Am J Clin Nutr 1980 Sommer 887 91

8/13/2019 Am J Clin Nutr 1980 Sommer 887 91

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T he m er ica n Jou rn a l o f lin ica l N u tri tion 33: A PR IL 1980, pp . 887-891 . Pr in ted in U .S .A . 88 7

H is to ry o f n igh tb lin dness : a s im p le too l fo rxe roph tha lm ia 2A lfr ed S om m er M D M H S G us ti H us sa in i M D M u hila l P h D

Igna tiu s T arw o tjo M S D jok o Su san to M S and J Su lia n ti Sa roso M D P h D

A B S T R A C T A m ong 5 925 presch oo l-age ch ild ren exam ined in a house to hou se ru ral fie ldstud y, X 1 B (B ito ts spo t w ith xe ros is) and /or an histo ry o fnig htb lin dne ss (X N ) w as prese nt in 325 .M e a n se rum vita m in A leve ls am ong tho se w ith iso lated X N (1 3.9 M g/d l), iso late d X 1B (13.4 ig Jd l), an d coe xis ten t X N /X 1B (12.1 g/d l) w ere s im ilar , an d sig nif ican tly below tha t ofn orm al a ge/sex/neighb orh oo d m atc hed con tro ls (1 7 .6 , 17 .1 , a nd 18 .3 g /d l, re sp ectively). T h e m ean serumv itam in A le vel of the m atc hed con tro ls w as sig nif ican tly below th at o f n orm al, rand om ly sam pledc hild ren fro m the s tud y p opu lat ion as a w h ole (20 .6 g /d l). A s ind epe nd ent scre en ing c rite ria ,d is regard ing the presence or absen ce of o ther sign s, tw ice as m any ch ild ren had a h isto ry of X N ash ad X lB (84 and 41 % of a ll clin ica lly abn orm al ch ild ren , respec tive ly ). O f random ly sam pledch ild ren 55% but on ly 15% of cases of X N and 10 % of X IB had se rum vita m in A leve ls ab ove 20g /d l . O f ch ildren w ith a his tory of nig htb lind ne ss 9 7% had im pa ired sco top ic v is ion o n ob jec tiv etesting , bu t the m e an se rum vitam in A lev els am on g test po sitiv es an d n ega tiv es w ere id en tica l.T hese resu lts sugg es t a p roperly elic ited h isto ry of n igh tb lindn ess can b e a lm ost as sp ec ific an d fa rm o re sen sitive an index o f v itam in A defic iency and early xeroph tha lm ia than the presen ce ofBito ts spo ts (X IB ), and th at vitam in A deficie ncy is a c lus tere d , n eig hbo rho od p hen om eno n rath erthan an iso la ted , sp orad ic occurren ce . A m J C l i n Nu t r 3 3: 8 87 -89 1, 198 0.

McL ar en 1 ) e s ti m at es 100 ,000 ch ild ren g ob lind from x eroph tha lm ia ev ery y ea r . R ecen tda ta su ggest the tru e figu re m ay be m an ytim es h igh er (2 ). S im plified field tech n iq uesfo r d ia gn os in g ea rly xe ro phtha lm ia an d v i-tam in A deficien cy are req u ired for gau gin gthe m ag nitud e an d d is tribu tio n o f th e pro b-lem and id en tify ing ch ild ren in need of treat-men t 3 .

B ito ts spo ts w ith co n ju nc tiv al x ero sis(X 1 B ) a re the m ost p rev alen t, accep ted cm -ica l c rite rion . B ut th is is lik ely a la te m anife s-ta tion of the d isease and requ ire s sk illed ob -se rve rs fo r accu ra te d iagno sis .

N igh tb lindn ess (X N ) is gene ra lly co nsid -ered th e earl ies t, m ild est ex pression of c lin icalxeroph th alm ia . B u t r ig orous , ob jective assess -m e n t o f sco to p ic v is ion is d iff icu lt if no tim po ssib le in yo un g ch ild ren , e sp ec ia lly u n -de r fie ld con dit ion s, w h ile a sk in g a pa ren t orgu ard ian w h eth er a ch ild is n igh tb lin d iscons idered to o su b jective to be o f va lue . B e-cause o f the se p rob lem s the recen t rec la ssif i-c atio n o f c lin ica l xe roph tha lm ia re lega tesn igh tb l indness to a seco nda ry ch aracte r is tican d om its it en tirely fro m preva lence c rite ria

u sed in de term in ing w he the r th e d isease po sesa sig n ifican t p ub lic health p rob lem (4).

O u r ob serv ations o n rura l, p re sch oo l-ageJavanese ch ild ren ind icate a p rop erly e lic itedh is to ry of n ig h tb lin dn ess can b e alm o st a sspec ific an d fa r m o re sen sitiv e a sign o f v i-tam in A defic iency than the presence of B i.to ts spo ts .Backg round

Ind on esia is a trop ical, d ev e lop ing co un tryo f 13 0 m ill ion peop le inh ab itin g o ve r 1 00 0is land s. O f th e po pu la tion 64% resides onJav a, o ne o fthe m ost d ensely p op ula ted a reasin th e w o rld . T h e m ean p er cap ita incom e,tho ug h ris in g , is s til l o n ly 22 5 U S ; 75 % o f

From the N utrition al B lin dness Preven tion P ro ject,B andu ng , Indones ia. T he N u tritiona l B lindn ess P reven-tio n Pro jec t is a jo in t und ertak ing of th e M in istry ofHeal th , G o ve rnm ent of In don esia, an d H ele n K ellerIn te rna tio nal, N ew Y ork, N .Y ., w ith su bs tan tial fund ingfrom th e O ffic e of N utrition , U n ite d S tate s A gen cy orIn tern atio nal D e ve lop m e nt, W a shington , D .C .

A dd ress reprin t reques ts to : A lfred So m m er , M .D .,H e len K eller In te rna tiona l, 22 W est 17 th S t., N ew Y ork ,N ew Y ork 10011 .


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H I ST O RY O F N I GH T B L I N D N ESS 889w i th i solated nightbl indness by history (X N )(excluding cases w i th any f orm of conj uncti -v al i nv olv em ent), i solated B i tot s spots (X 1B )(excluding cases w i th a history of nightbl ind-ness), and X N in the presence of X 1B w eresimilar, an d si gn if i can tl y P 0.001) belowl ev els f or thei r m atched controls (T able 2).B y pai rw ise anal ysis, the m ean di f ferences 2 SE betw een abnorm al s and controlsw ere -3.77 (-2.35 to -5.19), -3.67 (-1.07 to-6.25), and -6.07 (-4.19 to -7.95), respec-ti v ely . T he mean serum v i tami n A levelamong chi ldren posi ti v e f or both X N andX 1B w as l ow er than am ong chi ldren w i thei ther condi tion alone but not to a stati st i cal l ysi gni fi cant degree.

T he mean serum V i tam in A l ev el of sub-sam pl ed chi ldren w as stati sti cal l y si gni f i -cantl y hi gher than the col lecti ve m ean of thecontrols P < 0.001). Rem oving al l abnormalsand m atched controls f rom the subsam ple(T able 2) only increased this di f f erence. T hem ean serum v i tam in A l evel of these cl inical l ynormal chi ldren l i v ing in nei ghborhoods f reeof acti ve xerophthal m ia i s stati st i cal l y si gni f i -cantl y greater than the m ean of each sub-group of control , cl i nical l y norm al chi ldrenl i v ing i n the nei ghborhood of an acti ve case.Resul ts are unaf f ected by age/sex adjustm entof the corrected random sam ple to thecontrols.

Conventional distr ibution of serum vi -t m in l evels into def i cient , l ow , and adequate categories (7) i s show n i n T able3. A dequate levels w ere present in 55% ofcl inical l y normal chi ldren in the subsam ple,but only in 18% of chi l dren w i th isolated X N ,12% w i th i solated X 1B , and 9 w ith coex ist-

T A B L E 2Serum v i tam in A lev el by cl i ni cal status

C li ni cal st at us n M ean SEg s g / d I

X N + , X IB (-)Controls

X N (-) , X 1B (+ )ControlsX N + , X 1B (+ )Contro ls

SubsampleC orrected subsam -

pIe

174161

514576

268222

13.917.613.417.112.118.320.020.6

0.450.620.771.190.561.000.480.51

a X N , nightblindness; X 1B , conjunctiv al x erosi s w i thB i tot s spot; X N + , X 1B + , X N and X 1B coexistentin the same child. b A bn or ma an d c on tr ol s ex cl ud ed .

ing X N /X 1B . Only 15% of al l chi ldren w i thX N (w i th or w i thout X 1B ) and 10% w i th X 1B(w i th or w i thout X N ) had adequate levels.T he di f f erence in the distr ibution of v i tam inA lev el s betw een these l atter tw o groups isnot stati sti cal l y si gni fi cant, w h i le the di f fer-ence betw een each of them and the cl inical l ynormal , subsam pled chi ldren is P 0.00 1).

T he value of X N and X 1B as independentscreening cri teria are f urther analy zed inT ables 4 and 5, w here X N incl udes al l chi l -dren w i th a history of nightbl indness, includ-ing those w i th aty pical and mi l d conjuncti vallesions (conjuncti val x erosi s, X 1A and B i tot sspot w i thout xerosis) ex cluded f rom the ear-l ier tabulations. T he m ean serum vi tam in Alevel of chi ldren w i th X 1B (w i th or w i thoutX N ) w as only sl ightl y , but not stati sti cal l y

T A B L E 3D istr i buti on of serum v i tam in A level s

Clin ica lstatus n Range

P ercentage o f c ase s

( 0-9 g/dl )ef i ci ent { 176} M

X N (+ )X 1 B ( - ) 174 4-30 27 55 18X N ( - )X I B (+ ) 51 5-32 31 57 12X N (+ )X 1B (+ ) 1-29 38 53 9X N (+ )X1B(+o r - ) 253 1-30 30 55 15X 1B (+ )X N ( + o r - ) 130 1-32 35 55 10X N (-)X 1 B ( - ) 252 1-44 8 37 55

a X N , nightblindness; X 1B , conjuncti val x erosi s w i thB i tot s spot; X N + , X 1B + , X N and X 1B in the sam echi l d; X N (-) /X 1B (-) , cl in ical l y norm al chi l dren in thesubsample.

TA B L E 4N ightbl i ndness and B itot s spots as independentscreeni ng cri ter ia of cl ini cal xerophthalmia

Clin ica lstatus

n M ean serumvitamin SE

totalcases identi f ied g /d l

X N 273 13.4 0.35 84X 1BX N a nd/or X 1B

132325

12.613.4

0.460.31

41100

X N i ncl udes cases w i th and w i thout i solated con-j uncti val xerosis (X 1A ), isol ated B i tot s spot, orx l B . bSerum v i tam in A values w ere unavai lable onthree of 273 cases of nightbl i ndness (X N ) , tw o of 132cases ofconjuncti val xerosis w i t h ito t s sp o ts (X 1B ) andf our of 325 cases w ith ei ther.


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890 SO M M ER ET A L .T A B L E 5Prevalence5 of cl inical xerophthalm ia and hy pov i tam i nosis A

Clin ica lstatus

n

Deficient(0-9 gJdl )

r a te

Lo w( 10 -1 9 g sg /d l)

n r at e

A(

n

dequate20 gJdl)

r a te

T oY

n r ateX N 81 1.4 148 2.5 41 0.7 273 4.6X 1B 46 0.8 71 1.2 13 0.2 132 2.2X N and/o r X 1B 97 1.6 177 3.0 47 0.8 325 5.5Subsample 23 8.6 101 37.7 144 53.7 268 100

Rate per 100. B ase populati on (denom inator) f or cl i ni cal d isease (X N , X 1B , X N and/or X 1B )i s the total num berof chi ldren exam ined (5925), w hi l e f or the random subsam ple i t is onl y those in the subsam ple i tsel f (268). bXNi ncl ud es cases w i th and w i thout any form of conjuncti v al lesion (X lB , X IA , X B ), and X 1B , cases w ith and w ithoutX N . C BI { 216} unavai lab le on t h r ee of 273 cases of X N , tw o of 132 cases of X IB , and f our of 325 cases w i th ei ther. Total i ncl udes these m issi ng cases.

significantly l ow er than am ong chi ldren w i thX N (w i th or w i thout conj uncti val lesions)(T able 4). Over tw i ce as many chi ldren hada history of nightbl indness as had X 1B (273and 132, respect iv el y).T he prevalence of nightbl i ndness in thestudy populati on as a w hole w as 4.6% and ofB i tot s spots 2.2% (T able 5). B y w ay of con-tr st the prevalence of inadequate v i tam in Al ev els (def i cient and low ) among random lysam pled chi ldren w as 46.3% . T he prev al enceof def i cient v i tam in A lev els w as 1.6 tim esthat of cl i nical xerophthalm i a (X N and/orX 1 B ) 8.6/5.5 and of inadequate v i tami n Al ev els (def i cient and l ow com bined) 8.4 tim es46.3/5.5 .

I ndi v iduals w ith a history of nightbl indnessf or more than 2 m onths had a low er m eanserum v i tam in A level than those w hose dis-ease w as of shorter duration (12.9 versus 13.5g/dl , respecti v ely ), but the di f f erence w asnot stati sti cal ly si gni fi cant.

O f the 228 chi ldren resi ding in v i l l agesw here objecti v e assessment of ni ghtbl indnessw as carried out 92% w ere actual l y tested.Only seven (3% ) tested negative. T he m eanserum vi tam in A level of these test negativ es(13.7 jg/dl ) w as identi cal to that of the testposi ti ves. N one of the chi l dren lack ing a his-tory of nightbl indness appeared to be night-blind.

DiscussionA simple f ield test f or v i tam in A deficiency

and x erophthalm ia i s urgentl y needed (3).B iochem ical param eters of v i tamin A status,theoreti cal l y the m ost sensi t i ve cri teria, areim practi cal in most f ield and cl inic si tuati ons,w hi le a history of nightbl i ndness is consid-

ered to o s u je c tiv e to be of v alue. Obj ecti v elytesting scotopic v ision i n preschool -age chi l -dren is impracti cal f or m ost f i eld and cl inicwork .

T he present study suggests that a properlyel i ci ted history of nightbl indness can be asval id ev i dence of v i tam in A def ici ency as thepresence of X 1B . M ean serum vi tam in Alevels am ong chi ldren w i th isolated X N , iso-lated X 1B and coex istent X N /X 1B w ere cm -ical l y and stati sti cal l y si gni f i cantl y greaterthan among thei r age/sex /neighborhoodmatched control s (T able 2). D i f f erences i nmean serum v i tam in A l evels betw een thethree categories of cl inical disease w ere smal land stati sti cal l y insigni f i cant. T his is evenmore apparent w hen X N and X 1B are ana-l ysed as independent screening cri teri a, i g-nor ing the presence or absence of the otheras a coex ist ing sign (T able 4).

A sl ightl y greater proportion of chi ldrenw i th X N than X 1B (as isol ated si gns or in-dependent screening cri teria) had adequateserum v i tam in A l ev els (T able 3). T houghnot stati st i cal l y signi f i cant, this di f f erencesuggests ei ther the speci f i ci ty of X N is low erthan that of X 1B , som e cases of X N being f alse posi ti ves , or X N appears earl i er in thedisease process, at higher serum ,v i tamin Alev el s. T he latter seem s to hav e been the case.Objecti v e assessment of scotopic v i si on con-f i rmed the presence of nightbl indness in 97%of chi l dren w i th a posi ti ve history tested. T heremaining 3% probably suf fered m i lder night-blindness i ncapable of detection by our rathercrude test: thei r m ean serum vi tam in A lev elw as identi cal to that of the test posi t i ves.Studies on v i tam in A depleted adul t volun-teers indicate i nterf erence w i th scotopic v i -sion is the earm est, m i ldest cl i ni cal expression


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H I ST O RY OF N I GH T B L I N D N ESS 891o f v itam in A def iciency (8, 9), and can occurat serum l ev els abov e 20 g/dl (9).

T w ice as many chi ldren had a hi story ofX N as had X 1B . T his increased sensi t i v i ty i sinv aluable f or survey w ork , w here the higherprevalence w ould resul t in increased preci -sion, or al ternati vel y perm i t a reduction insample size, and in cl inic and screening pro-gram s w here a larger proport ion of chi l drenat ri sk of serious v i tam in A def iciency can beidenti f i ed and treated.

N ot al l chi l dren w i th impai red scotopicv ision w ere necessari l y i denti f i ed. W e w ereunable to test suf f i cient num bers of chi ldrenw i th a negative history to determ ine the pro-portion m issed by our questions. T he f actthat onl y 79 of 130 chi ldren (61% ) w i th X 1Bhad a posi ti ve history suggests i t m ay hav ebeen appreciable. N onetheless, a history ofnightbl indness w as present i n 84% of al l x e-rophthal m ia cases detected. T he ease w i thw hi ch a history of nightbl indness can be el i c-i ted, requi ring l i ttl e training and no cl inicalexperience, and the large proportion of x e-rophthal ni ia cases i t i denti f i es greatl y f aci l i -tate i ts use i n survey w ork and innovati v escreening program s. Plans are al ready under-w ay in Indonesia to determ ine w hetherschool chi l dren can ef f ecti v el y screen thei ryounger sibl i ngs.

T he prev al ence of low v i tamin A lev els(< 10 tg/d1) in the populati on, 8.6% w as com-parable to the prevalence of cl inical l y detect-able disease, 5.5% (T able 5). T he prev alenceof i nadequate (def i ci ent and low ) serum v i -tamin A lev els how ever w as m uch hi gher(46% ), indi cating the vast m ajori ty of chi ldrenw i th serum l ev els below 20 g/dl w ould goundetected. A n unex pected f m ding in thepresent study suggests a possi ble means ofdealing w i th this problem. M ean serum vi -tam in A l evels among neighborhood matchedcontrol of xerophthalm ia cases w ere consid-erabl y below age/sex adj usted random sam-plc norm s, indicati ng otherw ise normal chi ldren l i v ing in the imm ediate v icini ty ofcl inical l y apparent cases are m ore apt to bev i tam in A def ici ent, hence at higher ri sk ofx erophthalm ia, than those l i v ing f urtheraw ay . V i tam in A def i ciency , i n Java at least,appears to be a local , neighborhood-speci f icphenom enon rather than an isolated, spo-radic occurrence. T his clusteri ng of v i tam inA -def i cient chi ldren m ight be put to good

use, by treating al l chi ldren i n the neighbor-hood of a cl ini cal case instead of l im i ti ngtherapeuti c and prev enti v e m easures to thech i ld w ith dem onstrable disease.

A note of caution m ust be raised. W e ac-cepted a history of nightbl indness only w henth e parent or guardi an w as certain of i tspresence. I n addi tion, w hi le w e w ere preparedto describe the si gns and sy mptom s of night-bl i ndness thi s w as rarely necessary : the v astmajor i ty of respondants w ere fam i l i ar w i ththe local terms f or the condi tion. A l thoughconf i rming prev ious cl i nic-based observ a-ti ons in Java (10) these resul ts are not neces-sarily v al i d f or other cul tures, especi al l yw here local terms f or ni ghtbl indness do notexist or are not i n comm on usage.

T he authors thank D r. Susan T . Petti ss, Direc torB l indness Preventi on A cti v i t i es, H elen K el l er I nterna-ti onal , f or her adv ice a nd as si s ta nc e in carry ing out thi sstudy.

References1. M C L A R E N D . S. X erophthalm ia and bl i ndness. B ri t.

M ed. J. 2: 668, 1970.2. So,ssszR , A ., 0. H U S S A I N I T . S U G A N A E. N A N I A N DI. T A R W O T J O X e r o p h t h a lm i a D e t e r m i n a n ts and

control . Proceedings of the X X I I I I nternati onal Con-gress of O phthalm ology . A msterdam , Excerpta M ed-i c a 19 7 8 pp . 1 6 1 5 1 6 1 8 .

3. L A T H A M , M . C., J. C. B A U E R N F E I N D W . J. D A R B YAN D A . P I R I E Research needs i n present and futurev i tam i n A program s. I n: Guidel i nes f or the Eradi -cati on of V itam in A D ef i ciency and X erophthalm ia.N ew Y ork : IV A CG , 1976, p. IV -2.

4. V i tam i n A D ef iciency and X erophthal m ia. Reportofa Joint W H O /U SA ID M eeting. T echnical ReportSeries no. 590. Genev a: W orl d H eal th O rgani zati on,1976, pp. 18, 32.

5. Sotosea, A . Fiel d Guide to the D etecti on and Con-trol of X erophthalm ia. Genev a: W orl d H eal th O r-ganization, 1978, p. 11.

6. N E E L D J. R ., AN D W . N . P E A R S O N M a c r o andmicromethods f or the determ ination of serum vi -tam in A usi ng tri f l uoroaceti c acid. J. N utr. 79: 454,1963.

7. M anual f or N utri t i on Survey s. I nterdepartmentalCom mi ttee on N utri ti on for N at ional D efence (2nded.). B ethesda, M d.: 1963, p. 235.

8. H uM a, H . E., AN D N . A . K nans. V itam in A Require-m ents of H um an A dul ts. L ondon: M .R.C. Spec.Rept. 5cr. no. 264, 1949, p. 21.

9. S A U B E R L I C H , H . E., H oi xs, R. E., W uca, D . L .,K O L D E R H ., C tai , J. E., H O O D , N . RA I CA A N DL . K . L O W R Y V i t a m i n A m etabol ism and requi re-m ents i n the hum an studied w i th the use of l abel edreti nol . V itam ins H orm ones 32: 251, 1974.

10. B L A N K H A R T , D . M . I ndiv idual intak e of f ood inyoung chi l dren in relat ion to m alnutr i ti on and ni ght-bl indness. T rop. G eog. M ed. 19: 144, 196 7.

Am J Clin Nutr 1980 Sommer 887 91

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Transcript of Am J Clin Nutr 1980 Sommer 887 91