Comparative analysis of the Immunoglobulin G antibodies (IgG and IgG subclass) responses in children (≤15 years) with severe and uncomplicated malaria in Buea, South West region, Cameroon
https://doi.org/10.4081/idhm.2020.123
Submitted: 29 November 2020
Accepted: 27 December 2020
Published: 1 February 2021
Accepted: 27 December 2020
Abstract Views: 434
PDF: 258
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Studies assessing the immunoglobulin G (IgG) antibody responses in severe malaria are not readily available. This study was designed to compare the IgG and IgG1-4 antibody responses in severe malaria and its major clinical presentations (cerebral malaria, severe malarial anemia and respiratory distress) in children (≤15 years) in Buea, Cameroon. In a hospital-based cross-sectional comparative study, children presenting for consultation at the outpatient department/Emergency unit of the Buea Regional Hospital were enrolled and assigned into one of three groups: severe malaria, uncomplicated malaria and negative controls. Baseline characteristics were determined; blood glucose level was measured by glucometer, complete blood count was performed using an automated heamatology analyser and participants were screened for malaria parasites by light microscopy and severe malaria was categorized based on WHO criteria. Total IgG and IgG1-4 antibodies were measured using standard ELISA with Plasmodium falciparum 19-KDa C-terminal region of merozoite surface protein 1 (P.fMSP-119) antigen as capture antigen. A total of 236 participants were enrolled comprising: 66 severe malaria, 70 uncomplicated malaria and 100 negative controls. The participants in the different groups were similar with regards to their ages (p=0.06) and gender (p=0.900). Children with severe malaria had significantly higher levels of anti-P.fMSP-119 IgG4 (p<0.0001) antibodies and significantly lower levels of anti-P.fMSP-119 IgG1 (p<0.0001) and IgG3 (p<0.0001) antibodies. There was no significant variation in the IgG antibody responses between the major clinical forms of severe malaria. The study finding of significantly higher levels of the non-cytophilic antibody IgG4 is suggestive of the role the antibody plays in the pathogenesis of severe malaria. Larger studies investigating how these immune effector cells vary in the major phenotypes of severe malaria are recommended.
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11) Dongho DFF, Ngono NRA, Gouado I, Pankoui MJB, Mbackop KV, Ngwa V, et al. Predictors of childhood severe malaria in a densely populated area: Douala. Cameroon Afr J Biotechnol. 2011;10(33):6319–24.
12) Achidi EA, Apinjoh TO, Anchang-Kimbi JK, Mugri RN, Ngwai AN, Yafi CN. Severe and uncomplicated falciparum malaria in children from three regions and three ethnic groups in Cameroon: prospective study. Malar J. 2012;11:215.
13) Mbah-Mbole FG, Tufon KA, Meriki DH, Enow-Orock G, Mbah-Mbole P, Njunda LA, Wam Iwoi MD, Kwenti TE. Malaria and human immunodeficiency virus coinfection in febrile patients attending the Regional Hospital of Buea, Southwest region, Cameroon. Int J Adv Med Health Res 2019;6:46-51
14) Nebie I, Diarra A, Ouedraogo A, Soulama I, Bougouma EC, Tiono AB, et al. Humoral responses to Plasmodium falciparum blood stage antigens and association with incidence of clinical malaria in children living in an area of seasonal malaria transmission in Burkina Faso, West Africa. Infect Immun. 2008;76:759–66.
15) Medeiros MM, Fotoran WL, dalla Martha RC, Katsuragawa TH, da Pereira Silva LH, et al. Natural antibody response to Plasmodium falciparum merozoite antigens MSP5, MSP9 and EBA 175 is associated to clinical protection in the Brazilian Amazon. BMC Infect Dis. 2013;13:608.
16) Teo A, Feng G, Brown GV, Beeson JG, Rogerson SJ. Functional antibodies and protection against blood-stage malaria. Trends Parasitol. 2016;32:887–98.
17) Folegatti PM, Siqueira AM, Monteiro WM, Lacerda MV, Drakeley CJ, Braga ÉM. A systematic review on malaria sero-epidemiology studies in the Brazilian Amazon: insights into immunological markers for exposure and protection. Malar J. 2017;16:107.
18) Stanisic DI, Richards JS, McCallum FJ, Michon P, King CL, Schoepflin S, et al. Immunoglobulin G subclass-specific responses against Plasmodium falciparum merozoite antigens are associated with control of parasitemia and protection from symptomatic illness. Infect Immun. 2009;77:1165–74.
19) Ketema T, Bacha K, Alemayehu E, Ambellu A. Incidence of severe malaria syndromes and status of immune responses among khat chewer malaria patients in Ethiopia. PLoS ONE. 2015;10:e0131212.
20) Weaver R, Reiling L, Feng G, Drew DR, Mueller I, Siba PM, et al. The association between naturally acquired IgG subclass specific antibodies to the PfRH5 invasion complex and protection from Plasmodium falciparum malaria. Sci Rep. 2016;6:33094.
21) Changrob S, Han JH, Ha KS, Park WS, Hong SH, Chootong P, et al. Immunogenicity of glycophosphatidylinositol anchored micronemal antigen in natural Plasmodium vivax exposure. Malar J. 2017;16:348.
22) Aucan C, Traore Y, Tall F, Nacro B, Traore-Leroux T, Fumoux F, et al. High immunoglobulin G2 (IgG2) and low IgG4 levels are associated with human resistance to Plasmodium falciparum malaria. Infect Immun. 2000;68:1252–8.
23) Roussilhon C, Oeuvray C, Muller-Graf C, Tall A, Rogier C, Trape JF, et al. Long-term clinical protection from falciparum malaria is strongly associated with IgG3 antibodies to merozoite surface protein 3. PLoS Med. 2007;4:e320.
24) Leoratti FMS, Durlacher RR, Lacerda MVG, Alecrim MG, Ferreira AW, Sanchez MCA, Moraes SL. Pattern of humoral immune response to Plasmodium falciparum blood stages in individuals presenting different clinical expressions of malaria. Malaria Journal 2008; 7:186.
25) Olesen CH, Brahimi K, Vandahl B, Lousada-Dietrich S, Jogdand PS, Vestergaard LS, et al. Distinct patterns of blood stage parasite antigens detected by plasma IgG subclasses from individuals with different level of exposure to Plasmodium falciparum infections. Malar J. 2010;9:296.
26) Noland GS, Jansen P, Vulule JM, Park GS, Ondingo BN, Kazura JW, et al. Effect of transmission intensity and age on subclass antibody responses to Plasmodium falciparum pre-erythrocytic and blood stage antigens. Acta Trop. 2015;142:47–56.
27) Cowman AF, Crabb BS. Invasion of red blood cells by malaria parasites. Cell. 2006;124:755–66.
28) Corran PH, O’Donnell RA, Todd J, Uthaipibull C, Holder AA, Crabb BS, et al. The fine specificity, but not the invasion-inhibitory activity, of 19-kilo-dalton merozoite surface protein 1-specific antibodies is associated with resistance to malarial parasitemia in a cross-sectional survey in The Gambia. Infect Immun. 2004;72:6185–9.
29) Okech BA, Corran PH, Todd J, Joynson-Hicks A, Uthaipibull C, Egwang TG, et al. Fine specificity of serum antibodies to Plasmodium falciparum merozoite surface protein, PfMSP-1(19), predicts protection from malaria infection and high-density parasitemia. Infect Immun. 2004;72:1557–67.
30) Joos C, Varela ML, Mbengue B, Mansourou A, Marrama L, Sokhna C, et al. Antibodies to Plasmodium falciparum merozoite surface protein-1p19 malaria vaccine candidate induce antibody-dependent respiratory burst in human neutrophils. Malar J. 2015;14:409.
31) Pleass RJ, Ogun SA, McGuinness DH, van de Winkel JG, Holder AA, Woof JM. Novel antimalarial antibodies highlight the importance of the antibody Fc region in mediating protection. Blood. 2003;102:4424–30.
32) Shi J, McIntosh RS, Adame-Gallegos J, Dehal PK, van Egmond M, van de Winkel J, et al. The generation and evaluation of recombinant human IgA specific for Plasmodium falciparum merozoite surface protein 1–19 (PfMSP1 19). BMC Biotechnol. 2011;11:77.
33) Kwenti ET, Njunda LA, Tsamul B, Nsagha SD, Assob JCN, Tufon KA, et al. Comparative evaluation of a rapid diagnostic test, an antibody ELISA and a pLDH ELISA in detecting asymptomatic malaria parasitaemia in blood donors in Buea. Cameroon. Infect Dis Poverty. 2017;6:103.
34) Bigoga JD, Manga L, Titanji VP, Coetzee M, Leke RG. Malaria vectors and transmission dynamics in coastal south-western Cameroon. Malaria Journal 2007; 6: 5-10.
35) Kwenti, T.E., Kukwah, T.A., Kwenti, T.D.B. et al. Comparative analysis of IgG and IgG subclasses against Plasmodium falciparum MSP-119 in children from five contrasting bioecological zones of Cameroon. Malar J 18, 16 (2019). https://doi.org/10.1186/s12936-019-2654-9.
36) Njunda AL, Assob NJC, Nsagha SD, Kamga FHL, Mokenyu MD, Kwenti ET. Comparison of capillary and venous blood using blood film microscopy in the detection of malaria parasites: a hospital based study. Sci J Microbiol. 2013;2:89–94.
37) Kwenti, T.E., Moye, A.L., Wiylanyuy, A.B. et al. Variation in the immune responses against Plasmodium falciparum merozoite surface protein-1 and apical membrane antigen-1 in children residing in the different epidemiological strata of malaria in Cameroon. Malar J 16, 453 (2017). https://doi.org/10.1186/s12936-017-2105-4.
38) Njunda AL, Fon SG, Assob JCN, Nsagha DS, Kwenti TDB, Kwenti ET. Malaria and intestinal parasitic coinfection and their contribution to anaemia in children in Cameroon. Infect Dis Poverty. 2015;4:43.
39) Kwenti ET, Njilah SN, Assob NJ-C. Hematological Profile of Pregnant Women CoInfected with Malaria and HIV in Buea, South West Region of Cameroon. SCIOL Biomed 2018;2:128-135.
40) Kwenti ET. Malaria and HIV coinfection in sub-Saharan Africa: prevalence, impact, and treatment strategies. Res Rep Trop Med. 2018; 9: 123–136.
2) Kwenti, T.E., Kwenti, T.D.B., Latz, A. et al. Epidemiological and clinical profile of paediatric malaria: a cross sectional study performed on febrile children in five epidemiological strata of malaria in Cameroon. BMC Infect Dis 17, 499 (2017). https://doi.org/10.1186/s12879-017-2587-2
3) Langhorne J, Ndungu FM, Sponaas A-M, Marsh K. Immunity to malaria: more questions than answers. Nat Immunol. 2008;9:725–32.
4) Oduro AR, Koram KA, Rogers W, Atuguba F, Ansah P, Anyorigiya T, et al. Severe falciparum malaria in young children of the Kassena-Nankana district of northern Ghana. Malar J. 2007;6:96.
5) World Health Organisation. Severe malaria. Trop Med Int Health. 2014;19(1):7–131.
6) Kwenti TE, Nkume FA, Tanjeko AT, Kwenti TDB (2016) The Effect of Intestinal Parasitic Infection on the Clinical Outcome of Malaria in Coinfected Children in Cameroon. PLoS Negl Trop Dis 10(4): e0004673. https://doi.org/10.1371/journal.pntd.0004673
7) Antonio-Nkondjio C, Demanou M, Etang J, Bouchite B. Impact of cyfluthrin (Solfac EW050) impregnated bed nets on malaria transmission in the city of Mbandjock: lessons for the nationwide distribution of long-lasting insecticidal nets (LLINs) in Cameroon. Parasit Vectors. 2013;6.
8) World Health Organisation. Cameroon: WHO statistical profile. Geneva, Switzerland, WHO, 2015. http://www.who.int/gho/countries/
9) Kwenti, T.E., Kwenti, T.D.B., Njunda, L.A. et al. Identification of the Plasmodium species in clinical samples from children residing in five epidemiological strata of malaria in Cameroon. Trop Med Health 45, 14 (2017). https://doi.org/10.1186/s41182-017-0058-5
10) Forlack EA, Abena OMT, Beyeme OM, Manga E, Same-Ekobo A, Ondoa M. Outcome of severe malaria in two district hospitals in Cameroon. Clin Mother Child Health. 2005;2:247–52.
11) Dongho DFF, Ngono NRA, Gouado I, Pankoui MJB, Mbackop KV, Ngwa V, et al. Predictors of childhood severe malaria in a densely populated area: Douala. Cameroon Afr J Biotechnol. 2011;10(33):6319–24.
12) Achidi EA, Apinjoh TO, Anchang-Kimbi JK, Mugri RN, Ngwai AN, Yafi CN. Severe and uncomplicated falciparum malaria in children from three regions and three ethnic groups in Cameroon: prospective study. Malar J. 2012;11:215.
13) Mbah-Mbole FG, Tufon KA, Meriki DH, Enow-Orock G, Mbah-Mbole P, Njunda LA, Wam Iwoi MD, Kwenti TE. Malaria and human immunodeficiency virus coinfection in febrile patients attending the Regional Hospital of Buea, Southwest region, Cameroon. Int J Adv Med Health Res 2019;6:46-51
14) Nebie I, Diarra A, Ouedraogo A, Soulama I, Bougouma EC, Tiono AB, et al. Humoral responses to Plasmodium falciparum blood stage antigens and association with incidence of clinical malaria in children living in an area of seasonal malaria transmission in Burkina Faso, West Africa. Infect Immun. 2008;76:759–66.
15) Medeiros MM, Fotoran WL, dalla Martha RC, Katsuragawa TH, da Pereira Silva LH, et al. Natural antibody response to Plasmodium falciparum merozoite antigens MSP5, MSP9 and EBA 175 is associated to clinical protection in the Brazilian Amazon. BMC Infect Dis. 2013;13:608.
16) Teo A, Feng G, Brown GV, Beeson JG, Rogerson SJ. Functional antibodies and protection against blood-stage malaria. Trends Parasitol. 2016;32:887–98.
17) Folegatti PM, Siqueira AM, Monteiro WM, Lacerda MV, Drakeley CJ, Braga ÉM. A systematic review on malaria sero-epidemiology studies in the Brazilian Amazon: insights into immunological markers for exposure and protection. Malar J. 2017;16:107.
18) Stanisic DI, Richards JS, McCallum FJ, Michon P, King CL, Schoepflin S, et al. Immunoglobulin G subclass-specific responses against Plasmodium falciparum merozoite antigens are associated with control of parasitemia and protection from symptomatic illness. Infect Immun. 2009;77:1165–74.
19) Ketema T, Bacha K, Alemayehu E, Ambellu A. Incidence of severe malaria syndromes and status of immune responses among khat chewer malaria patients in Ethiopia. PLoS ONE. 2015;10:e0131212.
20) Weaver R, Reiling L, Feng G, Drew DR, Mueller I, Siba PM, et al. The association between naturally acquired IgG subclass specific antibodies to the PfRH5 invasion complex and protection from Plasmodium falciparum malaria. Sci Rep. 2016;6:33094.
21) Changrob S, Han JH, Ha KS, Park WS, Hong SH, Chootong P, et al. Immunogenicity of glycophosphatidylinositol anchored micronemal antigen in natural Plasmodium vivax exposure. Malar J. 2017;16:348.
22) Aucan C, Traore Y, Tall F, Nacro B, Traore-Leroux T, Fumoux F, et al. High immunoglobulin G2 (IgG2) and low IgG4 levels are associated with human resistance to Plasmodium falciparum malaria. Infect Immun. 2000;68:1252–8.
23) Roussilhon C, Oeuvray C, Muller-Graf C, Tall A, Rogier C, Trape JF, et al. Long-term clinical protection from falciparum malaria is strongly associated with IgG3 antibodies to merozoite surface protein 3. PLoS Med. 2007;4:e320.
24) Leoratti FMS, Durlacher RR, Lacerda MVG, Alecrim MG, Ferreira AW, Sanchez MCA, Moraes SL. Pattern of humoral immune response to Plasmodium falciparum blood stages in individuals presenting different clinical expressions of malaria. Malaria Journal 2008; 7:186.
25) Olesen CH, Brahimi K, Vandahl B, Lousada-Dietrich S, Jogdand PS, Vestergaard LS, et al. Distinct patterns of blood stage parasite antigens detected by plasma IgG subclasses from individuals with different level of exposure to Plasmodium falciparum infections. Malar J. 2010;9:296.
26) Noland GS, Jansen P, Vulule JM, Park GS, Ondingo BN, Kazura JW, et al. Effect of transmission intensity and age on subclass antibody responses to Plasmodium falciparum pre-erythrocytic and blood stage antigens. Acta Trop. 2015;142:47–56.
27) Cowman AF, Crabb BS. Invasion of red blood cells by malaria parasites. Cell. 2006;124:755–66.
28) Corran PH, O’Donnell RA, Todd J, Uthaipibull C, Holder AA, Crabb BS, et al. The fine specificity, but not the invasion-inhibitory activity, of 19-kilo-dalton merozoite surface protein 1-specific antibodies is associated with resistance to malarial parasitemia in a cross-sectional survey in The Gambia. Infect Immun. 2004;72:6185–9.
29) Okech BA, Corran PH, Todd J, Joynson-Hicks A, Uthaipibull C, Egwang TG, et al. Fine specificity of serum antibodies to Plasmodium falciparum merozoite surface protein, PfMSP-1(19), predicts protection from malaria infection and high-density parasitemia. Infect Immun. 2004;72:1557–67.
30) Joos C, Varela ML, Mbengue B, Mansourou A, Marrama L, Sokhna C, et al. Antibodies to Plasmodium falciparum merozoite surface protein-1p19 malaria vaccine candidate induce antibody-dependent respiratory burst in human neutrophils. Malar J. 2015;14:409.
31) Pleass RJ, Ogun SA, McGuinness DH, van de Winkel JG, Holder AA, Woof JM. Novel antimalarial antibodies highlight the importance of the antibody Fc region in mediating protection. Blood. 2003;102:4424–30.
32) Shi J, McIntosh RS, Adame-Gallegos J, Dehal PK, van Egmond M, van de Winkel J, et al. The generation and evaluation of recombinant human IgA specific for Plasmodium falciparum merozoite surface protein 1–19 (PfMSP1 19). BMC Biotechnol. 2011;11:77.
33) Kwenti ET, Njunda LA, Tsamul B, Nsagha SD, Assob JCN, Tufon KA, et al. Comparative evaluation of a rapid diagnostic test, an antibody ELISA and a pLDH ELISA in detecting asymptomatic malaria parasitaemia in blood donors in Buea. Cameroon. Infect Dis Poverty. 2017;6:103.
34) Bigoga JD, Manga L, Titanji VP, Coetzee M, Leke RG. Malaria vectors and transmission dynamics in coastal south-western Cameroon. Malaria Journal 2007; 6: 5-10.
35) Kwenti, T.E., Kukwah, T.A., Kwenti, T.D.B. et al. Comparative analysis of IgG and IgG subclasses against Plasmodium falciparum MSP-119 in children from five contrasting bioecological zones of Cameroon. Malar J 18, 16 (2019). https://doi.org/10.1186/s12936-019-2654-9.
36) Njunda AL, Assob NJC, Nsagha SD, Kamga FHL, Mokenyu MD, Kwenti ET. Comparison of capillary and venous blood using blood film microscopy in the detection of malaria parasites: a hospital based study. Sci J Microbiol. 2013;2:89–94.
37) Kwenti, T.E., Moye, A.L., Wiylanyuy, A.B. et al. Variation in the immune responses against Plasmodium falciparum merozoite surface protein-1 and apical membrane antigen-1 in children residing in the different epidemiological strata of malaria in Cameroon. Malar J 16, 453 (2017). https://doi.org/10.1186/s12936-017-2105-4.
38) Njunda AL, Fon SG, Assob JCN, Nsagha DS, Kwenti TDB, Kwenti ET. Malaria and intestinal parasitic coinfection and their contribution to anaemia in children in Cameroon. Infect Dis Poverty. 2015;4:43.
39) Kwenti ET, Njilah SN, Assob NJ-C. Hematological Profile of Pregnant Women CoInfected with Malaria and HIV in Buea, South West Region of Cameroon. SCIOL Biomed 2018;2:128-135.
40) Kwenti ET. Malaria and HIV coinfection in sub-Saharan Africa: prevalence, impact, and treatment strategies. Res Rep Trop Med. 2018; 9: 123–136.
Kwenti, T. E., Tufon, K. A. ., Nyasa, B. R. ., Mbah-Mbole, F. G. ., Khamesipour, F., & Njunda, L. A. (2021). Comparative analysis of the Immunoglobulin G antibodies (IgG and IgG subclass) responses in children (≤15 years) with severe and uncomplicated malaria in Buea, South West region, Cameroon. Infectious Diseases and Herbal Medicine, 1(1). https://doi.org/10.4081/idhm.2020.123
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