51, 2^ Correspondence^ 259

only revealed when the sensitive populationdisappeared.

2) Any lepromatous patient under satis-factory sulfone treatment is liable to catcha resistant form of leprosy, particularly ifsuch immunologically susceptible individ-uals are living in a place where other caseswith resistant organisms are likely to befound.

Some time ago I was asked to write anarticle for the "house paper" of a famousleprosari urn and I wrote to the effect thatleprosaria should be closed down—it wasnot published. It seems to me to be the heightof stupidity to send lepromatous patientsfor admission to a hospital where, almostby definition, they are likely to meet sul-lone-resistant mycobacteria. If this contin-ues (to repeat our warning of 15 years ago).

it is likely that more cases of this type willbe found.

—John FL S. Pettit. M.D.. F.R.C.P.Won/ .303China In.syrance Building174 Milan Twinkle Abdul RahmanKuala Lumpur„Ilala•.sla

REFERENCESI. PLARsoN, J. NI. IL.^ iii, I „I. II. S. and Rrrs. R. J.

W. Studies in sullone resistance in leprosy. 3. Acase of "partial - resistance. Int. J. Lei - . 36 (1968)171-178.

2. 1 3 1:1 - 1 it, .1. H. S. and RiTs, R. J. W. Sulphone re-sistance in leprosy. An experimental and clinicalstudy. Lancet 2 (1964) 673-674.

3. I, J. Ii. S.. RI rs, R. J. W. and Rummri. D. S.Studies in sullone resistance in leprosy. I. Detection()leases. Int. J. Leff. 34 (1966) 375-390.

Serum Levels of C3-activator (Antifactor B) in Leprosy

To rHe Eorroit:There have been previous reports that

during the eruption of crops of erythemanodosum leprosum (EN L) raised C2 and C3levels in the sera of patients have been ob-served ( 1' 7 ). These two components are in-volved in the classical immune complexpathway of complement activation.

(73-activator (Antifactor 13) is involved inthe alternative pathway activation of com-plement ( 1 ), and recently .1/ycobacteriumleprac bacilli have been shown to activatethe alternative pathway of complement ( 3 ).It was considered pertinent to determinehow the value of C3-activator varies in theleprosy sera, particularly during ENL wheninitially immune complexes and .11. lepracbacilli could activate both paths of comple-ment separately.

Sera were collected from 9 ENL, 3 non-ENL and I borderline patients from Japanand Addis Ababa, Ethiopia. The concen-trations of C3-activator, the third compo-nent of complement (C3c) and immuno-globulins (1gG, IgA and IgM) in the patients'sera were determined by the radial im-

munodiffusion method of Mancini. et al.('). using the standard immunoglobulin seraand the Partigen " immunodiflusion platesmanufactured by I3ehringwerke AG (1\ lar-burg-Lahn) of West Germany.

Measured 5 pl volumes of the standardsof Ig(i, IgA, IgM, C3c, and C3-activatorwere introduced into the first three wells andthe same volume of test sera introduced intothe remaining nine wells of each plate. The13 mg/m1 protein standard plasma used for(73-activator determination was used neat,diluted 1:2 and diluted 1:4 for the threestandard wells. All the plates were allowedto stand at room temperature for 48-72 hrbefore the diameters of precipitin ringswhich developed around the wells weremeasured, using a Behringwerke precisionmeasuring viewer. Graphs were plotted ofring diameters against the logarithm of thestandard concentration, and the concentra-tions in the samples were determined fromthe plots. The results are given in The Table.

Moderate increases in the serum levels ofC3-activator were observed only in ENLcases. The lowest values were observed in

260^ International Journal of Leprosy^ 1983

THE TABLE.^Concentrations of C3-activator, C3c, and immunoglobulins ill leprosy sera.

Patient IgG(I.U./m1)

IgA^IgM^C3c(I.U./m1)^(I.U./m1)^(mg/dl)

C3-activator(mg/di)

JapanENL

K.O. 501 254^188 204 35M.W. 479 150^347 94 17S.I. 468 202^150 108 19T.E. 309 219^126 138 19Y.T. 501 159^468 87

Non-ENLK.N. 490 180^137 69 10

BorderlineU.K. 437 197^116 62 14

Addis AbabaENL

No.^1304 214 206^138 102 28495 266 127^292 155 35415 229 337^120 170 38470 229 197^146 108 28

Non-ENLNo. 335 295 219^150 55 9

291 339 285^263 62 8Local Standards

299 148^143 82 19Western European Standards

125 116^141

non-ENL cases, being half of the lowest ob-served levels of ENL cases. There were alsocorresponding increases in the levels ofC3c.Both results suggest that the alternative andclassical pathways of complement activa-tion are employed at the height of immunereactions (ENL), indicating that the wide-spread damage of ENL is the sum total ofmany immunological processes.

The more common immunoglobulin(IgG, IgA, IgM) levels were also increasedin sera from Japan, when compared withlocal standards. Addis Ababa sera levelswere lagging behind generally, and could beconsidered increases if one took the lowerwestern European mean values as deter-mined by Rowe. et al. ( 4 ), suggestive of theCaucasian origin of most of the Ethiopianpopulation. Local standards of C3c and C3-activator are comparable to western Euro-pean values ( 5 ). It is only in the case of long-term workers (upwards of 15 years) in theroutine microbiology laboratory that suchhand-in-hand increases in C3c and C3-ac-tivator with high IgG, IgA, and IgM have

been observed (N); obviously these profes-sionals are not the healthiest individualsaround.

Increases in C3-activaIor levels in the se-rum with corresponding increases in C3c,IgG, IgA and IgM should be suggestive ofactive phases of immunologically chronicconditions.—S. N. C. Wemambu, M.D., Dip. Bact.

(London), F.M.C. Path. (Nig.)HeadDepartment of Medical MicrobiologyCollege of MedicineUniversity of BeninBenin City, Nigeria

Acknowledgment. This work received financial helpfrom the Nigerian Medical Research Council.

REFERENCES1. GOETZE, 0. and MUELLER-EIBIRILARD, H. J. The

C3-activator system: An alternate pathway of com-plement activation. J. Exp. Med. 134 (1971) 90-108.

51, 2^ Correspondence^ 261

2. MANCINI, G., CARBONARA, A. 0. and FIEREMANS,

J. F. Immunochemical quantification of antigensby single radial immunodilfusion. Int. J. Immu-nochem. 2 (1965) 235-254.

3. RANIANATIIAN, V. D., CURTIS, J. and TURK, J. L.Activation of the alternative pathway of comple-ment by mycobacteria and cord factor. Infect. Im-mun. 29 (1980) 30-35.

4. RowL, D. S. Concentration of serum immuno-globulin in healthy adult males estimated by assayagainst the international reference preparation.Lancet 2 (1972) 1232-1233.

5. Solui:rit., H. F. and I IrRENtANs, J. F. Mehvidar

Biology of Human Proteins. New York: AmericanElsevier, 1966.

6. SErrz, E. W., DIERKS, R. E. and SilEpAup, C. C.Complement and the second component of com-plement in leprosy. Int. J. Lepr. 36 (1968) 400-404.

7. WENIAMISU, S. N. C., TURK, J. L., WATrus, M. F.R. and Rees, R. J. W. Erythema nodosum lepro-sum: A clinical manifestation of the Arthus phe-nomenon. Lancet 2 (1960) 933-935.

8. WENIANIBU, S. N. C. Immunoglobulin and C3-ac-tivator profile of the microbiology laboratory work-er. J. Nig. Soc. Microbiol. (1983) (in press).

Sensitization and Immunization by Mycobacteria

To THE EDITOR:

The article of Ridley (') confirms againthat sensitization and immunization are bi-ologically different processes in mycobac-terial diseases (and hence also in leprosy).This is no geographical peculiarity but afact already recognized by Robert Koch. Itwas not taken into account by the currentconcepts of leprosy, but during the past 100years competent authors have repeatedlyproven the correctness of Koch's find-ings ( 2 ).

This fact is of great practical significance,as will be illustrated by the following points:

1. The reactivity to lepromin indicates sen-sitization (allergy), not immunity. Sen-sitization does not result in protection. 3.Non-reactivity to lepromin indicates onlythat no sensitization occurred, at leastnot in the skin. Reaction or non-reactionto lepromin is not correlated with theso-called state of immunity or defense(similar to the tuberculin reaction in tu-berculosis).

2. Depending on the transmitter of the dis-ease and the infected macroorganism, al-lergic reactions of varying degree are seen 4.in mycobacterial diseases as conse-quences of sensitization. In the case oftuberculosis caused by Mycobacteriumtuberculosis the consequences of sensi-tization may be dangerous for man (e.g.,cavities). In rats the same bacteriumcauses symptoms which apparently donot include allergic reactions. Rat tuber-

culosis is therefore similar to LL-leprosycaused by Al. /eprae in man. Large num-bers of bacteria are found in an almostnon-reactive tissue. Depending on thenumber of bacteria and their virulenceand, on the other hand, on the reactionof the macroorganism, both the infectingbacterium and the infected macroorgan-ism do produce the symptoms of the dis-ease through the reaction system they areproducing in common. It remains to beclarified whether in leprosy bone pro-cesses and glomerulonephritis, for in-stance, are typical consequences of sen-sitization, i.e., whether they are of anallergic nature, or whether they are dueto something else.The wide differences with regard to reac-tivity and kind of reaction of the ma-croorganism are not the only but a majorreason why, in animal tests, no conclu-sions on the causative mycobacterialspecies can be drawn from the patho-histological findings. Many misconcep-tions have crept into our picture of lep-rosy because this fact has not been takeninto account.In connection with studies aimed at thedevelopment of vaccines against leprosy,the opinion is often voiced that vaccineswill result in reactivity to lepromin, thusindicating the onset of protection. Thisopinion is scientifically unfounded, be-cause the difference between sensitiza-tion and immunization has not been tak-en into account. From the present state