- Email: [email protected]
The treatment of climatic bubo (lymphogranuloma venereum) in the African Negro
658 TraNSACTIONS OF T~m ROYALSOCIETYOF TROPICAL MEDICINE AND HYGIENE. Vol. 46. No. 6. November, 1952.
T H E T R E A T M E N T OF C L I M A T I C BUBO ( L Y M P H O G R A N U L O M A V E N E R E U M ) IN T H E AFRICAN N E G R O BY
R. R. WILLCOX, M.D. St. Mary's Hospital, W.2. At the present time the oral antibiotics aureomycin, chloramphenicol and terramycin are being tried in the treatment of lymphogranuloma venereum. WRmHT et al. (1948), employing 10 to 20 mg. of aureomycin daily by intramuscular injection, to a total dose of 160 to 1000 mg., had good results in eight patients with buboes and in three others with proctitis and, in a later series of 35 cases (1948a) in which the dose had been increased, this success was maintained. Likewise ALERC~T (1950) reported successful results in four out of six patients treated with 1 gramme of aureomycin daily for 1 week; BENHAMOUet al. (1949) and WIi~LCOX (1950) each had success in one case. On the other hand ROBINSONet al. (1950) stated that aureomycin administered intramuscularly in doses from 0.56 to 3.6 gramme over 4 to 15 days, or as 3.6 to 38 gramme given orally during 5 to 15 days, yielded disappointing results in nine patients. Others, too, have reported less encouraging findings. WAMMOCKet al. (1950) treated 17 patients with 5.25 to 85.0 gramme of aureomycin orally. Of those in whom the lesions had been present for less than 6 months the results Were good only in one, fair in four, and bad in one. The remaining 11 had had their lesions for 2 to 38 years and all had rectal stricture. Nine tolerated the drug and the results were considered good in six and poor in three. A later report by the same t e a m (GREENBLATTet al., 1950) states that there were only four successes in 13 early cases treated, and it is considered that the most favourable results may be obtained in the late cases, usually in females with rectal stricture and proctitis. Chloramphenicol was also tried and is considered inferior to aureomycin. There was no improvement in four early cases, and in only one of five late cases so treated. Using terramycin ANDREA (1950) gave 100 capsules over 7 days to four female patients with rectal stricture due to lymphogranuloma venereum, with improvement in all.
R. a . WlLLCOX
659
Penicillin has not been generally reported as being strikingly effective in lymphogranuloma venereum although in my experience it has not been unsuccessful. WILLCOX(1946) treated 25 Gold Coast Africans with what today would be regarded as extremely small doses of penicillin in oil-beeswax (100,000 to 200,000 units), and 15 recovered without additional measures. Two European patients given 1 million units over 3 days also responded. Similarly, in Southern Rhodesia, WILLCOX (1950) treated four cases of climatic bubo with single injections of 2,400,000 units of procaine penicillin with 2 per cent. aluminium monostearate. The bubo of one proceeded to fluctuation and was aspirated; all patients were discharged from hospital in an average of 7 days. Penicillin in high concentrations has also been shown to influence yolk suspensions of the virus, whereas streptomycin has no effect (HAMRE and RAKE, 1947). RAm~ (1948), carrying his studies further, confirmed the uselessness of streptomycin, and streptothricin also, and showed that the sulphonamides, while frequently effective, may produce the carrier state. He suggested that sulphamerazine was the most effective member of this group. The virus of lymphogranuloma venereum has been isolated from bubo pus, excised nodes, penile lesions and even from the blood and cerebrospinal fluid. The virus was noted in two untreated patients 95 days after the onset of the disease by HEYMn_~ et al. (1947). It could not usually be seen after sulphathiazole had been given for 2 to 3 weeks, although it was recovered from the lymph node of one patient 4 months after receiving no less than 120 gramme. Lymphogranuloma venereum has a world-wide distribution with a predeliction for the tropics: it is very prevalent in Africa. It was reported as common in Eritrea by MAFVI (1948) where it responded to sulphonamides. It is also extremely prevalent in West Africa, especially in Freetown, Sierra Leone, where rectal stricture in the female is not infrequently encountered (WILLCOX, 1946). In Southern Rhodesia, where other venereal diseases, especially chancroid, are rife in the native, the disease is less common than in other parts of the continent. Of 300 consecutive venereal diseases patients, seen in the Native Infectious Diseases Hospital, Salisbury, 11 such cases were diagnosed (WILLCOX, 1949). Whatever success the oral antibiotics may have in the treatment of the condition they are still very costly and, as they become available, they will for many years be reserved for more serious diseases. The fact that high doses of penicillin are apparently effective in climatic bubo of the African eliminates diagnostic worries in areas in which penicillin is being applied to the masses with genital sores. Syphilis, chancroid, gonorrhoea and lymphogranuloma venereum will all benefit, and the only venereal diseases which are unlikely to be cured are granuloma inguinale, which is relatively uncommon, and non-specific urethritis which, in comparison with the other often disabling diseases, is still regarded as trivial by the African. Although lymphogranuloma venereum may produce proctitis, rectal stricture,
660
TREATMENT OF C L I M A T I C BUBO I N AFRICAN NEGROES
esthiom~ne, and other severe complications in the female, in the male African native it is usually seen in the relatively mild form of climatic bubo. That the sulphonamides are capable of curing the majority of cases of climatic bubo may be Seen from the experience of treating 120 cases at Accra in the Gold Coast during 1944. CLIMATIC BUBO:
120 CASES TREATED ON THE GOLD COAST
O f 120 cases of climatic b u b o 54 were left sided, 48 were right sided and in 18 the infection was bilateral. A small herpetiform sore, or traces of it, was seen, or a history of it obtained, in about o n e - q u a r t e r of the cases, and the inguinal, and/or occasionally the femoral, l y m p h glands became swollen and tender within 7 to 70 days. These, at first shotty and tender, usually enlarge, become m a t t e d together, and f o r m multilocular abscesses which burst and m a y subsequently leave persistent sinuses which discharge a milky fluid. I n this series only a short course of sulphonamides, as 5 g r a m m e daily for 4 to 5 days, was employed. A t the end of this time, if the glands were still tender, anthiomaline - - an a n t i m o n y preparation - - was given in two ml. doses on alternate days for up to four to five doses, or until the condition had subsided. Fluctuant glands were aspirated as required. I f these measures failed a second course of sulphonamides was administered combined with fever therapy in the f o r m of intravenous injections of 50 and 100 million organisms, respectively, of T . A . B . vaccine given on the 2nd and 4th days. N o local treatment, apart f r o m aspiration of those buboes showing fluctuation, was given to the groins unless there was a sinus or an open lesion, in which case sulpbonamide p o w d e r was applied locally. I n a few cases there was a persistent inguinal sinus after the glands themselves had apparently become inactive. If this did not dry up after the second course of sulphonamides and fever, the sinus was infiltrated with local anaesthetic, probed, and laid bare w i t h scissors, after which time the w o u n d was packed with B.I.P.P. or sulphonamide powder and allowed to granulate. O f the 120 cases, 80 received sulphanilamide, 30 sulphadiazine and 10 sulphapyridine. T h e short course of sulphonamide was immediately successful in 60 (50 p e r cent.), while 60 had one or m o r e doses of anthiomaline in addition. I n 24 instances the buboes had to be aspirated, and in four they had burst spontaneously prior to admission to hospital. T w e n t y two of the aspirations were p e r f o r m e d within 5 days of c o m m e n c i n g treatment, indicating that further progression is unlikely after sulphonamide therapy has been fully established. I n only 13 of the 120 patients was a second course of sulphonamides c o m b i n e d with fever therapy considered necessary. Frei tests were p e r f o r m e d in 42 of these cases with 35 positive results. While u n d e r treatment evidence of arthritis appeared in two cases, in one of the knee and in the other of the hand. W h e t h e r this was due to l y m p h o g r a n u l o m a venereum, to yaws which was extremely prevalent in the area, or to some other cause, is not known. T h e average time before the 120 patients were fit for discharge f r o m hospital was 9.1 days (extremes 4 and 32). T h e patients, all of w h o m were African soldiers, were then r e t u r n e d to their units stationed in the area. T h e clinic was the only one to which they could return. T h e r e were only eight known relapses (6.6 per cent.) ocurring within 3 to 56 days after discharge: in six the lesions were on the same side, and in two on the opposite side. All but three of these received one or m o r e injections of anthiomaline in addition to the sulpha drugs.
Thus the treatment given proved completely adequate for the bulk of the patients seen. Later the anthiomaline was abandoned and the sulphonamide course extended to 7 days.
R. R. WILLCOX
661
SUMMARY AND CONCLUSIONS
(1) Lymphogranuloma venereum is a common condition in the African Negro. (2) Although cases of proctitis, rectal stricture, and esthiom6ne-like lesions may be encountered in females, and scrotal oedema in males, the disease in the African male usually runs the relatively benign course of climatic bubo. (3) Climatic bubo may be influenced favourably by aureomycin, terramycin and possibly chloramphenicol, but in Africa these oral antibiotics are at present too expensive, and have other more important priorities. (4) Climatic bubo, as chancroid, may respond to penicillin and the condition, therefore, can be included in any mass treatment campaigns employing single injections of procaine penicillin with aluminium monostearate when administered without precise diagnosis. It, too, is a relatively expensive treatment for the individual. (5) Cheaper than all the antibiotics and yet effective, and therefore the most satisfactory drug to use on mass scale in Africa for cases of climatic bubo which have been competently diagnosed, are the sulphonamides. (6) One hundred and twenty cases of climatic bubo seen in the Gold Coast and treated with sulphonamides and anthiomaline are described. T h e r e were only eight (6.6 per cent.) known relapses. REFERENCES ALERGANT, C. D. (1950). Lancet, 1, 950. ANDI~A, F. (1950). Trab. Soc. portug. Derm., 8, 238.
BENHAMOU, E., DESTAINC, F., GAUTHIER,J. & SORREL, G. (1949). Paris, 65, 832-7.
Bull. Soc. Mdd. H@.
GREENBLATT, R. B., WAMMOCK,V. S., CHEN,C. H., DIENST,R. B. & WEST,R. M. (1950). J. vener. Dis. Inform., 31, 45. HAMRE, D. & RAISE, G. (1947). J. infect. Dis., 81, 175. HEYMAN, A., WALL, M. J. & BEESON,P. B. (1947). Amer. J. Syph., 31, 81. MAVl~I, M. (1948). Arch. ital. Sci. med. colon. Parasit., 29, 52. RAKE, G. (1948). Amer. J. trop. Med., 28, 555. ROBINSON, R. C. V., ZHEUTLIN,H. E. C. & TRICE, E. R. (1950). Amer. J. Syph., 34, 67.
WAMMOCK,V. S., GREENBLATT,R. B., DIENST, R. B., CHEN, C. H. & WEST, R. M. (1950). J. invest. Dermat., 14, 427-34. WILLCOX,R. R. (1946). Post Grad. reed. J., 22, 96. ---(1946a). Brit. J. vener. Dis., 22, 63. (1949). Report of a Venereal Diseases Survey of the African in Southern Rhodesia. South Rhodesian Govt., p. 17. - (1950). Nature, Lond., 166, 466. ---(1950a). J. R. Army reed. Cps., 94, 126. V~TRIGHT,L. T., SANDERS,M., LOGAN,M. A., PRIGOT,A. & HILL, L. M. (1948). J. Amer. -
-
reed. Ass., 138, 408.
--
,
,
,- -
&- -
(1948).
Ann. N.Y. Acad. Sci., 31, 318.
T H E T R E A T M E N T OF C L I M A T I C BUBO ( L Y M P H O G R A N U L O M A V E N E R E U M ) IN T H E AFRICAN N E G R O BY
R. R. WILLCOX, M.D. St. Mary's Hospital, W.2. At the present time the oral antibiotics aureomycin, chloramphenicol and terramycin are being tried in the treatment of lymphogranuloma venereum. WRmHT et al. (1948), employing 10 to 20 mg. of aureomycin daily by intramuscular injection, to a total dose of 160 to 1000 mg., had good results in eight patients with buboes and in three others with proctitis and, in a later series of 35 cases (1948a) in which the dose had been increased, this success was maintained. Likewise ALERC~T (1950) reported successful results in four out of six patients treated with 1 gramme of aureomycin daily for 1 week; BENHAMOUet al. (1949) and WIi~LCOX (1950) each had success in one case. On the other hand ROBINSONet al. (1950) stated that aureomycin administered intramuscularly in doses from 0.56 to 3.6 gramme over 4 to 15 days, or as 3.6 to 38 gramme given orally during 5 to 15 days, yielded disappointing results in nine patients. Others, too, have reported less encouraging findings. WAMMOCKet al. (1950) treated 17 patients with 5.25 to 85.0 gramme of aureomycin orally. Of those in whom the lesions had been present for less than 6 months the results Were good only in one, fair in four, and bad in one. The remaining 11 had had their lesions for 2 to 38 years and all had rectal stricture. Nine tolerated the drug and the results were considered good in six and poor in three. A later report by the same t e a m (GREENBLATTet al., 1950) states that there were only four successes in 13 early cases treated, and it is considered that the most favourable results may be obtained in the late cases, usually in females with rectal stricture and proctitis. Chloramphenicol was also tried and is considered inferior to aureomycin. There was no improvement in four early cases, and in only one of five late cases so treated. Using terramycin ANDREA (1950) gave 100 capsules over 7 days to four female patients with rectal stricture due to lymphogranuloma venereum, with improvement in all.
R. a . WlLLCOX
659
Penicillin has not been generally reported as being strikingly effective in lymphogranuloma venereum although in my experience it has not been unsuccessful. WILLCOX(1946) treated 25 Gold Coast Africans with what today would be regarded as extremely small doses of penicillin in oil-beeswax (100,000 to 200,000 units), and 15 recovered without additional measures. Two European patients given 1 million units over 3 days also responded. Similarly, in Southern Rhodesia, WILLCOX (1950) treated four cases of climatic bubo with single injections of 2,400,000 units of procaine penicillin with 2 per cent. aluminium monostearate. The bubo of one proceeded to fluctuation and was aspirated; all patients were discharged from hospital in an average of 7 days. Penicillin in high concentrations has also been shown to influence yolk suspensions of the virus, whereas streptomycin has no effect (HAMRE and RAKE, 1947). RAm~ (1948), carrying his studies further, confirmed the uselessness of streptomycin, and streptothricin also, and showed that the sulphonamides, while frequently effective, may produce the carrier state. He suggested that sulphamerazine was the most effective member of this group. The virus of lymphogranuloma venereum has been isolated from bubo pus, excised nodes, penile lesions and even from the blood and cerebrospinal fluid. The virus was noted in two untreated patients 95 days after the onset of the disease by HEYMn_~ et al. (1947). It could not usually be seen after sulphathiazole had been given for 2 to 3 weeks, although it was recovered from the lymph node of one patient 4 months after receiving no less than 120 gramme. Lymphogranuloma venereum has a world-wide distribution with a predeliction for the tropics: it is very prevalent in Africa. It was reported as common in Eritrea by MAFVI (1948) where it responded to sulphonamides. It is also extremely prevalent in West Africa, especially in Freetown, Sierra Leone, where rectal stricture in the female is not infrequently encountered (WILLCOX, 1946). In Southern Rhodesia, where other venereal diseases, especially chancroid, are rife in the native, the disease is less common than in other parts of the continent. Of 300 consecutive venereal diseases patients, seen in the Native Infectious Diseases Hospital, Salisbury, 11 such cases were diagnosed (WILLCOX, 1949). Whatever success the oral antibiotics may have in the treatment of the condition they are still very costly and, as they become available, they will for many years be reserved for more serious diseases. The fact that high doses of penicillin are apparently effective in climatic bubo of the African eliminates diagnostic worries in areas in which penicillin is being applied to the masses with genital sores. Syphilis, chancroid, gonorrhoea and lymphogranuloma venereum will all benefit, and the only venereal diseases which are unlikely to be cured are granuloma inguinale, which is relatively uncommon, and non-specific urethritis which, in comparison with the other often disabling diseases, is still regarded as trivial by the African. Although lymphogranuloma venereum may produce proctitis, rectal stricture,
660
TREATMENT OF C L I M A T I C BUBO I N AFRICAN NEGROES
esthiom~ne, and other severe complications in the female, in the male African native it is usually seen in the relatively mild form of climatic bubo. That the sulphonamides are capable of curing the majority of cases of climatic bubo may be Seen from the experience of treating 120 cases at Accra in the Gold Coast during 1944. CLIMATIC BUBO:
120 CASES TREATED ON THE GOLD COAST
O f 120 cases of climatic b u b o 54 were left sided, 48 were right sided and in 18 the infection was bilateral. A small herpetiform sore, or traces of it, was seen, or a history of it obtained, in about o n e - q u a r t e r of the cases, and the inguinal, and/or occasionally the femoral, l y m p h glands became swollen and tender within 7 to 70 days. These, at first shotty and tender, usually enlarge, become m a t t e d together, and f o r m multilocular abscesses which burst and m a y subsequently leave persistent sinuses which discharge a milky fluid. I n this series only a short course of sulphonamides, as 5 g r a m m e daily for 4 to 5 days, was employed. A t the end of this time, if the glands were still tender, anthiomaline - - an a n t i m o n y preparation - - was given in two ml. doses on alternate days for up to four to five doses, or until the condition had subsided. Fluctuant glands were aspirated as required. I f these measures failed a second course of sulphonamides was administered combined with fever therapy in the f o r m of intravenous injections of 50 and 100 million organisms, respectively, of T . A . B . vaccine given on the 2nd and 4th days. N o local treatment, apart f r o m aspiration of those buboes showing fluctuation, was given to the groins unless there was a sinus or an open lesion, in which case sulpbonamide p o w d e r was applied locally. I n a few cases there was a persistent inguinal sinus after the glands themselves had apparently become inactive. If this did not dry up after the second course of sulphonamides and fever, the sinus was infiltrated with local anaesthetic, probed, and laid bare w i t h scissors, after which time the w o u n d was packed with B.I.P.P. or sulphonamide powder and allowed to granulate. O f the 120 cases, 80 received sulphanilamide, 30 sulphadiazine and 10 sulphapyridine. T h e short course of sulphonamide was immediately successful in 60 (50 p e r cent.), while 60 had one or m o r e doses of anthiomaline in addition. I n 24 instances the buboes had to be aspirated, and in four they had burst spontaneously prior to admission to hospital. T w e n t y two of the aspirations were p e r f o r m e d within 5 days of c o m m e n c i n g treatment, indicating that further progression is unlikely after sulphonamide therapy has been fully established. I n only 13 of the 120 patients was a second course of sulphonamides c o m b i n e d with fever therapy considered necessary. Frei tests were p e r f o r m e d in 42 of these cases with 35 positive results. While u n d e r treatment evidence of arthritis appeared in two cases, in one of the knee and in the other of the hand. W h e t h e r this was due to l y m p h o g r a n u l o m a venereum, to yaws which was extremely prevalent in the area, or to some other cause, is not known. T h e average time before the 120 patients were fit for discharge f r o m hospital was 9.1 days (extremes 4 and 32). T h e patients, all of w h o m were African soldiers, were then r e t u r n e d to their units stationed in the area. T h e clinic was the only one to which they could return. T h e r e were only eight known relapses (6.6 per cent.) ocurring within 3 to 56 days after discharge: in six the lesions were on the same side, and in two on the opposite side. All but three of these received one or m o r e injections of anthiomaline in addition to the sulpha drugs.
Thus the treatment given proved completely adequate for the bulk of the patients seen. Later the anthiomaline was abandoned and the sulphonamide course extended to 7 days.
R. R. WILLCOX
661
SUMMARY AND CONCLUSIONS
(1) Lymphogranuloma venereum is a common condition in the African Negro. (2) Although cases of proctitis, rectal stricture, and esthiom6ne-like lesions may be encountered in females, and scrotal oedema in males, the disease in the African male usually runs the relatively benign course of climatic bubo. (3) Climatic bubo may be influenced favourably by aureomycin, terramycin and possibly chloramphenicol, but in Africa these oral antibiotics are at present too expensive, and have other more important priorities. (4) Climatic bubo, as chancroid, may respond to penicillin and the condition, therefore, can be included in any mass treatment campaigns employing single injections of procaine penicillin with aluminium monostearate when administered without precise diagnosis. It, too, is a relatively expensive treatment for the individual. (5) Cheaper than all the antibiotics and yet effective, and therefore the most satisfactory drug to use on mass scale in Africa for cases of climatic bubo which have been competently diagnosed, are the sulphonamides. (6) One hundred and twenty cases of climatic bubo seen in the Gold Coast and treated with sulphonamides and anthiomaline are described. T h e r e were only eight (6.6 per cent.) known relapses. REFERENCES ALERGANT, C. D. (1950). Lancet, 1, 950. ANDI~A, F. (1950). Trab. Soc. portug. Derm., 8, 238.
BENHAMOU, E., DESTAINC, F., GAUTHIER,J. & SORREL, G. (1949). Paris, 65, 832-7.
Bull. Soc. Mdd. H@.
GREENBLATT, R. B., WAMMOCK,V. S., CHEN,C. H., DIENST,R. B. & WEST,R. M. (1950). J. vener. Dis. Inform., 31, 45. HAMRE, D. & RAISE, G. (1947). J. infect. Dis., 81, 175. HEYMAN, A., WALL, M. J. & BEESON,P. B. (1947). Amer. J. Syph., 31, 81. MAVl~I, M. (1948). Arch. ital. Sci. med. colon. Parasit., 29, 52. RAKE, G. (1948). Amer. J. trop. Med., 28, 555. ROBINSON, R. C. V., ZHEUTLIN,H. E. C. & TRICE, E. R. (1950). Amer. J. Syph., 34, 67.
WAMMOCK,V. S., GREENBLATT,R. B., DIENST, R. B., CHEN, C. H. & WEST, R. M. (1950). J. invest. Dermat., 14, 427-34. WILLCOX,R. R. (1946). Post Grad. reed. J., 22, 96. ---(1946a). Brit. J. vener. Dis., 22, 63. (1949). Report of a Venereal Diseases Survey of the African in Southern Rhodesia. South Rhodesian Govt., p. 17. - (1950). Nature, Lond., 166, 466. ---(1950a). J. R. Army reed. Cps., 94, 126. V~TRIGHT,L. T., SANDERS,M., LOGAN,M. A., PRIGOT,A. & HILL, L. M. (1948). J. Amer. -
-
reed. Ass., 138, 408.
--
,
,
,- -
&- -
(1948).
Ann. N.Y. Acad. Sci., 31, 318.