Histoplasmin and coccidioidin sensitivity in Ceylon.

Notes Histoplasmin and Coccidioidin Sensitivity in Ceylon by C. G. URAGODA,' A. WIJENAIKE,2 & EUNG Soo HAN 3 There is wide variation in the incidence of some fungal diseases in different geographical areas of the world. This is true of histoplasmosis and cocci- dioidomycosis, which are caused by Histoplasma capsulatum and Coccidioides immitis, respectively. Surveys based on intradermal skin-testing of delayed hypersensitivity to histoplasmin and coccidioidin have shown that these two conditions have assumed epidemic importance in some countries, while they are extremely rare, or even absent, in others. The highest prevalence of histoplasmin reactors occurs in North, Central, and South America, especially in the east-central region of the USA, where some studies have demonstrated an infection rate of up to 900 of the population. It is present to a much lesser degree in some African countries, such as the Sudan and the Republic of South Africa, and it is least common in Europe. Histoplasmin studies in some South-East Asian countries indicate that it is of little significance in this region. Edwards et al. (1956) reported the prevalence in Indonesia to be 1.8-7 %, and in India and Burma they found no cases. Tucker & Kvisselgaard (1952) found infection rates between 40% and 27.1 % in Burma, while in India, Wahi (1955) reported a rate of 1.7% in Agra, and Viswanathan et al. (1960) found 12.3%, 4.9%, and 2.90% infected in different parts of Delhi. Coccidioidomycosis is endemic in the arid south- west of the USA, where in some areas up to 70% of the young adults reacted to the antigen (Edwards & Palmer, 1957). The infection has also been reported from Central and South America. As in the case of histoplasmosis, it is much rarer outside the Americas, but cases have been reported from Italy and from Hawaii (Conant et al., 1963). The present study was undertaken to find out if these infections existed to any significant extent in Ceylon, where so far no clinical case of either fungal disease has been reported. ' Physician, Chest Clinic, Kandy, Ceylon. 2Medical Officer, Vidyalankara University, Kelaniya, Ceylon. 3Medical Officer, National Tuberculosis Institute, Colombo, Ceylon. Materials and methods The following antigens were used in the study: his- toplasmin, lot No. H-42, 1:100 dilution; coccidioidin, lot No. 1, 1: 100 dilution; and tuberculin PPD-S. The test population for this survey, which was carried out in June and July 1969, consisted of 1 366 students and prisoners, of whom 842 were females and 524 males (Table 1). Vidyalankara University is situated close to Colombo, while the other institutions are located in or near Kandy, 116 km away from Colombo. All the subjects were over 18 years of age and came from different parts of the country. In addition to this study population, a total of 133 tuberculosis patients who had either bacterio- logically proved pulmonary tuberculosis or histo- logically confirmed extra-pulmonary disease were also skin-tested with the same antigens. They were all patients in hospitals in and around Kandy. The procedure adopted in the survey was similar to that described by Han (1966). A 70-mm radio- graph was taken of the chest of every subject at the time of skin-testing except in those cases where this had been done as part of a routine physical examina- tion 7 months before. Results Skin reactions. Fig. 1 shows the frequency dis- tribution of histoplasmin sensitivity among the 1 366 non-tuberculous subjects. There were only 78 persons (5.7 %) with reactions of 8 mm or over. Fig. 2 shows the corresponding frequency distribu- tion of cocccidioidin sensitivity. Only 4 persons (0.3 %) had reactions of 8 mm or more. The reac- tions to histoplasmin and coccidiodin were much stronger in the 133 tuberculosis patients, in contra- diction to the rest of the findings. One might have speculated that these reactions were cross-reactions to delayed sensitivity caused by tuberculosis, as the possibility of such cross-reactivity was tentatively suggested by Palmer & Petersen (1950). This explana- tion was not mentioned, however, in more recent publications (Edwards & Palmer, 1957; Edwards et al., 1958) and in view of the doubt about the meaning of our results for this group, the data are not reported in this paper. 2760A 689 NOTES Table 1. Number of persons tested No. tested Institution Location _______________________________________________________M ales le tal Junior Technical University Polgolla, Kandy 13 183 196 Teachers' Training College Uyanwatte, Kandy 2 332 334 Vidyalankara University Kelaniya, Colombo 278 327 605 Prison Kandy 231 0 231 Total 524 842 1 366 Radiological calcification. Radiological evidence of calcification was seen in 17 (1.2%) of the 1 366 subjects: 15 persons showed it in the hilar iegion. The histoplasmin reactions in the group with calcifi- cations ranged from 0 to 9 mm (average 2.7 mm), while the range for coccioidin reactions was from 0 to 5 mm (average 1.6 mm). On the other hand, there were clear tuberculin reactions in the group with radiological calcifications, ranging from 3 to 21 mm (average 14 mm). These results suggest that calcification in this survey was more likely to be due to infection by Myco. tuberculosis rather than to either Histoplasma or Coccidioides infection. Fig. 1. Frequency distribution of histoplasmin reactions by size in 1 366 non-tuberculous subjects. Discussion In the absence of reported cases of histoplasmosis or coccidioidomycosis in Ceylon, the general impres- sion among clinicians is that these infections are non-existent in the country, or if present, are so rare as not to be considered in the differential diagnosis of pulmonary disease. Palmer et al. (1957) point out that fungal infections are closely tied to geography. Since these two fungal infections are uncommon in the neighbouring countries, it is reasonable to expect the same pattern to prevail in Ceylon. Various studies have shown that the ecological requirements of a micro-organism affect the geo- Fig. 2. Frequency distribution of reactions to cocci- doidin by size in 1 366 non-tuberculous subjects. 50 40 a,zaC.) 108980 me~ ~ ~ Daee o nuain(m WHO 10898 50 40 w 30 Oa80) >20_ L 10_ WHO 10899 2 4 6 8 10 12 Dlameter of Induration (mm) l 690 HISTOPLASMIN AND COCCIDIOIDIN SENSITIVITY IN CEYLON 691 graphical distribution of the infection. Maddy (1958) reports that the conditions required by C. immitis for propagation are a mean temperature within the range 27-32°C. in July and 4-12°C in January, and an annual rainfall of 12.7-50.8 cm. These requirements are fulfilled in the arid south-west of the USA, and the endemicity of coccidioidomycosis in this area may be explained on this basis. In Ceylon there is no single area where all these requirements are satisfied, and therefore it would appear that the Ceylon climate is not conducive to the growth of C. immitis. In the epidemiological study of skin sensitivity, it is no longer acceptable arbitrarily to fix the size of the induration that divides a positive from a negative reaction as was done in the past for tuberculin, histoplasmin, and coccidioidin sensitivity (Palmer & Petersen, 1950). In most studies a person was con- sidered as infected with Histoplasma or Coccidioides if his skin reaction reached a certain size-e.g., 5 or 8 mm. In the subjects studied in this survey the use of an 8-mm limit would have indicated that 5.7% were infected with Histoplasma and 0.3 % with Coccidioides. The histograms, however, do not indicate any clear division between positive and negative and it seems better to report that only a small percentage reacted to histoplasmin and that virtually none did so to coccidioidin. Even for the histoplasmin reactions the possibility cannot be excluded that they were cross reactions to some other fungal infection. ACKNOWLEDGEMENTS We are much indebted to Dr P. Q. Edward of the US Public Health Service for the supply of antigens. We also wish to thank Mrs M. Mallawarachchi, BCG Nurse, National Tuberculosis Institute, Colombo, Ceylon, for carrying out all the skin testing in this survey. REFERENCES Conant, N. F., Smith, D. T., Baker, R. D., Callaway, J. L. & Martin, D. S. (1963) Manual of clinical mycology, 2nd ed., W. B. Saunders Company, Philadelphia and London, p. 93 Edwards, P. Q., Geser, A. 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