Symposium on the EPIDEMIOLOG Y OF LEPROSY, Geilo . Norway , 1 98 1 Lepr Rev ( 1 98 1 ) 5 2 , Suppl 1 , 137-146

Non-specific factors that influence susceptibility to leprosy

RJW REES Laboratory for Leprosy & M ycobacterial Research , National I nst i tute for Medical Research , M i l l H i l l , London , ,NW7 l AA , Engl and .

My b r i e f for this s e c t i on wa s t o p r e s e n t a nd d i s c us s a s pec t s o f non- s pe c i f i c fa c t o r s inc l ud i ng nu t r i t i ona l , env i ronmen ta l a nd o th e r s oc ia - e c onomic f a c t or s tha t may infl uenc e s u s c e p t i b i l i ty t o l e pr o sy a nd whe ther a ny o f the s e fa c t ors c a n be us ed t o d e f ine h igh r i s k g roup s . I have chosen to d e fine "non- s pe c i f ic immun i ty " in i t s b roa d e s t s e n s e i . e . the immune s ta tus o f the non- l e pr o sy ind i v i dua l or l e prosy pa t i en t no t s pe c i f i ca l ly d e t e rmined by expo sure to Myc oba c t e r ium l e p ra e . By thi s d e f in i t ion a nd c r i t i c a l a na ly s i s o f pa s t c la ims , a pa r t o f my p r e s enta t ion wi l l a l s o whe re nec e s s a ry cha l l enge or re fu t e t h e ev idenc e f o r such nons p ec i f i c a s s oc ia t ions .

N u t r i t i ona l Fa c t o r s

I t i s we l l - known tha t M . l e pra e d oe s no t infe c t a l l huma ns expo s e d t o i t , n o r d o e s i t produce t h e s ame degree o f i l l ne s s in th o s e who d o b e c ome infec t ed . A l though a v a r i e ty o f r i s k fa c t or s have b e e n invoked t o exp l a i n th i s va ria t i on , i t i s no t surpri s i ng tha t the s ta t e of nu t r i t i on of the i nd iv idua l a t r i s k had been c ons i d e re d a p o s s i b l e a nd impor t a n t fa c t or , b e a r i ng i n mind tha t curren t ly l ep r o sy predomina t e s in pa r t s of the wor l d where ma l nu t r i t i on i s r i fe . Thus a p o s i tive a s s oc ia t ion b e tween ma l nu t r i t i on a nd inc rea s ed s us c e p t i b i l i ty a nd s eve r i ty t o l eprosy h a s b e e n freque n t ly r e f e rred t o in the l e prosy l i t e ra ture and i n pa r t i c u l a r a nd mo s t for c i b ly b y Ry r i e ( 1 ) a nd Skinsnes ( 2 , 3 ) . On the o th e r ha nd Dav ey ( 4 ) a nd Leiker ( 5 ) c onc l ud e tha t the nu t r i t iona l s ta tus d id no t s eem t o have s ig n i f i c a n t inf l uenc e on the s u s c ep t i b i l i ty t o l e prosy , nor on the c ours e o f d i s ea s e . B e fore c ons ide r i ng the l imi ted l i t e ra ture on l e prosy a nd ma l nu t r i t i on , I wi l l b r ie f ly rev iew the pe r t inent informa t i on on ma l nu t r i t i on , a nd immun i ty .

The e f fec t of nu tri t i ona l s ta tus on the immune c a pa c i ty a nd immune r e s p ons e s

1 38 RJW Rees

In the dev e l op ing wor l d , ma lnu t r i t ion and infec t i on c oun t for the ma j o r i ty of dea ths , pa r t i c u l a rly among ch i l d re n . The two i n t e rre a c t syne rg i s t i c a l ly in tha t infec t i ous i l l ne s s b r i ng s a b o u t a de t e r i ora t i on in the nu t r i t i ona l s ta tus and ma lnu t r i t i on wor s ens infe c t ion . The mo s t impor t a n t mechani sms res pons i b l e for th i s i n t e ra c t i on a re a d e c re a s e in immune c a pa c i ty a s s oc ia ted wi th ma l nu t r i t ion and c a t a b o l i sm c a u s e d b y feb r i l e i l l ne s s e s . The huma n nu t r i t i ona l s tud i e s have f oc u sed princ i pa l ly on s evere p r o t einc a l o r i e ma l nu t r i t i on ( PCM) , re s u l t ing in kwa sh i o rko r o r ma ra smus a s we l l a s the more preva l e n t but mi l d e r f o rms o f PCM , re s u l t ing in g rowth re ta rda t i on . Th i s re t a rda t i on ha s been mea s ured on a we igh t- f or- a g e ba s i s a nd s ta nd a r d i s e d a s · a percent i l e o f the Ha rv a rd med i um . The re is now a v a s t amount of da t a on i nd iv i dua l s wi th v a ry ing deg ree s o f PCM . The immuno l og i c a l pa rame t e r s me a s ured have inc l ud e d c e l l -med ia t e d immune ( CM I ) a nd hum ra l immune , r e s pons e s . CMI ha s been mo s t c ommonly mea sured by pos t - B CG tubercu l in s ens i t iv i ty , wh ich a s a myc oba c t e r i um i s o f pa r t i c u l a r re l eva nc e t o l e prosy . Hum ora l immune re s p on s e s hav e fre quen t ly b een mea s ured by mean s of t e t a nus or d ip th e r i a a n t i b ody produc t i on f o l l owing the r e s p e c t iv e va c c ines . Immunog l ob u l ins A , G a nd M a nd comp l emen t C

3 have a l s o been s tudied . A l l the s e s t ud i e s have

shown tha t kWa shi orko r , ma ra smus and more s ev e r e PCM ( 80% or l e s s o n the Ha rva rd s c a l e ) c r i p p l e CMI re s pons e s more tha n the immunog l ob u l in- forming sy s tem . Us ua l ly norma l or ev en e l eva ted s e rum immunog l ob u l in c onc e n t ra t i ons have been found a s we l l a s g o od t e t a nus or d i p theria a n t i b ody p r oduc t i on in PCM . Ra i s ed IgG l ev e l c a n f re quen t ly b e found and , o f i n t e re s t t o l e p r o sy , s ome s t ud i e s have shown reduc ed IgA a nd C3 l eve l s in t h e more s ev e re PCM . A n examp l e of reduced CMI re s pon s e s in chi ldren w i th v a r i ous l eve l s o f PCM o n the Ha rva rd s c a l e a re shown i n Ta b l e 1 from a s tudy c a r r i e d ou t in We s t Benga l me a s uring the pos t BCG re s p on s e s t o P . P . D . ( 6 ) .

Ta b l e 1 . Compa ri s on o f Po s t - B CG ( 6 - 8 we eks ) r e s p on s e t o P . P . D . a nd N u t r i t i ona l S ta tus o f Ch i l d ren

P . P . D . ( 5T . U . ) r e s p o n s e (mm)

0 - 4

>5

N o . o f ch i l d ren per Ha rva rd nu t r i t i ona l s ta tus (%)

> 80 6 0- 80

10 69

1 4 ( 5 8 . 3 ) 6 9 ( 50 . 0)

< 6 0

26

9 ( 2 5 . 7 )

F igure s i n pa re n the s i s re s pons e .

% o f ch i ld ren wi th p o s i t ive P . P . D .

Non-specific factors and susceptibility 139

In a s imi l a r s tudy on PCM ch i l d re n in Uga nda i t wa s shown tha t tho s e wh o fa i l ed to conve r t to P . P . D . fo l l ow i ng BCG va c c i na t i on re s p onde d p o s i t iv e ly ( 1 0 mm indura t i on) to a fur th e r P . P . D . t e s t , two we eks a f t e r the chi l d ren we re g iven a d i e t c o n ta ining 4 g p ro t e i n /Kg b ody we igh t ( 7 ) . The d imini shed CMI r e s pons e s in the s e BCG s tud i e s showe d a s a fa i l u re t o b e c ome s e n s i t i s e d ra the r tha n a s a d imi ni shed r e s ponse to P . P . D . , s o tha t there wa s no s ig n i f i c a n t d i f fe rence be twee n the s i z e s o f the re a c t i ons a nd the s ev e r i ty of PCM in the ch i ld ren .

Ma lnut r i t i on a s a r i s k fa c t o r in l e pr osy

S ince CM I , wh ich a l s o requ i r e s i n t a c t ma c ro pha g e func t i on , is the ma j o r de fenc e me cha n i sm of the b ody aga ins t l e prosy a nd o t h e r my c oba c t e ria l infec t i ons , PCM , pa r t i c u l a r ly chron i c PCM , wh i ch i s known t o s uppre s s CM I , c o u l d we l l be a r i s k fa c t o r in l e p r o sy . Fur the rmore , CMI i s ope ra t ive i n the reve r s a l - ty pe re a c t i ons a s s o c i a ted w i th BT a nd b o rd e r l ine l e p rosy as i s a c t iva t i on of c omp l emen t ope ra t ive in ENL- type rea c t i ons in l e p roma t ou s l e pr o sy. The refore a s s o c i a ted PCM , wh ich i s known t o re s u l t in l ow leve l s o f C3 , wou l d a l s o a l t e r the c ou r s e o f the d i s e a s e . Un f o r t una te ly the ava i l a b l e a nd re l ev a n t da ta on ma l nu t r i t i on in l e prosy a nd expe r ime n t a l a n ima l infe c t i on s i s mea g re .

S tud i e s i n an ima l s

The mo s t a ppropr ia te expe rime n t s c once rned wi th PCM we re und e rt a ken in mi c e ( 8 ) a nd in ra t s ( 3 ) wi th My c oba c t e rium l e p ra emurium i nfe c t i ons . Ta ke n t oge the r the s t udy s howed tha t the pro found ly p r o t e in- c a l o r i e d e f i c i en t a nima l s , c ompa red wi th the we l l - fed a nima l s , had a mo re s eve re a nd d i s emina ted infec t i on . Moreove r , the ma c r opha g e s i n the PCM a n ima l s formed fewe r g ra nu l oma , c onta ined more ba c i l l i a nd were en zyma t i c a l ly d e f i c i e n t c omp a red wi th the we l l - fed a nima l s . The re s u l t s of the M . l e p ra emu rium exp e r ime n t s a re c ons i s t e n t wi th o th e r Myc ob a c t e r i um tubercu l o s i s s tud i e s showing d e f i c i e n t a n t i - ba c te ria l d e fe nc e s i n s ev e re PCM .

S tud i e s in ma n

One o f the ma i n c l a ims for a s s oc ia t i on be twe en ma lnu t r i t ion a nd s�v e r i ty o f l e prosy wa s b a s ed on 2 5 le prosy pa t i e n t s a u tops ied in Hong Kong in Wor l d Wa r I I wi th s evere ma l nu t r i t i on . Two o f the s e w i th l e proma tous l e p rosy had l ow l ev e l s of s e rum p r o t e i n s a nd l ow b ody we igh t s a nd s igns of kwa s h i orko r . Moreove r , the s e two pa t i e n t s a t a u t opsy ha d mo re wid e s pread le prosy tha n wa s ob s e rved in the o the r 23 a u t o p s i e s a nd they a l s o had s eve re u l c e ra t i on of the s kin , i nd i c a t ive of La za rine l e p rosy ( 3 ) . The

140 RJW Rees

o the r mos t quo t e d refe renc e in support o f incre a s e d su s c e p t i b i l i ty to l e pr o sy a s s oc ia t e d wi th ma lnu t r i t i on i s ba sed on the s ta rva t i on s i t ua t i on ( l e s s tha n 7 00 c a l o r i e s /d ay) f a c i ng the 2 , 500 pa t i e n t s in t h e Sung e i B u l oh L e p ro s a r i um , Ma lay s i a , a l s o dur i ng t h e S e c ond Wo rld Wa r ( 1 ) . In s p i t e of the horr i f i c mor t a l i ty ( 7 3%) dur ing th i s p e r i od , i t wa s no t c la imed tha t the s e d e a ths r e s u l ted s p e c i f i c a l ly from l e p r o sy . Howev e r , it wa s ob s e rved , for a l l p ra c t i c a l purpos e s , tha t the a c u t e rea c t i ona l ma ni fe s t a t i on s a s s oc i a ted wi th a l l ty pe s o f l e p rosy d i s a ppea red throughou t the p e r i od o f g r o s s s ta rv a t i on . Thu s from a ra t e o f 100 c a s e s /mon th of l e proma t ou s r e a c t i ons ( p re s uma b ly ENL ) b e fore the wa r the ra t e fe l l to 2- 3 /mon th d u r i ng the wa r a nd s imi la rly f o r tub e rc u l o id r e a c t i ons ( pr e s uma b ly rev e r s a l rea c t i ons ) the ra t e wa s 2 0 /mon th a nd for nerv e reac t i ons 3 0- 40 /month b e fore the wa r wi th no c a s e s o f e i th e r s uch reac t i ons d u r i ng the wa r !

Conc l u s i ons

I c onc l ud e from the pub l i shed l i t e ra ture tha 't there is no d e f i n i t iv e ev idence s up p o r t ing ma l nu t r i t i on a s a r i s k fa c t or in l ep r o sy . Thi s d o e s no t d i s p rov e such an a s s oc ia t i on b u t und e r l ine s the l a c k o f a ny re l eva n t a s s e s smen t s o n the nu t r i t iona l s t a tu s o f pa t i e n t s wi th l e p r o s y . Howev e r , the immuno- d e f i c ienc i e s known t o b e a s s o c i a t e d w i th more s evere PCM a re j u s t tho s e tha t wou l d b e l ike ly t o inc re a s e b o th the r i s k o f deve l o p ing l e prosy a nd the s ev e r i ty o f t h e infe c t i on once e s ta b l i s h e d . The l a t t e r i s s up p o r t ed b y the l imi ted anima l s tud i e s wi th M . l e p ra emur i um infec t i ons . Fur th e r m o r e the a lmo s t c omp l e te a b s ence o f rea c t i ona l e p i s od e s among the l e p r o sy pa t i e n t s in Ma l a y s i a d ur i ng the p e r i od of s ev e re s ta rva t i on c ou l d have re s u l t e d from the immune d e f i c ienc i e s a s s oc ia t e d wi th PCM . Thu s t h e a s s oc ia t e d r e d u c e d CMI c ou l d have a c c oun t e d for t h e a b s ence o f reve r s a l rea c t i ons , a s c o u l d h a v e the a s s o c i a red reduc ed l ev e l of C3 b e e n re s pons i b l e for the reduc e d i nc i d e nc e o f ENL .

A l though the ev idenc e for ma lnut r i t i on a s a r i s k fa c t or in l e pr o sy is meagre and unsub s t an t i a t e d , I wa s surp r i s e d t o f i nd a t the t ime o f wr i t ing th i s s e c t i on tha t g ood ev idence even for a n � s s oc ia t ion b e tween ma l nu t r i t i on a nd p u lmona ry tuber cu l o s i s wa s s c a n ty . The d i f f i c u l ty ha s b e en t o d i s a s s oc ia t e the s evera l o th e r f a c t o r s tha t s o f r e quent ly a re a s s o c i a t e d wi th s ta rva t i on s i tua t i ons . Therefore , ou t o f i n t e re s t f o r thi s mee t ing , Ta b l e 2 p re s en t s the d a ta quo t e d by tubercu l o s i s au th ori t i e s a s mo s t c onv i nc i ng ly i l lus tra t i ng ma l nu t r i t i on a s a r i s k fa c tor . The da t a show s c l e a r l y the s ig n i f i c a n t ly h i g h e r i nc idence o f tub e rcu l o s i s among the Rus s ian Pr i s one r s of Wa r c ompa red wi th tha t o f the B r i t i sh and the French b e fore 1 9 4 5 . Whi l e the e nv i ronmenta l c ond i t ions were the s ame for a l l na t i ona l i t i e s a s wa s the c amp d i e t ( 1 , 300- 1 , 6 00 ca l o r i e s /d a y ) f o r the p e r i o d c ov e re d , the B r i t i sh , a nd F rench ( un t i l 1 9 4 5 ) rec e iv e d reg u l a r ly a nd we ekly Red Cros s

Non -specific factors and susceptibility 1 4 1

pa rce l s o f food a d d i ng a bou t 1 , 500 c a l o r i e s /d ay t o the i r c amp d i e t , the Rus s ia n s nev e r rece ived s uch pa r c e l s , a nd the French none a f t e r Ja nua ry , 1 945 ( 9 ) .

TABLE 2 Preva lence of Tub e r cu l o s i s among Pri s oner s o f Wa r in G e rma ny

1943 , J u ly - Dec . 1944 , Jan . - June

" Ju ly - Dec .

1945 , Ja n . - A p r i l ( 3 mon th s )

F rench ( l , 200)

o

1 1 4

Rus s ia n ( 1 , 200- 1 , 000)

6 14 3 1 1 1

The Ro l e o f N on- S p e c i f i c CM I a s a R i s k F a c tor i n L e pr o sy

B ri t i sh ( 2 50)

o

o

o

o

S inc e the f i r s t ev id enc e o f the immune mecha n i sms i nv o lv e d i n c ont ro l l ing M . l e pra e infec t i on s wa s e s ta b l i shed us i ng exp e r imen ta l a n ima l mode l s a nd pa r t i cu l a r ly the mou s e foo t pa d infec t i on ( 10) , th i s s e c t i on wi l l b e c on f i ne d to M . l e p ra e infec t ions i n a n ima l s . Mu l t i p l i c a t i on o f M . l e p r a e in t h e foo t pa d s o f no rma l mi c e wa s l imi ted to a l oca l y i e l d o f a p proxima te ly 106 b a c i l l i a nd then on ly wi th i nocu l a r s ome two l og s o r more l e s s tha n 106 • A n examp l e o f th i s l imi t ed infec t i on i s i l l u s t ra ted i n F ig ure 1 .

7

, , , ,

20 100 1 20

Figure 1 . Gr owth c u r ve of M. lepr ae i n the ear s and footpad s of normal mice fol low i ng loca l i nocu l a t ion

1 42 RJW Rees

I t wa s hy po the s i s ed tha t the s e fea tures of l imi t ed mu l t i p l ic a t i on a nd d o s e de pendenc e were contro l l ed by the c a pa c i ty of the mou s e t o moun t a n immuge - c on t ro l l ing mechan i sm when cha l l enged wi th a p p r oxima t e ly 10 M . l e p ra e . Wi th the knowl e d g e then tha t tub e rcu l o s i s infec t i ons a nd o th e r i n t ra c e l l u l a r infec t i ons we re c on t ro l l ed by GM I ra ther tha n humora l immuni ty , we s e t out t o e s ta b l i sh tha t t h e s ame immune me cha n i sm a pp l i e d t o M . l ep ra e . Thi s wa s e s t a b l i shed by d emons t ra t ing tha t when the GMI c a pa c i ty o f m i c e wa s ob l i t e ra t e d (by thyme c t omy ( T ) f o l l owed by 9 00 R t o ta l b ody i r ra d i a t i on) , th e s e T- c e l l d e f i c i e n t m i c e we re c a pa b l e of s uppor t i ng un l imi t e d mu l t i p l i c a t i on o f M . l e pra e in the i r f oo t p a d s , w i th inoc u l a r fa r i n exc e s s o f 1 04 b a c i l l i (F igure 2 ) a nd the infec t i on s pread sy s t emica l ly from the foo t pa d s ( 1 1 ) .

F i g u r e 2 . Growth c u r ves of M . lepr ae i n foot pads o f normal and thymec tom i sed i r r ad i ated mice ( T/9 0 0 r)

9

OL---�-----r----�---.r---�IO T I M E ( MONTH S )

Fur the rmore , it wa s d emons t ra t e d tha t the unre s t r i c ted a nd sys temic infec t i on re s u l t i ng in T /9 00 R m i c e c ou l d b e ha l t ed by the t r a n s fus i on o f lymphocy t e s from uninfec t e d syng enic mice ( 1 2) . Wh i l e the s e exp e r iment a l s tud i e s e s ta b l i shed for the f i r s t t ime the r o l e of GMI in M . l e pra e infec t i ons a nd i t s impor tanc e in exp l a ining a pa r t of the s pe c t rum of l e pr o sy a s s een in ma n , inc l ud i ng the impor ta nc e o f GMI in reve r s a l rea c t i on s ( 1 2 ) , i t i s impor ta n t t o a pprec ia t e tha t th e i n i t i a l d e t e rmining GMI mecha ni sms in the s e exp e r imenta l mod e l s were non- s pe c i f ic . S imi la r non- s p e c i f i c d ep l e t ion o f CMI ha s b e e n e s ta b l i shed by d emon s tra t ing tha t neona ta l ly thymec t omi s ed r a t s ( 13 ) a nd thymec d e f i c ien t N u-Nu s t ra ins o f m i c e ( 14 ) a l s o s uppo r t unre s t r i c t e d a nd sy s t emic

Non-specific factors and susceptibility 1 43

mu l t i p l ic a t i on o f M . l e p ra e . F i na l ly , in 1 9 7 1 ( 1 5 ) , i t wa s d emon s t ra ted tha t the nine

b a nd e d a rma d i l l o wa s na tura l ly s u s c e p t i b l e to exp e r imen ta l M . l e pra e infe c t i o n a nd tha t 50% o f such a n ima l s s u p p o r t e d unl imi ted mu l t i p l i c a t i on o f M. lepr a e wi th d i f f u s e sy s temic s p read .

C onc l u s i on

Wh i l e the s e T- d e f i c ient a n ima l mod e l s were impor t a n t in s ug g e s t ing the impor t a n t r o l e of CMI in h uma n l e prosy. infec t i ons , they a l s o i nd i c a t e tha t CM I d e f i c i e ncy , non- s pe c i f i c a l ly d e r ived , wou l d b e l i ke ly t o increa s e the r i s k fa c tor o f infec t i on i n ma n , a s we l l a s immuno l og i c a l ly d e t e rm i n i ng the ou t c ome o f the infe c t i on onc e e s ta b l i shed in ma n . S ince we d o no t know why a propor t i on o f nineb a nd e d a rma d i l l o s is high ly s u s c e p t i b l e t o infec t i ons wi th M . l e prae the que s t i on o f na t ive - s u s c e p t i b i l i ty mus t be re- c ons i d e re d .

Pregna ncy a nd La c ta t i on a s Ri s k Fa c t o r s i n L e p r o sy

I t ha s b e e n a pprec ia t e d f o r ma ny y e a r s tha t l e prosy may wor s e n or p r e s e n t for the f i r s t t ime d u r i ng p regna ncy a nd i n the pue r p e r i um ( 4 ) , th i s a p p l i e s a l s o t o t u b e r cu l o s i s ( 1 6 ) . The t iming s o f the l ep r o sy exa c e rb a t i ons dur i ng pregna ncy a re o f pa r t i c u l a r i n t e re s t a nd have b e e n mo s t prec i s e ly de f ined f r om a recent s t udy in E th i o p i a ( 1 7 , 1 8 ) . Thu s the c r i t i c a l p e r i od for exa c e rba t i ons in b o th t u b e rc u l o i d a nd l e proma t ou s l e pr o s y is dur ing the th i rd t r i me s t re a nd t h e f i r s t three mon ths o f la c ta t i on ( Ta b l e 3 ) whe rea s the inc i d e nc e o f reve r s a l rea c t i on s pea ke d during th e f i r s t t r i me s t re a nd a g a in d u r i ng la c ta t i on .

TA BLE 3 Wor s en i ng o f L e p r o s y Dur i ng Preg na ncy a nd La c ta t i on

Type o f N o . of N o . o f l e prosy women pregna nc i e s

BL 40 4 1

LL 3 2 3 5

N o . o f pa t i e n t s d e t e r i ora t ing

Pregna ncy ( t rime s t r e )

I s t 2nd 3 rd

3 3 7

Tota l

2 4 1 3

To ta l

1 7

2 1

L a c ta t ion (mon th )

0- 3 4- 6 7 - 1 2

3 1 0

( 5 )

1 0 1

( 9 ) F ig u r e s i n pa ren the s i s = t ra ns i e n t d e t e riora t ion .

1 44 RJW Rees

The s e t ime s e quenc e s of the l e pr o s y s ta tus in pregna ncy c o inc i d e w i th the waning o f eMI during pregnancy a nd i t s g ra d ua l rec ov e ry a f t e r d e l ivery . The p regna ncy- a s s oc i a ted wa ning o f eMI , a d d e d t o a l l t h e h i g h e r l ev e l s o f c o r t i c o s t e r o id s , pa r t i c u l a r l y in t h e th i rd t r ime s t re , c o u l d s t i l l fu r th e r b e exa c erba t ed by ma l nu t r i t i on .

C onc l u s i on

L e p r o sy i s undoub t e d ly a s e r i ou s r i s k fa c t or in pregna ncy , nec e s s i ta t ing o p t imum chemo the ra py for women wi th a c t iv e l e pr o sy a nd prophy l a c t i c the ra py for thos e wi th "cured ' " l ep r o sy , a nd for a l l t o be fed a h i gh pro t e i n d i e t througho u t pregna ncy a nd l a c ta t i on .

C l ima t i c F a c t o r s in L e p rosy .

Though there i s ev e r inc rea s ing ev id enc e tha t l e prosy i s a n a i rb orne i n f e c t i on a nd the r e f o re the por ta l o f en t ry may b e via the l ung fo l l owing the inha l a t i on of M . l e pra e - infec ted nuc l e i ( 1 9 ) , a s in t ube rc u l o s i s , much o f the ev idence f o r th i s rou t e o f t r a n s mi s s i on s temmed f rom in tens iv e s tud i e s on na s a l d i s cha rge s from pa t i e n t s wi th a c t iv e l e p roma tous l e prosy . F r om one o f the s tud i e s i t wa s s h own tha t M . l e p r a e rema ined v ia b l e i n d r i ed na s a l s e c re t i ons f o r p e r i od s u p t o 1 0 day s ( 20 , 2 1 ) , b u t tha t s urv iva l wa s o p t ima l a t high humid i t i e s ( Ta b l e 4 ) . The re fore i f the l ung i s no t the only p o r ta l o f e n t ry the r i s k o f i nd i rec t t ra nsmi s s ion wou l d b e g re a t e s t i n a rea s wi th h igh humid i t i e s .

TABLE 4 Surv iv a l of M . l epra e i n Dried N a s a l S e c re t i ons Re l a t e d t o

Env i ronmenta l Temp e r a ture ( TOC ) a nd Humid i ty (H%)

Time d r ied ( d ay s )

o 1 2 3 6 7 9

1 0

S urv iva l

T36 . 7o

C /H7 7 . 6% T20 . 6o

C /H43 . 7%

6 /8 �'<

3 /8 4 / 8 6 /8

2 /4

1 00 100

10 0

2 / 1 2

0

ide

*

* Propor t ion o f p o s i t iv e f o o t pa d s . ** Pe rcent s u rv iva l .

Non-specific factors and susceptibility 1 45

Re ferenc e s

1

2

3

4

5

6

7

8

9

1 0

1 1

1 2

l 3

1 4

1 5

1 6

Ryr i e GA . S ome impres s i on s of S unge i Bul oh Lep er hosp i ta l under Japane s e occ upa tion , Lepr . Rev , 1 948 , � , 1 0- 1 7 . S kinsnes OK . The immunol og ica l s pec t rum o f l e prosy . In L e p r o sy in Theory and Pra c t i c e . C ochrane RG a nd Davey TF . Ed� B r i s t � l : J ohn Wrigh t a n d S ons L td . 1 9 6 4 i 2nd ed . 1 56 . S ki n s ne s OK a nd Higa H . · The r o l e o f pro t e i n ma l nu t r i t i o n in the pa thog e ne s i s o f u l c e ra t ive "La za r i ne " l e prosy . I n t . J . L epr . 19 7 6 , 44 , 346 - 3 5 8 . Dav ey TF a nd S chenc k RR . The end o c r i ne s in l eprosy . In L e p r o s y in Theory a nd Pra c t i c e . Cochrane RG a nd Davey-rF Ed s . J ohn Wr i g h t & S on s Ltd � Br i s t o l . 1 9 6 4 , 2nd ed . , 1 9 5 . L e i ke r DL . S ome a s pec t s of the e p i d emi o l ogy o f l e prosy . I n t . J . L e p r . 1 9 7 1 , 39 , 6 1 0- 6 1 5 . S inha DP a nd Ba ng FB . Pro t e i n a nd ca l o r i e ma l nu t r i t i on , c e l l med i a ted immun i ty , a nd B CG va cc i na t i on i n c h i ld ren from rura l We s t Benga l . La nc e t 1 9 7 6 , i i , 53 1 - 534 . Ha r l a nd PSE . Tub e r c u l in rea c t i ons in ma l nour i sh e d c h i l d ren . L a nc e t , 1 9 6 5 , i i , 7 1 9 - 7 2 1 . Y a ng HY a nd S k i n s ne s OK . I n t ra c e l lu l a r modu l a t i on in c e l l u l a r immuni ty . 2 . Ma c ropha g e enzyme s i n immuni zed , pro te i nd e pe ted a nd c o n t r o l m i c e du r i ng M . l epra emuri um infe c t i on . I n t . J . L e p r . 1 9 6 9 , 1 7 , 2 53 . Cochra ne AL . Tub e rc u l o s i s among p r i s one rs o f wa r i n G e rma ny . B r i t . Med . J . 1 9 4 5 , i i , 6 56 - 6 58 . Shepa rd CC . The exp e r ime n t a l d i s ea se tha t fo l l ow s the i nj e c t i on o f huma n l ep r o sy b a c i l l i i n t o foo t - pa d s o f m i c e . J . Exp . Med . 1 9 6 0 , V o l . 1 1 2 , N o . 3 , 445- 454 . Re e s RJW . Enhanced s u s c e p t i b i l i ty o f thymec t omi zed a nd i r ra d ia ted m i c e t o infec t i on w i th My c ob a c t e r i um l e pra e . N a ture , 2 1 1 , N o . 5049 , 6 57 , A ugu s t 6 , 1 9 6 6 . Re e s RJW . The impa c t o f exp e r imen t a l huma n l e prosy in the mou s e on l e prosy re s ea rch . I n t . J . L e p r . 39 , 1 9 7 1 , 20 1 - 2 1 5 . F i e l d s t e e l A H a nd Mc I n t o sh AH . E f fec t o f ne ona t a l thymec t omy and a n t i thymocy t i c s e rum on s u s c e p t ib i l i ty o f ra t s t o My c ob a c t e r i um l e p ra e infec t i on . Proc . S o c . Exp . B i o I . a nd� . 1 9 7 1 , 1 3 8 , N o . 2 , 408- 4 1 3 . Koh s ahka K , Y oneda K , Makino M , M o r i T a nd I to T . Exp e r imenta l l e prosy w i th nude m i c e . N ip pon Ri Ga kka Za s sh i , 1 9 7 9 , 48 , N o . 1 , 3 7 - 41 .

--

Ki rchh e imer WF a nd S t o r r s EE . A t temp t s to e s ta b l i sh the a rma d i l l o ( Da sypus novemc inc t u s , L inn) a s a mod e l for the s tudy o f l e pr o sy . I n t . J . L e p r 1 9 7 1 , 39 , 6 9 3 - 7 02 . I n The Pa thog ene s i s of t ub e rcu l o s i s . Rich AR E d . B l a c kwe l l S c i en t i f i c Pub l i c a t i on s , Oxford , 1 9 50 .

1 46 RJW Rees

1 7 Dunc an ME , M e l s om R , Pea r s on JMH a nd R i d l ey DS . Th e a s s oc i a t i on o f pregna ncy a nd l e p r o sy : I . N ew c a s e s , re l a p s e o f cured pa t ie n t s a nd d e t e r i ora t i on in pa t i e n t s on t r e a tme nt dur ing pregna ncy and l a c ta t i on - re s u l t s of a p r o s p e c t ive s tudy o f 1 54 pregna nc i e s in 1 4 7 E th i op i an wome n . L e p r . Rev . In Pre s s . 1 9 8 1 .

-

1 8 Dunc a n ME , Pea r s on JMH , Rid l ey ' DS , Me l s om R a nd B j une G . Pregnancy a nd l e pr o sy : the c ons e quenc e s o f a l t e ra t i ons of c e l l med i a t e d and humora l immun i ty during pregna ncy a nd l a c ta t i on . Am . J . Ob s t e t . Gyne c o l . S ubm i t t e d for pub l ic a t ion .

1 9 Ree s RJW a nd Mc Doug a l l AC . A i rb o rne infec t ion w i th My c o b a c t e r i um l e p r a e i n mi c e . J . Med . M i c rob i o l . 1 9 7 7 , 1 0 , 6 3- 6 8 .

20 Da vey TF a nd Re e s RJW . The na s a l d i s cha rge in l e p ro sy ; c l i ni c a l a nd b a c t e r i o l og i c a l a s pe c t s . L e p r . Rev . 1 9 7 4 , 4 5 , 1 2 1 - 1 34 .

-

2 1 De s i ka n KV . huma n b ody �

V ia b i l i ty o f My c oba c te r i um l e p ra e ou t s i d e th e L e p r . Rev . 1 9 7 7 , 48 , 23 1 - 23 5 .