITARIA PANAMERICANA

(OPPICERS 'OY THE PAN AMERICAN SANITARY BUREAU)

DIRECTORDR. HUGH S. CUMMING

Sureon General (Reired), U. 8. Publio H&lMh 8~erI

VICEDIRECTOR

DR. JOAO DE BARROS BARRETOBrasil

CONSEJEROS (COUNSELORS)DR. MIGUEL SUSSINI

Argentina

DR. ANTONIO PEÑA CHAVARRIACosta Rica

OIRECTOR AUXILIAR (ASSISTANT DIRECTOR)DR. EDWARD C. ERNST

Sericio de Sanidad Ptiblica de los Estados Unidoa

SECRETARIO (SECRETARY)DR. ARISTIDES A.'MOLL

8edactor CientifJco, Bdoletín de la Ofcina Sanitaria Panameriocan

VOCALE8 (MEMBERS)

DR, ATILIO MACCHIAVELLO

DR. LUIS MANUEL DEBAYLENicaragua

DR. A. L. BRICEÑO ROSSIVenesudea

DR. DAGOBERTO E. GONZÁLEZPeri

DR, MANUEL MARTINEZ BÁEZM&iico

DR. PEDRO MACHADOCuba

DR. JUAN ANTONIO MONTALVANEcuador

MIEMBROS DE HONOR (HONORARY MEMBERS)

DR. JORGE BEJARANO, Presidente de HonorColombia

DR, CARLOS ENRIQUE PAZ SOLDÁNPertl

DR. LUIS GAITANGuatemala

COMISIONADOS VIAJEROS INGENIEROS SANITARIOS(TRAVELING REPRESENTATIVES) (SANITARY ENGINEERS)DR. JOHN D. LONG SR. EDWARD -D, HOPKINSDR. JOHN R. MURDOCK SR. WALTER N, DASHIELLDR. ANTHONY DONOVANDR. VERNON W. FOSTERDR. JOSEPH S. SPOTO

THE WILD FIRE (PEMPHIGUS FOLIACEUS) OF BRAZIL

One of the reports attracting most attention at the X Pan AmericanSanitary Conference was that on virus diseases, prepared by Dr. G.Travassos and presented by the Brazilian delegation.' Of specialinterest was the paragraph dealing with the form of pemphigus knownin Brazil by the name of fogo selvagem, or wild fire, in which it wasstated that the etiology has been linked with a filterable virus found inthe blood of patients (Lindenberg).2 While it has not yet been pos-sible to verify this thesis,3 much interesting information has been col-lected by Brazilian observers in the last two decades. The problem issufficiently important for the State of Sao Paulo to have established aspecial Service and hospital ("Adhemar de Barros" Institute) for studyof the disease, and the epidemiological picture of its course in Brazilappears to afford a basis for revision of the accepted concepts in regardto it.

Early writers stated that pemphigus foliaceus was "neither epidemic nor con-tagious."4 Others have ignored its existence insofar as any manifestations pecu-liar to the tropics are concerned.S The cause has been attributed to toxins (saidby Ormsby to be the most popular theory), to neuropathic influences, and to theBacillus pyocyaneus (Hazen). s Dermatologists apparently agreo that, whateverits origin, the condition is rare. °

The Brazilian experience contradicts a number of these views. First,all Brazilian authors agree on the contagiousness of fogo selvagem.Second, the disease is far from rare, as is shown by the fact that theSao Paulo Service of Pénfigo Foliáceo (created in September, 1938) had,by June 6, 1941, 500 cases registered, of which from 15 to 20% hadproven fatal. The "Adhemar de Barros" Institute, inaugurated Sep-tember, 1940, had by June of the following year hospitalized 117 cases. 7

Orsini de Castro reported in 1927 that in 15 years, 70 cases of pemphigusfoliaceus had been registered in Belo Horizonte (200,000 inhabitants)8;another figure is 108 in 15 years. In 1937, Vieira reported that in Sáo

i "Actas X Conferencia Sanitaria Panamericana," 1938, p. 103.2 Ibid., and Lindenberg, Adolpho: "Un nouveau point de vue dans l'étude étiologique des derma-

toses," Ann. Dermat. & Syphil., Nov.-Dec., 1938, p. 929.a Travassos, supra (Note 1); and Vieira, Jouo Paulo: "Algumas Pesquizas sobre o "Fogo Selvagem'

no Estado de S. Paulo," Bras. Méd., Aug. 16, 1941, p. 562.4 Montgomery, D. W.: in "Reference Handbook of the Medical Sciences," Wm. Wood & Co., 1917,

Vol. 7, p. 96.5 Manson describes a tropical "pemphigus contagiosus" which does not seem to resemble the pemphi-

gus foliaceus of Brazil, and does not mention the latter (Manson-Bahr, P.: "Manson's Tropical Disease,"

10th ed., 1936, p. 632); Stitt refers only to Manson's "pemphigus contagiosus," classing it as Impetigo

(Strong, R. P.: "Stitt's Diagnosis, Prevention and Treatment of Tropical Diseases," Blakiston, 1942, p.

1602.)6 Ormsby, O. S.: "Diseases of the Skin," Lea and Febiger, 1934, p. 399.

7 Vieira, Note 3.8 Lindenberg, Note 2.

1

2 PAN AMERICAN SANITARY BUREAU

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WILD FIRE

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Pemphigus Foliaceus. (a), (b), (c), Initial outbreak; (d) Invasion period ofthe disease. (Photographs courtesy of J. P. Vieira, Sao Paulo.)

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PAN AMERICAN SANITARY BUREAU

Carlos, Sao Paulo, (population 30,000) there had been 40 cases in 10years9 ; in a Jau fazenda or plantation (population 200) there were eightcases in 10 years; in one ward of a hospital 10 or 15 beds were alwaysoccupied by pemphigus cases. 8 ,9

INCIDENCE OF PEMPHIGUS FOLIACEUS (175 CASES)

90 1888 - 1939

70

50- _10

Date of Onset1868 a 1909 1910 ct 1919 1920 a 1929 1930 a 1939 Date of Onset

Incidence of Pemphigus Foliaceus in Sao Paulo State, Brazil (175 cases).(From the graph by J. P. Vieira, Sao Paulo, 1942)

Although the clinical symptoms of pemphigus foliaceus in Brazilare the same as those found elsewhere, the subjective phenomena(itching, burn ng, acute pain) are much more severe, and have givenrise to the popular name for the condition. The disease occurs in theinterior of Sao Paulo, Minas Gerais, Goiaz, Matto Grosso, and Baía;and has apparently not been reported in the coastal area from Santosto Rio.9 It has a tendency to form endemic foci which are in turn thesources for the formation of new foci.

The first recorded observations of the disease were apparently those of A.Cerqueira, who saw cases in Baía in 1900 and earlier, according to hospital records.The first studies in Sao Paulo State wore those made by Caramurú Paes Leme, whoin 1902 published a thesis in which he confused the disease with Tokelau, an errorlater corrected by L. Gualberto, Lindenberg, O. da Fonseca Filho, J. P. Vieira,and others. At the seventh Brazilian Congress of Medicine and Surgery in 1917,

9 Vieira, J. P.: "Novas contribuiçoes ao Estudo da Pénfigo Foliáceo (Fogo-Selvagem) no Edo. de S.Paulo," 1940.

4

WILD FIRE 5

INCIDENCE OF PEMPHIGUS FOLIACEUS WITH RELATION TO COLOR,SEX, AND NATIONALITY (IN 460 CASES)

NATIONALITY400

20 Et- 200

~~~~~~~~~~~~~O OI0 100

U 2H MMHH U2

I 9U2

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TOTAL NUMBER OF BRAZILIANS TOTAL NUMBER OF FOREIGNEI RS

Incidence of Pemphigus Foliaceus in Sao Paulo State, Brazil, with Relation toColor, Sex, and Nationality (460 cases). (From the graphs by J. P. Vieira,Diretor do ServiVo de Penfigo Foliáceo, Sao Paulo, 1942.)

4O

50

PAN AMERICAN SANITARY BUREAU

Pemphigus Foliaceus. (a) Invasive phase of the disease: (b) Generalizedform; (c) and (d) dystrophic form. (Photographs courtesy of J. P. Vieira, SáoPaulo.)

6

WILD FIRE

B

O

Pemphigus Foliaceus. (a) Severely foliaceus form; (b) Hyperpigmented

type (in a Japanese); (e) Herpetiform type; (d) Dystrophic form, with alopecia.

(Photographs courtesy of J. P. Vieira, Sao Paulo.)

7

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PAN AMERICAN SANITARY BTJREAIT

Aleixo of Minas, Luciano Gualberto of Sáo Paulo, and Fernando Terra of Rioreported on cases of pemphigus. In 1919, U. Paranhos and E. Bertarelli triedunsuccessfully to identify the causative germ (inoculation of liquid from a bullainto the cornea of a rabbit), and also made studies of the leukocytic formula ofthe clinical picture. J. P. Vieira bcgan calling attention to the disease in 1921.There followed the work of Olinto Orsini (thesis, 1929) and Aleixo, who tried toassociate the germ with cocci and motile bacilli. In 1937 Lindenberg expressedhis conviction that the disease was caused by a virus. Other writers on the sub-ject included Artigas, Mourao, Flaviano Silva, Alípio Azevedo, Aranha Campos,Silva Araújo Filho, Werneck Machado, etc.' 0

The characteristic, elementary lesion in fogo selvagem is a serous purulentbulla, often located on the face, thorax, or the legs, and the eruption tends to be-come generalized. There is a period of evening fever, which may become veryhigh and even fatal, though the fatal cases are in the minority. At various pe-riods the disease must be distinguished from Duhring's dermatitis (in which thegeneral health continucs to be good and the localizations differ from those ofpemphigus foliaceus), sub-acute pemphigus with extensive bullae (Brocq's type);true acute infectious pemphigus, and bullous impetigo. Nikolsky's sign is animportant aid in diagnosis; it is always present in pemphigus foliaceus.

The fogo selvagem, once initiated, may develop into one of four types: acute,sub-acute (most common), super-acute (ending fatally after a short period ofillness) or chronic (frustrate; extensively bullous; intensely foliaceous; pustulousand bullous; dystrophic; hyperpigmented; papillomatous or verrucose; erythro-dermic; or herpetiform). In the chronic form there is ankylosis of the largejoints, due to mineral loss and disturbances of the calcium metabolism withsymptoms of osteoporosis. The nails are involved, with change of color (some-times yellowish, as if dipped in iodine-J. P. Vieira's sign) and sometimesbleached and lifeless; they may drop off and are rapidly replaced. Great epi-dermic exfoliation accompanies this process. The nail color change usuallyappears about six months after the onset of the disease. In some cases itching isa predominant symptom, but not generally; the sensation is usually one of warmthor burning. In some cases the generalization of the bullae persists for a longperiod. As the general health improves, the bullae become sparser, larger, andpainful. In addition to notable hyperpigmentation, there is papillomatosis, or athickening of the epidermis, lcsions persisting without complete restoration ofthe skin. On passing the fingers over the cutis of these chronic patients, one findsa roughened condition in the persisting lesions. These, under the microscope,reveal histologic bullae, para-keratose, keratosc, and granulous. Other phe-nomena observed in cases of pemphigus foliaceus in Brazil have been palmer andplantar keratoses, alopecia, papillomatosis of the scalp, pediculate lesions,elephantiasis of the ears due to lymphangitis (first reported by Vieira), andmuscular atrophy. The hypertrophy of the ears is probably due to an associatedinfection. There are also endocrine disturbances, with dystrophy of the organismand physical transformation almost amounting to a change in sex, the diseaserunning a graver course in women than in men. Of 35 male patients in the Ad-hernar de Barros Hospital, 24 showed symptoms of testicular insufficiency. 12of these had testicular retention and 27 out of 36 cases were impotent, five azoo-spcrmic, and four oligiospermic. These changes are not observed in frustrate orinitial forms of the disease. Of 44 women, 41 suffered from amenorrhea. Folicu-lin treatment brought about restoration of menstruation, and some improvement

10 Vieira, J. P.: "Semana de Combate ao Fogo Selvagem," 1939.

WILD FIRE 9

PRINCIPAL LOCALIZATIONS AT BEGINNING OF DISEASE(IN 460 CASES)

150

100'·I ' ra1e3 I I t I I

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AGE AT WHICH THE DISEASE BECAME MANIFEST (IN 460 CASES)

Pemphigus Foliaceus, Sao Paulo State, Brazil. Principal Localizations atBeginning of Disease; Age at which Disease Became Manifest (460 cases). (Fromthe graphs by J. P. Vieira, Sao Paulo, 1942.)

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A

PAN AMERICAN SANITARY BUREAU

1-

Pemphigus Foliaceus. (a) and (b) Facies; (c) Severely foliaceus form; (d) '

Invasion period. (Photographs courtesy of J. P. Vieira, Sao Paulo.)

10

WILD FIRE 11

Pemphigus Foliaceus. (a) Familial pemphigus foliaceus. Left, frustrate

form, right, invasion period; (b) Regression of the disease; (c) Hands of a patient;

(d) Regression (back of patient "b"); (e) Hands of a chronic case (case "f");

(f) Chronic pemphigus foliaceus of 30 years duration. (Photographs courtesy of

J. P. Vieira, Sao Paulo.)

PAN AMERICAN SANITARY BUREAU

in health, in nearly all these cases. Death may ensue from syncope, cardiacinsufficiency, nephritis, an intercurrent disease, and, often, after extensive pleuraleffusions." Vieira recently reported that according to his study of 460 cases ofpemphigus foliaceus, the maximum incidence of the disease was between the agesof 14 and 18. The lowest age of incidence was from 4 to 43 years.'2

The disease is more common in women; 66% of 460 S. Paulo cases. (Of 88cases in the "Adhemar de Barros Hospital" 54% were women; 26 cases werechildren, 11 boys and 15 girls; the youngest was six years old.) Some requirehospitalization in the second month of illness; others have had the disease for asmuch as 10 years before internment; the oldest case in the "Adhemar de Barros"had had it for 27 years."

The ages from 15 to 19 and from 25 to 29 seem to be the most susceptible. Fogoselvagem attacks both natives and foreigners, though most frequently Brazilians:it attacks both whites and blacks, most commonly the former. In Sao Paulo, nocases have been reported in the coastal zone where nutrition is admittedly poor;this would seem to eliminate avitaminosis as a cause.'3 The disease is found in thepurple- or red-earth, sandy-soiled area. In Minas Gerais, the chief foci arethe Charity Hospital area of the Capital and the Minas Triangle, on the Goiazborder; and in Sao Paulo, the north-eastern, north-western and western parts ofthe State. Further north, pemphigus foliaceus has appeared on the borders ofthe Araguaia, and it is frequently found in Mato Grosso. In Sao Paulo, the in-fected zones are generally in the vicinity of streams, where large numbers ofsimulidae are found. Trialoma are also prevalent in some foci, as are bats, bugs,rats, and fleas. Sanitary conditions are always poor. The disease is most com-mon in rural areas, although autochthonous cases have been reported from in-terior towns and cities. Altitudes vary from 530 to 985 meters; two of the townsaffected (Franca and Ribeiráo Preto) have temperatures of from 17.3 to 23.5 C.,2, 9

Experimental work.-Lindenberg, after failing to find a visiblemicrobie cause of pemphigus foliaceus, decided that, in view of theobviously infective nature of the condition, a virus must be responsible,and in 1937, he announced this conviction and the successful experi-mental transmission of the disease in rabbits by injection into the tes-ticle of serum from the blood of pemphigus cases. He'was able to carry

"L Vieira, Notes 9 and 3; Bol. Acad. Nac. Med., June, 1941, p. 33. José Ricardo Guimaráes (An. PaulMed. & Cir., 245, mzo. 1942), in a preliminary report on 18 cases, observed that all had contracted thedisease before puberty, that 17 showed disturbances in growth (stature), only one being apparentlynormal, that 4 had been backward in statural growth before the disease, 6 had been at a stationary stageat its onset; and 7 showed a stationary condition in regard to height after the onset of the disease. Thedwarfism appears to be pituitary. Improvement was shown after endocrine treatment. Commentingon this paper, Vieira observed that the maximum incidence of pemphigus foliaceus was between theages of 14 and 18; and Artom considered its apperance in infancy as one of the characteristics differen-tiating it from European pemphigus. José Aranha Campos in the same journal (p. 249) remarked thatsince 1938 he had been observing that certain fogo selvagem cases revealed a marked tendency to endo-crinological disturbances. Family studies showed in some cases an apparently hereditary dispositionto such disorders, including hyperpituitarism, and thyroid-pituitary deficiency. Wihen the discasebegan before puberty, the usual changes of that stage did not occur, the victims remaining children,without development of the gonads, but without cretinism. Studies in women revealed cases in thosewho had borne children and in those who had not. Endocrinological anomalies of the dental arch werealso seen. Vieira added that it was probable that mal-nutrition was a factor, inasmuch as pemphigusattacked the rural zones, where nutrition was poorer.

"1 An. Paul. Med. & Cir., 246, mzo. 1942.1" However, José Aranha Campos (An. Paul. Med. Cir., 250, mzo. 1942) reported cases with nutritional

disturbances such as hypopituitary, hypothyroid, and hypogonad obesity, often of family type and oc-curring before onset of the disease.

12

WILD FIRE

the virus through several passages in animals and to transmit the dis-ease to guinea pigs.8 Vieira and collaborators have not been able toconfirm these results, but are still experimenting along this line.7

Vieira and his coworkers have also made extensive studies of the chemicalcomposition of the blood in pemphigus foliaceus. Among 48 or 50 cases, acidosiswas found in certain patients; an increase in plasma was always seen; the proteinindex was always inverted, etc. The low alkaline reserve suggests the desirabil-ity of a special diet. Of 86 hemocultures, 70 were negative; 13.9% were positivefor streptococcus; 4.6% positive for staphylococcus; streptococci isolated in-cluded two of the inert group; one, non-virulent, of the viridans; nine ofthe hemolytic (five virulent, two non-virulent, two undetermined); staphylococci:four strains, all albus.7

Treatment.-To date cures (10%) have been obtained only whenenergetic treatment has been carried on from the very early stages offogo selvagem. Vieira declares that the essentials are hygiene, anti-septic baths, quinine by mouth (one gram daily), and protection of theskin with boricated vaseline. Experiments with arsenicals and sul-fanilamides have not been satisfactory and are not recommended.14

About 15% of cases may become well spontaneously, but the benefitsof hospitalization are nevertheless very great. ?7

Control.-Control measures recommended are: widespread knowledgeof the symptoms so that early treatment is assured; confinement of thesick in special hospitals; home isolation of frustrate forms; intensiveeducational work; prevention of the entrance of carriers into healthyzones. By decree of September 17, 1938, the State of Sao Paulocreated the Pemphigus Foliaceus Service (Serviço de Pénfigo Folidáceo),and a hospital (the "Adhemar de Barros" Institute) was opened inSeptember, 1940 for pemphigus cases. The Ministry of Education ofBrazil was authorized in 1939 to spend 128,400,000 for the completionof a Hospital in Ponta Pora, Mato Grosso, for cases of this disease (60beds, to be increased gradually to 100 beds).'5. 6

14 Vieira, J. P.: Bol. Acad. Nac. Med., June, 1941, p. 33. However, in an earlier paper, Vieira reports

that chaulmoogra apparently showed some efficiency, as did "Germanine-Bayer" in frustrate forms andsome early cases. In more advanced cases the arsenicals and other powerful drugs are not only useless,but harmful. He then suggested, on the basis of experience, quinine dihydrochloride, one gram dailyorally, and ampules, intramuscularly, of a special preparation of the Cooíde de Lara Institute, madeaccording to the following formula: camphorated peanut oil at 10% . .. . Icc; ethyl chaulmoogra, cold,0.5 cc; cinnanlate of benzine, 0.05 cc; cholesterin, 0.05 cc., all sterilized by tyndallization at 60 C. Inthe beginning of treatment, he used the cold esters of cod liver oil and peanut oil, together with daily bathsof potassium permanganate (0.15 gm for each packet for a batb). If there are pustulous lesions, yellowoxide of mercury (1%) is used locally; tle mucosae must be examined to guard against stomatitis. Later,boricated vaseline may be used on the skin. A diet low in chlorides is recommenided, as well as the dailyuse of fifteen grams of sodium bicarbonate after meals. (Novas contribuivoes, etc ," 1940, p. 157.) Aranha(An. Paul. Med. & Cir., 250, mzo. 1942) likewise calls attention to the contraindications in the case ofarsenicals. Commenting, Vieira remarked that any drug, even sulfanilamide, was apt to be harmfulduring the dystrophic stage. He believed that arsenic could be a good treatment for frustrate forms.

Is Folha Méd., April 5, 1939, XVII.16 The most recent work on the subject, J. P. Vieira's "Peénfigo Foliáceo e Siudromo de Senear-

Uscher," was not yet available for consultation.

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Supplies. 4 pages.No. 149.-Half a Century of Medical and Public Health Progress. 20 pages.No. 150.-Medio Siglo de Adelanto en Medicina y Sanidad. 22 páginas.No. 151.-IV Pan American Conference of National Directors of Health (Final Act). 8 pages.No. 152.-Medical and Public Health Journals of Latin America (Revistas de Medicina y Sanidad

de la América Latina). 51 páginas.No. 153.-Annual Report of the Director of the Pan American Sanitary Bureau: 1939-1940. 34 pages.No. 154.-Reacción a la tuberculina. 6 páginas.No. 155.-Informe Anual del Director de la Oficina Sanitaria Panamericana: 1939-1940. 39 páginas.No. 156.-Pan American Public Health Quiz. 14 pages.No. 157.-Epitome del Segundo Suplemento (1939) de la Farmacopea E.U. XI. 20 páginas.No. 158.-Public Health and Medicine in Stamps of the Americas. 7 pages.No. 159.-Some Pan American Pioneers in Public Health. 5 pages.No. 160.-Scientific Institutiona in Latin America: Part I. 47 pages.No. 161.-Indices Sanitarios Panamericanos. 3 páginas.No. 162.-IV Conferencia Panamericana de Directores Nacionales de Sanidad: Resumen de su

labores. 29 páginas.No. 163.-Huertos escolares. 7 páginas.No. 164.-Clave diagnóstica para la clasificación en columna (tabulación) de las causas de morbidad.

18 páginas.No. 165.-Contribuciones al estudio de la peste bubónica en el nordeste del Brasil. 331 páginas.No. 166.-Health and Living Conditions in Latin America. 11 pages.No. 167.-The Work of the Pan American Sanitary Bureau in Relation to Child Welfare. 4 pages.No. 168.-La enseñanza médica en Estados Unidos. 22 páginas.No. 169.-El lanzallamas en la lucha antipestosa. 9 páginas.No. 170.-El entierro de la basura bajo un recubrimiento eficaz en Cristóbal, Zona del Canal. 11

páginas.No. 171.-Fourth Pan American Conference of National Directors of Health: Resumé. 26 pages.No. 172.-Pautas mInimas para el saneamiento de las minas del Perú en lo relativo a viviendas. 8

páginas.No. 173.-La fiebre amarilla en las Américas. 15 páginas.No. 174.-Diagnóstico y tratamiento de ciertas afecciones de los tropicos. 12 páginas.No. 175.-Housing and Hospital Projects of Latin American Social Security Systems. 15 pages.No. 176.-Annual Report of the Director of the Pan American Sanitary Bureau: 1940-1941. 39 pages.No. 177.-Public Health in the Americas. 68 pages.No. 178.-Tratamiento de las quemaduras. 4 páginas.No. 179.-Informe Anual del Director de la Oficina Sanitaria Panamericana.No. 180.-La mosca. 9 páginas.No. 181.-Child Nutrition in Latin America. 17 pages.No. 182.-Tratamiento de las afecciones venéreas en el ejército de Estados Unidos. 9 páginas.No. 183.-Técnicas y procedimientos para las encuestas o censos dietéticos. 6 páginas.No. 184.-Tratamiento de las heridas de guerra. 4 páginas.No. 185.-Alphabetical List of Medical and Publio Health Journals of Latin America. (Lista Alfa-

bética de las Revistas de Medicina, incluso Sanidad y Ciencias Aliadas, de la AmericaLatina.) 60 páginas.

No. 186.-Manual de Bromatologia. 611 páginas.No. 187.-Reglamento del Servicio Nacional Antipestoso del Perú. 3 páginas.No. 188.-The Wild Fire (Pemphigus Foliaceus) of Brazil. 13 pa~ges.

Adresser toutes les demandes a M. le Directeur de l'Office Sanitaire Panaméricain.Dirijanse todos los pedidos al Director de la Oficina Sanitaria Panamericana.Todos os pedidos devem ser enderezados ao Diretor da Reparticao Sanitária Panamericana.Address all requests for publications to the Director of the Pan American Sanitary Bureau.

THE PAN AMERICAN SANITARY BUREAU is an independent internationalpublic health organization. It was created by the Second International Amer-

ican Conference (1901-1902), organized by the First Pan American SanitaryConference (1902), and reorganized by the Sixth (1920). It is governed by aDirecting Council elected, together with the Director, at each Pan AmericanSanitary Conference, and supported by annual quotas contributed pro rata by allthe American Republics. The Bureau is interested primarily in the preventionof the international spread of communicable diseases, and also in the maintenanceand improvement of the health of the people of the 21 American Republics. Underthe provisions of the Pan American Sanitary Code (1924), it has become the centerof coordination and information in the field of public health, in the AmericanRepublics. It also acts as a consulting body at the request of national healthauthorities, carries on epidemiological and scientific studies, and publishes amonthly Bulletin, as well as other educational material. Pan American HealthDay is celebrated annually on December 2 in all American Republics. Addressall correspondence to the Director of the Pan American Sanitary Bureau, Wash-ington, D. C.