Control of chagas disease in Brazil

Parasitology Today, vol. 3, no. II, 1987

336

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Control of Chagas Disease in Brazil

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ofTrypanosomacruzi causative agent of Chagas disease.

Joao Carlos Pinto Dias is Director of the Chagas Disease Division, SUCAM, Ministry of Health, 70058 Brasi~iaDF, Brazil.

Chagas disease (South-American trypanosomiasis) is a chronic but often fatal disease endemic throughout much of Latin America. Serological surveys suggest around 24 million people seropositive for the causative agent, Trypanosoma cruzi (Fig. 1), with over 65 million living in the endemic areas and at risk to infection. In Brazil, over 25 million people are considered at risk, and control of the disease constitutes one of Brazil's public health priorities. Treatment or vaccination against T. cruzi is impossible at the public health level because suitable drugs or vaccines are not available. But it is well recognized that transmission can be interrupted by eliminating the domestic vectors - blood-sucking reduviid bugs of the subfamily Triatominae. In Brazil, eradication of Triatoma infestans - the major domestic vector of T. cruzi- is now seen as a feasible target by the Ministry of Health. However, although other domestic vectors can also be controlled, they will retain their sylvatic ecotopes from which they can reinvade houses. In this article, Joao Carlos Pinto Dias explains the current Brazilian policy, highlighting the successful elimination ofT. infestansfrom much of the southern part of the country. Chagas disease is not an isolated problem. In its endemic areas k is closely associated with other diseases such as malnutrition, diarrhoea, tuberculosis and other parasitic infections that affect a particular social stratum. These diseases both limit, and are limited by, the social context in which they occur I . Direct observations, and even mathematical models, are showing that the social and political development of endemic regions is sufficient to achieve control of Chagas disease (and associated problems) 1-6, yet this

route is complex and slow in the less developed countries - largely because it concerns rural areas that traditionally receive little or no political priority4-6. But unlike many other parasitic diseases, Chagas disease can also be controlled by eliminating vector populations, chiefly by using insecticides and housing improvements2-9. Brazil offers the largest endemic area for Chagas disease, involving about 3 million square kilometres, 2400 municipalities (counties) and over 25 million people at risk to infection 1,1°. A recent national survey showed that about 4.4% of the rural population present antibodies to T. crugi 11, and we now estimate that about 5 million chagasic people live in Brazil. Many of these people, who generally come from the poorest levels of rural society, migrate to urban areas where a new problem is emerging because of the transmission of T. cruz/ through blood transfusion 1,7,n,12. The social impact of Chagas disease is very high. In Brazil, considering that at least 10% of infected people develop severe cardiac or digestive problems, we estimate that the medical costs alone for the necessary pacemakers and oesophageal and colonic surgery could reach US$250 m i l l i o n per year 1. Similarly, the minimum absenteeism of 75 000 chagasic workers with serious heart disease could represent losses of US$5625 million per year 1,6. Social welfare costs can also be high: in the state of Minas Gerais alone in 1976 there were 1184 pension awards because of disability due to Chagas disease- signifying costs at that time of US$399 600 (Ref. 1). For comparison, the total operating costs of the National Chagas Disease Programme for 1986 were about US$35 million (Box 1), which provided for ~ ) 1987, Elsevier Publications, Cambridge 0 b69~,758/87/$02 00

Parasitology Today, vol. 3, no. I I, 1987

investigation of 5 miUion houses and spraying of 650 000 of them 1°'. Non-vector Transmission Apart from transmission by the triatomine vectors, transmission of T. cruzi by blood transfusion is also becoming very important in Brazil. For example, positive serology is found in about 0.5-5.2% of blood donors in the states of Minas GerMs and Sao Paulo 12, and we estimate that about 10 000-20 000 new cases of infection arise each year in Brazil tkrough transfusional

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Box 2. Vectors and Reservoirs of Trypanosoma cruzi in Brazil

43 species of Triatominae have been found in Brazil, but most are associated only with sylvatic ecotopes such as palm tree crowns, opossum lodges, armadillo burrows and bird nests. However, six species are considered important as vectors of Chagas disease because they frequently colonize houses, emerging at night from cracks and crevices in the walls and roof to

t r a n s m i s s i o n l , 12.

The problem of transfusional transmission of T. cruz/has long been recognized in Brazil. Even in 1969 the then National Commission of Haemotherapy laid down guidelines for screening and rejecting chagasic blood donors, followed in 1974 by definitions of the minimum requirements for blood bank operation which included further regulations designed to eliminate this problem. However, although many blood services in our country do operate to the highest standards, it has become clear that some of these commercial services suffer from poor screening techniques or disinterest in the legislation. Now, after strong campaigning by the sci~mtific and medical community, the govenmaent through its National Blood Policy (PROSANGUE) is installing active systems :for serodiagnosis in endemic areas in order to screen blood donors for Chagas disease, syphilis, hepatitis-B and the acqtdred immune deficiency syndrome (AIDS). Transfusional Chagas disease can also be avoided by the addition of gentian violet: to blood stored for 24 hours. This effective and cheap method has been used for many years in Brazil and Argentina, where more than 70 000 transfusions have been made, with such treated blood without side effects. Congenital transmission of T. cruz/can also be significant, and we estimate a risk of around 1% that children born to infected mothers will be congenitally infected 1. The only preventive approach for this problem is by precocious diagnosis and treatment of infected new-borns with drugs such as nifurfimox (Lampit) or benznidazole (Rochagan). Other route.s of T. cruz/transmission, such as by hi:oratory accidents, kidney transplant or oral ingestion of infected material, have been recorded in Brazil but are without elaidemiological significance1,7. Vector Control More than 80% of Chagas disease is

cycles of T. cruz/transmission. Nevertheless, due to the lack of suitable drugs, neither specific treatment of infected people nor elimination of other reservoirs can constitute an attainable objective of the Chagas disease control programmesl,2, 8. Control must rely on elimination of the domestic insect vectors, and also on the control of transfusional transmission of the parasite.

attributable to transmission by the triatomine bug vectors (Box 2). For this reason, control of domestic triatomine bugs is the chief target of the Brazilian Chagas Disease Programme. This progrmnme is mainly implemented by SUCAM (Superintendencia de Campanhas de Saude Publica) which represents the executive ann of the Ministry of Health and operates in all Brazilian States and Territories except Sao Paulo state which has its own organization Superintendencia Controle de Endemias (SUCEN). The programme is financed partly by SUCAM itself, and to a lesser extent by funds from other government New Brazilian legislation organizations (Box 1). (Projeto de lei No. 6554 de The Brazilian Chagas Disease Pro- 1985) - expected to be gramme is based upon several B r o g a n approved this year- will studies and results from political decisions require laboratory screening taken over the past 10 years. The rationale of all blood donors for hepatitis-B, syphilis, Chagas for these decisions are based primarily on disease and AIDS, with the following: rejection of all positive - recognition of the importance of Chagas donors. The legislation does not specifically refer to disease in the country; treatment of stored blood.

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Fig. 2. Chagas disease control activities begin with a geographical reconnaissance of the target area (a) with each house inspected for bugs by trained field personnel (b). During the attack phase, all houses are sprayed while those that were positive for bugsare then resprayed 3-6 months later (c).

Outbreaks of dengue transmitted by Aedes aegypti and Ae. albopictus along the Atlantic coast and some inland areas of Brazil meant that around 3000 SUCAM personnel had to be diverted from Chagas disease control to dengue control in 1986. But by August 1987 most of these workers could be returned to the Chagas programme as new personnel were contracted for dengueand yellow fever control.

programme follows phases7,1° (Fig. 2):

- development of suitable vector control methods, both in trials against Chagas disease itself, and from experience with malaria control; - the trend to urbanization of Chagas disease due to human migration from endemic rural areas to cities; - evidence of the social and economic costs of the disease, and continuous campaigning by scientists including demonstrations that vector control was feasible and could bring political credit to the governorsS,6,8,13. Early studies during 1947-61 by Emmanual Dias and others had demonstrated that regular and continuous application of residual insecticides to houses was effective in interrupting transmission of T. cruz/to man in endemic areasS, 9. Moreover, at the beginning of the current programme, SUCAM's resources were only sufficient to mount attacks with insecticides, but this policy is now being modified towards a less centralized approach including community participation and involvement of the primary health care network - especially in epidemiological surveillance and in the control of transfusional transmission from blood banks 1°,12. Organization of the vector control

three

[ The Preparatory Phase. This ncludes mapping the area to be xeated, and manual sampling of ~ugs from each house and peritomestic habitats in the region. From this information, the costs md activities in terms of personael, insecticides, equipment and xansport can be programmed. The Attack Phase. The initial ;praying of an area is known as attack one' or massive attack, during which all houses and outbuildings are sprayed regardless of whether or not they were found to be infested. A second selective spraying is then carried out 3-6 months later only in houses known to have been infested. This is followed by successive evaluations and spraying of houses still found to be infested (evaluation attack phase). This phase ends when the number of infested dwellings in a locality is reduced below 5% and T. infestans is no longer found in houses. It is recognized that for success in this objective, the attack phase must be strictly continuous over time, and contiguous over the chosen geographic areas,9. 3 The Vigilance Phase. When the attack phase objective is reached, the vigilance phase comprises periodic sampling of houses by SUCAM personnel, and by the local community, to detect any residual foci of domestic triatomine bugs. Regional voluntary posts are established in each municipality to coordinate any denunciation of infested premises, confuan identification of the bugs and organize immediate spraying of the infested dwellings. During 1984-85, the programme could cover all the endemic areas of the country. This has involved about 8000 spraymen and 1000 other professionals (inspectors, laboratory technicians and drivers) working in more than 5 million dwellings in 2400 municipalities 1°. The spraying activities peaked in 1985-86, with 1 102 613 houses

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sprayed. In most cases, SUCAM used benzene hexachloride (BHC; 30% gamma isomer), but during ~te past three years there have been problems in obtaining this insecticide and increasing concern about its possible environmental impact. This has obliged the programme,, to switch to other products such as malathion and synthetic pyrethroids (chiefly deltamethrin and cypermethrin) (Box 3). Pyrethroids, although more expensiLve than BHC, are used at lower doses and have a longer residual effect, so that operating costs work out much the same7,10. Insecticide resistance has not been recorded among triatomine bugs in Brazil.

Programme Results The results of the Chagas disease vector control programme have generally been good, with domestic bug populations drasticaUy reduced in all worked areas. But the programme has not yet ,achieved all its aims, mainly through recent shortages of insecticides and personnel. Insecticides are imported, and represent a high cost in foreign exchange. Moreover, with the outbreaks of dengue fever in 1986, about 40% of SUCAM personnel had to be diverted to control of Aedes mosquitoes in several parts of the country. This put at risk the advances of the Chagas disease control programme in some areas. Greatest success has been achieved against T. infestans, which has been virtually

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1975-83 97 (39.8) 90(30.9) 38(59.4) 168 (23.3) 5 (9.1) 162 (66.4) 122(36.3) 12(10.5) 17 (10.4)

1986 57 (23.4) 9 (3.1) 6 (9.4) 35 ( 4 . 8 ) 2 (3.6) 22 ( 9 . 0 ) 42(12.5) 8 (7.0) 5 (3.0)

% reduction 41.24 90.00 84.22 79.17 60.00 86.42 65.58 33.37 70.59

Total

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T. infestans (%)

No. of municipalities 244 291 64 722 55 244 336 114 164

Municipalities with

340

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0.8

is a particular problem in central Brazil; it has a wide range of sylvatic ecotopes but can also build up quite large populations in peridomestic habitats such as chicken houses. It thus seems less vulnerable to control activities because houses from which T. infestans has been eliminated can be quickly recognized by T. sordida from untreated peridomestic areas or from its sylvatic ecotopes. Nevertheless, in regions with extensive agriculture or reforestation with pine and eucalyptus, the natural sylvatic fauna tends to decline and recolonization of houses by sylvatic bugs is less of a prob-

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Accumulated experience indicates that the Brazilian Chagas disease control programme is feasible. Technical problems have been largely overcome, leaving only operational and financial problems. In eradicated from Sao Paulo state and from 1987, just four years after the first complete many municipalities elsewhere (Fig. 3). coverage of all the endemic area, the vigiIn parallel, Fig. 4 shows the progressive lance phase was already reached in 538 reduction in prevalence of T. cruz/infection municipalities representing 23% of the total among schoolchildren in Sao Paulo, which endemic area (Fig. 5). The great challenge follows the success of T. infestans control. is now to maintain the vigilance phase by Similar declines in domestic bug popula- mobilizing local communities to participate tions are seen with other species in some effectively in vector surveillance. At the areas, but in a few areas, species such as T. same time, increased emphasis is being sordida and T. brasiliensis continue to pre- placed on complementary activities such as sent difficulties for vector control because housing improvements, active control of they retain sylvatic ecotopes and can readily blood banks to eliminate transfusional recolonize sprayed houses when the transmission, and development of a realistic residual insecticide activity ends. T. sordida medical care system for rural areas to provide attention for chronic sufferers of the disease. For even if Chagas disease transmission is completely interrupted, several million people will remain infected and will require attention throughout their generation. Political priority is still the great question in Chagas disease control, for without this any control activities will be starved of the necessary resources. Scientists too must continue their research but should devote more attention to operational questions that can help to improve the control activities in the field. For example, we urgently need better methods for detecting bugs in infested houses, and for monitoring the effects of control interventions. Moreover, although the biology of T. infestans and P. meg/stus is relatively well understood, especially as it relates to their population biology and control, we have much less knowledge about other vector species which are now increasingly presenting difficulties. The importance of such work extends not just to Brazil, but also to other affected countries that may benefit from the Brazilian experience in control policy and techniques. As

Fig. 4. In Sao Paulo, the prevalence of Chagas seropositivity in schoolchildren has declined in parallel with successful vector control activities. Total seropositivity ( ); seropositivity in children born in Sao Paulo state (- .... -).

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Carlos C h a g a s h i m s e l f said in 1911, "undoubtedly the control of American t r y p a n o s o m i a s i s offers several practical difficulties, all o f t h e m o f an e c o n o m i c a l n a t u r e . B u t as the p r o b l e m is also l i n k e d to h u m a n i t a r i a n q u e s t i o n s , to the p r i d e o f a p e o p l e a n d to the m o r a l g r e a t n e s s o f a nation, surely o n e d a y w e will n o t lack t h e necessary energy to face it in a decisive m a n n e r ''15. Politically, t h e t i m e f o r this has never b e e n better, a n d the objectives a n d targets o f the Brazilian Chagas disease prog r a m m e h a v e n o w b e e n clearly laid d o w n (Box 4). W e believe these objectives to b e m o r a l l y , politically a n d e c o n o m i c a l l y justifiable, a n d are feasible b o t h operationally a n d technically. References 1 Dias, J.C.P. (1987) in Chagas" Disease Vectors (Brenner, R. and Stoka, A. eds), CRC :PressInc. (in press) 2 TDR (WB/UNDP/WHO) (1980) Workshop on Mathematical Computer Models in the Control of Chagas"

D/sease(Rabinovich~J., ed.), 38 pp. 3 Dias, J.C.P. and Borges Dias, R. (1982) Bull. PAHO 16, 117-128 4 Bucher, E.H. and Schofield, C.J. (1981) New Sc/. 92, 321-324 5 Dias, J.C.P. (1985) Bol. Of,~. Sanit. Panarn. 99, 244256 6 Dias, J.C.P. and Borges Dias, R. (1979) C/~. Cu/t. 31 (suppl.), 105-118 7 Garcia Zapata, M.T.A. and Marsden, P.D. (1986) Clin. Trop. Med. Comrmm/c.D/s. 1,557-585 8 Silva, E.O.R. (1979) in Tr~panosoma cruzi e doer~a de Chagas (Brener, Z. and Anchade, Z., eds), pp. 425-449, Guanabara Koogan, Rio de Janeiro 9 Dias, E. (1957)Hospital 51,285-298 10 Dias, J.C.P. (1986) Rev. Soc. Bras. Med. Trop. 19, 129133 11 Lima, J.T.F. and Silveira, A.C. (1985) in Cardiopatia Chagdsica (Can~ado, J.R. and Chuster, J.M., eds), pp. 371-380, Funda~io Carlos Chagas, Belo Horizonte

12 Dias, J.C.P. and Brener, S. (1984) Oswa/do Cruz 79, (Suppl.) 139-148 13 Dias, J.C.P. (1986) in FactoresBiologicosy Ecologicos en la Enfermedad de Chagas (CarcavaUo,R., ed.), pp. 289304, Buenos Aires 14 Forattini, O.P. (1980) Rev. Safde P,',blica 14, 265-299 15 Chagas, C. (1911) in Carlos Chagas, Coletdmea de Trabalhos Ciemificos, pp. 167-192, Universidade de Brasilia (1981), Brasilia 16 Dujardin, J-P. et al. (1987)J. Med. Entomol. 24, 40-45 17 Silva, L.J. (1985) Rev. Inst. Med. Trop. (S[toPaulo) 27, 219-223 18 Sehofield, C.J. in Biosystematics of Haematophagous Insects (Service, M.W., ed.), Oxford University Press (in press) 19 Marques, A.C. (1987) Parasitol. Today 3, 166-170 20 Silveira,A.C., Feitosa, V.R. and Borges, R. (1984)Rev. Bras. Malariol. Doen~as Trop. 36, 15-312

Trematode Eggshells: Novel Protein Biopolymers J.S. Cordingley In the past few years recombinant DNA technology has somewhat serendipitously shed new light on the formation of trematode eggshells, with the publication of the sequences of highly expressed female-specific genes encoding protein components of the schistosorne eggshellI-5 and with the isolation of DOPA-rich proteins and one of the corresponding genes6 from Fasciola7. These proteins and other structural polypeptides with repetitive structures were the subject of a recent meeting Bioengineering for Material Applications (sponsored by the Office of Naval Research in Bethesda, USA,June 1987). In this article, based on that meeting, John Cordingley explains how the structure of trematode eggshells appears to show features common to several other biopolyrners. In 1959 Smyth and Clegg wrote a review 8 which is still required reading for anyone interested in the question of eggshell formation in trematodes. These authors described (and accurately predicted) most of the features of eggshell formation as we understand them today and recent data have largely served to ~1987, ElsevierPublications,Cambridge0169-4758/87/$02.00

confirm their view of the mechanisms at work. A trematode egg is formed from 3040 vitetline cells and one fertilized ovum which become encapsulated in a crosslinked protein eggshell. The eggshell is formed from proteinaceous granules (the so-called vitelline droplets) which

are exocytosed from the vitelline cells and fuse around the cell mass. After exocytosis from the vitelline cells, the eggshell proteins become rapidly crosslinked due to the action of an enzyme (or enzymes) referred to as 'phenol oxidase' (Box I). Diethyl-dithiocarbamate, a copper-chelating compound, prevents eggshell formation in schistosomes 9 by inhibiting the schistosome phenol oxidasel°; the effect is reversible in viva. Smyth and Clegg 8 had proposed that the 'tanning' reaction was an oxidation of tyrosine-rich proteins to 'DOPAquinones' which then condensed with the lysines of adjacent proteins to crosslink the eggshell. The crosslinking reactions are accompanied by changes in the