Efetividade Abate Leishmaniose

8/3/2019 Efetividade Abate Leishmaniose

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evista da Sociedade Brasileira de Medicina ropical 44(2):232 242, mar abr, 2011

INTRODUCTION

1. Depar amen o de Medicina Comuni ria, Universidade Federal do Piau, eresina, PI, 2. Ins i u o deDoenas ropicais Natan Portella, eresina, PI. Address to: Dr. Carlos Henrique Nery Cos a. Ins i u o de Doenas ropicais Na an Por ella. Rua Ar urde Vasconcelos 151-Sul, 64049-750 eresina,PI, Brasil.Phone: 55 86 3237-1075; Fax: 55 86 3221-2424e-mail: chncos [email protected]

eceived in14/05/2010 Accepted in29/11/2010

How effective is dog culling in controlling zoonotic visceralleishmaniasis? A critical evaluation of the science, politics and ethics

behind this public health policy

Quan o e e ivo o aba e de ces para o con role do calazar zoon ico? Uma avaliada cincia, pol ica e ica por rs des a pol ica de sade pblica

Carlos Henrique Nery Costa1,2

ABS RCIntroduction: Zoono ic kala-azar, a le hal disease caused by pro ozoa o he genus Leishmania is considered ou o con rol in par s o he world, par icularly in Brazil, where ransmission hasspread o ci ies hroughou mos o he erri ory and mor ali y presen s an increasing rend.

Al hough a highly deba able measure, he Brazilian governmen regularly culls seroposi ivedogs o con rol he disease. Since con rol is ailing, cri ical analysis concerning he ac ionsocused on he canine reservoir was conduc ed. Methods: In a review o he li era ure, a

his orical perspec ive ocusing mainly on comparisons be ween he success ul Chinese andSovie s ra egies and he Brazilian approach is presen ed. In addi ion, analyses o he principals udies regarding he role o dogs as risk ac ors o humans and o he main in erven ion s udiesregarding he e cacy o he dog killing s ra egy were under aken. Brazilian poli ical reac ion

o a recen ly published sys ema ic review ha concluded ha he dog culling program lackede ciency and i s e ec on public policy were also reviewed.esults: No rm evidence o

he risk con erred by he presence o dogs o humans was veri ed; on he con rary, a lack o scien i c suppor or he policy o killing dogs was con rmed. A bias or dis or ing scien i cda a owards main aining he policy o culling animals was observed.Conclusions: Since hereis no evidence ha dog culling diminishes visceral leishmaniasis ransmission, i should beabandoned as a con rol measure. E hical considera ions have been raised regarding dis or ingscien i c resul s and he killing o animals despi e minimal or absen scien i c evidence

eywords: Kala-azar. Visceral leishmaniasis. Con rol. Dogs. China. Brazil.

ESUMOIntroduo: O calazar zoon ico, uma doena a al causada por pro ozorios do gnero Leishmania , considerada ora de con role, par icularmen e no Brasil, onde se urbaniza e ale alidade aumen a. Apesar de ser uma medida mui o con roversa, o governo brasileiro aba eces soroposi ivos regularmen e para con rolar a doena. Assim, dian e da alha do con role, oie e uada uma anlise cr ica das aes para o con role do reserva rio canino. Mtodos:Em umareviso da li era ura, oi ei a uma abordagem his rica ocalizada principalmen e na comparaodas bem sucedidas en a ivas chinesas e sovi icas de con rolar a doena. ambm oi e e uadauma anlise dos principais es udos acerca do papel de ces como a ores de risco para humanose dos principais ensaios de in erveno acerca da eliminao des es animais. A reao pol icado Brasil a uma reviso sis em ica recen emen e publicada que concluiu pela ine ccia doprograma de eliminao de ces e os seus e ei os nas pol icas pblicas so revisadas.esultados:No oram encon radas evidncias rmes do risco con erido por ces para os seres humanos. Alm dis o, oi con rmada a al a de apoio cien co pol ica de eliminao de ces. Foi no adauma endncia para dis oro dos dados cien cos para o supor e da pol ica de eliminao dosanimais.Concluses: Uma vez que no exis em evidncias de que o aba e de ces diminui a

ransmisso de leishmaniose visceral, es e programa deve ser abandonado como es ra gia decon role. So levan adas as implicaes icas acerca da dis oro da cincia e sobre a eliminaode animais na ausncia de mnima ou nenhuma evidncia cien ca.Palavras chaves: Calazar. Leishmaniose visceral. Con role. Ces. China. Brasil.

Kala-azar, or visceral leishmaniasis, is a curiousdisease wi h peculiar geographical dis ribu ion. In

he Indian subcon inen , where mos o he cases inhe world have occurred, he disease occupies a very

limi ed area o he nor heas , a ec ing cer ain dis ric so Bihar S a e, India, Bangladesh and Nepal1. In heseplaces, he disease is exclusively an hropono ic; i.e., isonly ransmited be ween people. Te predominan

ransmission among humans is also observed inEas A rica, mainly in Kenya, Sudan, Uganda andE hiopia. I was also an hropono ic in he plainso eas ern China, bu was ex inguished rom helowlands in he 1950s2. In he res o he world,par icularly in he highlands o China, Cen ral Asia,

he Middle Eas , ranscaucasia, he Medi erranean,Sou h and Cen ral America, i is a zoonosis; i.e., iis ransmited be ween animals and, secondarily, opeople. Te main known reservoirs are domes icdogs, coyo es and oxes, al hough o her mammalsmay be involved in ransmission3. Te agen s o hean hropono ic and zoono ic diseases are di eren bu very similar. Tey are pro ozoa o he species Leishmania donovaniand L. in antum , respec ively, which appear o have gene ically diverged a million years ago in Cen ral Asia4. American parasi es are

o en re erred o as L. chagasi , bu hey are gene ically iden ical o L. in antum , and have probably beenin roduced on many di eren occasions by Europeansetlers5,6; however, i is possible ha indigenouspopula ions may also exis . Tey are ransmited by species o sand fies ha breed in decomposingsolid organic mater and belong o several specieso he genus Phlebotomus(in he Old World) and Lutzomyia(in he Americas). he geographicaldis ribu ion o he vec or species de ermines hegeographical dis ribu ion o he disease, so ha he

ac ors ha limi i should be he same as hose ha

guide he dis ribu ion o he disease3

. Despi e heecological di erences, he disease is very similar indi eren regions: a al i un rea ed, charac erized by

Opinion Article/Artigo de Opinio

DOI: 10.1590/S0037-86822011005000014


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Costa CHN Dog culling and visceral leishmaniasis

prolonged ever, weigh loss, anemia, bleeding, enlarged liver andspleen and accompanied by bac erial in ec ions ha are o en severe7.I has been es ima ed ha a leas 59,000 people die annually o hedisease around he world, par icularly in India and Sudan8.

Much has been opined on he elimina ion o domes ic dogs ocon rol zoono ic visceral leishmaniasis, bu ew s udies have ac ually assessed he e ciency o such a measure. A recen ly published

sys ema ic review o s ra egies or con rolling he disease summarizeshese s udies and indica es direc ions ha his cruel policy shouldake9. Since here are some indica ions ha despi e his sys ema ic

review, ac ions involving dog killing will con inue, I decided ospeci cally review his s ra egy. Te li era ure review was res ric ed

o research and programs whose e ec s are rela ed only o people.Te au hor conduc ed a PubMed search wi h combina ions o he

ollowing keywords: visceral leishmaniasis, kala-azar, con rol, dogs,his ory, and he name o coun ries and con inen s where he diseaseis endemic. Excep or a his oric descrip ion, only s udies wi h con rolgroups and wi h a s a is ical analysis were used o evalua e he roleo dogs and he e ec o con rol measures. Tis work also quo espreviously iden i ed heses and con erence abs rac s and severalre erences ha were iden i ed in he ex s examined. I only consul edre erences ha were in English, French, Spanish or Por uguese.

HIS O ICAL BAC G OUND

Old WorldTe rs proposal concerning a program o elimina e dogs in

order o con rol leishmaniasis appears o have come rom Adler &chernomore z10. Since he au hors were unable o cure dogs in

Pales ine when using pen avalen an imony or aroma ic diamidine, hey sugges ed ha he removal o dogs o o her places or heir elimina ion would be viable al erna ives or con rol. I was probably hese remarks

ha riggered con rol opera ions hrough he elimina ion o dogs. Tisconcep was la er emphasized by Hoare in his pres igious review o 196211. In he 1950s, wo ex ensive programs o disease con rol beganin China and in he Cen ral Asian republics o he hen Sovie Union,given he broad dis ribu ion o he disease and i s high incidence.

hese programs were implemen ed under he aegis o socialispolicies and under he man le o revolu ionary and cen ralized s a es.

Al hough no precise gures exis , he si ua ion in China w wors and really desola ing. I is assumed ha here were a s500 o 600 housand people wi h he disease in 195112 , wi h he very high prevalence o 3 o 5 individuals per housand inhabiincluding he capi al Beijing13. Moreover, access o rea men was verdi cul or he majori y o pa ien s14 , which sugges s ha kala-azarkilled Chinese pa ien s by he housands. Te disease was dis rib

in 16 o he 33 adminis ra ive areas, all nor h o he Yangzi Rihree dis inc ecological paterns: a) he main ype, responsiblhe vas majori y o cases, was an hropono ic, loca ed mainl

crowded eas ern plains in river valleys, he ransmission o w was soon in errup ed; b) zoono ic, associa ed wi h he presein ec ed dogs, loca ed in moun ainous areas o he nor heasand nor hwes ; c) presumably zoono ic, bu wi h no known areservoir, in he ex reme nor hwes deser region(Figure 1)2, 12, 13, 15, 16.Te main vec or o he disease, bo h in he plains and he mounhas always been Ph. chinensis , which is more endophilic, bu in hedeser , Ph. longiductusandPh. alexandris ill prevail, which are exophilicand more di cul o con rol17.

In hese diverse areas, he orce o ransmission could be es by age and delayed ype hypersensi ivi y (D H). Tus, in he pla

he mean age was grea er, similar o Indian kala-azar, while inmoun ains and he deser , mos o he pa ien s consis ed ochildren12,13,18,19 , which indica es a lower s reng h o ransmisin he plains. In eres ingly, in he deser , no in ec ed dogiden i ed, while mos o he popula ion presen ed reac iv

he Mon enegro es (unlike in he areas o canine zoonosis moun ains)16 , which sugges s ha he grea er s reng h o he inin zoono ic regions han in he plains is no due o he presedogs, bu he resul o a s ill poorly unders ood process, perela ed o vec or eeding pre erences15.

Given he hypo hesis ha he Chinese an hroponosis w be similar o Indian kala-azar caused by L. donovaniand ha heChinese zoono ic visceral leishmaniasis would have L. in antum as he e iological agen15 , a care ul geno ypic analysis o isolao Leishmaniain di eren regions was conduc ed. Tis analysishighligh ed he he erogenei y o he isola es, bu show L. donovanipredomina ed in he eas ern plains and ha L. in antum was concen ra ed in he moun ain areas o Beijing and Gal hough some L. in antumisola es were iden i ed in he plains an

FIGU E 1 Maps o China be ore (A) and a er (B) actions to control kala azar in the 1950s. Dots represent the number o cases and colors indicate the areas where only human disease was veri ed (olive) and areas where dogs were also veri ed asin ected (blue). Based on Leng, 1982, and Xu, 1989.

A B


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isola es o L. donovanialso came rom he moun ains, includingone rom a dog. In he nor hwes ern deser , s rains o bo h species were isola ed20. Tus, al hough a spa ial correspondence be weenenvironmen and he species o Leishmaniahas been shown,

he coexis ence o di eren species in hese areas has also beendemons ra ed. hese biological and ecological varia ions haveincurred enormous consequences regarding con rol e or s21,22.

Immedia ely a er he communis s ook power in 1949, wo majors eps were aken o reduce he impac o he disease in a drama ic way ha embodied he revolu ionary spiri : mass rea men o hesick and con rol o vec ors15. In rela ion o mass rea men , Chineselabora ories began manu ac uring pen avalen an imony 14 , Cen ral An i-kala-zar S a ions were es ablished and over a housand an i-kala-azar uni s atended by hundreds o specially rained personnelhelped he doc ors2,14. Wi h his s ruc ure, 150 o 200 housandpeople were rea ed rom 1951 o 1953 alone14,18. Ano her priori y was given o comba ing he vec ors, which began in 1951, since P.chinensis was an easy arge since a Chinese la i udes, i has only one or wo genera ions per year and lands on walls a er eeding.

Te coun ry s ar ed o produce he organochlorine insec icides dichlorodiphenyl richloroe hane (DD ) and gammexane andexperimen s were conduc ed ha showed heir e iciency andprolonged residual e ec . DD became widely used inside andou side houses, and in ou houses and was applied in all householdso densely popula ed villages14,15. Al hough he applica ion was ona large scale, he precise ex en o i s use in he cri ical years o he1950s is no men ioned2. Since he 80s, DD and gammexane haveno longer been used and have been replaced by pyre hroids, oday res ric ed o areas o zoono ic visceral leishmaniasis16,23.

Te program or he disposal o dogs in China was as even moredi cul o assess han he use o insec icides, since i is no known

precisely where and o wha ex en i was applied, perhaps due o helarge varia ion in he prevalence o canine in ec ion by Leishmania in he coun ry ( rom zero or minimal in he plains and deser o7% in moun ainous areas)2,12,19. Tis he erogenei y led o di erenin erpre a ions concerning he e ciency o elimina ing dogs, becausesome au hors have relega ed he core o he success o he con rolsimply o he mass rea men and o he use o insec icides14,24,25 , while o hers atribu ed a relevan role o he elimina ion o dogs inareas o zoono ic visceral leishmaniasis2,13,18. One ac wor h no ingis ha he elimina ion o he animals was no per ormed using any de ni ive selec ion me hod, bu indiscrimina ely, killing any dog insigh in endemic areas24. o provide some idea o he magni ude o

his program, i was es ima ed ha he killing would only be e cieni i elimina ed a leas 3/4 o all dogs in an area, whe her or noevidence o leishmaniasis was available16. However, despi e he ac

ha an enormous number o dogs were sacri ced, ransmissionamong dogs resumed our years la er23.

Te huge Chinese e or s were rewarded in spec acular ashion, because by 1958, ransmission was already en irely in errup ed inareas o an hropono ic leishmaniasis15,19 , and his nally became areali y in he 1970s26 , accompanied by reduc ion o near-ex inc iono P. chinensis rom he plains24 , making leishmaniasis a rela ively rare disease in China13. Te annual incidence dropped o around200-300 cases, res ric ed o moun ainous regions o he nor h and

nor hwes , where exophilic vec or popula ions con inued16, 24

. A erhe ini ial success, comple e elimina ion o kala-azar in he coun ry was predic ed o occur by he 1960s19 , bu in he 1980s, an increase

in he number o cases occurred23 , atribu ed o he disman ling o he an i-kala-azar ne work during he Cul ural Revolu ion o 1966o 19762,12.

I is no easy o specula e regarding he e ec iveness o he Chinecon rol program, wi h i s many nuances. A good explana ion or hegrea success in he plains may have been he low orce o ransmissioin hose areas, and he dense popula ion, where con rol was eviden ly

easier and more no iceable. In con ras , in he nor hwes areas, hehigh orce o in ec ion and more dispersed popula ions did noenabled such an abrup drop in he incidence o number o cases, as veri ed in he lowlands. A grea deal can be learned rom he s rikingdi erences be ween he success o con rol in he an hropono ic andzoono ic areas seen in he ruly gigan ic Chinese con rol program.Obviously, he con rol o he an hroponosis canno be atribu ed

o he elimina ion o dogs, which leads o he conclusion ha hransmission o an hropono ic leishmaniasis in China can only be

atribu ed o mass rea men and he use o DD and gammexane.Te real reason or he success o he Chinese con rol o an hropono icleishmaniasis seems o have been he use o organochlorine pes icides

ha eradica ed P. chinensis, he main vec or in he lowlands. Tis rslesson should remain. However, he ques ion o wha he e ec waso he elimina ion o dogs in he areas o a zoonosis con inues. Apa

rom wo s udies ha showed a reduc ion in he number o humancases ollowing mass removal o dogs and rea men o people16 ,

he simul aneous use o organochlorine insec icides in he areas o zoono ic visceral leishmaniasis preven s any de ni ive conclusionregarding he rela ive e ec iveness o he disposal o dogs. Temain enance o ransmission in he highlands demons ra es ha

he use o organochlorine insec icides did no have he same successin con rolling zoono ic visceral leishmaniasis as i did wi h hean hropono ic disease. However, in spi e o he overall success o

he Chinese program, wha he resul s mos clearly indica e is howdi cul i is o con rol zoono ic visceral leishmaniasis.Te experiences o he con rol s ra egies or leishmaniasis used

in he ranscaucasian and Cen ral Asian Republics o he ormerSovie Union are help ul, since hey provide in orma ion ha is very relevan oday. In hese areas, he disease is only caused by L. in antumand a ec s people and dogs22,27. I was an urban diseaseand a ec ed owns and ci ies, such as bilisi (in Georgia), Yerevan,(Armenia), Kyzylorda (Kazakhs an), and ashken and Samarkand(Uzbekis an)28. Te vec ors were P. chinensis , which was ex inguished,and P. longiductusand P. sminov22. O par icular in eres was hesi ua ion inoblast Kyzylorda, where he propor ion o sick children

under wo years o age reached 92.9%, showing a huge orce o in ec ion, similar o he deser regions o nor hwes ern China21.In hese coun ries, in erven ion was also a combina ion o

radi ional me hods: he de ec ion and rea men o human caseand disposal o dogs, bu he main success was achieved only a erDD use or rea men o dwellings in a radius o 500 me ers rom micro ocus, and in some places, s ree s and ci y blocks22. Since hesemeasures were implemen ed, visceral leishmaniasis has also becomescarce in he area o he Sovie Union, excep in Kyzylorda22. In hisadminis ra ive region, an in errup ion in ransmission occurredin he capi al, bu here was no response o he con rol ac ions i

he coun ryside and no reduc ion in he number o cases in he

region. Al hough dogs are ound na urally in ec ed, a cycle involvingcoyo es has been veri ed, which may help o explain he di cul y incon rolling he disease. Never heless, he main reason or con inued


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ransmission in hisoblast seems o have been he scan use o DD21 , which was subsequen ly banned in he Sovie Union in 197029. Tecon rol ailure in his area indica es ha , like China, he in errup iono ransmission in L. in antumoci wi h a high orce ransmission may no be possible, even wi h he use o DD .

Te experience o he Indian subcon inen reveals he as onishingimpac ha he con rol o malaria wi h DD had on he con rol o

leishmaniasis. In he region o Bihar, India, and in Bangladesh andNepal, he disease presen ed epidemic cycles un il he end o he1940s. In 1953, he na ional program or malaria con rol began wi h he use o DD , reaching i s apex in 1958, which led o hedisappearance o he vec or P. argentipes rom he in erior o houses.

hus, leishmaniasis disappeared and also became rare in India.However, wi h he end o he Global Malaria Eradica ion Campaignin 1971, resurgence o he in ec ion was observed, which reached i szeni h in 1977, probably a ec ing a million people, wi h a a ali y ra e o abou 7%30,31. Curren ly, India has been implemen ing he useo DD in he S a e o Bihar since 1971, bu con rol has no beenachieved32 , even hough he coun ry plans o eradica e he disease by 201533. Some curren s udies have compared he e ec iveness o residual spraying o insec icides wi h mosqui o ne s impregna ed wi hlong- erm insec icides and wi h environmen al modi ca ion, and he bes resul s have been wi h indoor residual spraying34,35.

New WorldIn he New World, some local experiences in Brazil are also

relevan o assessing he e ec iveness o elimina ing in ec ed dogs as

a con rol measure. In his coun ry, he disease is caused by L. chagasi (= L. in antum), wi h dogs, oxes, o her species o mammals apeople as ver ebra e reservoirs, and is ransmited by he Lutzomyialongipalpissand fy, which presen s bo h exophilic and endophilihabi s. I was a disease o he semi-arid regions where con rol have been conduc ed since he 1950s. Despi e his, ransmisssmaller ci ies had already been regis ered. Te presen phenomen

o large scale urbaniza ion s ar ed in 1981, when epidemics hi eand hen So Luis, in he mid-nor h, spread hroughou he coo he wes and sou h, a ec ing several s a es, including S

and Rio Grande do Sul, and larger ci ies, such as Belo Horizonand he capi al, Brasilia(Figure 2). Moreover, he o al numbero cases in he coun ry nearly doubled despi e all e orcon rol36,37. Te annual cumula ive incidence ra e increased morediscre ely, bu he mor ali y ra e rose signi can ly despi e advances and he developmen o speci c guidelines or he mospresen a ion o his disease38,39. Recen ly, urban ou breaks have begun

o occur in neighboring Argen ina40. Te si ua ion o leishmaniasisin Brazil is he opposi e o ha o China, because a er

30 years o rying o con rol he disease, ha coun ry ha10 imes ewer cases han China had in 1950 and curren ly haimes more han China now has. Tis di erence is probably due he success ul con rol o he vas number o cases o an hr

visceral leishmaniasis in China, whereas Brazil has ried o conhe emergen process o urbaniza ion by priori izing he sel

elimina ion o dogs.

FIGU E 2 Spread o urban kala azar in Brazil. Dots indicate cities with more than 100,000 inhabitants withmore than ten cases o kala azar in a year.

Te con rol o leishmaniasis in Brazil began in he S a e o Cear, in he semarid nor heas , in 1953, and jus as in Chinand he Sovie Union, his was based on

he rea men o people, he use o D

and he elimina ion o dogs. Te di erence be ween hese coun ries is ha , in Braonly dogs wi h reac ive serology wereelimina ed41. In 1953, only one reagendog was killed, bu in 1954 and 1955, henumber rose o 42 and was higher han2,000 in 1960. No analysis o he e eco removing dogs was conduc ed, bu in14 coun ies sprayed wi h DD , a 58.2%reduc ion in he incidence o humancases (765 cases be ore and 320 a er)occurred, agains an increase o 11.9% in

14 municipali ies where only dog culling was carried ou (89 cases be ore and101 a er)(Figure 3)42. Un or una ely,

he use o DD was discon inued inhe 1960s41. In any case, DD proved

capable o reducing he incidence ozoono ic visceral leishmaniasis, al hough

he resul s were a lo less e ec ive hhose veri ed or an hropono ic viscera

leishmaniasis in China and India.Te only con rol experience ha was

a de ini e long- erm success in Brazi

occurred in he la e 1960s in he Rio Doc valley, Minas Gerais, in he sou heasregion. Te classical measures were used,



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FIGU E 3 Teoretical and observed efciency o control measures or zoonotic kala azar. In A, the theoreticalefcacy starting rom a given initial human incidence and according to the variation o the parameters that are critical

or each measure; data rom Dye, 1996. In B, the observed variation o human incidence in Cear, Brazil; data rom Alencar, 1961.

including he applica ion o DD , or abou 10 years. Be orehand, upo 40% o dogs were seroposi ive. Te incidence ell rom 169 cases

in 1965 o zero in 1978 and in subsequen years43. However, despi ehe con inui y o he program, bu wi h he help o pyre hroids

ins ead o DD , in ec ion among dogs is reemerging44. Ano hersuccess ul experience in Brazil occurred in a small ou break in Rio de Janeiro, be ween 1979 and 198545 , where hey used organochlorines,

ollowed by pyre hroids. However, here was no in errup ion o heransmission.

Te applica ion o con rol measures on a large scale in Brazil was secondary o he epidemic ou breaks ha s ar ed he process o urbaniza ion and expansion o he disease in he early 1980s in hes a e o Piau. Similarly o India, ac ions agains o her diseases hadsome repercussion on leishmaniasis, since limi ed spraying wi h DD

or malaria seems o have pro ec ed agains he in ense ransmissiono leishmaniasis (in he ou break o 1981-1986). Fur hermore, in

hose municipali ies wi h ex ensive spraying wi h gammexane orChagas disease, he incidence o leishmaniasis was he lowes46.However, gammexane was never used or leishmaniasis and heindoor use o DD or his disease was minimal. Ins ead, he useo organophospha es and la er, ul ra-low volume pyre hroids, waspredominan41. Aside rom he observa ions in he 1950s, here has

never been a con rolled s udy o he use o insec icides or leishmaniasis by L. chagasianywhere in he world. Nowadays, Brazil is he only na ion wi h a large-scale program o sys ema ic elimina ion o dogs o con rolzoono ic visceral leishmaniasis.

HE IMPO ANCE OF DOG INFEC IONFO HUMAN KLA-AZA

Nei her he role o dogs in he ransmission o L. in antum ohumans, nor he bene s o disposing o dogs have ever achievedconsensus in he li era ure15,47,48. However, he evidence sugges s

ha in ec ions in humans and dogs are in erdependen , al houghransmission be ween dogs may be independen o he presence o sand fies and no associa ed wi h human in ec ion49. As a general

rule, where ransmission o L. in antumamong humans occurs, ialso occurs among dogs19,23,50. In one s udy, he highes prevalenceo in ec ion among dogs was no associa ed wi h he highesincidence among humans51 , bu in wo o her s udies in Brazil andin a hird in Iran, his associa ion was shown52-54. Tese discordanresul s demons ra e ha he associa ion be ween human and caninin ec ions is no s rong and sugges ha he in ec ions be w

he wo hos s may have dis inc dynamics, wi h a more complexrela ionship han previously hough . Te exis ence o a sylva ichos ransmiting he disease o bo h humans and dogs, as observed

in Cen ral Asia, canno be discarded. In Brazil, his common sourcemay well origina e rom he ou skir s o ci ies, as indica ed by associa ion o he human disease wi h peri-urban vege a ion55.

An indirec way o analyzing he dependence be ween hein ec ion in humans and he in ec ion in dogs is o assess he presenco dogs as a risk ac or or humans. Even hou, he resul s are alsoinconsis en( able 1). Five cross-sec ional s udies sugges ha dogsare risk ac ors. wo o hem, in he Old World, show ha bo h number o dogs and he ra e be ween dogs and humans increase

he risk o seroposi ivi y in children52,56. Ano her s udy, involvingmul i-level analysis, showed ha he presence o dogs may increase

he risk o clinical mani es a ion54 , while ano her showed ha he

presence o dogs (and poul ry) increases he risk o seroconversion57. Ye ano her s udy showed ha he ime ha a dog remains in home increases he risk o skin reac ivi y o Leishmania58. However,longi udinal s udies revealed borderline or confic ing resul s. wocase-con rol s udies showed no signi can associa ion be ween hepresence o dogs and he disease among people59,60 , al hough herisk o he disease was sligh ly higher among hose domes ic groups

ha lived wi h dogs. Ano her cohor s udy showed a con radic orassocia ion, depending on whe her he ou come was measured usingskin reac ion or serology 61 , while ye ano her repor ed no associa ion be ween he presence o dogs and he developmen o he diseasein people62. Tese airly ambiguous resul s sugges ha s udies ha

can measure he propor ion o he fow o parasi es o humans roma canine source have ye o be developed63. In order o achieve his,i is essen ial o conduc speci cally designed cohor s udies.



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ABLE 1 Studies investigating the risk o the presence dogs in relation to the acquisition o human visceral leishmaniasis or asymptomatic in ection with Leishmania infantum.

Study designs Units o analysis Exposures Outcomes esults* e erences

In erven ion Individuals Dog collars wi h insec icides Serology (a) risk (a) & no risk (b) Gavgani e al, 2002Mon enegro skin es (b)

Cohor Individuals Dog ownership Disease No risk Nascimen o, 1996Cohor Individuals Dog ownership Serology (a) risk (a) & risk (b) Caldas e al, 2002

Mon enegro skin es (b)

Cohor Individuals Dog ownership DNA hybridiza ion (a) risk (a) & no risk (b) Moreno e al, 1998DNA hybridiza ion plus serology (b)

Case-con rol Individuals Dog ownership Disease No risk Navin e al, 1985

Case-con rol Individuals Dog ownership Disease No risk Cos a e al, 1999Mixed ecological Census rac Previous canine seroprevalence Disease risk Werneck e al, 2006Mixed ecological Urban clus ers Previous canine seroprevalence Disease risk Oliveira e al, 2001

Cross-sec ional & ecological Individuals Dog ownership & size o dog popula ion Serology risk (bo h) Gavgani e al, 2002Cross-sec ional Urban area Dog ownership 3 years Mon enegro skin es risk Gouvs e al, 2007Cross-sec ional Individuals Dog ownership Serology risk Ko ka , 1996

Ecological Neighborhood Canine seroprevalence Disease No risk Cos a e al, 1995

* risks wi h p value 0.05.

While i is in ui ive o believe ha dogs are signi can reservoirs because hey are more compe en a in ec ing sand lies hanpeople47, 63-68 , o her parame ers ha depend on he vec ors (vec orialcapaci y) are much more signi can or he basic reproduc ive numbero he disease (e.g., he number o secondary cases emerging rom anin ec ious case) and, here ore, or he incrimina ion o reservoirs.For example, some observa ions and ma hema ical models show ha

he impor ance o a reservoir is regula ed no only by i s compe encein in ec ing vec ors, bu also by he parame ers ha measure a) hedegree o exposure o ver ebra e hos s o vec ors and b) he vec ordaily mor ali y. Bo h parame ers have a nonlinear (quadra ic andexponen ial) e ec on he ransmission o he disease69,70. Tis means

ha small e or s aimed a con rolling vec ors can have s rong resul sconcerning he ransmission o he disease. In con ras , since hecompe ence o he ver ebra e reservoirs a in ec ing he vec ors hasa merely linear e ec on ransmission, propor ionally much grea ere or s are needed o con rol he reservoirs, hus demons ra ing why

he s ra egy o removing reservoirs is less e cien han con rolling vec ors. Indeed, Dye71and Buratini72modeled he impac o di erens ra egies on he ransmission o leishmaniasis and showed ha he

elimina ion o ver ebra e reservoirs is much less e cien han vaccines,nu ri ional in erven ions or he use o insec icides(Figure 3).Tese heore ical uncer ain ies have led o he need or es s

o assess he e ec o removing dogs on he ransmission o kala-azar o humans. Four in erven ion rials were conduc ed in Brazil( able 2). o some ex en , all o hem evalua ed he e ec o selec iveelimina ion o seroreac ive dogs. Te ou come o he rs o hese

rials was seroconversion o humans, conduc ed in wo rural areas.No di erence be ween he areas o in erven ion and con rol (20% vs. 22% and 26% vs. 27% respec ively) were veri ed a er periods o 6-mon hs and 1-year73. Te second s udy compared he e ec o heelimina ion program wi h he incidence o pedia ric cases in wo

urban dis ric s and showed ha he annual incidence was lower in hein erven ion areas han in he con rol areas (5/1,000 vs. 20/1,000), bu due o several ac ors, he au hors could no a ribu e he

protective e ect to the elimination o dogs74. Another study expandedthe sample size and used random allocation o interventions and

actorial design to evaluate seroconversion. Te study area consistedo 34 plots measuring about 200 x 200m in one neighborhood, wherthe interventions took place in the internal 100 x 100m area, leavinga bu er o 200m between each intervention area. Due to the ethicaconsiderations, all houses were sprayed indoors with a synthesispyrethroid, included those within the bu er area. Tus, the ollowingadditional interventions were compared, and were randomly assignedas: a) spraying in residential outhouses; b) selective removal oseroreactive dogs; c) spraying in residential outhouses and selectiveremoval o seroreactive dogs; d) no other intervention apart romindoor spraying. Afer six months to one year o intervention, theincidence in the area where the removal o dogs was conducted witindoor spraying (but not outdoor spraying) ell rom 46% to 16.1%However, this e ect o eliminating dogs disappeared (40% to 37.9%in the area where removal o dogs was conducted with simultaneouindoor and outdoor spraying. No reduction also occurred whenonly additional outdoor spraying was conducted. Te three mainproblems in this study were the large proportion o non intervention- bu er areas (which corresponded to 75% o the study area), theloss o up to 46% o the studied population and the allocation o indoor spraying und, which hindered the assessment o the e ect elimination o dogs in the absence o insecticide use75. An additionalstudy compared the strategies o : a) no intervention, b) spraying with pyrethroid insecticide, and c) area under the combinationo insecticide spraying and screening with the elimination oseropositive dogs, in three districts o Feira de Santana in Bahia Stat Afer a year, the seroconversion incidence densities were, respectively3.02, 2.86 and 1.65 per 100 children-years. Te di erences were notstatistically signi cant to distinguish the e ect on transmission76. Although all the studies presented signi cant problems, it seemsthat there is a dubious, tenuous and evanescent trend o additionalprotection by removing dogs, but ar less than the theory predicts



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CONFLIC S BE WEEN SCIENCE AND CON OLP OGRMMES

Science and public policy do no always agree or go handin hand. Incorpora ion o scien i ic knowledge in o policy depends on poli ical, economical and e hical issues, he grade o scien i c evidence and agreemen be ween scien is s and evenon he corpora ive in eres s o decision-makers77. Due o he worsening o he si ua ion o zoono ic kala-azar in Brazil and

he lack o scien i c consensus, choosing he bes heal h policy or he con rol o he disease has been prone o disregarding or

misin erpre ing he available science. Moreover, he s ra egy o killing dogs is hampered or numerous reasons, such as helow accuracy o he me hods in assessing he in ec ivi y o dogs, he in ensi y o e or s needed o remove he dogs, hereplacemen o animals48 or simple re usal o owners o handover heir valuable and cherished crea ures. Knowing hesedi cul ies, he Pan American Heal h Organiza ion (PAHO)commissioned a sys ema ic review o evalua e programs aimeda he con rol o kala-azar. Te conclusion was ha in spite o allthese limitations, the relevant number o reports could be reviewedin detail, showing no strong evidence or a signi cant impact on VLtransmission or any o the interventions reviewed. Canine culling seems to be the least acceptable intervention at community level or obvious reasons and has low efciency due to the high replacement rate o eliminated dogs with susceptible puppies and other culturalobstacles9. Tis las evalua ion, despi e he limi a ions o hes udies analyzed, nally showed ha he hypo hesis o Adlerand chernomore z has no empirical suppor . Te review was

hen presen ed o a panel o consul an s as par o he Project or the establishment o a regional cooperative research agenda in the

eld o neglected diseases convened by PAHO, he World Heal hOrganiza ion (WHO), DR and BIREME or a consensusmee ing, which was also atended by represen a ives o heal hminis ries o La in American coun ries wi h leishmaniasis

ransmission. Te mee ing was held in Sep ember 21-22, 2009,in Foz do Iguau, Parana, Brazil, and agreed wi h he sys ema icreviews conclusions ha programs o sys ema ic killing o dogs

o con rol kala-azar lacked evidence in he li era ure as rela ed ohe pro ec ion o humans (PAHO, a s ill unpublished repor ).

In order o clari y he process o cons ruc ing guidelines orcon rolling neglec ed diseases, he linking o scien i c evidence

o he main enance o he dog killing programs o con rol

kala-azar will be discussed in he ollowing paragraphs. On heollowing day, also in Foz do Iguau, a mee ing was held by he chie s o programs or visceral leishmaniasis con rol o he

Sou hern Cone (Mee ing regarding Surveillance, Preven ionand Con rol o Visceral Leishmaniasis in he Sou hern Coneo Sou h America) and hey decided o recommend he cullingo in ec ed dogs, allegedly suppor ed by he par icipan s o heprevious research agenda mee ing, despi e he ac ha a posi ionpaper had no writen or approved, and in clear opposi ion o

he ndings o he sys ema ic review 78. Abou 10 days a er hepanel convened by he PAHO, he Minis ry o Heal h o Brazilconsul ed a orum o exper s o assess he ban on he rea men

o dogs ha had been de ermined by he Heal h Minis ry in200879. Members o he Forum rea rmed he ban, also in plaindisagreemen wi h he conclusions o he sys ema ic review. Te


T A B L E

2 - R e s u l t s o f t h e m a i n p u b l i s h e d i n t e r v e n t i o n s t u d i e s f o r t h e c o n t r o l o f z o o n o t i c k a l a - a z a r .

E x p o s u r e s

O u t c o m e

T i m e o f f o l l o w - u p

R e s u l t s *

M a i n l i m i t a t i o n s

R e f e r e n c e s

N o

i n t e r v e n t i o n

( a )

S e r o c o n v e r s i o n

S i x m o n t h s

& o n e y e a r

N o p r o t e c t

i o n

N o n - r

a n d o m

a l l o c a t i o n

D i e t z e e t a l

, 1 9 9 6

D o g c u

l l i n g

( b )

N o


( c )

D i s e a s e

O n e t o

o u r y e a r s

P r o t e c t

i o n

i n t h e

N o n - r

a n d o m

a l l o c a t i o n

A s h

o r d e t a l

, 1 9 9 7

D o g c u

l l i n g

( d )

f r s t t w o y e a r s * *

I n d o o r s , o u t

d o o r s

& a n

i m a l p e n s


S i x m o n t h s t o o n e y e a r

- P r o t e c t

i o n o

i n

d o o r s s p r a y i n g +

d o g c u

l l i n g

- H i g h l o s s o

o

l l o w - u

p

C o s t a e t a l

, 2 0 0 7

s p r a y i n g

- N o p r o t e c t i o n o

i n d o o r s , o u t

d o o r s

& a n

i m a l p e n s s p r a y i n g

- 3 / 4 o t h e s t u

d y a r e a u n

d e r

i n d o o r s

, o u t d o o r s

&

w

i t h p y r e t h r o

i d s

( b a s e l

i n e )

( a )

w i t h p y r e t h r o

i d s +

d o g c u

l l i n g

a n i m a l p e n s s p r a y i n g w

i t h p y r e t h r o

i d s

I n d o o r s s p r a y i n g +

d o g c u

l l i n g

( b )

- N o p r o t e c t

i o n o

i n d o o r s s p r a y i n g

- N o n o n - i

n t e r v e n t i o n

b a s e

l i n e

I n d o o r s , o u t

d o o r s

& a n

i m a l p e n s s p r a y i n g

w i t h p y r e t h r o

i d s +

d o g c u

l l i n g

( c )

I n d o o r s s p r a y i n g

( d )

N o


( b a s e l

i n e )

( a )


O n e a n

d t w o y e a r s

N o p r o t e c t

i o n

N o n - r

a n d o m

a l l o c a t i o n

S o u z a e t a l

, 2 0 0 8

I n d o o r s

& o u t d o o r s s p r a y i n g w

i t h

p y r e t h r o

i d s

( b )

I n d o o r s

& o u t d o o r s s p r a y i n g w

i t h

p y r e t h r o

i d s +

d o g c u

l l i n g

( a )

* e e c t s w

i t h p

v a l u e

0 . 0 5

. * * t h e a u t h o r s r e

u s e

d t o c l a i m

a c a u s e e e c t r e l a t

i o n s h

i p b e t w e e n t h e e x p o s u r e a n

d t h e o u t c o m e .


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prohibi ion was based on he agreemen ha a) he in ec ed dogsmus be he source o L. in antum or humans and o her dogs, b)any rea men would be ine cien in reducing in ec ivi y, c) couldalso lead o drug resis ance and d) hinder he coopera ion o hepopula ion wi h he program o sys ema ic elimina ion o animals.

his rea irma ion is a more ex reme measure han sys ema icelimina ion, because i preven s all atemp s o rescue he in ec ed

animals ha are iden i ed in rou ine screenings and whose ownersry o save hem wi h rea men , even wi h no scien i c evidenceha killing hem will pro ec people. Curren ly, a legal measure or

s reng hening he policy o killing o all seroposi ive animals is beingdeveloped by he Minis ry o Heal h and he Brazilian Legal Advisory and Consul ing O ce (Parecer/CODELEGIS/CONJUR/GABIN/MS/LP N 1243/2009). Fur hermore, ar more ex reme measureso reservoir con rol can be predic ed due o he recen movemen s

owards des roying pups and endangered wild canines. Tere ore, iis clear ha he Brazilian governmen will no ake in o accoun heconclusions o he sys ema ic review.

here are serious problems concerning he validi y o heconclusions o his orum o dog rea men consul ed by he Minis ry o Heal h o Brazil, since i pursued no in erna ional recommendednorms or elabora ing guidelines80-83and he ollowing neu rali y issues were incurred: a) he par icipan s were selec ed hroughcri eria ha were no made public; b) here was bias in he conveningo he componen s, because i was already public knowledge ha alarge number o he par icipan s were in avor o canine elimina ionand po en ial par icipan s who were known o pro ess an opposingopinion were no invi ed, which led o bias in he spec rum o opinions; c) here was no exper in developmen o guidelines among

he members o he orum and some o he par icipan s had noexper ise in epidemiology and leishmaniasis con rol (despi e beingdis inguished scien is s), which are undamen al requiremen s or hedevelopmen o guidelines81; and d) he decisions were no preceded by a sys ema ic review, as he brie li era ure ha was consul ed didno ollow he rules o his ype o evalua ion o evidence80 , he only sys ema ic review available9 was no ci ed and he orum omitedpublica ions wi h resul s ha could lead o di eren conclusions,according o he ci a ions men ioned inable 1. Tis sugges s hapar icipan s did no have access o he sys ema ic review and o wha wen on in Foz do Iguacu, despi e he presence o memberso he Minis ry o Heal h and he PAHO a bo h mee ings. Tus, by no using in erna ional recommenda ions or he cons ruc iono sys ema ic reviews and he developmen o guidelines, hecase or banning he rea men o dogs o con rol leishmaniasis

in Brazil reveals a sys ema ic loss o scien i c neu rali y or herecommenda ion o a highly deba able heal h measure83.Tere are numerous reasons or ignoring he science ha is

orien ed owards heal h policy 77 , and some seem plausible in his case.One would be he ragili y o knowledge concerning he con rol o leishmaniasis, as revealed in he sys ema ic review 9. Ano her is he

erri orial expansion o he disease and increase in incidence andmor ali y 36,37 , which genera es expec a ions and pressures on decisionmakers. Tird, he lack o al erna ives wi h recognized e ec s regardingzoono ic visceral leishmaniasis, which, in he ace o poli ical pressuremay push he decision-makers o ake irra ional ati udes. A our hpossibili y would be confic s o in eres . Even wi hou considering

possible lobbies and research groups in eres ed in vaccines and es sor he diagnosis o dogs or o collars wi h pes icides, o her unde nedac ors, such as radi ions or pas recommenda ions based on con rol

measures used in o her programs, such as rabies, may be infuencidecision makers nega ively and leading o resis ance o chang

he policy or he con rol o visceral leishmaniasis. Tis coulcrea ed by he perceived hrea o innova ions, because chan

he decisions aken could possibly be in erpre ed as pas mis akmay have implica ions in rela ion o he pres ige o he insand wi hin he ins i u ions.

Formal recommenda ions or he elabora ion o ur her guidregarding o her subjec s o he diseases caused by Leishmaniaandmany o her ropical diseases are also are in use in Brazil39,84-88 , which would seem o con rm he widespread na ure o dis or ing scievidence. In any case, perhaps he mos impor an ac or hled o noncompliance wi h he ormali y o adherence o scevidence appears o have been a lack o ins i u ional cul u

os ering scien i c in egri y. Tis sys em o evalua ing scevidence or public policy is governed by he promo ion o sysreviews and by he developmen and adop ion o ormal guidel77.I his clima e o in egri y had already been es ablished, i is

he science would have been misin erpre ed. Las ly, he loneu rali y during he in erpre a ion o he scien i c in ormoccurred wi hin he S a e i sel was probably acili a ed by zoono ic visceral leishmaniasis is a neglec ed disease ha a ecleas expressive par o he popula ion and whose con rol and redepend almos en irely on he bureaucracy o he S a e.

CONCLUSIONS

Beside he hree s ra egies used, he rea men pa ieno indoor residual insec icides and he elimina ion o dogs, o her s ra egies or he con rol o zoono ic visceral leishmhave been assessed. In Iran, a rial ook place involving con by impregna ing dog collars wi h del ame hrin in nine co villages and nine in erven ion villages paired by he prevalenprevious seroposi ivi y and immuni y was measured a er one o observa ion. A 43% reduc ion in he incidence o he in(measured using serology) was de ermined, bu he reduc io

he incidence o D H was no signi can52. In Sudan, a vaccineagains leishmaniasis was es ed ha consis ed o au o L. major plus BCG, which was compared wi h BCG. Pro ec ion ooccurred in 6%, bu he group ha began o presen D H presa lower incidence o he disease89. Finally, he e ec o mosqui o neimpregna ed wi h insec icide is curren ly under assessmen in In90.Excellen reviews regarding he use o insec icides and vaccin

leishmaniasis have been published91-94

and should be consul ed.Tere ore, here are promising e cien al erna ives or he conleishmaniasis besides he radi ional measures ha widen he ho he gh agains his disease.

Since he zoono ic kala-azar is now a hrea o o her American coun ries, he decision over wha o do based onconclusions o he sys ema ic review has become urgenimpera ive. Given ha here is no hard evidence on how mdogs con ribu e owards human in ec ion, or on he einsec icides, par icularly organochlorines, and here are no analo he opera ional obs acles o con rol measures used in largeurban environmen s, and since he biological, social or ecolog

even s ha led o urbaniza ion and he spread o leishmaare absolu ely unknown36 , inves men in research ha addressehese problems mus be a priori y. Finding vaccines seems o



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immedia e challenge. A recen in erna ional symposium iden i edhe priori ies or advancing he developmen o vaccines and his

allows agencies o develop a view o crucial inves men s in hesec or (Working Group on Research Priori ies or Developmeno Leishmaniasis Vaccines: PLoS Neglec ed ropical Diseases,in press). As a nal poin , he resump ion o economic grow h inemerging economies ha are endemic wi h kala-azar, pu s pressure

on na ions like Brazil, India and Iran o ake on responsibili ies o science and echnology and o promo e serious inves men s in hedevelopmen o vaccines o a quali y adequa e or use in humans.Despi e he grea con roversy surrounding he use o DD , becauseo i s persis ence in he environmen and oxici y 29,95,96 , es s should be urgen ly conduc ed concerning i s applica ion o con rol urbankala-azar. Un il hen, he mos ha can be done would be a gradual,scheduled and moni ored demobiliza ion o he elimina ion o dogs,accompanied by ex ensive independen es ing and evalua ion o di eren s ra egies or spraying and o her al erna ives, such as hee ec o vaccines already licensed or dogs, or collars and mosqui one s impregna ed wi h insec icides.

ropical and developing coun ries should also ake advan age o his lesson given by he sys ema ic review 9 on he con rol measuresor leishmaniasis and i s poli ical consequences. Tey should seek he bes available scien i c knowledge, based on he bes evidence,o ob ain he bes public heal h programs. Indeed, ar icle 43 o he In erna ional Heal h Regula ions97 , o which Brazil and many

endemic coun ries in neglec ed diseases are signa ories, requirescien i c evidence or policy developmen aimed a public heal hin one o i s clauses. Moreover, he World Heal h Organiza ion, likemany o her organiza ions, provides guidelines or he developmeno consensus98. Tus, he s imulus or policies aimed a promo ingin egri y 99is an easily achievable goal and essen ial or he orma iono scien i ically neu ral environmen s. here ore, he lesson o zoono ic kala-azar can be use ul or a quali y review o currenrecommenda ions or public heal h in di eren coun ries.

Te awakening o he conserva ionis movemen and he righ so minori ies, coupled wi h he recogni ion o complex eelingsamong mammals has subs an ially changed he moral rela ionship be ween human beings and animals100, 101. Wi hin his change in hee hics o rela ionships wi h o her living beings, dogs are one o hemos sociable and a ec iona e species and canno be regarded asmorally irrelevan beings ha can be disposed o wi hou causingirre u able harm o humans. Tus, progressively more accura e andsensi ive human values imply he requiremen o repu able and rmscien i c jus i ca ion in order o be morally valid, which has never

been he case wi h any program or he disposal o dogs or he con rolo leishmaniasis. Finally, some good may come rom he con usedknowledge and decisions o he pas , since he housands o dogsneedlessly sacri ced may a leas serve o encourage a revolu ionin scien i c quali y and in he e hics o heal h policies aimed aneglec ed diseases.

ACKNOWLEDGMENTS

Te au hor owns wo dogs.CONFLICT OF INTEREST

FINANCIAL SUPPORT

REFERENCES

Te au hor is gra e ul o Dr. Dorcas Cos a and Dr. Isabel San osor kindly reviewing he manuscrip .

CNPq gran 306503/3008-5.

1. Joshi A, Narain JP, Prasitisuk C, Bha ia R, Hashim G, Jorge A ,e al.Can visceralleishmaniasis be elimina ed rom Asia? J Vec or Borne Dis 2008; 45:105-111.

2. Zhi-Biao X. Presen si ua ion o visceral leishmaniasis in China. Parasi oloday 1989; 5:224-228.

3. Commitee o exper s on leishmaniasis. Con rol o he leishmaniases. Geneva: World Heal h Organiza ion. echnical Repor Series; 1993.

4. Lukes J, Mauricio IL, Schonian G, Dujardin JC, So eriadou K, Dede JP , e al. Evolu ionary and geographical his ory o he Leishmania donovanicomplex wi h arevision o curren axonomy. Proc Na l Acad Sci U S A 2007; 104:9375-9380.

5. Mauricio IL, Gaun MW, S o hard JR, Miles MA. Glycopro ein 63 (gp63)genes show gene conversion and reveal he evolu ion o Old World Leishmania.In J Parasi ol 2007; 37:565-576.

6. Mauricio IL, S o hard JR, Miles MA. Te s range case o Leishmania chagasi.Parasi ol oday 2000; 16:188-189.

7. Herwald BL. Leishmaniasis. Lance 1999; 354:1191-1199.8. Desjeux P. Leishmaniasis: curren si ua ion and new perspec ives. Comp Immunol

Microbiol In ec Dis 2004; 27:305-318.9. Romero GA, Boelaer M. Con rol o visceral leishmaniasis in La in America:

a sys ema ic review. PLoS Negl rop Dis 2010; 4:e584.10. Adler S, chernomore z I. Failure o cure na ural canine visceral leishmaniasis.

Ann rop Med Parasi ol 1946; 40:320-325.11. Hoare A. Reservoir hos s and na ural oci o human pro ozoal in ec ions. Ac a

ropica 1962; 19:281-317.12. Leng YJ. A review o kala-azar in China rom 1949 o 1959. rans R Soc rop

Med Hyg 1982; 76:531-537.13. Zhong HL, Zhang NZ. S udies on leishmaniasis in China. His orical background,

epidemiology, clinical aspec s, legisla ure and con rol program. Chin Med J (Engl)1986; 99:281-300.

14. Lu C, Chung H, Ling C, Wu C, Wang C, Chiang Y. New China's achievemen s inhe rea men and preven ion o kala-azar. Chin Med J (Engl) 1955; 78:91-99.

15. Wang C , Wu CC. S udies on kala-azar in new China. Chin Med J 1959;78:55-71.

16. Guan LR, Shen WX. Recen advances in visceral leishmaniasis in China. Sou heas Asian J rop Med Public Heal h 1991; 22:291-298.

17. Zhang LM, Leng YJ. Eigh y-year research o phlebo omine sandfies (Dip era:Psychodidae) in China (1915-1995). II. Phlebo omine vec ors o leishmaniasisin China. Parasi e 1997; 4:299-306.

18. Chung H-L. A rsum o kala-azar work in China. Chin Med J (Engl) 1953;71:421-464.

19. Wu C. Some achievemen s on he s udy o kala-azar in New China. Chin Med J(Engl) 1958; 77:307-309.

20. Lu HG, Zhong L, Guan LR, Qu JQ, Hu XS, Chai JJ ,e al.Separa ion o Chinese Leishmaniaisola es in o ve geno ypes by kine oplas and chromosomal DNA he erogenei y. Am J rop Med Hyg 1994; 50:763-770.

21. Lysenko A, Lubova V. Epidemiology and geography o visceral leishmanisis inhe URSS. Colloque In erna ionaux du CNRS n 239; 1977; Paris: cologie de

leishmanioses; 1977. p. 253-256.22. Kellina OI. Problem and curren lines in inves iga ions on he epidemiology

o leishmaniasis and i s con rol in he U.S.S.R. Bull Soc Pa hol Exo Filiales.1981; 74:306-318.

23. Guan LR. Curren s a us o kala-azar and vec or con rol in China. Bull WorldHeal h Organ 1991; 69:595-601.

24. Mao SB. Con rol o parasi ic diseases in China: achievemen s and prospec s.

Chin Med J (Engl) 1987; 100:445-453.25. Yu S. Con rol o parasi ic diseases in China. Curren s a us and prospec s. ChinMed J (Engl) 1996; 109:259-265.



10/11

241

26. Bao Y, Wang S , Shao QF. A ur her s udy o LD and IFA es s in evalua inghe con rol o kala-azar in China. J rop Med Hyg 1994; 97:357-361.

27. Alam MZ, Haralambous C, Kuhls K, Gouzelou E, Sgouras D, So eriadou K , e al. he paraphyle ic composi ion o Leishmania donovanizymodemeMON-37 revealed by mul ilocus microsa elli e yping. Microbes In ec 2009;11:707-715.

28. Lysenko AJ. Dis ribu ion o leishmaniasis in he Old World. Bull World Heal hOrgan 1971; 44:515-520.

29. urusov V, Raki sky V, oma is L. Dichlorodiphenyl richloroe hane (DD ):ubiqui y, persis ence, and risks. Environ Heal h Perspec 2002; 110:125-128.

30. Sen Gup a P. Re urn o kala-azar. J Indian Med Assoc 1975; 65:89-90.31. Takur CP, Kumar M, Pa hak PK. Kala-azar hi s again. J rop Med Hyg 1981;

84:271-276.32. Kumar V, Kesari S, Kumar AJ, Dinesh DS, Ranjan A, Prasad M , e al. Vec or

densi y and he con rol o kala-azar in Bihar, India. Mem Ins Oswaldo Cruz2009; 104:1019-1022.

33. Dhillon GP, Sharma SN, Nair B. Kala-azar elimina ion programme in India. J Indian Med Assoc 2008; 106:664,666-668.

34. Joshi AB, Das ML, Akh er S, Chowdhury R, Mondal D, Kumar V ,e al.Chemicaland environmen al vec or con rol as a con ribu ion o he elimina ion o visceralleishmaniasis on he Indian subcon inen : clus er randomized con rolled rials

in Bangladesh, India and Nepal. BMC Med 2009; 7:54.35. Bern C, Cour enay O, Alvar J. O catle, sand fies and men: a sys ema ic review

o risk ac or analyses or Sou h Asian visceral leishmaniasis and implica ions orelimina ion. PLoS Negl rop Dis 2010; 4:e599.

36. Cos a CH. Charac eriza ion and specula ions on he urbaniza ion o visceralleishmaniasis in Brazil. Cad Saude Publica 2008; 24:2959-2963.

37. Bern C, Maguire JH, Alvar J. Complexi ies o assessing he disease burdenatribu able o leishmaniasis. PLoS Negl rop Dis 2008; 2:e313.

38. Minis rio da Sade. Srie his rica de bi os e casos de doenas de no i caocompulsria no Brasil (1980-2005). Braslia: Minis rio da Sade. Secre aria de Vigilncia em Sade. Depar amen o de Vigilncia Epidemiolgica. CoordenaoGeral de Vigilncia Epidemiolgica; 2006.

39. Commitee o exper s on primary heal hcare (Brasil). Manual de Vigilncia eCon role da Leishmaniose Visceral: Minis rio da Sade. Braslia: Secre aria de Vigilncia em Sade. Depar amen o de Vigilncia Epidemiolgica; 2004.

40. Salomon O, Sinagra A, Nevo M, Barberian G, Paulin P, Es evez J , e al. Firs visceral leishmaniasis ocus in Argen ina. Mem Ins Oswaldo Cruz 2008;103:109-111.

41. Lacerda MM. Te Brazilian leishmaniasis con rol program. Mem Ins OswaldoCruz 1994; 89:489-495.

42. Alencar J. Pro laxia do calazar no Cear, Brasil. Rev Ins Med rop Sao Paulo1961; 3:175-180.

43. Magalhaes PA, Mayrink W, Cos a CA, Melo MN, Dias M, Ba is a SM , e al. Calazar na zona do Rio Doce-Minas Gerais. Resul ados de medidas pro l icas.Rev Ins Med rop Sao Paulo 1980; 22:197-202.

44. Malaquias LCC, Romualdo RC, do Anjos Jr JB, Giuncheti RC, Correa-Oliveira R,Reis AB. Serological screening con rms he re-emergence o canine leishmaniosisin urban and rural areas in Governador Valadares, Vale do Rio Doce, Minas Gerais,Brazil. Parasi ol Res 2007; 100:233-239.

45. Marzochi MC, Fagundes A, Andrade MV, Souza MB, Madeira MF, Mouta-Con ort E , e al. Visceral leishmaniasis in Rio de Janeiro, Brazil: eco-epidemiological aspec sand con rol. Rev Soc Bras Med rop 2009; 42:570-580.

46. Cos a CHN, Pereira HF, Araujo MV. Epidemia de leishmaniose visceral no Es adodo Piau, Brasil (1980-1986). Rev Saude Publica 1990; 24:361-372.

47. Deane LM, Deane MP. Visceral leishmaniasis in Brazil: geographical dis ribu ionand ransmission. Rev Ins Med rop Sao Paulo 1962; 4:198-212.

48. Cos a CH, Vieira JB. Changes in he con rol program o visceral leishmaniasisin Brazil. Rev Soc Bras Med rop 2001; 34:223-228.

49. Schan z PM, S eurer FJ, Duprey ZH, Kurpel KP, Barr SC, Jackson JE , e al. Au och honous visceral leishmaniasis in dogs in Nor h America. J Am Ve Med

Assoc 2005; 226:1316-1322.50. Margonari C, Frei as CR, Ribeiro RC, Moura AC, imbo M, Gripp AH , e al.

Epidemiology o visceral leishmaniasis hrough spa ial analysis, in Belo Horizon e

municipali y, s a e o Minas Gerais, Brazil. Mem Ins Oswaldo Cruz 2101:31-38.

51. Cos a C, Moura M, Pereira F. Fa ores de risco urbanos para a ocorrncia leishmaniose visceral. Rev Soc Bras Med rop 1995; 28(supl I):7

52. Gavgani AS, Hodja i MH, Mohi e H, Davies CR. E ec o insec icide-impredog collars on incidence o zoono ic visceral leishmaniasis in Iranian childra ma ched-clus er randomised rial. Lance 2002; 360:374-379.

53. Oliveira CD, Assuncao RM, Reis IA, Proieti FA. Spa ial dis ribu ion o hand canine visceral leishmaniasis in Belo Horizon e, Minas Gerais S a e, B1994-1997. Cad Saude Publica 2001; 17:1231-1239.

54. Werneck GL, Cos a CH, Walker AM, David JR, Wand M, Maguire JH. Mul imodelling o he incidence o visceral leishmaniasis in eresina, Brazil. EpideIn ec 2007; 135:195-201.

55. Werneck GL, Cos a CH, Walker AM, David JR, Wand M, Maguire JH. Turban spread o visceral leishmaniasis: clues rom spa ial analysis. Epidemio2002; 13:364-367.

56. Ko ka A, el-Daly S, el-Daaw A, Baraka R. Immunological inves iga ion oleishmaniasis among school children in Alexandria. J Egyp Soc Parasi ol 1916:449-456.

57. Moreno EC, Melo MN, Genaro O, Lamber ucci JR, Seru o JC, Andrade A ,e al. Risk ac ors or Leishmania chagasiin ec ion in an urban area o

Minas Gerais S a e. Rev Soc Bras Med rop 2005; 38:456-463.58. Gouvea MV, Werneck GL, Cos a CH, Amorim Carvalho FA. Fac ors associo Mon enegro skin es posi ivi y in eresina, Brazil. Ac a rop

104:99-107.59. Navin R, Sierra M, Cus odio R, S eurer F, Por er CH, Ruebush

2nd Epidemiologic s udy o visceral leishmaniasis in Honduras, 1975-198 Am J rop Med Hyg 1985; 34:1069-1075.

60. Cos a CH, Pereira HF, Pereira FC, avares JP, Araujo MV, Goncalves MJ. Is household dog a risk ac or or American visceral leishmaniasis in Brazil? R Soc rop Med Hyg 1999; 93:464.

61. Caldas AJ, Cos a JM, Silva AA, Vinhas V, Barral A. Risk ac ors associaasymp oma ic in ec ion by Leishmania chagasiin nor h-eas Brazil. rans R Soc

rop Med Hyg 2002; 96:21-28.62. Nascimen o MDSB. Epidemiologia da leishmaniose visceral na Ilha de S

Luis, Maranho, Brasil: anlise da dinmica de ransmisso e dos a ores de rrelacionados ao desenvolvimen o da doena. [Doc or in Medicine]. [So PauloUniversidade Federal de So Paulo; 1996.

63. Quinnell RJ, Cour enay O. ransmission, reservoir hos s and con rol o zoo visceral leishmaniasis. Parasi ology 2009; 136:1915-1934.

64. Adler S, Teodor O. ransmission o disease agen s by phlebo omine sand fi Annual Rev En . 1957; 2:203.

65. Sherlock IA, Sherlock V. Sbre a in eco experimen al de Phlebotomus longipalpis pela Leishmania donovani. Rev Bras Biol 1961; 21:409-418.

66. Molina R, Amela C, Nie o J, San-Andres M, Gonzalez F, Cas illo JA , e al. In ec ivi y o dogs na urally in ec ed wi h Leishmania in antumo colonized Phlebotomus perniciosus. rans R Soc rop Med Hyg 1994; 88:491-493.

67. Michalsky EM, Rocha MF, Rocha Lima AC, Franca-Silva JC, Pires MOliveira FS , e al. In ec ivi y o seroposi ive dogs, showing di eren clin

orms o leishmaniasis, o Lutzomyia longipalpisphlebo omine sand lies. Ve Parasi ol 2007; 147:67-76.

68. Cos a CH, Gomes RB, Silva MR, Garcez LM, Ramos PK, San os RS , e al. Compe ence o he human hos as a reservoir or Leishmania chagasi. J In ecDis 2000; 182:997-1000.

69. Rogers DJ. Te dynamics o vec or- ransmited diseases in human communiPhilos rans R Soc Lond B Biol Sci 1988; 321:513-539.

70. Ma her , Wilson M, Moore S, Ribeiro J, Spielman A. Comparing rela ive po en ial o roden s as reservoirs o he Lyme disease spiro( Borrelia burgdor eri). Am J Epidemiol 1989; 130:143-150.

71. Dye C. Te logic o visceral leishmaniasis con rol. Am J rop Med Hyg 1955:125-130.

72. Bura ini M, Cou inho F, Lopez L, Massad E. Modelling he dynamileishmaniasis considering human, animal hos and vec or popula ions. J BioloSys ems 1998; 4:337-356.



11/11

242

73. Die ze R, Barros GB, eixeira L, Harris J, Michelson K, Falque o A ,e al. E eco elimina ing seroposi ive canines on he ransmission o visceral leishmaniasisin Brazil. Clin In ec Dis. 1997; 25:1240-1242.

74. Ash ord DA, David JR, Freire M, David R, Sherlock I, Eulalio MC ,e al.S udies oncon rol o visceral leishmaniasis: impac o dog con rol on canine and human visceralleishmaniasis in Jacobina, Bahia, Brazil. Am J rop Med Hyg 1998; 59:53-57.

75. Cos a CH, ape y CM, Werneck GL. Con role da leishmaniose visceral em meiourbano: es udo de in erveno randomizado a orial. Rev Soc Bras Med rop

2007; 40:415-419.76. Souza V, Bisino o , Julio F, Lima A, Neves R. Communi ary assay or assessmen

o e ec iveness o s ra egies or preven ion and con rol o human visceralleishmaniasis in he municipali y o Feira de San ana, S a e o Bahia, Brazil.Epidemiol Serv Saude 2008; 17:97-106.

77. McGari y O, Wagner WE. Bending Science: how special in eres s corrup publicheal h research. 1s ed. Cambridge: Harvard Universi y Press; 2008.

78. Organizacin Panamericana de la Salud. Organizacin Mundial de la Salud.Encuen ro sobre vigilancia, prevencin y con rol de leishmaniasis visceral (LV)en el Cono Sur de Sudamrica. Foz do Iguaz, Brasil. 2009 - [ci ed 2010 Nov 21] Available rom: htp://new.paho.org/pana osa/index.php?op ion=com_docman& ask=doc_download&gid=79/.

79. Commitee o exper s on leishmaniasis. II Forum de discusso sobre o ra amen oda leishmaniose visceral canina. Brasilia: Minis rio da Sade. Secre aria de Vigilncia em Sade; 2009.

80. Manchikan i L. Evidence-based medicine, sys ema ic reviews, and guidelines inin erven ional pain managemen , par I: in roduc ion and general considera ions.Pain Physician 2008; 11:161-186.

81. Schunemann HJ, Fre heim A, Oxman AD. Improving he use o research evidencein guideline developmen : 1. Guidelines or guidelines. Heal h Res Policy Sys2006; 4:13.

82. Fre heim A, Schunemann HJ, Oxman AD. Improving he use o research evidencein guideline developmen : 3. Group composi ion and consul a ion process.Heal h Res Policy Sys 2006; 4:15.

83. Diamond GA, Den on A. Al erna ive perspec ives on he biased ounda ionso medical echnology assessmen . Ann In ern Med 1993; 118:455-464.

84. Commitee o exper s on dengue. Dengue: diagns ico e manejo clnico - adul o

e criana. 3a

ed. Braslia: Dire oria cnica de Ges o. Secre aria de Vigilncia emSade. Minis rio da Sade; 2007.85. Commitee o exper s on leishmaniasis, Commitee o exper s on HIV in ec ion

and Aids. Recomendaes para diagns ico, ra amen o e acompanhamen oda co-in eco Leishmania-HIV. Braslia: Programa Nacional de DS e Aids.Secre aria de Vigilncia em Sade. Minis rio da Sade; 2004.

86. Commi ee o exper s on primary heal h care. Vigilncia em sade: dengue,esquis ossomose, hansenase, malria, racoma e uberculose. 2 ed. Braslia: Secre ariade A eno a Sade. Depar amen o de A eno Bsica. Minis rio da Sade; 2008.

87. Commitee o exper s on egumen ar leishmaniasis. Leishmaniose VisceralGrave: Normas e Condu as. 1s ed. Braslia: Coordenao Geral de VigilnciaEpidemiolgica. Depar amen o de Vigilncia Epidemiolgica. Secre aria de Vigilncia em Sade. Minis rio da Sade; 2006. p.51.

88. Commitee o exper s on egumen ar leishmaniasis. Manual de vigilncia daleishmaniose egumen ar americana. 2 ed. Braslia: Edi ora do Minis rio daSade; 2010.

89. Khalil EA, El Hassan AM, Zijls ra EE, Mukh ar MM, Ghalib HW, Musa B ,e al. Au oclaved Leishmania major vaccine or preven ion o visceral leishmaniasis:a randomised, double-blind, BCG-con rolled rial in Sudan. Lance 2000;356:1565-1569.

90. Picado A, Das ML, Kumar V, Kesari S, Dinesh DS, Roy L ,e al.E ec o village- wide use o long-las ing insec icidal ne s on visceral Leishmaniasis vec ors inIndia and Nepal: a clus er randomized rial. PLoS Negl rop Dis 2010; 4:e587.

91. Alexander B, Maroli M. Con rol o phlebo omine sandfies. Med Ve En omol2003; 17:1-18.

92. Pala nik-de-Sousa C. Vaccines or leishmaniasis in he ore coming 25 years. Vaccine 2008; 26:1709-1724.

93. Khamesipour A, Ra a i S, Davoudi N, Maboudi F, Modabber F. Leishmaniasis vaccine candida es or developmen : a global overview. Indian J Med Res2006; 123:423-438.

94. Kedzierski L, Zhu Y, Handman E. Leishmaniavaccines: progress and problems.Parasi ology. 2006; 133(suppl):S87-112.

95. Rogan WJ, Chen A. Heal h risks and bene s o bis(4-chlorophenyl)-1,1,1-richloroe hane (DD ). Lance 2005; 366:763-773.

96. Guimaraes RM, Asmus CI, Meyer A. DD rein roduc ion or malaria con rol: hecos -bene deba e or public heal h. Cad Saude Publica 2007; 23:2835-2844.

97. Da a WLC-i-P. In erna ional Heal h Regula ion. 2005 - [ci ed April 32010]. Available rom: h p://whqlibdoc.who.in /HQ/2003/EIP_GPE_

EQC_2003_1.pd /.98. World Heal h Organiza ion. Global Programme on Evidence or Heal h Policy.

Guidelines or WHO guidelines. Geneva: World Heal h Organiza ion; 2003.99. Commi ee on Assessing In egri y in Research Environmen s. In egri y in

scien i c research: crea ing an environmen ha promo es responsible conduc . Washing on (DC): Te Na ional Academies Press; 2002.

100. Te moral s a us o animals. S an ord Encyclopedia o Philosophy 2003 - [ci edFeb 21h2010]. Available rom: h p://pla o.s an ord.edu/en ries/moral-animal/.

101. Emery NJ, Clay on NS. Compara ive social cogni ion. Annu Rev Psychol2009; 60:87-113.


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