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Manipulation by Plasmodium Parasites of Anopheles Mosquito Behavior and Human Odors

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Abstract

Purpose

The phenomenon of parasites manipulating host phenotypes is well documented; the best-known examples are manipulations of host behavior. More recently, there has been interest in whether parasites can manipulate host odor phenotypes to enhance their attractiveness to vectors. We review here evidence that Plasmodium-infected mosquitoes have enhanced attraction to human hosts, especially when the parasite is sufficiently developed to be transmissible. We also review evidence suggesting that malaria-infected host odors elicit greater mosquito attraction compared to uninfected controls.

Methods

We reviewed and summarized the relevant literature.

Results

Though evidence is mounting that supports both premises we reviewed, there are several confounds that complicate interpretation. These include differences in Plasmodium and mosquito species studied, stage of infection tested, age of human participants in trials, and methods used to quantify volatiles. In addition, a key requirement to support the hypothesis of manipulation by parasites is that costs of manipulation be identified, and ideally, quantified.

Conclusions

Substantial progress has been made to unlock the importance of odor for enhancing transmission of Plasmodium. However, there needs to be more replication using similar methods to better define the odor parameters involved in this enhancement.

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Data availability

Data supporting conclusions in this article are cited or included within.

Code availability

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Abbreviations

ADP:

Adenosine diphosphate

ATP:

Adenosine triphosphate

GCMS:

Gas chromatography mass spectrometry

GC–EAG:

Gas chromatography–electroantennography

HMBPP:

(E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate

MTP:

Methylthio-propane

MTPNE:

(E)-1-methythio-1-propene

MTPNZ:

(Z)-1-methylthio-1-propene

RBCs:

Red blood cells

VOCs:

Volatile organic compounds

References

  1. Moore J (2002) Parasites and the behavior of animals. Oxford University Press

    Google Scholar 

  2. Hudson PJ, Dobson AP, Newborn D (1992) Do parasites make prey vulnerable to predation? Red grouse and parasites. J Anim Ecol 61:681–692. https://doi.org/10.2307/5623

    Article  Google Scholar 

  3. Busula AO, Bousema T, Mweresa CK, Masiga D, Logan JG, Sauerwein RW et al (2017) Gametocytemia and attractiveness of Plasmodium falciparum–infected Kenyan children to Anopheles gambiae mosquitoes. J Infect Dis 216:216–291. https://doi.org/10.1093/infdis/jix214

    Article  CAS  Google Scholar 

  4. Bush AO, Lafferty KD, Lotz JM, Shostak AW (1997) Parasitology meets ecology on its own terms: Margolis et al. revisited. J Parasitol 83:575–583. https://doi.org/10.2307/3284227

    Article  CAS  PubMed  Google Scholar 

  5. Roberts LS, Janovy J Jr (2005) Foundations of parasitology, 7th edn. McGraw-Hill, New York, NY

    Google Scholar 

  6. Friend WG, Smith JJ (1977) Factors affecting feeding by bloodsucking insects. Annu Rev Entomol 22:309–331. https://doi.org/10.1146/annurev.en.22.010177.001521

    Article  CAS  PubMed  Google Scholar 

  7. Foster WA (1995) Mosquito sugar feeding and reproductive energetics. Annu Rev Entomol 40:443–474. https://doi.org/10.1146/annurev.en.40.010195.002303

    Article  CAS  PubMed  Google Scholar 

  8. Gu W, Müller G, Schlein Y, Novak RJ, Beier JC (2011) Natural plant sugar sources of Anopheles mosquitoes strongly impact malaria transmission potential. PLoS One 6:e15996. https://doi.org/10.1371/journal.pone.0015996

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Nyasembe VO, Teal PEA, Mukabana WR, Tumlinson JH, Torto B (2012) Behavioural response of the malaria vector Anopheles gambiae to host plant volatiles and synthetic blends. Parasit Vectors 5:1–11. https://doi.org/10.1186/1756-3305-5-234

    Article  Google Scholar 

  10. Costantini C, Gibson G, Sagnon N, Della Torre A, Brady J, Coluzzi M (1996) Mosquito responses to carbon dioxide in a west African Sudan savanna village. Med Vet Entomol 10(3):220–227. https://doi.org/10.1111/j.1365-2915.1996.tb00734.x

    Article  CAS  PubMed  Google Scholar 

  11. Kennedy JS (1940) The visual responses of flying mosquitoes. Proc Zool Soc Lond 109:221–242

    Article  Google Scholar 

  12. Busula AO, Verhulst NO, Bousema T, Takken W, de Boer JG (2017) Mechanisms of Plasmodium-enhanced attraction of mosquito vectors. Trends Parasitol 33(12):961–973. https://doi.org/10.1016/j.pt.2017.08.010

    Article  PubMed  Google Scholar 

  13. Cator LJ, Lynch PA, Read AF, Thomas MB (2012) Do malaria parasites manipulate mosquitoes? Trends Parasitol 28(11):466–470. https://doi.org/10.1016/j.pt.2012.08.004

    Article  PubMed  PubMed Central  Google Scholar 

  14. Smallegange RC, van Gemert G-J, van de Vegte-Bolmer M, Gezan S, Takken W et al (2013) Malaria infected mosquitoes express enhanced attraction to human odor. PLoS One 8(5):e63602. https://doi.org/10.1371/journal.pone.0063602

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Nguyen PL, Vantaux A, Hien DF, Dabiré KR, Yameogo BK et al (2017) No evidence for manipulation of Anopheles gambiae, An. coluzzii and An. arabiensis host preference by Plasmodium falciparum. Sci Rep 7(1):9415. https://doi.org/10.1038/s41598-017-09821-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Vantaux A, de Sales Hien DF, Yameogo B, Dabiré KR, Lefèvre T (2015) Host-seeking behaviors of mosquitoes experimentally infected with sympatric field isolates of the human malaria parasite Plasmodium falciparum: no evidence for host manipulation. Front Ecol Evol 3:1–12. https://doi.org/10.3389/fevo.2015.00086

    Article  Google Scholar 

  17. Batista EP, Costa EF, Silva AA (2014) Anopheles darlingi (Diptera: Culicidae) displays increased attractiveness to infected individuals with Plasmodium vivax gametocytes. Parasit Vectors 7:1–4. https://doi.org/10.1186/1756-3305-7-251

    Article  Google Scholar 

  18. Koella JC, Sørensen FL, Anderson RA (1998) The malaria parasite, Plasmodium falciparum, increases the frequency of multiple feeding of its mosquito vector, Anopheles gambiae. Proc Roy Soc Lond B: Biol Sci 265(1398):763–768. https://doi.org/10.1098/rspb.1998.0358

    Article  CAS  Google Scholar 

  19. Rossignol PA, Ribeiro JM, Spielman A (1984) Increased intradermal probing time in sporozoite-infected mosquitoes. Am J Trop Med Hyg 33(1):17–20. https://doi.org/10.4269/ajtmh.1984.33.17

    Article  CAS  PubMed  Google Scholar 

  20. Rossignol PA, Ribeiro JM, Spielman A (1986) Increased biting rate and reduced fertility in sporozoite-infected mosquitoes. Am J Trop Med Hyg 35(2):277–279. https://doi.org/10.4269/ajtmh.1986.35.277

    Article  CAS  PubMed  Google Scholar 

  21. Koella JC, Rieu L, Paul REL (2002) Stage-specific manipulation of a mosquito’s host-seeking behavior by the malaria parasite Plasmodium gallinaceum. Behav Ecol 13(6):816–820. https://doi.org/10.1093/beheco/13.6.816

    Article  Google Scholar 

  22. Anderson RA, Koella JC, Hurd H (1999) The effect of Plasmodium yoelii nigeriensis infection on the feeding persistence of Anopheles stephensi Liston throughout the sporogonic cycle. Proc Roy Soc Lond B Biol Sci 266(1430):1729–1733. https://doi.org/10.1098/rspb.1999.0839

    Article  CAS  Google Scholar 

  23. Ribeiro JM, Rossignol PA, Spielman A (1984) Role of mosquito saliva in blood vessel location. J Exp Biol 108:1–7. https://doi.org/10.1242/jeb.108.1.1

    Article  CAS  PubMed  Google Scholar 

  24. Lehane MJ (2005) The biology of blood-sucking in insects. Cambridge Univ Press, Cambridge

    Book  Google Scholar 

  25. Thiévent K, Zilio G, Hauser G, Koella JC (2019) Malaria load affects the activity of mosquito salivary apyrase. J Insect Physiol 116:10–16. https://doi.org/10.1016/j.jinsphys.2019.04.003

    Article  CAS  PubMed  Google Scholar 

  26. Li X, Sina B, Rossignol PA (1992) Probing behaviour and sporozoite delivery by Anopheles stephensi infected with Plasmodium berghei. Med Vet Entomol 6(1):57–61. https://doi.org/10.1111/j.1365-2915.1992.tb00036.x

    Article  CAS  PubMed  Google Scholar 

  27. Lacroix R, Mukabana W, Gouagna LC, Koella J (2005) Malaria infection increases attractiveness of humans to mosquitoes. PLoS Biol 3(9):1590–1593. https://doi.org/10.1371/journal.pbio.0030298

    Article  CAS  Google Scholar 

  28. Robinson A, Busula AO, Voets MA, Beshir KB, Caulfield JC et al (2018) Plasmodium-associated changes in human odor attract mosquitoes. Proc Natl Acad Sci USA 115(18):E4209–E4218. https://doi.org/10.1073/pnas.1721610115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Schaber CL, Katta N, Bollinger LB, Mwale M, Mlotha-Mitole R et al (2018) Breathprinting reveals malaria-associated biomarkers and mosquito attractants. J Infect Dis 217(10):1553–1560. https://doi.org/10.1093/infdis/jiy072

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Pombi M, Jacobs F, Verhulst NO, Caputo B, della Torre A, Takken W (2014) Field evaluation of a novel synthetic odour blend and of the synergistic role of carbon dioxide for sampling host-seeking Aedes albopictus adults in Rome, Italy. Parasit Vectors 7(1):1–5. https://doi.org/10.1186/s13071-014-0580-9

    Article  CAS  Google Scholar 

  31. Kingsolver JG (1987) Mosquito host choice and the epidemiology of malaria. Am Nat 130(6):811–827. https://doi.org/10.1086/284749

    Article  Google Scholar 

  32. Kelly M, Su C-Y, Schaber C, Hsu FF, Carlson JR, Odom AR (2015) Malaria parasites produce volatile mosquito attractants. MBio 6(2):e00235-e315. https://doi.org/10.1128/mbio.00235-15

    Article  PubMed  PubMed Central  Google Scholar 

  33. Kasstan B, Hampshire K, Guest C, Logan J, Pinder M et al (2019) Sniff and tell: the feasibility of using bio-detection dogs as a mobile diagnostic intervention for asymptomatic malaria in sub-Saharan Africa. J Biosoc Sci 51(3):436–443. https://doi.org/10.1017/s0021932018000408

    Article  PubMed  Google Scholar 

  34. Mauck KE, De Moraes CM, Mescher MC (2010) Deceptive chemical signals induced by a plant virus attract insect vectors to inferior hosts. Proc Natl Acad Sci USA 107(8):3600–3605. https://doi.org/10.1073/pnas.0907191107

    Article  PubMed  PubMed Central  Google Scholar 

  35. Verhulst NO, Qiu YT, Beijleveld H, Maliepaard C, Knights D et al (2011) Composition of human skin microbiota affects attractiveness to malaria mosquitoes. PLoS One 6(12):e28991. https://doi.org/10.1371/journal.pone.0028991

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. De Moraes CM, Wanjiku C, Stanczyk NM, Pulido H, Sims J et al (2018) Volatile biomarkers of symptomatic and asymptomatic malaria infection in humans. Proc Natl Acad Sci USA 115(22):5780–5785. https://doi.org/10.1073/pnas.1801512115

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Correa R, Coronado LM, Garrido AC, Durant-Archibold AA, Spadafora C (2017) Volatile organic compounds associated with Plasmodium falciparum infection in vitro. Parasit Vectors 10(1):1–8. https://doi.org/10.1186/s13071-017-2157-x

    Article  CAS  Google Scholar 

  38. Stanczyk N, De Moraes C, Mescher M (2018) Can we use human odors to diagnose malaria? Future Microbiol 14(1):5–9. https://doi.org/10.2217/fmb-2018-0312

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Fuchs P, Loeseken C, Schubert JK, Miekisch W (2010) Breath gas aldehydes as biomarkers of lung cancer. Int J Cancer 126(11):2663–2670. https://doi.org/10.1002/ijc.24970

    Article  CAS  PubMed  Google Scholar 

  40. Peng G, Tisch U, Adams O, Hakim M, Shehada N et al (2009) Diagnosing lung cancer in exhaled breath using gold nanoparticles. Nat Nanotechnol 4(10):669–673. https://doi.org/10.1038/nnano.2009.235

    Article  CAS  PubMed  Google Scholar 

  41. Phillips M, Basa-Dalay V, Bothamley G, Cataneo RN, Lam PK et al (2010) Breath biomarkers of active pulmonary tuberculosis. Tuberculosis 90(2):145–151. https://doi.org/10.1016/j.tube.2010.01.003

    Article  CAS  PubMed  Google Scholar 

  42. Koo S, Thomas HR, Daniels SD, Lynch RC, Fortier SM et al (2014) A breath fungal secondary metabolite signature to diagnose invasive aspergillosis. Clin Infect Dis 59(12):1733–1740. https://doi.org/10.1093/cid/ciu725

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Nakhleh MK, Amal H, Jeries R, Broza YY, Aboud M et al (2017) (2017) Diagnosis and classification of 17 diseases from 1404 subjects via pattern analysis of exhaled molecules. ACS Nano 11(1):112–125. https://doi.org/10.1021/acsnano.6b04930.s001

    Article  CAS  PubMed  Google Scholar 

  44. Peterson JW (2011) Bacterial pathogenesis. In: Baron S (ed) Medical microbiology. University of Texas Medical Branch at Galveston, Galveston

    Google Scholar 

  45. Berna AZ, McCarthy JS, Wang RX, Saliba KJ, Bravo FG et al (2015) Analysis of breath specimens for biomarkers of Plasmodium falciparum infection. J Infect Dis 212(7):1120–1128. https://doi.org/10.1093/infdis/jiv176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Berna AZ, McCarthy JS, Wang XR, Michie M, Bravo FG et al (2018) Diurnal variation in expired breath volatiles in malaria-infected and healthy volunteers. J Breath Res 12(4):046014. https://doi.org/10.1088/1752-7163/aadbbb

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. de Lacy CB, Amann A, Al-Kateb H, Flynn C, Filipiak W et al (2014) A review of the volatiles from the healthy human body. J Breath Res 8(1):p014001. https://doi.org/10.1093/infdis/jiv176

    Article  CAS  Google Scholar 

  48. Emami SN, Lindberg BG, Hua S, Hill SR, Mozuraitis R et al (2017) A key malaria metabolite modulates vector blood seeking, feeding, and susceptibility to infection. Science 355(6329):1076–1080. https://doi.org/10.1126/science.aah4563

    Article  CAS  PubMed  Google Scholar 

  49. Miller JJ, Odom John AR (2020) The malaria metabolite HMBPP does not trigger erythrocyte terpene release. ACS Infect Dis 6(10):2567–2572. https://doi.org/10.1021/acsinfecdis.0c00548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Fan Y, Pedersen O (2020) Gut microbiota in human metabolic health and disease. Nat Rev Microbiol 19:55–71. https://doi.org/10.1038/s41579-020-0433-9

    Article  CAS  PubMed  Google Scholar 

  51. Mutoni d’A J, Coutelier JP, Rujeni N, Mutesa L, Cani PD (2022) Possible interactions between malaria, helminthiases and the gut microbiota: a short review. Microorganisms 10:721. https://doi.org/10.3390/microorganisms10040721

    Article  Google Scholar 

  52. Day JF, Ebert KM, Edman JD (1983) Feeding patterns of mosquitoes (Diptera: Culicidae) simultaneously exposed to malarious and healthy mice, including a method for separating blood meals from conspecific hosts. J Med Entomol 20(2):120–127. https://doi.org/10.1093/jmedent/20.2.120

    Article  CAS  PubMed  Google Scholar 

  53. Verhulst NO, Beijleveld H, Knols BG, Takken W, Schraa G et al (2009) Cultured skin microbiota attracts malaria mosquitoes. Malar J 8:1–12. https://doi.org/10.1186/1475-2875-8-302

    Article  CAS  Google Scholar 

  54. Verhulst NO, Andriessen R, Groenhagen U, Bukovinszkiné Kiss G, Schulz S et al (2010) Differential attraction of malaria mosquitoes to volatile blends produced by human skin bacteria. PLoS One 5(12):e15829. https://doi.org/10.1371/journal.pone.0015829

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Hurd H (2003) Manipulation of medically important insect vectors by their parasites. Annu Rev Entmol 48:141–161. https://doi.org/10.1146/annurev.ento.48.091801.112722

    Article  CAS  Google Scholar 

  56. Brown S (1999) Cooperation and conflict in host-manipulating parasites. Proc Roy Soc Lond B Biol Sci 266:1899–1904. https://doi.org/10.1098/rspb.1999.0864

    Article  Google Scholar 

  57. Thomas F, Adamo S, Moore J (2005) Parasitic manipulation: where are we and where should we go? Behav Processes 68(3):185–199. https://doi.org/10.1016/j.beproc.2004.06.010

    Article  PubMed  Google Scholar 

  58. Poulin R, Fredensborg B, Hansen E, Leung T (2005) The true cost of host manipulation by parasites. Behav Processes 68:241–244. https://doi.org/10.1016/j.beproc.2004.07.011

    Article  PubMed  Google Scholar 

  59. Shirasu M, Touhara K (2011) The scent of disease: volatile organic compounds of the human body related to disease and disorder. J Biochem 150(3):257–266. https://doi.org/10.1093/jb/mvr090

    Article  CAS  PubMed  Google Scholar 

  60. Gould S, Lewontin R (1979) The spandrels of San Marco and the Panglossian paradigm: a critique of the adaptationist programme. Proc Roy Soc Lond B: Biol Sci 205(1161):581–598. https://doi.org/10.1098/rspb.1979.0086

    Article  CAS  Google Scholar 

  61. Logan JG, Birkett MA, Clark SJ, Powers S, Seal NJ et al (2008) Identification of human-derived volatile chemicals that interfere with attraction of Aedes aegypti mosquitoes. J Chem Ecol 34(3):308–322. https://doi.org/10.1007/s10886-008-9436-0

    Article  CAS  PubMed  Google Scholar 

  62. Berna AZ, Schaber CL, Bollinger LB, Mwale M, Mlotha-Mitole R et al (2019) Comparison of breath sampling methods: a post hoc analysis from observational cohort studies. Analyst 144(6):2026–2033. https://doi.org/10.1039/c8an01823e

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Berna AZ, DeBosch B, Stoll J, Odom John AR (2019) Breath collection from children for disease biomarker discovery. J Vis Exp 144:e59217. https://doi.org/10.3791/59217

    Article  CAS  Google Scholar 

  64. De Boer JG, Robinson A, Powers SJ, Burgers SL, Caulfield JC et al (2017) Odours of Plasmodium falciparum-infected participants influence mosquito-host interactions. Sci Rep 7(1):1–9. https://doi.org/10.1038/s41598-017-08978-9

    Article  CAS  Google Scholar 

  65. Pulido H, Stanczyk NM, De Moraes CM, Mescher MC (2021) A unique volatile signature distinguishes malaria infection from other conditions that cause similar symptoms. Sci Rep 11(1):1–9. https://doi.org/10.1038/s41598-021-92962-x

    Article  CAS  Google Scholar 

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Acknowledgements

We thanks two reviewers for their helpful comments that improved the manuscript.

Funding

TS was supported by an Undergraduate Summer Research Award from the Natural Sciences and Engineering Research Council (NSERC) of Canada, and DS was supported by a Discovery Grant from NSERC.

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  1. Department of Biology, Acadia University, Wolfville, NS, B4P 2R6, Canada

    Tristan Sanford & Dave Shutler

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  1. Tristan Sanford
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Contributions

TS and DS: conceived and designed the review. TS: collected the data. TS and DS: analyzed and interpreted the literature. TS: drafted the initial manuscript. TS and DS: did iterative revisions. Both authors reviewed the results and approved the final version of the review.

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Correspondence to Dave Shutler.

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Sanford, T., Shutler, D. Manipulation by Plasmodium Parasites of Anopheles Mosquito Behavior and Human Odors. Acta Parasit. 67, 1463–1470 (2022). https://doi.org/10.1007/s11686-022-00621-6

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