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Focus on the effect of bednets on malaria morbidity and mortality
Letters Focus on the Effect of B~:dnet~.s on Malaria Morbidity and H o r t a l i t y Trape and Ro~ier i shed new and interesting light on the relationship between malaria transmission intensity and the number of morbidity episodes in a life, However, we cannot a~ree with their extrapolation of these morbidity data to malaria mortality. A careful examination of the evidence presented in the inb-oduction reveals serious problems with each of the four examples. First, the data from Trape et ol. f, om Brazzaville 2 indeed fail to show variations in severe malaria disease :ares between areas in the city with highly different transmission rates. However, these data come from an urban area in a relatively high-income country [The Congo in the 1980s had a GN2 (gross national product) of $880 per head] 3, and they are clearly unrepresentative of most of sub-Saharan Africa. According to the authors' own summary, the rates of severe disease that they (ound (overall I.t5 per 1000 in the 0-4 year olds) are '... 30 times lower than those expected from the results of previous studies of the mortality due to malaria in intertropical Afnca'. The second work they cite I compared two arc.,s in East Africa differing by a factor of ten ,n transmission intensiL'y, but with apparently similar malari~ hospitalization rates. Beside [he problem of defining an adequat, ~_ base population and attendance bias, Trape and i~ogler rail to point out that ;he rate of severe malaria disease admissions, as defined by severe anaemia or" cerebral disease, was twice as high in Ifakara (the area with the h ,her"transmission) than in Kilifi on the Ken ,an Coast (21.7 vs 11.8 per 1000).
20 18
F; ,u u~; icr ~J~t~ set £ um K~i,F,~ dido ~oses problems of attendance b~s, and because the number of deaths in ti(e nine subgroups
,s so small the interpretatir~n is very difficult. Despite this. it is ~nt.~resbn~ to note that the cqe site with the hi£hest admission rate (i~!tondia) a:so had a much higher rate of b3nsmission [eqtomological inoculabon rale (~IP,) 0[60. compared to E!P-,~From 0 to 18 in the eight other sites], The fact that th~s same site also had the lowest rate of severe disease in th£ baseline period indicates that disease admission rates are subject to major vanation in space and time with no obvious cause ~. Finally. Trape and Ro~]ier mention the recem paper by Snow and Marsh/. that tamed out an 'ecological companson', ie. the comparison of mortality rates across distinct socio-economlc and ecolo~icai eqvironments. We have corr,g~,ented earlier on the problems associated wtth th~s approach, such as the high vahabllity o1" mortality rates and the unreliability of,,erl~al autopsies leadin~ to under-reporting at N~htransmission imensities 8. The recent letter by Carme ~ further illustrates the major problem of confoundin~ by socio-economtc factors. Furthermore, few data are available. and the picture ~]iven by such a review can change dramatically as new information becomes available. To illustrate th~s, we have re-worked the Fi~une Jnttially presented by Snow and l~la~sh (F~ I fiom Ref. 7). With new and updated ev!dence ) i3 and with the removal of one point from Congo ~ (for reasons givep above) as well as two data points from the 1950s (because of the enormous
downward b end in mot ~ i ~y over dec~d~s. it is not reasonable to assume that these data are still comparable to contemporary data), the picture that emerges (Fi~. I ) is Uiat of a continuous increase in malana-
specific mortali*:/with increasin~ transmission, with the exception of the situation in western Kenya ~n the 1980s (Ref. 17). The evidence in favour of equahty of malaria-speciflc mortality rates regardless of transmission is, therefore, weak As the whole argument of To, De and Rogier, including their extrapo!ated mortality rates, largely m!ies on this assumption, the data presen[ed hl their Table should be regarded critically. Unfortunately. the evidence to su~e~ that there is indeed a long-terrn survival benefit with vector-control interventions alone is equally weak In a careful review of historical evidence. Moiineaux t9 showed that, in Sn Lanka (a countrf with a go0d vital registration system) overall death rates correlated well wiLh spleen rates (as a proxy for transm.:sion intensity) before il ,door spraying wia, ODT on a large scale. The introduction oi" this vector-controi intervention was then followed by a substantial and lasting reduction in ir/ant and child mortality. Similar effects were se.en in Guyana and in other South ,amencan countries after the introduction of" houre spraying. The only data set wah a Ionx-[erm follow-up after vector control alone in Afiica (from the Pare Taweta scheme in Tanzania and Kenya) gives no indication cf a 'rebound' or a delay in mortality ~o~'. Rates in the protected group remained low even after control was discontinued. Rates n a new generation or infants, however, returned to pre-con[rol {evels after cessation of spraying.
15 Tanzania II
Fig. I. Possible relationship between transmission intensity (entomological inoculation rate) and malaria-speclfic mortality in children below five yea,'s of age. Based on a Figure by Snow and Narsh ~, with substantial modifications (see ,exc). Numbers over points indicate references for mortality data.
16Tanzanial BurundilO 18 Ghana
I
~g
~
~°
G a ~ b i a IV 13
Gambial111
~c
•
-
Gambia III i2 •
14 Sierra Leone
• 10 Gambia I
17 Kenya
4
2 0
10
100
1000
Entomological inoculation rate (EIR)
Purasitolo~y Today, vol. 13, no. 3. 1997
12]
I
Letters Clearly the Question of increased survival fc,!lowing w~ctor cot;tin! has major implications and it deserves p r i o r y attention. The reality is that evidence to date is insufficient to make an informed assassmenL It is useful to recall that in atLempting to measure relative!y small differences, such as 20~30,o reductions in overall morta!ity in an environment of high v~aiability and strong s~cular trends, the ,methodological problems encountered are considerable ~2. So, v,,'~at should we recommend to, in 'p!ementing agencies? We agree witr, Rogier and Trape that improving access m timely and effective treatment for all mala~a patients repn~s~nL~ a r-~o~t desirable goal. The African reality it, that ~.' ,h!~. health services have been o~iy partiall) successful in the fight against rna~ana morb, !iW and mortality. Future prosFect., are r ) better. Should we therefore wait anoth r decade and the certainty of f0 million child deaths? O r should we move ahead with insecticidet~a~ed b=~.~ts. which, besides being highly effe~ive in i"t-~. short telm, a~v also in high
demand because oftJ~e reduction in nui:'ance biting? Our" choica iS easy:get the nets.
References I Trape J-F.and Rogier C (1996) Parasitol, Toda). 12, 236-240 2 Trape. J-F, et al. (19~7) Trans ~ Sac Trap Meg. Hy,~. 81 (SuppL 2). 34-42 3 Carme, B. (1996) Fara::tteLToday I Z 206-208 4 "~n.,'~., I~VV et al. (1994) Acta Trap. 57. 789-3~, 5 14~o~o,C.,%~ ~t ~1. (1995) Am, J. Trap, Mcd ~i~7 52, 201 206 6 5now, R.W et aL (1993) Trans.K Suc. Trap /Vlea HKq.o7 386-3~0 7 Snow. FLW ~n" ,*4a~.~h.K. (1995) Parasltol Todcy I i, 138 190 8 Le;,~eter, C.. Armstrong Schelie~,~. JA. and .................................. T~day! ! . . . 425 9 ~elacollette. C~and ~arutwanayo, F'1.{1996) B.tL Sac.PatheL Exot. 8& 373-379 I0 De Franosco, A. e~al. 0993)Ann. Top, Paed~atr 13, 345-352 I I Greenwood, B. et aL 0987) Ann. Trot" Paed,atr. 7. 91-99 2 Alonso, P.L et aL (1993) Trans.& Soc.'¢,c:, Ivied H~,g,87 (Supp' 2), 37-44
Concerns on Long-term Efficacy of an Insecticide-treated Bednet Programme on Child Mortality Can inten~entions of insecticide-treated bednets @TBNs) r~duc ~' Child rnnrtalilv in Africa? The answer is 'yes' when considering the results of three large cont~!!ed trials i- J aad ef a national programme canied out in The Garnbia, v~ich showed that it is possible to have a sigmficant impact on child mortality even it, non-r ~,ntrelled condition~ and on a national scale% However, concerns on long-term eff~ca~ of an ITBN programme on child mortality have been
raised by severalauthor~s,~.T~pe and Rogier a believe that vanabons of mo~idity and ~'otential mortality from m:t!ada a ~ ~ c3.'.~pared to the considerable range of t~nsmission l~vels and that only a considerable reduction of transmission (mud-; hi~her than that achieved by ITBNs) ';¢n,_,!~ biz able to reduce, on a long.term basis, the burden of malaria. Thus, according ~o them. the only effecave ways of fighting rna!aria in Africa a'e the improvement of e~tirnalaSa', dru~s. Nobody .Jenies that these a~c in!portant aspects of ar y t,,~alth project aiming at corilro!l~ng tnalari~ morbidity and mortality/, However, atthcugh :,'.~era~ questions abou~ the efficacy of ITBN; -~main unanswered there is no reason to delay the implementation of an intervention that could ~ w e n t thousandsof deaths in
Africa7. The evidenceon which Trapc .rod Rogier s bast-.-thair hypoU~e~ is not tok~iiy convincing a~-,drelies mainly on the results O.ra large stud7 ~.zrried out in ~zzawlle, I~
where it was shay. n that e x t ~ m e differences in malta m transmission may be associa'.ed with only minor differences in severe malaria incidence rates 8. However, it should be noted that these were much lower than ti~ose reported from other regions of Africa 9. The widespread use of antimalar;al~ in Brazzaville may have reduced not only the incidence of severe malaria, but possibly any difference between areas with different transmission. Other reports on the differences of malaria-specific mortality between a,~as of variable transmission are more difflcu~t to interpret as estimations are likely to be biased and imprecise ~0, The favors that determine whether a child develops mild or severe malaria are complex and mu!tifactodal ~ and the relationship between clinical disease and death is not well understood. This is why an estimation of the icng term impact of !T~N.% wh'.':h i~ b~sed o!~ the incidence ef uncomplic~,ted malaria a~L~cksin twO villages with different transmission, is likely ~o be approximate. Another point when cons[danng maima nlo~MiiCy k; ,.V,qCLhe,Lhe
13 D'Alessandro, U, et aL (1995) Lancet 345, 479-483 14 Bamish.G. et aL (1993) Ann. "&op.Meal Porositol. 87, 125--136 IS Premji, Z. Acta Trap.(in press) i 6 Salum, F.M. et a!. (1994) Acta Trr,p. 58, 29-34 17 Spencer, H.C et 01 (!987) Ann Top. Mad. Paros~tol.81 (Suppl. I), 36-45 18 Binka. F.N. et al. (1996) Trap.Med. Int. HeaI~ I, 147-15'1 19 ~olir,eaux. L. (1985) in Health Policy. Social Policy and Moaatity Prospecis (Vallin. J. and Lopez, A.I ~., eds), pp 13-44. International Un,on ~or the Scientific Study of Populations 20 Bradley, D.]. ( 1991) ~nDiseas~ and Mo~tahty ~n Sub-SaharanAfnca (Feachem, FLG.and Jarnlson. D. eds). pp 248-262. Oxford
Un~ve~,ty Press 21 Lengeler, C. and Sn~,, p~VV.0996) Buff WHO 74. 325 332 ..............................
Christian Le~geler Tom A. Smith l)epartment of Pub:it Health and Epidem~oi~gf Swiss T,-op;cal Institute, PO Box, CH-4002 Basel 5wilzedand Joanna Armsr~'o~;~ ~:hellenb~.rg Ifakal~ Center, PO Box 53, If~kara, Tanzal~a
before five years of age is much higher than it is in areas of low transmission (F-!d;op): a two-year-old child in Dielmo will experience six clinical attacks per year, Wnile in NOop a child of similar age will have only two attacks per year. In the same manner, the classification of different areas of transmission by means of the annua! entomological inoculation rate (Eli°,) should be treated with caution, as this figure is no~ informative on the disthbution of infective bites over shorter periods of time. Therefore, or; the basis of the available data, we believe it is unjustified to dismiss ITBNs as ineffective on a long-term basis, when they have been defined as one of ~he most promising tools that have emerged in recent yea~ for the fight against malari& The long-term benef~ of ITBNs are unknown and it is un[ike!y tl" ey will be as great as those observed among highly immune children immediately after an intervention 12. The possibili~ of changing the clinical spectrum of disease, from severe anaemia to cerebral malaria in areas of intense transmission and with an ITBN intervention, has been raised 9. There is an urgent need to solw these questions b;, monitoring the impact of ITBNs f~r at [ea~! 4-5 years. This, and not estimations based on doubtful assumptions, is the only way of knowing the right answer.
number of dinicai atblcks experienced over an entire lifetime really matters. Their distribution over time, particulariy during the 'vulnerable' l:~riod before five yea"s of age,
R~teren¢~ I Alonso, P.L et uL (I 90~ ) Lancet 37; ', 1499-1502 2 Binl~. |'.N. et aL (1996) Trap. Mad. InE Healh~
is probably more importanL From the figure presented by Trape and Rog~r ~, i~ s.~ems obviou,~, that in areas of high transmission (Dielmo) the incidence of climcai malaria
"~ Nevill, C.~. el ol. 0996) Trap. Med. Int. Health I. 139-146 4 D' ~,le~.~n0n0,U. et al. (1995) Lancet 345, 4 ' ~ -~,83
i. 147- !54
Paro,'~itology Today, vol, 13, no. 3, 1997
20 18
F; ,u u~; icr ~J~t~ set £ um K~i,F,~ dido ~oses problems of attendance b~s, and because the number of deaths in ti(e nine subgroups
,s so small the interpretatir~n is very difficult. Despite this. it is ~nt.~resbn~ to note that the cqe site with the hi£hest admission rate (i~!tondia) a:so had a much higher rate of b3nsmission [eqtomological inoculabon rale (~IP,) 0[60. compared to E!P-,~From 0 to 18 in the eight other sites], The fact that th~s same site also had the lowest rate of severe disease in th£ baseline period indicates that disease admission rates are subject to major vanation in space and time with no obvious cause ~. Finally. Trape and Ro~]ier mention the recem paper by Snow and Marsh/. that tamed out an 'ecological companson', ie. the comparison of mortality rates across distinct socio-economlc and ecolo~icai eqvironments. We have corr,g~,ented earlier on the problems associated wtth th~s approach, such as the high vahabllity o1" mortality rates and the unreliability of,,erl~al autopsies leadin~ to under-reporting at N~htransmission imensities 8. The recent letter by Carme ~ further illustrates the major problem of confoundin~ by socio-economtc factors. Furthermore, few data are available. and the picture ~]iven by such a review can change dramatically as new information becomes available. To illustrate th~s, we have re-worked the Fi~une Jnttially presented by Snow and l~la~sh (F~ I fiom Ref. 7). With new and updated ev!dence ) i3 and with the removal of one point from Congo ~ (for reasons givep above) as well as two data points from the 1950s (because of the enormous
downward b end in mot ~ i ~y over dec~d~s. it is not reasonable to assume that these data are still comparable to contemporary data), the picture that emerges (Fi~. I ) is Uiat of a continuous increase in malana-
specific mortali*:/with increasin~ transmission, with the exception of the situation in western Kenya ~n the 1980s (Ref. 17). The evidence in favour of equahty of malaria-speciflc mortality rates regardless of transmission is, therefore, weak As the whole argument of To, De and Rogier, including their extrapo!ated mortality rates, largely m!ies on this assumption, the data presen[ed hl their Table should be regarded critically. Unfortunately. the evidence to su~e~ that there is indeed a long-terrn survival benefit with vector-control interventions alone is equally weak In a careful review of historical evidence. Moiineaux t9 showed that, in Sn Lanka (a countrf with a go0d vital registration system) overall death rates correlated well wiLh spleen rates (as a proxy for transm.:sion intensity) before il ,door spraying wia, ODT on a large scale. The introduction oi" this vector-controi intervention was then followed by a substantial and lasting reduction in ir/ant and child mortality. Similar effects were se.en in Guyana and in other South ,amencan countries after the introduction of" houre spraying. The only data set wah a Ionx-[erm follow-up after vector control alone in Afiica (from the Pare Taweta scheme in Tanzania and Kenya) gives no indication cf a 'rebound' or a delay in mortality ~o~'. Rates in the protected group remained low even after control was discontinued. Rates n a new generation or infants, however, returned to pre-con[rol {evels after cessation of spraying.
15 Tanzania II
Fig. I. Possible relationship between transmission intensity (entomological inoculation rate) and malaria-speclfic mortality in children below five yea,'s of age. Based on a Figure by Snow and Narsh ~, with substantial modifications (see ,exc). Numbers over points indicate references for mortality data.
16Tanzanial BurundilO 18 Ghana
I
~g
~
~°
G a ~ b i a IV 13
Gambial111
~c
•
-
Gambia III i2 •
14 Sierra Leone
• 10 Gambia I
17 Kenya
4
2 0
10
100
1000
Entomological inoculation rate (EIR)
Purasitolo~y Today, vol. 13, no. 3. 1997
12]
I
Letters Clearly the Question of increased survival fc,!lowing w~ctor cot;tin! has major implications and it deserves p r i o r y attention. The reality is that evidence to date is insufficient to make an informed assassmenL It is useful to recall that in atLempting to measure relative!y small differences, such as 20~30,o reductions in overall morta!ity in an environment of high v~aiability and strong s~cular trends, the ,methodological problems encountered are considerable ~2. So, v,,'~at should we recommend to, in 'p!ementing agencies? We agree witr, Rogier and Trape that improving access m timely and effective treatment for all mala~a patients repn~s~nL~ a r-~o~t desirable goal. The African reality it, that ~.' ,h!~. health services have been o~iy partiall) successful in the fight against rna~ana morb, !iW and mortality. Future prosFect., are r ) better. Should we therefore wait anoth r decade and the certainty of f0 million child deaths? O r should we move ahead with insecticidet~a~ed b=~.~ts. which, besides being highly effe~ive in i"t-~. short telm, a~v also in high
demand because oftJ~e reduction in nui:'ance biting? Our" choica iS easy:get the nets.
References I Trape J-F.and Rogier C (1996) Parasitol, Toda). 12, 236-240 2 Trape. J-F, et al. (19~7) Trans ~ Sac Trap Meg. Hy,~. 81 (SuppL 2). 34-42 3 Carme, B. (1996) Fara::tteLToday I Z 206-208 4 "~n.,'~., I~VV et al. (1994) Acta Trap. 57. 789-3~, 5 14~o~o,C.,%~ ~t ~1. (1995) Am, J. Trap, Mcd ~i~7 52, 201 206 6 5now, R.W et aL (1993) Trans.K Suc. Trap /Vlea HKq.o7 386-3~0 7 Snow. FLW ~n" ,*4a~.~h.K. (1995) Parasltol Todcy I i, 138 190 8 Le;,~eter, C.. Armstrong Schelie~,~. JA. and .................................. T~day! ! . . . 425 9 ~elacollette. C~and ~arutwanayo, F'1.{1996) B.tL Sac.PatheL Exot. 8& 373-379 I0 De Franosco, A. e~al. 0993)Ann. Top, Paed~atr 13, 345-352 I I Greenwood, B. et aL 0987) Ann. Trot" Paed,atr. 7. 91-99 2 Alonso, P.L et aL (1993) Trans.& Soc.'¢,c:, Ivied H~,g,87 (Supp' 2), 37-44
Concerns on Long-term Efficacy of an Insecticide-treated Bednet Programme on Child Mortality Can inten~entions of insecticide-treated bednets @TBNs) r~duc ~' Child rnnrtalilv in Africa? The answer is 'yes' when considering the results of three large cont~!!ed trials i- J aad ef a national programme canied out in The Garnbia, v~ich showed that it is possible to have a sigmficant impact on child mortality even it, non-r ~,ntrelled condition~ and on a national scale% However, concerns on long-term eff~ca~ of an ITBN programme on child mortality have been
raised by severalauthor~s,~.T~pe and Rogier a believe that vanabons of mo~idity and ~'otential mortality from m:t!ada a ~ ~ c3.'.~pared to the considerable range of t~nsmission l~vels and that only a considerable reduction of transmission (mud-; hi~her than that achieved by ITBNs) ';¢n,_,!~ biz able to reduce, on a long.term basis, the burden of malaria. Thus, according ~o them. the only effecave ways of fighting rna!aria in Africa a'e the improvement of e~tirnalaSa', dru~s. Nobody .Jenies that these a~c in!portant aspects of ar y t,,~alth project aiming at corilro!l~ng tnalari~ morbidity and mortality/, However, atthcugh :,'.~era~ questions abou~ the efficacy of ITBN; -~main unanswered there is no reason to delay the implementation of an intervention that could ~ w e n t thousandsof deaths in
Africa7. The evidenceon which Trapc .rod Rogier s bast-.-thair hypoU~e~ is not tok~iiy convincing a~-,drelies mainly on the results O.ra large stud7 ~.zrried out in ~zzawlle, I~
where it was shay. n that e x t ~ m e differences in malta m transmission may be associa'.ed with only minor differences in severe malaria incidence rates 8. However, it should be noted that these were much lower than ti~ose reported from other regions of Africa 9. The widespread use of antimalar;al~ in Brazzaville may have reduced not only the incidence of severe malaria, but possibly any difference between areas with different transmission. Other reports on the differences of malaria-specific mortality between a,~as of variable transmission are more difflcu~t to interpret as estimations are likely to be biased and imprecise ~0, The favors that determine whether a child develops mild or severe malaria are complex and mu!tifactodal ~ and the relationship between clinical disease and death is not well understood. This is why an estimation of the icng term impact of !T~N.% wh'.':h i~ b~sed o!~ the incidence ef uncomplic~,ted malaria a~L~cksin twO villages with different transmission, is likely ~o be approximate. Another point when cons[danng maima nlo~MiiCy k; ,.V,qCLhe,Lhe
13 D'Alessandro, U, et aL (1995) Lancet 345, 479-483 14 Bamish.G. et aL (1993) Ann. "&op.Meal Porositol. 87, 125--136 IS Premji, Z. Acta Trap.(in press) i 6 Salum, F.M. et a!. (1994) Acta Trr,p. 58, 29-34 17 Spencer, H.C et 01 (!987) Ann Top. Mad. Paros~tol.81 (Suppl. I), 36-45 18 Binka. F.N. et al. (1996) Trap.Med. Int. HeaI~ I, 147-15'1 19 ~olir,eaux. L. (1985) in Health Policy. Social Policy and Moaatity Prospecis (Vallin. J. and Lopez, A.I ~., eds), pp 13-44. International Un,on ~or the Scientific Study of Populations 20 Bradley, D.]. ( 1991) ~nDiseas~ and Mo~tahty ~n Sub-SaharanAfnca (Feachem, FLG.and Jarnlson. D. eds). pp 248-262. Oxford
Un~ve~,ty Press 21 Lengeler, C. and Sn~,, p~VV.0996) Buff WHO 74. 325 332 ..............................
Christian Le~geler Tom A. Smith l)epartment of Pub:it Health and Epidem~oi~gf Swiss T,-op;cal Institute, PO Box, CH-4002 Basel 5wilzedand Joanna Armsr~'o~;~ ~:hellenb~.rg Ifakal~ Center, PO Box 53, If~kara, Tanzal~a
before five years of age is much higher than it is in areas of low transmission (F-!d;op): a two-year-old child in Dielmo will experience six clinical attacks per year, Wnile in NOop a child of similar age will have only two attacks per year. In the same manner, the classification of different areas of transmission by means of the annua! entomological inoculation rate (Eli°,) should be treated with caution, as this figure is no~ informative on the disthbution of infective bites over shorter periods of time. Therefore, or; the basis of the available data, we believe it is unjustified to dismiss ITBNs as ineffective on a long-term basis, when they have been defined as one of ~he most promising tools that have emerged in recent yea~ for the fight against malari& The long-term benef~ of ITBNs are unknown and it is un[ike!y tl" ey will be as great as those observed among highly immune children immediately after an intervention 12. The possibili~ of changing the clinical spectrum of disease, from severe anaemia to cerebral malaria in areas of intense transmission and with an ITBN intervention, has been raised 9. There is an urgent need to solw these questions b;, monitoring the impact of ITBNs f~r at [ea~! 4-5 years. This, and not estimations based on doubtful assumptions, is the only way of knowing the right answer.
number of dinicai atblcks experienced over an entire lifetime really matters. Their distribution over time, particulariy during the 'vulnerable' l:~riod before five yea"s of age,
R~teren¢~ I Alonso, P.L et uL (I 90~ ) Lancet 37; ', 1499-1502 2 Binl~. |'.N. et aL (1996) Trap. Mad. InE Healh~
is probably more importanL From the figure presented by Trape and Rog~r ~, i~ s.~ems obviou,~, that in areas of high transmission (Dielmo) the incidence of climcai malaria
"~ Nevill, C.~. el ol. 0996) Trap. Med. Int. Health I. 139-146 4 D' ~,le~.~n0n0,U. et al. (1995) Lancet 345, 4 ' ~ -~,83
i. 147- !54
Paro,'~itology Today, vol, 13, no. 3, 1997