CHAPTER XI
Yaws
James H. Dwinelle, M.D.
Yaws, or frambesia, is a specific infectious, contagious, tropical disease caused by the Treponema pertenue. A primary granulomatous lesion appears at the site of inoculation, followed by similar secondary generalized skin lesions. Hyperkeratotic plantar lesions frequently occur in the secondary stage also. Some cases go on to a late or tertiary stage with lesions which break down with considerable destruction to the skin and underlying bone
While this disease is limited by the Tropics of Cancer and Capricorn, it is endemic only in hot, damp, rural areas. It is common in the West Indies, the northern part of South America, and French Equatorial Africa. In the Far East, it is widespread in Siam, the Malay States, the Netherlands Indies, Ceylon, certain areas of India, Burma, Indochina, the East Indies, the Philippines, and other Pacific islands, especially the Samoa Islands. In Haiti, the incidence of the disease among the rural population is said to be 80 percent.
Yaws is essentially a disease of childhood, and 60 percent of the children in Haiti acquire the disease before puberty. Children in tropical countries wear very little clothing and almost never wear shoes. The unprotected skin is subject to cuts and abrasions through which the spirochetes may easily penetrate. Crowding and lack of personal hygiene favor the spread of the disease by direct contact or indirectly from infected articles. According to Kumm,1 a tiny fly, Hippelates pallipes, may carry the spirochete from an infected wound to an open cut on another person's skin. Open sores, when uncovered, are often teeming with these flies.
Immunity is slow in developing as compared with syphilis. Superinfections can take place in up to 3 years, but after 10 years almost complete immunity has developed. There is no known racial immunity to the disease.2
Yaws is essentially a disease of rural areas. Where it is prevalent, syphilis is rare, while the reverse is true in cities. There is considerable evidence that one disease confers an immunity to the other.3
1Kumm, H. W., Turner, T. B., and Peat, A. A. : The Duration of Motility of the Spirochaetes of Yaws in a Small West Indian Fly-Hippelates pallipes Loew. Am. J. Trop. Med. 15 : 209-223, March 1935.
2Strong, Richard P.: Stitt's Diagnosis, Prevention and Treatment of Tropical Diseases. 7th ed. Philadelphia : The Blakiston Co., 1944, pp. 392-407.
3(1) Sch?bl, O., and Miyao, I. : Immunologic Relation Between Yaws and Syphilis. Philippine J. Sc. 40 : 91-109, September 1929. (2) Turner, T. B. : Studies on the Relationship Between Yaws and Syphilis. Am. J. Hyg. 25 : 477-506, May 1937.
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The following control measures have been found desirable: Avoidance of direct contact with people who have open sores and with articles which have become contaminated from discharges from these sores; keeping parts of body subject to injury covered, especially the feet and legs; prompt treatment of all cuts and abrasions of the skin with a suitable antiseptic dressing to exclude flies and prevent infection; attention to good soap and water hygiene; and isolation and treatment of cases.
Army personnel should avoid natives in endemic areas, and those natives necessary as employees should be examined carefully to see that they are free from disease.
HISTORICAL NOTE
Yaws was first described by Oviedo in the 16th century. In 1881, Char louis carried out several inoculation experiments to prove the contagiousness of the disease. In 1891, Dr. Numa R?t published a monograph giving quite an accurate and detailed description of yaws.4 In February 1905, Castellani, working in Ceylon, discovered the causative organism which he later named Treponema pertenue.5 He also produced the disease in monkeys. The next advance was made in 1911 when Nichols employed salvarsan in the treatment of the disease.6 Since the discovery of salvarsan and the later pentavalent and trivalent arsenicals, these drugs have been used by the Government in the treatment of natives in the Philippines, American Samoa, the Canal Zone, and other territories administered by the United States where yaws was prevalent.
Yaws was not a military problem in World War I because the active arena was for the most part outside the tropics.
During the American military occupation of Haiti, the National Public Health Service of Haiti, under the direction of U.S. Navy Medical Corps personnel, carried out an extensive campaign against yaws. Large numbers of the rural population were given treatment. Extensive research was carried out as to the epidemiology, etiology, and pathology of, and immunity to, the disease.
In Jamaica, the Jamaica Yaws Commission, under the International Health Division of the Rockefeller Foundation, carried out careful studies of the disease from 1932 to 1937. Systematic treatment with regular followup observations, including serology, was instituted. It was found that the estimated attack rate in the total population for one control area had been reduced by 89.9 percent after 3 years.
4R?t, Joseph Numa : Yaws; Its Nature and Treatment ; An Introduction to the Study of the Disease. London : Waterlow and Sons. 1891.
5Castellani, A.: On the Presence of Spirochaetes in Two Cases of Ulcerated Parangi (Yaws). Brit. M.J. 2: 1280, 11 Nov. 1905.
6Nichols, H. J. : Further Observations on Certain Features of Experimental Syphilis and Yaws in the Rabbit. J. Exper. Med. 14 : 196-216, August 1911.
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EXPERIENCE IN WORLD WAR II
During World War II,U.S. troops were stationed in many places in the tropical zone where yaws was endemic or epidemic. In order to prevent infections among the soldiers, contacts with the natives were discouraged, open wounds were kept dressed, and insect control was practiced.
Army medical officers in the Pacific had an opportunity to observe many cases of yaws. They set up clinics for the natives on most of the islands in military areas. The success of this procedure was reflected by the very low incidence of the disease among military personnel (table 31).
TABLE 31.-Admissions for yaws in the U.S. Army, by theater or area and year, 1942-45
Theater or area | 1942-45 | 1942 | 1943 | 1944 | 1945 | |||||
Number | Rate | Number | Rate | Number | Rate | Number | Rate | Number | Rate | |
Continental United States | 5 | 0 | --- | 0 | 4 | 0 | 1 | 0 | --- | 0 |
Overseas: | ||||||||||
| North America | 1 | 0 | 1 | .01 | --- | 0 | --- | 0 | --- | 0 |
| Middle East | 1 | .01 | --- | 0 | 1 | .02 | --- | 0 | --- | 0 |
| Pacific Ocean areas | 5 | 0 | --- | 0 | 5 | .02 | --- | 0 | --- | 0 |
| Southwest Pacific | 20 | .01 | 1 | .01 | 1 | .01 | 3 | 0 | 15 | .01 |
| Other areas | --- | 0 | --- | 0 | --- | 0 | --- | 0 | --- | 0 |
| Total overseas | 27 | 0 | 2 | 0 | 7 | 0 | 3 | 0 | 15 | 0 |
| Total Army | 32 | 0 | 2 | 0 | 11 | 0 | 4 | 0 | 15 | 0 |
In spite of the low rates of infections in U.S. troops, the staff of the Preventive Medicine Service, Office of the Surgeon General, because of its interest in the control of infectious diseases among the civilian populations, decided to investigate the possibility of utilizing penicillin for the control of yaws in such regions. After considering various locations where adequate numbers of yaws patients might be made available for study, arrangements were made with the Division of Health and Sanitation, Office of the Coordinator of Inter-American Affairs, and with the Government of the Republic of Haiti to conduct such experiments in that country.
In December 1944, the chief of the Preventive Medicine Service, Brig. Gen. James S. Simmons, accompanied by Lt. Col. (later Col.) Thomas H. Sternberg, MC, Chief, Venereal Disease Control Division, Lt. Col. Douglass W. Walker, MC, Executive Officer, Preventive Medicine Service, and Lt. Col. Charles R. Rein, MC, Chief, Division of Serology, Army Medical Center,
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visited Port-au-Prince, Haiti, for a series of conferences with the author, who was chief of a field party and director of the American Sanitary Commission to Haiti, and with the President of the Republic of Haiti and members of his Department of Health. As a result, a cooperative field research project was set up in Haiti to determine the value of penicillin administered in various ways for the treatment and control of yaws.
At that time, there was very little information concerning the effect of penicillin on yaws. Mahoney, Arnold, and Harris7 had demonstrated the effectiveness of penicillin therapy in early syphilis, and there were a few scattered references to the use of the drug in cases of yaws. It therefore seemed important to make a careful study of the problem, and especially to determine whether a method of administration might be developed by which yaws could be controlled with a single injection. The status of knowledge at that time is indicated by the following brief review:
Whitehill and Austrian8 reported the treatment of 17 cases of primary and secondary yaws among Fijians. They used total doses of approximately 500,000 Oxford units of penicillin in aqueous solution, giving 15,000 Oxford units intramuscularly every 4 hours for 5 or 6 days. Dark-field examinations became negative in 16 hours after treatment, and most lesions healed in 1 week. No cases were rendered permanently seronegative with the Kahn test within 20 weeks, the extent of their followup period at the time of publication. Lofgren9 reported the treatment of a white sailor who had contracted yaws on American Samoa. He used a total dose of 1,500,000 Oxford units of penicillin in aqueous solution over a period of 12 days. The dark-field examination became negative in 18 hours. All secondary lesions healed in 5 days, and the primary lesion, which had been ulcerated, in 13 days. The Kahn test became negative 5 weeks after treatment. Da Cunha, Area Le?o, Nery Guimar?es, and Cardoso10 treated seven cases of yaws in Brazil with total doses of 9,600 to 52,000 Oxford units of penicillin, and obtained clinical cures in from 12 to 44 days. They stated that serologic reactions (Wassermann test) became negative 60 days after treatment in all cases. Da Cunha and Area Le?o treated an additional five cases in Brazil with similar results. Findlay, Hill, and Macpherson11 reported the treatment of 24 cases of yaws in children in Africa with 50,000 to 100,000 Oxford units of penicillin in aqueous solution over a period of 12 to 24 hours. Clinical cures were obtained in 6 to 7 days. Reversal of the Kahn test in two of the primary cases was attained in 7 days. In two of the secondary cases, the Kahn test remained
7Mahoney, J. F., Arnold, R. C., and Harris, A.: Penicillin Treatment of Early Syphilis; a Preliminary Report. Am. J. Pub. Health 33 : 1387-1391, December 1943.
8Whitehill, R., and Austrian, R.: Treatment of Yaws With Penicillin. Bull. U.S. Army M. Dept. (No. 86) 3 : 84-91, March 1945.
9Lofgren, R. C.: Yaws Treated With Penicillin; Report of Case. U.S. Nav. M. Bull. 43: 1025?1030, November 1944.10Foreign Letters (Brazil): Penicillin in the Treatment of Yaws (Spirochetosis). J.A.M.A. 126: 1163, 30 Dec. 1944.
11Findlay, G. M., Hill, K. R., and Macpherson, A. : Penicillin in Yaws and Tropical Ulcer. Nature, London 154 : 795-796, 23 Dee. 1944.
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positive after 6 weeks. Tompsett and Kauer12 reported five eases of yaws among Melanesians on New Guinea treated with total doses of 250,000 to 400,000 Oxford units of penicillin aqueous solution over a period of 2 to 4 days. The dark-field examination became negative in 24 hours, and the lesion healed in from 1 to 3 weeks. No serologic tests were made after treatment.
The survey of the literature seemed to indicate that the use of penicillin in the treatment of yaws invariably resulted in complete clinical cure, even in relatively small doses. On the other hand, only a few of the cases were observed to attain seronegativity with the Kahn or Wassermann test after treatment. Therefore, the value of penicillin in the treatment of yaws had not been definitely established.
Special Study in Haiti
A cooperative study was made by the Preventive Medicine Service of the Army, the Division of Health and Sanitation of the Office of Inter-American Affairs, and the Government of the Republic of Haiti to determine the effectiveness of penicillin for the treatment and control of yaws.
An account of the study appears in the final report of 12 months' followup observations.13 Five hundred patients with primary and secondary yaws infections were treated. Clinical and serologic followup observations were made at monthly intervals for 1 year. The patients were divided into three series as follows:
Series A.-Two hundred patients were hospitalized and given a total of 1,200,000 units of penicillin sodium in aqueous solution each over a period of 4 days. They received 30 intramuscular injections of 40,000 units each, 1 injection every 3 hours during both day and night. All patients received the same total dose, regardless of age.
Series B.-One hundred and fifty-one patients were treated on a 2-day ambulatory schedule with penicillin calcium in peanut oil with 4.8 percent beeswax by weight (300,000 units per cubic centimeter). The dosage was graded down for children. Patients from 6 to 12 years of age received 600,000 units; those aged from 13 to 16 years, 900,000 units; and those 17 years of age or older, 1,200,000 units. The drug was given by intramuscular injection in divided doses 24 hours apart.
Series C.-One hundred and forty-nine patients were treated on a 1-day ambulatory schedule with penicillin calcium in oil with beeswax. The dosage was graded down for children as in series B. The drug was given by intramuscular injection in divided doses 10 or 12 hours apart. Figures 72, 73, and 74 illustrate the results in three patients 1 week after treatment.
A medical history was taken, and blood for serologic testing was collected, from each patient before treatment. Physical examination was limited
12Tompsett, R. R., and Kauer, G. L.: Penicillin Treatment of Early Yaws. Am. J. Trop. Med. 25: 275-276, May 1945.
13Dwinelle, J. H., Sheldon, A. J., Rein, C. R., and Sternberg, T. H.: Evaluation of Penicillin in the Treatment of Yaws. Final report. Am. J. Trop. Med. 27: 633-641, September 1947.
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to close observation of the skin and mucocutaneous borders. Blood serum was placed in vials containing powdered Merthiolate (thimerosal), 1 mg. per cubic centimeter of serum, and shipped by air to the Division of Serology, Medical Department Professional Service Schools, Army Medical Center, Washington, D.C. Fewer than 1 percent of the specimens arriving there were unsatisfactory for testing as a result of bacterial contamination. A battery of serologic tests was performed on each specimen: Kline diagnostic, Kline exclusion, a new microflocculation test employing cardiolipin antigen, Mazzini, quantitative Kahn, and quantitative Kolmer. Only the quantitative Kahn titers were reported in this paper. The other tests employed in serodiagnostic battery were more sensitive than the Kahn and gave higher titered reactions, but in all tests there was a similarity in the general pattern and in the amount of serologic improvement.
Followup clinical and serologic observations were made at monthly intervals on patients in series A and at 3-month intervals on those in series B and C. In a number of instances, blood specimens were lost, the tubes were broken in shipment, or the quantities of serum were insufficient for testing. In these instances, although a clinical examination had been made on each patient during the month concerned, the clinical observations have not been included in this analysis since a corresponding serologic observation could not be made.
The clinical improvement of patients in series A during and immediately following treatment was rapid and remarkable. Joint pains disappeared in from 24 to 48 hours; plantar and palmar "crab" lesions became painless in from 48 to 72 hours. Dark-field examinations gave negative results in from 8 to 10 hours. Stained sections made from biopsy material showed numerous
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spirochetes for as long as 12 hours, only an occasional isolated spirochete for from 12 to 22 hours, and none thereafter. Both primary and secondary lesions began to dry up in 24 hours. Epithelium grew in from the periphery and completely covered most lesions in 3 or 4 days. The great majority of patients who returned for observation 1 month after treatment showed complete healing of all lesions. A few ulcerated primary lesions with secondary bacterial infections were still draining pus at this time. Most of these healed spontaneously between the first and second month after treatment. Since patients in series B and C were treated on an ambulatory basis, it was not possible to follow their immediate clinical courses. However, on the first followup observation 3 months after treatment, these patients, in most instances, showed complete healing of all lesions. Histological studies were made on biopsy specimens taken before and after treatment on 10 patients in series A.
No severe toxic reactions were encountered. Approximately one-half of the patients in series A had a rise in temperature from 100? to 104? F., 2 to 8 hours after treatment was started. All temperatures gradually returned to normal in from 10 to 12 hours. Approximately one-fifth of the patients showed a brief secondary elevation of temperature on the third, fourth, and fifth days of treatment.
Clinical response to treatment was uniformly excellent, but serologic response was not. Fifty-four cases were dropped from time original series of 500 because the pretreatment or posttreatment serums were either unsatisfactory for testing or not obtained. Only 16.6 percent of the remaining 446 patients were considered to show "apparent cure." An additional 75.1 percent showed "satisfactory progress," totaling 91.7 percent. The remaining 8.3 percent of the patients showed "unsatisfactory progress." In the latter group were included cases of "reinfection," "clinical relapse," and "serologic relapse."
The proportion of "apparent cures" in the group of hospitalized patients (those treated over a 4-day period with penicillin in aqueous solution) was 26.7 percent. This was a high proportion when compared with the 11 percent and 6.4 percent of apparent cures in two groups treated for 2 days and 1 day respectively with penicillin in oil with beeswax on an ambulatory basis. However, there was a correspondingly higher proportion of cases showing satisfactory progress in the latter two groups of patients so that when one combines cases of apparent cure with those showing satisfactory progress the total percentage is almost identical in the three groups of patients, 90.2, 92.9, and 92.8, respectively.
The results of these studies indicate that penicillin was the most effective and speedy therapeutic agent to quickly render yaws patients noninfective and was suitable for mass treatment of natives in any area. Penicillin given
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over a longer period produces a serologic cure as well as a clinical cure. The serologic response is much slower than that of the corresponding stage of syphilis.
It is appreciated that followup observation over a period of 10 to 12 months after treatment is not sufficient to permit a comprehensive evaluation of the efficacy of penicillin in the treatment of yaws. Also, it is not possible to make a strict comparison of the results of treatment of penicillin in aqueous solution with penicillin in oil with beeswax, because of the difference in treatment schedules employed. However, it is felt that penicillin is probably the present-day drug of choice in the treatment of yaws, and that penicillin in oil with beeswax is of considerable public health value in countries such as Haiti where large numbers of patients must be treated on an ambulatory basis in rural clinics. Its use can be expected to control cutaneous lesions successfully and therefore prevent the spread of infection.
After the completion of these field studies, a program of yaws eradication was started in Haiti. The help of the World Health Organization was subsequently obtained in carrying this eradication program forward.
