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Tube rculo sis lo ad: re fle ctio ns o n a the m e
AN TON IO RUFFIN O N ETTO
Pat h o g en ic o rg an ism s, as p art o f a n at u ral process, in t eract wit h t he en viron m en t , searchin g for dyn amic st abilit y as well as for t heir ecological n ich es, wh et h er in t ern a l o r ext ern a l t o o t h er organ isms.
El u c i d a t i n g t h e c o m p l e x i t y o f t h e s e in t e rre la t io n sh ip s p o se s a re a l ch a lle n g e fo r epidem iologist s. Qu an t it at ive t heoret ical an alysis has been in su fficien t becau se of t he lim it at ion im p o sed b y q u est io n s su ch a s “Ho w m u ch ? ” “Wh e re ? ” a n d “Wh ich o n e ? ” Alt h o u g h t h e y s u c c e e d in q u a n t if yin g , c a t e g o r iz in g a n d correlat in g, t he an swers t o t hese qu est ion s do n ot always provide a sat isfact ory explan at ion of t he process. There is a real n eed for qu eries su ch as “Why?” an d “How?”, represen t in g t he t arget s of qu alit at ive m et hodology, which is an in - dept h, h o l i s t i c a p p r o a c h a n d e n c o m p a s s e s in t erdisciplin ary t hin kin g, abst ract m ean in gs an d su bt le implicat ion s.
An swers t o m a n y q u est io n s rela t ed t o t h e pat hogen icit y of t u bercu losis m ay be fou n d in qu an t it at ive an alysis. Nevert heless, t he dyn am ics of t u bercu losis can n ot be fu lly u n derst ood wit hou t also t akin g a qu alit at ive approach. As an exercise, let u s exam in e t he disease an d it s dyn am ics.
The pat hogen ic power of an in fect iou s disease has lon g been defin ed as a fu n ct ion of m icrobe viru len ce (V) an d t he resist an ce (R) of t he in fect ed organ ism , in t errelat ed as follows:
R
V
=
1
Bier(1 )p o in t ed o u t t h at t he pat hogen icit y (P)
of t he process shou ld be a join t fu n ct ion of t hese t wo co m p o n en t s. If we rep resen t V a n d R a s perpen dicu lar vect ors, t he pat hogen icit y wou ld be expressed by t he an gle of t he vect or resu lt in g from t he su m of t he t wo, as represen t ed in t he diagram b elo w:
V
R
P
Theobald Smit h su ggest s t he “formu la”:”
R
V
N
P
=
.
where N is t he n u m ber of germ s t hat pen et rat e t he organ ism.
Ric h a d d s ye t a n o t h e r c o m p o n e n t : t h e t u bercu lin allergy, whose n ecrosis pot en t ial cou ld ag g ravat e t h e lesio n . Th erefo re, t h e “fo rm u la” wou ld be:
R
H
V
N
P
=
.
.
If we u n derst an d resist an ce (R) as bein g n at u ral (n) or acqu ired (a), we wou ld have:
)
(
.
.
a
n
R
H
V
N
P
+
=
The expression above, which is well est ablished in t h e lit e ra t u re ,(2 ) h a s t h e so le f u n ct io n o f
399
exp ressio n t h a t g en era t es n u m erica l so lu t io n s.Man y hypot heses have been proposed in at t empt s t o explain t he physiopat hology an d im m u n it y of TB. It has been su ggest ed t hat t he t ype of immu n e re sp o n se (wh e t h e r Th 1 o r Th 2 ) is cru cia l. In addit ion , Beyer et al.(2) emphasized t he roles played
by IL- 4 an d IL- 12, Speller & Edwards(3) su ggest ed
t h a t IL- 2 a n d INF- ³ a re in vo lved , a n d Elln er(4 )
im plicat ed CD4 T cells, m acrophages, IL- 1, IL- 6 a n d TNF- ± . Ne ve rt h e le ss, c e rt a in q u e st io n s pert ain in g t o t he hu man immu n it y t o t u bercu losis h a ve yet t o b e a n swered . Th e m o st in t rig u in g fin din g is t hat on ly 10% t o 20% of t he people in fect ed wit h Mt b d evelo p t h e d isea se, wh ich m ean s t hat 80% t o 90% of t hose in dividu als are somehow prot ect ed. Why? On t he ot her han d, it is im port an t t o poin t ou t t hat , in t he case of TB, we ca n sa fely rely o n ea sily p erfo rm ed d ia g n o st ic t echn iqu es an d dru g t herapy regim en s t hat have proven effect ive.
THE TUBERCULOSIS BURDEN
Th e Wo rld Hea lt h Org a n iza t io n (WHO) h a s recently declared tuberculosis to be a “global health em ergen cy”, based on t he fin din g t hat on e- t hird of t he world popu lat ion has been in fect ed(5). The
WHO, ackn owledgin g it s n eed for assist an ce in d ea lin g wit h t h e q u est io n o f TB co n t ro l, h a s creat ed a program called STOP TB. This program is a part n ership am on g t he WHO, t he World Ban k, t he In t ern at ion al Un ion Again st Tu bercu losis an d Lu n g Disea se, t h e Cen t ers fo r Disea se Co n t ro l (At la n t a , GA, USA), t h e Ro ya l Ne t h e r la n d s Tu b e rc u lo s is As s o c ia t io n a n d t h e Am e ric a n Thoracic Societ y.
This m ight be an opport u n e m om en t t o re-exam in e t he form u las previou sly shown an d add or m odify som e of t heir com pon en t s in order t o propose n ew perspect ives from which t o view t he t u b ercu lo sis b u rd en a s a g lo b a l p u b lic h ea lt h con cern .
If an expression was previou sly u sed in order t o presen t pat hogen icit y, t he sam e cou ld be don e here, su ggest in g t hat t he t u bercu losis bu rden (TBb) be expressed as:
) ).( ).( ( ). ).( ( ).) ).( ).( )( ).( ).( ( GPP RHSS NUT EDU N DOT DOSS EPOP MMIG PR PABT PHIV DSOC CTb + ≈
Not ably, t he most import an t of all compon en t s is so cia l in e q u a lit y, sin ce p o ve rt y re su lt s in maln u t rit ion , in adequ at e livin g con dit ion s, limit ed edu cat ion , et c., t hereby in flu en cin g m ost of t he ot her com pon en t s.
We m u st a lso h ig h lig h t t h e fa ct t h a t t h e in ciden ce of prim ary resist an ce is in dicat ive of an ep id em io lo g ical ag g ravat in g fact o r t h at is m o re sig n ifican t t h an t h at o f acq u ired resist an ce. In applyin g t he expression above, we m u st bear in m in d t he fact t hat it does n ot gen erat e n u m erical solu t ion s bu t on ly facilit at es ou r con siderat ion of t h e p ro b lem .
The WHO est imat ed t hat 80% of all t uberculosis c a s e s in t h e w o r ld a r e c o n c e n t r a t e d in 2 2 cou n t ries:(6) In dia, Chin a, In don esia, Ban gladesh,
Pakist an , Nigeria, t he Philippin es, Sou t h Africa, Et hiopia, Viet n am, Ru ssia, t he Democrat ic Repu blic o f Co n g o , Bra z il, Ta n z a n ia , Ke n ya , Th a ila n d , Myan m ar, Afghan ist an , Ugan da, Peru , Zim babwe an d Cambodia. We can immediat ely perceive t hat , in som e cou n t ries, t he problem m ay be locat ed at t he n u m erat or level, at t he den om in at or level in ot hers, an d at bot h levels in som e cases.
In Ru ssia, t he qu est ion of high in ciden ce of m u lt id ru g - re sist a n ce is a m a t t e r o f p re ssin g con cern . In African cou n t ries, all t he com pon en t s of bot h t he n u m erat or an d t he den om in at or are h ig h ly in f lu e n t ia l. Br a z il m a y r e p r e s e n t a n in t e rm e d ia t e sit u a t io n , sin ce t h e p ro b le m o f m u lt id ru g - resist a n ce is, fo r n o w, a m in o r o n e, alt hou gh social in equ alit y is pron ou n ced an d t he ot her com pon en t s of t he form u la are in flu x. In Peru , t h ere h a s b een a su b t le b u t p ro g ressive redu ct ion in t he t u bercu losis bu rden over t he past few years as a resu lt of a reorgan izat ion of pu blic healt h services, specifically in t he t u bercu losis field, in volvin g implemen t at ion of su pervised t reat men t , which has redu ced t he percen t age of pat ien t s who aban don t reat m en t . In Sou t heast Asian cou n t ries, d esp it e t h e fact t h at all t h e co m p o n en t s o f b o t h t h e n u m e ra t o r a n d t h e d e n o m in a t o r o f t h e expression are qu it e sign ifican t , t here is m arked social in equ alit y an d lim it ed dru g availabilit y in pu blic healt h clin ics.
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Reflect ion on t his n ew “form u la” m ay m ake it possible t o perceive t hat , while t here have been advances in TB- related technical, biological, clinical a n d e p id e m io lo g ic a l k n o w le d g e , it s s o c ia l dim en sion m u st be con sidered, valu ed an d u sed as a quality- of- life indicator. It would be worthwhile t o in t ro d u ce t h is fo rm u la in o t h er fo ru m s o f discu ssion su ch as, amon g ot hers, t he World Healt h Assembly, t he Int ernat ional Labor Organizat ion and t he World Trade Organ izat ion .
An t on io Ru ffin o Net t o
Professor Em erit u s of Social Medicin e Ribeirão Pret o School of Medicin e- USP
e- mail: aru ffin o@ fmrp.u sp.br
REFERENCES
1 . Bi e r, Ot t o - M i c ro b i o l o g i a e Im u n o l o g i a . Ed . Melh o ra m en t o s, 2 4 º ed içã o . 1 9 8 5
2 . Beyer DA, Rie A, Ad a m s J , Fen h a lt s G, Gie R Beyers N. Si g n a l s t h a r e g u l a t e h t e h o s t r e s p o n s e t o Myc o b a c t e r iu m t u b e r c u lo s is . No va r t is Fo u n d a t io n Sym p o siu m , 1 9 9 8 ; 71 7 : 1 4 5 - 5 7
3 . Sp ellb erg B e Eswa rd s J E- Tyo e 1 / Tyo e 2 im m u n it y in in fect io u d d isea ses. Clin ica l In fect io u s Disea ses 2 0 01 ; 3 2 : 7 6 - 1 0 2
4 . Elln er J J . Th e im m u n e resp o n se in h u m a m t u b ercu lo is – im p lica t io n s fo r t u b ercu lo sis co n t ro l. Th e J o u rn a l o f In fect io u s Disea ses 1 9 9 7 : 1 7 6 : 1 31 - 9
5 . Ra vig lio n e MC Sn id er DE, Ko ch i A. Glo b a l Ep id em io lo g y o f Tu b ercu lo sis. J .A.M.A. 1 9 9 5 ; 2 7 3 : 2 2 0 - 6
