Role of Human Twin Studies to Identify Genetic Linkage of Malaria Pathogenesis and Outcomes

Shibani Biswas ICMR-National Institute of Malaria Research, New Delhi, India;
Academy of Scientific and Innovative Research, Ghaziabad, India;

Search for other papers by Shibani Biswas in
Current site
Google Scholar
PubMed
Close
,
Minu Nain ICMR-National Institute of Malaria Research, New Delhi, India;

Search for other papers by Minu Nain in
Current site
Google Scholar
PubMed
Close
,
Sundus Shafat Ahmad ICMR-National Institute of Malaria Research, New Delhi, India;

Search for other papers by Sundus Shafat Ahmad in
Current site
Google Scholar
PubMed
Close
, and
Amit Sharma Academy of Scientific and Innovative Research, Ghaziabad, India;
Molecular Medicine, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India

Search for other papers by Amit Sharma in
Current site
Google Scholar
PubMed
Close
Restricted access

ABSTRACT.

Malaria remains a major public health challenge that needs attention, especially when the world is aiming at malaria elimination in the near future. It is crucial to understand the underlying genetic factors and epigenetics involved in malaria susceptibility and the dynamics of host immune responses that affect disease outcomes and relapses in Plasmodium vivax and Plasmodium ovale. Studies in newborn and adult twins can help in understanding the comparative roles of environmental and genetic factors on disease pathogenesis and outcome. These studies can help in providing insights into the factors responsible for malaria susceptibility, clinical presentation, responsiveness toward existing as well as candidate antimalarials, and even identification of novel therapeutic targets. The results and outcomes from twin studies can be further applied to the entire population. In the present manuscript, we analyze the available literature on malaria and human twins and discuss the significance and benefits of twin studies to help in better understanding malaria.

Author Notes

Address correspondence to Amit Sharma, Molecular Medicine, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India. E-mail: amit.icgeb@gmail.com

These authors contributed equally to this work.

Authors’ addresses: Shibani Biswas, ICMR-National Institute of Malaria Research, New Delhi, India, and Academy of Scientific and Innovative Research, Ghaziabad, India, E-mail: shibanibiswas1095@gmail.com. Minu Nain and Sundus Shafat Ahmad, ICMR-National Institute of Malaria Research, New Delhi, India, E-mails: minu345r@gmail.com and sundus_ahmad13@hotmail.com. Amit Sharma, Academy of Scientific and Innovative Research, Ghaziabad, India, and Molecular Medicine, International Centre for Genetic Engineering and Biotechnology, Aruna Asaf Ali Marg, New Delhi, India, E-mail: amit.icgeb@gmail.com.

  • 1.

    WHO , 2022. World Malaria Report 2022. Geneva, Switzerland: World Health Organization. Available at: https://www.who.int/teams/global-malaria-programme/reports/world-malaria-report-2022. Accessed January 5, 2023.

    • Search Google Scholar
    • Export Citation
  • 2.

    Pandey M, Rahi M, Sharma A, 2021. The Indian burden of malaria in pregnancy needs assessment. CellPress Med 2: 456–504.

  • 3.

    Rasti N, Wahlgren M, Chen Q, 2004. Molecular aspects of malaria pathogenesis. FEMS Immunol Med Microbiol 41: 9–26.

  • 4.

    Roberts DJ, Biggs BA, Brown G, Newbold CI, 1993. Protection, pathogenesis and phenotypic plasticity in Plasmodium falciparum malaria. Parasitol Today 9: 281–286.

    • Search Google Scholar
    • Export Citation
  • 5.

    Dayanand KK, Achur RN, Gowda DC, 2018. Epidemiology, drug resistance, and pathophysiology of Plasmodium vivax malaria. J Vector Borne Dis 55: 1–8.

    • Search Google Scholar
    • Export Citation
  • 6.

    Wertheimer SP, Barnwell JW, 1989. Plasmodium vivax interaction with the human Duffy blood group glycoprotein: identification of a parasite receptor-like protein. Exp Parasitol 69: 340–350.

    • Search Google Scholar
    • Export Citation
  • 7.

    Craig JM, Calais-Ferreira L, Umstad MP, Buchwald D, 2020. The value of twins for health and medical research: a third of a century of progress. Twin Res Hum Genet 23: 8–15.

    • Search Google Scholar
    • Export Citation
  • 8.

    Kwok AJ, Mentzer A, Knight JC, 2021. Host genetics and infectious disease: new tools, insights, and translational opportunities. Nat Rev Genet 22: 137–153.

    • Search Google Scholar
    • Export Citation
  • 9.

    Cohen RJ, Sachs JR, Wicker DJ, Conrad ME, 1968. Methemoglobinemia provoked by malarial chemoprophylaxis in Vietnam. N Engl J Med 279: 1127–1131.

    • Search Google Scholar
    • Export Citation
  • 10.

    Sahu M, Prasuna JG, 2016. Twin studies: a unique epidemiological tool. Indian J Community Med 41: 177–182.

  • 11.

    Liew SH, Elsner H, Spector TD, Hammond CJ, 2005. The first ā€œclassicalā€ twin study? Analysis of refractive error using monozygotic and dizygotic twins published in 1922. Twin Res Hum Genet 8: 198–200.

    • Search Google Scholar
    • Export Citation
  • 12.

    Bouchard TJ Jr , Lykken DT, McGue M, Segal NL, Tellegen A, 1990. Sources of human psychological differences: the Minnesota Study of twins reared apart. Science 250: 223–228.

    • Search Google Scholar
    • Export Citation
  • 13.

    Mucci LA, Hjelmborg JB, Harris JR, Czene K, Havelick DJ, 2016. Familial risk and heritability of cancer among twins in Nordic countries. JAMA 315: 68–76.

    • Search Google Scholar
    • Export Citation
  • 14.

    Thomsen SF, 2015. The contribution of twin studies to the understanding of the aetiology of asthma and atopic diseases. Eur Clin Respir J 2: 27803.

    • Search Google Scholar
    • Export Citation
  • 15.

    Polderman TJC, Benyamin B, de Leeuw CA, Sullivan PF, van Bochoven A, Visscher PM, Posthuma D, 2015. Meta-analysis of the heritability of human traits based on fifty years of twin studies. Nat Genet 47: 702–709.

    • Search Google Scholar
    • Export Citation
  • 16.

    Jepson AP, Banya WAS, Sisay-Joof F, Hassan-King M, Bennett S, Whittle HC, 1995. Genetic regulation of fever in Plasmodium falciparum malaria in Gambian twin children. J Infect Dis 172: 316–319.

    • Search Google Scholar
    • Export Citation
  • 17.

    Goncalves BO et al., 2022. Natural history of malaria infections during early childhood in twins. J Infect Dis 227: 171–178.

  • 18.

    Jepson A, Sisay-Joof F, Banya W, Hassan-King M, Frodsham A, Bennett S, Hill AV, Whittle H, 1997. Genetic linkage of mild malaria to the major histocompatibility complex in Gambian children: study of affected sibling pairs. BMJ 315: 96–97.

    • Search Google Scholar
    • Export Citation
  • 19.

    Hill AV, Allsopp CE, Kwiatkowski D, Anstey NM, Twumasi P, Rowe PA, Bennett S, Brewster D, McMichael AJ, Greenwood BM, 1991. Common west African HLA antigens are associated with protection from severe malaria. Nature 352: 595–600.

    • Search Google Scholar
    • Export Citation
  • 20.

    Bennett S, Allen SJ, Olerup O, Jackson DJ, Wheeler JG, Rowe PA, Riley EM, Greenwood BM, 1993. Human leucocyte antigen (HLA) and malaria morbidity in a Gambian community. Trans R Soc Trop Med Hyg 87: 286–287.

    • Search Google Scholar
    • Export Citation
  • 21.

    Troye-Blomberg M, Lepers JP, Sjƶberg K, Rahalimalala L, Larsson A, Olerup O, Perlmann P, 1994. Presentation of the Plasmodium falciparum antigen Pf155/RESA to human T cells. Variations in responsiveness induced by antigen presenting cells from different but MHC class II identical donors. Immunol Lett 43: 59–66.

    • Search Google Scholar
    • Export Citation
  • 22.

    Troye-Blomberg M, Olerup O, Larsson A, Sjƶberg K, Perlmann H, Riley E, Lepers JP, Perlmann P, 1991. Failure to detect MHC class II associations of the human immune response induced by repeated malaria infections to the Plasmodium falciparum antigen Pf155/RESA. Int Immunol 3: 1043–1051.

    • Search Google Scholar
    • Export Citation
  • 23.

    Troye-Blomberg M, Sjƶberg K, Olerup O, Riley EM, Kabilan L, Perlmann H, Marbiah NT, Perlmann P, 1990. Characterization of regulatory T cell responses to defined immunodominant T cell epitopes of the Plasmodium falciparum antigen Pf155/RESA. Immunol Lett 25: 129–134.

    • Search Google Scholar
    • Export Citation
  • 24.

    Riley EM, Bennett S, Jepson A, Hassan-King M, Whittle H, Olerup O, Carter R, 2007. Human antibody responses to Pfs 230, a sexual stage-specific surface antigen of Plasmodium falciparum: non-responsiveness is a stable phenotype but does not appear to be genetically regulated. Parasite Immunol 16: 55–62.

    • Search Google Scholar
    • Export Citation
  • 25.

    Taylor RR, Egan A, McGuinness D, Jepson A, Adair R, Drakely C, Riley E, 1996. Selective recognition of malaria antigens by human serum antibodies is not genetically determined but demonstrates some features of clonal imprinting. Int Immunol 8: 905–915.

    • Search Google Scholar
    • Export Citation
  • 26.

    Troye‐Blomberg M, Fogdell A, el-Ghazali G, Larsson A, King MH, Sisay-Joof F, Olerup O, Grunewald J, Jepson A, 1997. Analysis of the T‐cell receptor Vβ usage in monozygotic and dizygotic twins living in a Plasmodium falciparum endemic area in West Africa. Scand J Immunol 45: 541–545.

    • Search Google Scholar
    • Export Citation
  • 27.

    Mahamar A et al., 2017. Host factors that modify Plasmodium falciparum adhesion to endothelial receptors. Sci Rep 7: 13872.

  • 28.

    Starck T, Dambach P, Rouamba T, Tinto H, Osier F, Oldenburg CE, Adam M, BƤrnighausen T, Jaenisch T, Bulstra CA, 2022. The effect of malaria on childhood anemia in a quasi-experimental study of 7,384 twins from 23 Sub-Saharan African countries. Front Public Health 10: 1009865.

    • Search Google Scholar
    • Export Citation
  • 29.

    Perlmann P, Perlmann H, ElGhazali G, Blomberg MT, 1999. IgE and tumor necrosis factor in malaria infection. Immunol Lett 65: 29–33.

  • 30.

    Duah NO, Weiss HA, Jepson A, Tetteh KKA, Whittle HC, Conway DJ, 2009. Heritability of antibody isotype and subclass responses to Plasmodium falciparum antigens. PLoS One 4: e7381.

    • Search Google Scholar
    • Export Citation
  • 31.

    Balatbat AB, Jordan GW, Halsted C, 1995. Congenital malaria in a nonidentical twin. West J Med 162: 458–459.

  • 32.

    Cummins D, Brain C, Davies SC, 1990. Congenital malaria in one identical twin. J Clin Pathol 43: 609.

  • 33.

    Opare DA, 2012. Congenital malaria in newborn twins. Ghana Med J 46: 163–165.

  • 34.

    Bradbury AJ, 1977. Congenital malaria in one non-identical twin. BMJ 2: 613.

  • 35.

    Mudji JE, Blum J, Rice TD, Baliraine FN, 2017. Congenital malaria and neonatal bacterial co-infection in twins prematurely born to a mother with sickle-cell anaemia in the Democratic Republic of the Congo. MalariaWorld J 8: 14.

    • Search Google Scholar
    • Export Citation
  • 36.

    Sjƶberg K, Lepers JP, Raharimalala L, Larsson A, Olerup O, Marbiah NT, Troye-Blomberg M, Perlmann P, 1992. Genetic regulation of human anti-malarial antibodies in twins. Proc Natl Acad Sci USA 89: 2101–2104.

    • Search Google Scholar
    • Export Citation
  • 37.

    Conroy AL et al., 2019. Case report: birth outcome and neurodevelopment in placental malaria discordant twins. Am J Trop Med Hyg 100: 552–555.

    • Search Google Scholar
    • Export Citation
  • 38.

    Devlin HR, Bannatyne RM, 1977. Neonatal malaria. CMAJ 116: 20.

Past two years Past Year Past 30 Days
Abstract Views 516 516 55
Full Text Views 27 27 3
PDF Downloads 38 38 6
 
Membership Banner
 
 
 
Affiliate Membership Banner
 
 
Research for Health Information Banner
 
 
CLOCKSS
 
 
 
Society Publishers Coalition Banner
Save