Infernorronal Journalfor Parasilo/ogy Vo/. 21, No. 2,pjx 271-274, Printed in Grear Britain
1991 0
W2&7519/91 $3.00 + 0.00 Pergamon Press p/c 1991 Australian Society/or Parosifology
RESEARCHNOTE RELATIONSHIPS BETWEEN CLINICAL PROTECTION AND ANTIBODIES TO PLASMODIUM FALCIPARUM RESA (RINGINFECTED ERYTHROCYTE SURFACE ANTIGEN) PEPTIDES BERNABE F. F.CHUMPITAZI,*$PHILIPEDELORON,? FRANCOIS PEYRON,* CHRISTIAN BOUDIN,*$ STEPHANE PICOT* and PIERRE AMBROISE-THOMAS* *Departement
de Parasitologic-Mycologic Medicale et Moleculaire (DP3M), CNRS URA 1344, Faculte de Medecine, Universite Joseph Fourier-Grenoble I, Domaine de La Merci, 38706, La Tronche Cedex, France TINSERM U 13, Hopital Claude Bernard, 75944 Paris Cedex 19, France fORSTOM, Centre Muraz, Bobo-Dioulasso, Burkina Faso, West Africa (Received 1 November 1990; accepted 22 January 1991)
Abstract-CHuMP~TAz~ B. F. F., DELORON P., PEYRON F., BOUDIN C., PICOTS. and AMBROISE-THOMAS P. 1991. Relationships between clinical protection and antibodies to Pksmodium falciparum RESA (Ringinfected Erythrocyte Surface Antigen) peptides. International Journal for Parasitology 21: 271-274. A longitudinal study involving 76 individuals living in Dafinso and Vallee du Kou (near Bobo-Dioulasso, Burkina Faso, West Africa) was performed in June 1987 (beginning of the transmission period), AugustSeptember 1987 (during) and January 1988 (after). The serological antibody (Ab) responses against synthetic peptides representing repeat amino acid sequences of the P. falciparum Ring-Infected Erythrocyte Surface Antigen (RESA): (EENV),, (EENVEHDA),, (DDEHVEEPTVA)Z were evaluated by ELISA. The clinical longitudinal study during the transmission period allowed us to define three different groups in terms of age and occurrence of clinical malarial attack (2 5000 parasites mm -3 of blood and axillary fever z 37.7”C). Levels (A,) of Ab to (EENVEHDA), and (DDEHVEEPTVA), were correlated with age. The adult group (III) had the highest prevalences of Ab to RESA peptides. No significant difference was found between groups of children with or without malaria attack. Nevertheless, at the beginning of the transmission period, children who had at least one malaria attack during the study presented the lowest level of antibodies to RESA peptides. INDEX KEY WORDS: RESA peptides; IgG; malaria; Plasmodium falciparum; protective immunity.
RESA is found in merozoites and in the membranes of ring-infected erythrocytes (Cop+, Cowman, Anders, Bianco, Saint, Lingelbach, Kemp & Brown, 1984; Perlmann, Berzins, Wahlgren, Carlson, Bjijrkman, Patarroyo & Perlmann, 1984) and has a M, of 155,000. This Ag presents two regions of repetitive amino acid sequences. The first region, located near the carboxy terminal end, contains a repeating 1 l-amino acid sequence (DDEHVEEPTVA). The second one, located in the amino terminal end, includes some repeats of an eight-amino acid sequence (EENVEHDA) and a more extensive set of a repeating tetrapeptide (EENV). Merozoite invasion in vitro is inhibited by anti-RESA Ab (Wahlin, Wahlgren, Perlmann, Berzins, Bjorkmann, Patarroyo & Perlmann, 1984) which have been related to clinical immune protection (Deloron, Le Bras, Save1 & Couland, 1987; Wahlgren, Bjorkmann, Perlmann, Berzins & Perlmann, 1986). Aotus trivirgatus immunized with recombinant RESA protein were partially
5 To whom all correspondence should be addressed.
protected against P. falciparum infection, the best protection being achieved with constructs including the first repeat region located near the carboxy terminal end (Collins, Anders, Pappaioanou, Camp bell, Brown, Kemp, Coppel, Skinner, Andrysiak, Favarolo, Corcoran, Broderson, Mitchell Kc Campbell, 1986). The aim of this study was to determine the relationship between the levels of antibodies to RESA peptides and the clinical immunoprotection status against malaria in individuals living in a mesoendemic area near Bobo-Dioulasso (Burkina Faso). Two small villages, Dafinso and Vallee du Kou No.4 (VK4), were chosen for this study. The seasonal transmission of malaria, due generally to Anopheks gumbiae, begins in June and ends in November/ December after the rainy season. The number of infected bites per man per year is about 50 in both villages (Robert, Gazin, Boudin, Molez, Ouedraogo & Carnevale, 1985). Eighty-two individuals were included in this study but only 76 were longitudinally examined from June 1987 to January 1988. Clinical data were recorded for each person by a physician 271
B. F. F. CHUMPITAZI et al.
212
twice a week during the transmission period. A malarial attack (MA) was defined as P. jiilciparum density over 5000 parasites mm -3 and axillary fever > 37.7”C. Chloroquine was also administered by the physician. At the beginning of the transmission period in June, during August/September and after January blood samples were collected by venipuncture in heparin tubes. Asexual forms of P. falciparum, the most prevalent species in these areas, were counted on thick film assuming a constant leukocyte count of 8000 ~1~’ of blood. An ELISA using the Falcon Assay Screening Test (FAST) system (Hancock & Tsang, 1986) was used to determine Ab reactivity to RESA synthetic peptides reproducing each of the repeats present in the RESA molecule. These peptides were (EENV), referred to as RESA4, (EENVEHDA), as RESA8 and (DDEHVEEPTVAh as RESAl 1. All three peptides were kindly provided by Drs P. Nguyen-Dinh and G.H. Campbell of the Center for Disease Control (Atlanta, Georgia, U.S.A.) These peptides were conjugated with bovine serum albumin (BSA) at a molar ratio of 2O:l (peptide to BSA) in the presence of glutaraldehyde (Sigma grade II, 0.15% final concentration) in PBS, pH 7.2 (Deloron, Campbell, Brandling-Bennett, Roberts, Schwartz, Odera, Lal, Osanga, De La Cruz & McCutchan, 1989). After passage over a G-25 Sephadex column, the material was stored frozen at a concentration of 2 mg ml-‘. Then, Ab to RESA were detected with the FAST system as also described by Deloron et al. (1989). Briefly, 5 pg of peptide-BSA glutaraldehyde per ml was used to coat polystyrene knobs (Falcon, Becton, Dickinson, France). Plasma was diluted to 1:50 and peroxidase-conjugated goat antibodies (Miles, France) to human IgG to 1:750. Prevalence
Prevalence
%
%
Tetramethyl benzidine-H,O, (Sigma, France) was used as the chromogenic substrate (Deloron & Cot, was determined on a multiscan 1990). The A, photometer. The positive cut-offs used were calculated from 90 naive sera. They were 0.282 for RESA4, 0.371 for RESA8 and 0.305 for RESAll. Levels of Ab to RESA peptides were compared by variance analysis, Student’s t test and linear regression was established with age. Three groups of individuals were obtained as a function of both the age and the occurrence of MA. Group I was composed of 18 patients (s 15 years old; average age 9.1 f 3.1) who had at least one MA during the transmission period. Group II was formed of 20 children ($ 15 years old; average age 10.6 f 3.0) who did not have any MA and group III was composed of 38 adults (> 15 years old; average age 33.3 f 14.3) who did not have any MA, and therefore were considered protected against P. falciparum malaria. No cerebral malaria was diagnosed in the investigated population. Due to similarities in age, sex, socioeconomic factors and frequency of MA both Dafinso and VK4 groups were analysed together. Considering all groups, 15.6% of slides were positive for P. falciparum in June, 56.1% in August/ September and 28.4% in January. The prevalence (% of plasma from the investigated population which have A,, higher than those of the cut-off values found with the naive sera) of Ab against repetitive sequences of amino acids (RESA4, RESAI and RESAll) is shown in Fig. 1. RESAll prevalence (37.8%) was the highest in comparison to that of RESA8 (28.9%; P-c 0.05) and RESA4 (24%; P< 0.02). This could indicate that RESAl 1 is the most antigenic peptide used and that RESA4 is the Prevalence
56 IgG Ab to RESAll
5or-
IgG Ab to RESAB IgG Ab to RESAP
40
30
20
10
0I
Groups Jun. FIG. 1. IgG Ab to RESA
Aug.lSep.
Jan.
Periods
peptides. Ab was measured in individuals in a longitudinal survey in a malaria mesoendemic region of Bobo-Dioulasso (Burkina Faso). Prevalence in individuals with higher than naive serum levels of Ab to RESA peptides is presented as a percentage of the total group. Ab to RESA4 n ; Ab to RESAS 0; Ab to RESAll 0. Groups: I, patients ($15 years old) who had at least one malarial attack (MA) (5000 parasites 111111~~ and fever) during the transmission season; II, individuals (5 15 years old) who did not have any MA during the transmission season; III, adults (> 15 years old) who did not have any MA during the study.
Reseal .ch Note
least antigenic. This conclusion is supported by the previous study of Collins et al. (1986), who showed that the protective humoral responses in non-human primates appear to be specific for the repeating 1 lamino acid sequence (DDEHVEEPTVA). The prevalences obtained in this area are lower than those found in a recent study conducted in the village of VK2, inside the rice field area of Vall&e du Kou, 30 km north of Bobo-Dioulasso (Deloron & Cot, 1990). They obtained prevalences of 32, 82 and 80% to RESA4, RESA8 and RESAl 1, respectively at the end of the dry season. This could be explained by the fact that our survey was conducted in a neighbouring area (VK4 and Dafinso) and in the previous transmission period. The most important difference in prevalence of the groups was observed between groups I and II at enrolment in June (beginning of the transmission). In fact, only four out of 18 children from group I were positive for Ab to RESA peptides as opposed to eight out of 20 in group II. For comparative purposes, 23 of the 38 adults were positive in Ab against RESA peptides (RESA4 and/or RESA8 and/or RESAl 1) in June. MA occurred mainly between the first and the second observation period. When the first observation period was analysed for each group, significant differences (P< 0.01)were observed in the levels of Ab to RESA8 between groups 1 (A,,, mean f S.D. = 0.12 f 0.39) and 111 (A,, mean = 0.39 f 0.42) and with group II (A, mean = 0.33 f 0.40). Similarly, a significant difference was observed in the levels of Ab to RESAll between groups I (A,, mean = 0.19 f 0.45) and III (A,, mean = 0.44 & 0.54; P ~0.01) and between groups II (A, mean = 0.26 f 0.45) and III (P< 0.02). Taking into account the entire studied population, no significant difference of A,, was noticed between observation periods. This may be due to the parasite specific immunosuppression of Ab production to RESA peptides as suggested for RESAll by Deloron et al. (1989). In addition, no correlation was observed between Ab to RESA synthetic peptides Q&,) and parasitemias, S-Ag (personal observations) and soluble IL-2R (Chumpitazi, Peyron, Simon, Boudin, Sheick-Zakiuddin, Picot & Ambroise-Thomas, 1990). However, levels (A& of Ab to RESAS (r = 0.248; n = 228; P < 0.02) and to RESAll (r = 0.192; n = 228; P < 0.05) were found to be correlated with age. Similar results were also observed by Deloron et al. (1989) in two Kenyan villages. Nevertheless in this study, levels of Ab to RESA4 were neither found to be related to age nor to the protective immunity. This was not the case in the study of Petersen, Hergh, Marbiah, Perlmann, Willcox, Dolapaie, Hanson, Bjijrkman & Perlmann (1990), who suggested that high titres of antibodies to RESA antigen or to (EENV), peptides may play a role in protective immunity in adult Liberians. In our study, we did not find significant differences in the Ab levels to RESA peptides between children
273
from groups I and II. Thus, confer
immunity
against
these Ab alone could not P. falciparum malaria attack.
Acknowledgements-This research was supported by ARC (Association pour la Recherche contre le Cancer) and Dr Bruno Chumpitazi. The authors would like to thank Drs P. Nguyen-Dinh and G. H. Campbell from the Malaria Branch of the Center for D&ease Control (Atlanta, Georgia. U.S.A.) for kindly providing the RESA svnthetic peptides used in ‘this study iid Dr F.Santoro for a critical reading of the manuscript. REFERENCES CHUMPITAZIB. F. F., PEYRON F., SIMON J., BOUDIN C., SHEICK-ZAKUIDDIN I., PICOT S. & AM~ROISE-THOMAS P. 1990. Longitudinal survey in an endemic region of plasma soluble interleukin-2 receptor and antibody levels in Plasmodium falciparum malaria. Journal of Clinical Microbiology 28: 1545-l 550. COLLINS W. E., ANDERS R. F., PAPPAIOANOUM., CAMPBELL G. H., BROWN G. V., KEMP D. J., COPPEL R. L., SKINNER J. C., ANDRYSIAK P. M., FAVAROLOJ. M., CORCORAN L. M., BRODERSONJ. R., MITCHELL G. F. & CAMPBELLC. C. 1986. Immunization of Aotus monkeys with recombinant proteins of an erythrocyte surface antigen of Plasmodium falciparum. Nature (London) 323: 259-262. COPPEL R. L., COWMANA. F., ANDERS R. F., BIANCOA. E., SAINT R. B., LINGELBACHK. R., KEMP D. J. & BROWN G. V. 1984. Immune sera recognize on erythrocytes a Plasmod&m falciparum antigen composed of repeated amino acid sequences. Nature (London) 310: 789-792. DELORON P., LE BRAS J., SAVELJ. & COULAUDJ. P. 1987. Antibodies to the Pf155 antigen of Plasmodium falciparum: measurement by ce&ELISA and correlation with expected immune protection. American Journal of Tropical Medicine and Hygiene 37: 22-26. DELORON P., CAMPBELLG. H., BRANDLING-BENNETTD. A., ROBERTSJ. M., SCHWARTZI. K., ODERA J. S., LAL A. A., OSANGA C. O., DE LA CRUZ V. & MCCU~CHAN T. M. 1989. Naturallv acquired antibodies to the Plasmodium falciparum Ring-Infected Erythrocyte Surface Antigen and to P. fakiparum and P. malariae circumsporozoite proteins: seasonal prevalence in two Kenyan villages. American Journal of Tropical Medicine and Hygiene 41: 395-399. DELORON P. & COT M. 1990. Antibodies to the ring-infected erythrocyte surface antigen and the circumsporozoite protein of Plasmodium falciparum in a rural community from Burkina Faso. Transactions of the Royal Society if Tropical Medicine and Hygiene 84: 191-195. HAN&K K. & TSANG V.-c. W. 1986. Development and optimization of the FAST-ELISA for detecting antibodies to Schistosoma mansoni. Journal of Immunological Methods 92: 167-176. PERLMANN H., BERZINS K., WAHLGREN M., CARLSON J., B(IRKMANA., PATARROYOM. E. & PERLMANNP. 1984. Antibodies in malarial sera to parasite antigens in the membrane of erythrocytes infected with early asexual stages of Plasmodium falcioarum. Journal of _ Exverimental . Me‘hcine 159: 168&1%4. _ PETERSENE.. HBGH B., MARBIAH N. T., PERLMANNH.. WILLCOXM., DOLOPAIEE., HANSONA. P., BJORKMAN A. dt PERLMANNP. 1990. A longitudinal study of antibodies to the Plasmodium fakiparum antigen pfl55/RESA and immunity to malaria infection in adult Liberians. Transactions of the Royal Society of Tropical Medicine and
274
B. F.F.
CHUMPITAZI etal. Liberia
Hygiene 84: 339-345. ROBERT V., GAZIN P., BOUDIN C., MOLEZ J. F., OUEDRAOGO V. & CARNEVALE P. 1985. La transmissission du paludisme en zone de savane arbor&e et en zone rizicole aux environs de Bobo-Dioulasso (Burkina-Faso). Annales de
la Soci&C Beige de Mkiecine
Tropicale 65: 201-214.
WAHLGREN M., BJ~RKMANNA., PERLMANNH., BERZINSK. & PERLMANN P. 1986. Anti-Plasmodium falciparum antibodies acquired by residents in a holoendemic area of
during
development
of
clinical
American Journal of Tropical Medicine 22-29.
immunity.
and Hygiene 35:
WAHLIN B., WAHLGREN M., PERLMANN H., BERZINS K., BJ~RKMANNA., PATARROYO M. E. & PERLMANNP. 1984. Human antibodies to a Mr 155 000 Plasmodium falciparum antigen efficiently inhibit merozoite invasion. Pro-
ceedings of the National Academy of Science of the United States of America 81: 7912-7916.
1991 0
W2&7519/91 $3.00 + 0.00 Pergamon Press p/c 1991 Australian Society/or Parosifology
RESEARCHNOTE RELATIONSHIPS BETWEEN CLINICAL PROTECTION AND ANTIBODIES TO PLASMODIUM FALCIPARUM RESA (RINGINFECTED ERYTHROCYTE SURFACE ANTIGEN) PEPTIDES BERNABE F. F.CHUMPITAZI,*$PHILIPEDELORON,? FRANCOIS PEYRON,* CHRISTIAN BOUDIN,*$ STEPHANE PICOT* and PIERRE AMBROISE-THOMAS* *Departement
de Parasitologic-Mycologic Medicale et Moleculaire (DP3M), CNRS URA 1344, Faculte de Medecine, Universite Joseph Fourier-Grenoble I, Domaine de La Merci, 38706, La Tronche Cedex, France TINSERM U 13, Hopital Claude Bernard, 75944 Paris Cedex 19, France fORSTOM, Centre Muraz, Bobo-Dioulasso, Burkina Faso, West Africa (Received 1 November 1990; accepted 22 January 1991)
Abstract-CHuMP~TAz~ B. F. F., DELORON P., PEYRON F., BOUDIN C., PICOTS. and AMBROISE-THOMAS P. 1991. Relationships between clinical protection and antibodies to Pksmodium falciparum RESA (Ringinfected Erythrocyte Surface Antigen) peptides. International Journal for Parasitology 21: 271-274. A longitudinal study involving 76 individuals living in Dafinso and Vallee du Kou (near Bobo-Dioulasso, Burkina Faso, West Africa) was performed in June 1987 (beginning of the transmission period), AugustSeptember 1987 (during) and January 1988 (after). The serological antibody (Ab) responses against synthetic peptides representing repeat amino acid sequences of the P. falciparum Ring-Infected Erythrocyte Surface Antigen (RESA): (EENV),, (EENVEHDA),, (DDEHVEEPTVA)Z were evaluated by ELISA. The clinical longitudinal study during the transmission period allowed us to define three different groups in terms of age and occurrence of clinical malarial attack (2 5000 parasites mm -3 of blood and axillary fever z 37.7”C). Levels (A,) of Ab to (EENVEHDA), and (DDEHVEEPTVA), were correlated with age. The adult group (III) had the highest prevalences of Ab to RESA peptides. No significant difference was found between groups of children with or without malaria attack. Nevertheless, at the beginning of the transmission period, children who had at least one malaria attack during the study presented the lowest level of antibodies to RESA peptides. INDEX KEY WORDS: RESA peptides; IgG; malaria; Plasmodium falciparum; protective immunity.
RESA is found in merozoites and in the membranes of ring-infected erythrocytes (Cop+, Cowman, Anders, Bianco, Saint, Lingelbach, Kemp & Brown, 1984; Perlmann, Berzins, Wahlgren, Carlson, Bjijrkman, Patarroyo & Perlmann, 1984) and has a M, of 155,000. This Ag presents two regions of repetitive amino acid sequences. The first region, located near the carboxy terminal end, contains a repeating 1 l-amino acid sequence (DDEHVEEPTVA). The second one, located in the amino terminal end, includes some repeats of an eight-amino acid sequence (EENVEHDA) and a more extensive set of a repeating tetrapeptide (EENV). Merozoite invasion in vitro is inhibited by anti-RESA Ab (Wahlin, Wahlgren, Perlmann, Berzins, Bjorkmann, Patarroyo & Perlmann, 1984) which have been related to clinical immune protection (Deloron, Le Bras, Save1 & Couland, 1987; Wahlgren, Bjorkmann, Perlmann, Berzins & Perlmann, 1986). Aotus trivirgatus immunized with recombinant RESA protein were partially
5 To whom all correspondence should be addressed.
protected against P. falciparum infection, the best protection being achieved with constructs including the first repeat region located near the carboxy terminal end (Collins, Anders, Pappaioanou, Camp bell, Brown, Kemp, Coppel, Skinner, Andrysiak, Favarolo, Corcoran, Broderson, Mitchell Kc Campbell, 1986). The aim of this study was to determine the relationship between the levels of antibodies to RESA peptides and the clinical immunoprotection status against malaria in individuals living in a mesoendemic area near Bobo-Dioulasso (Burkina Faso). Two small villages, Dafinso and Vallee du Kou No.4 (VK4), were chosen for this study. The seasonal transmission of malaria, due generally to Anopheks gumbiae, begins in June and ends in November/ December after the rainy season. The number of infected bites per man per year is about 50 in both villages (Robert, Gazin, Boudin, Molez, Ouedraogo & Carnevale, 1985). Eighty-two individuals were included in this study but only 76 were longitudinally examined from June 1987 to January 1988. Clinical data were recorded for each person by a physician 271
B. F. F. CHUMPITAZI et al.
212
twice a week during the transmission period. A malarial attack (MA) was defined as P. jiilciparum density over 5000 parasites mm -3 and axillary fever > 37.7”C. Chloroquine was also administered by the physician. At the beginning of the transmission period in June, during August/September and after January blood samples were collected by venipuncture in heparin tubes. Asexual forms of P. falciparum, the most prevalent species in these areas, were counted on thick film assuming a constant leukocyte count of 8000 ~1~’ of blood. An ELISA using the Falcon Assay Screening Test (FAST) system (Hancock & Tsang, 1986) was used to determine Ab reactivity to RESA synthetic peptides reproducing each of the repeats present in the RESA molecule. These peptides were (EENV), referred to as RESA4, (EENVEHDA), as RESA8 and (DDEHVEEPTVAh as RESAl 1. All three peptides were kindly provided by Drs P. Nguyen-Dinh and G.H. Campbell of the Center for Disease Control (Atlanta, Georgia, U.S.A.) These peptides were conjugated with bovine serum albumin (BSA) at a molar ratio of 2O:l (peptide to BSA) in the presence of glutaraldehyde (Sigma grade II, 0.15% final concentration) in PBS, pH 7.2 (Deloron, Campbell, Brandling-Bennett, Roberts, Schwartz, Odera, Lal, Osanga, De La Cruz & McCutchan, 1989). After passage over a G-25 Sephadex column, the material was stored frozen at a concentration of 2 mg ml-‘. Then, Ab to RESA were detected with the FAST system as also described by Deloron et al. (1989). Briefly, 5 pg of peptide-BSA glutaraldehyde per ml was used to coat polystyrene knobs (Falcon, Becton, Dickinson, France). Plasma was diluted to 1:50 and peroxidase-conjugated goat antibodies (Miles, France) to human IgG to 1:750. Prevalence
Prevalence
%
%
Tetramethyl benzidine-H,O, (Sigma, France) was used as the chromogenic substrate (Deloron & Cot, was determined on a multiscan 1990). The A, photometer. The positive cut-offs used were calculated from 90 naive sera. They were 0.282 for RESA4, 0.371 for RESA8 and 0.305 for RESAll. Levels of Ab to RESA peptides were compared by variance analysis, Student’s t test and linear regression was established with age. Three groups of individuals were obtained as a function of both the age and the occurrence of MA. Group I was composed of 18 patients (s 15 years old; average age 9.1 f 3.1) who had at least one MA during the transmission period. Group II was formed of 20 children ($ 15 years old; average age 10.6 f 3.0) who did not have any MA and group III was composed of 38 adults (> 15 years old; average age 33.3 f 14.3) who did not have any MA, and therefore were considered protected against P. falciparum malaria. No cerebral malaria was diagnosed in the investigated population. Due to similarities in age, sex, socioeconomic factors and frequency of MA both Dafinso and VK4 groups were analysed together. Considering all groups, 15.6% of slides were positive for P. falciparum in June, 56.1% in August/ September and 28.4% in January. The prevalence (% of plasma from the investigated population which have A,, higher than those of the cut-off values found with the naive sera) of Ab against repetitive sequences of amino acids (RESA4, RESAI and RESAll) is shown in Fig. 1. RESAll prevalence (37.8%) was the highest in comparison to that of RESA8 (28.9%; P-c 0.05) and RESA4 (24%; P< 0.02). This could indicate that RESAl 1 is the most antigenic peptide used and that RESA4 is the Prevalence
56 IgG Ab to RESAll
5or-
IgG Ab to RESAB IgG Ab to RESAP
40
30
20
10
0I
Groups Jun. FIG. 1. IgG Ab to RESA
Aug.lSep.
Jan.
Periods
peptides. Ab was measured in individuals in a longitudinal survey in a malaria mesoendemic region of Bobo-Dioulasso (Burkina Faso). Prevalence in individuals with higher than naive serum levels of Ab to RESA peptides is presented as a percentage of the total group. Ab to RESA4 n ; Ab to RESAS 0; Ab to RESAll 0. Groups: I, patients ($15 years old) who had at least one malarial attack (MA) (5000 parasites 111111~~ and fever) during the transmission season; II, individuals (5 15 years old) who did not have any MA during the transmission season; III, adults (> 15 years old) who did not have any MA during the study.
Reseal .ch Note
least antigenic. This conclusion is supported by the previous study of Collins et al. (1986), who showed that the protective humoral responses in non-human primates appear to be specific for the repeating 1 lamino acid sequence (DDEHVEEPTVA). The prevalences obtained in this area are lower than those found in a recent study conducted in the village of VK2, inside the rice field area of Vall&e du Kou, 30 km north of Bobo-Dioulasso (Deloron & Cot, 1990). They obtained prevalences of 32, 82 and 80% to RESA4, RESA8 and RESAl 1, respectively at the end of the dry season. This could be explained by the fact that our survey was conducted in a neighbouring area (VK4 and Dafinso) and in the previous transmission period. The most important difference in prevalence of the groups was observed between groups I and II at enrolment in June (beginning of the transmission). In fact, only four out of 18 children from group I were positive for Ab to RESA peptides as opposed to eight out of 20 in group II. For comparative purposes, 23 of the 38 adults were positive in Ab against RESA peptides (RESA4 and/or RESA8 and/or RESAl 1) in June. MA occurred mainly between the first and the second observation period. When the first observation period was analysed for each group, significant differences (P< 0.01)were observed in the levels of Ab to RESA8 between groups 1 (A,,, mean f S.D. = 0.12 f 0.39) and 111 (A,, mean = 0.39 f 0.42) and with group II (A, mean = 0.33 f 0.40). Similarly, a significant difference was observed in the levels of Ab to RESAll between groups I (A,, mean = 0.19 f 0.45) and III (A,, mean = 0.44 & 0.54; P ~0.01) and between groups II (A, mean = 0.26 f 0.45) and III (P< 0.02). Taking into account the entire studied population, no significant difference of A,, was noticed between observation periods. This may be due to the parasite specific immunosuppression of Ab production to RESA peptides as suggested for RESAll by Deloron et al. (1989). In addition, no correlation was observed between Ab to RESA synthetic peptides Q&,) and parasitemias, S-Ag (personal observations) and soluble IL-2R (Chumpitazi, Peyron, Simon, Boudin, Sheick-Zakiuddin, Picot & Ambroise-Thomas, 1990). However, levels (A& of Ab to RESAS (r = 0.248; n = 228; P < 0.02) and to RESAll (r = 0.192; n = 228; P < 0.05) were found to be correlated with age. Similar results were also observed by Deloron et al. (1989) in two Kenyan villages. Nevertheless in this study, levels of Ab to RESA4 were neither found to be related to age nor to the protective immunity. This was not the case in the study of Petersen, Hergh, Marbiah, Perlmann, Willcox, Dolapaie, Hanson, Bjijrkman & Perlmann (1990), who suggested that high titres of antibodies to RESA antigen or to (EENV), peptides may play a role in protective immunity in adult Liberians. In our study, we did not find significant differences in the Ab levels to RESA peptides between children
273
from groups I and II. Thus, confer
immunity
against
these Ab alone could not P. falciparum malaria attack.
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