Skip to main content
Log in

Chemical profiling of the human skin surface for malaria vector control via a non-invasive sorptive sampler with GC×GC-TOFMS

  • Research Paper
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Volatile organic compounds (VOCs) and semi-VOCs detected on the human skin surface are of great interest to researchers in the fields of metabolomics, diagnostics, and skin microbiota and in the study of anthropophilic vector mosquitoes. Mosquitoes use chemical cues to find their host, and humans can be ranked for attractiveness to mosquitoes based on their skin chemical profile. Additionally, mosquitoes show a preference to bite certain regions on the human host. In this study, the chemical differences in the skin surface profiles of 20 human volunteers were compared based on inter-human attractiveness to mosquitoes, as well as inter- and intra-human mosquito biting site preference. A passive, non-invasive approach was followed to sample the wrist and ankle skin surface region. An in-house developed polydimethylsiloxane (PDMS) passive sampler was used to concentrate skin VOCs and semi-VOCs prior to thermal desorption directly in the GC inlet with comprehensive gas chromatography coupled to time-of-flight mass spectrometry (GC×GC-TOFMS). Compounds from a broad range of chemical classes were detected and identified as contributing to the differences in the surface skin chemical profiles. 5-Ethyl-1,2,3,4-tetrahydronaphthalene, 1,1′-oxybisoctane, 2-(dodecyloxy)ethanol, α,α-dimethylbenzene methanol, methyl salicylate, 2,6,10,14-tetramethylhexadecane, 1,2-benzenedicarboxylic acid, bis(2-methylpropyl) ester, 4-methylbenzaldehyde, 2,6-diisopropylnaphthalene, n-hexadecanoic acid, and γ-oxobenzenebutanoic acid ethyl ester were closely associated with individuals who perceived themselves as attractive for mosquitoes. Additionally, biological lead compounds as potential attractants or repellants in vector control strategies were tentatively identified. Results augment current knowledge on human skin chemical profiles and show the potential of using a non-invasive sampling approach to investigate anthropophilic mosquito-host interactions.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. De Lacy CB, Amann A, Al-Kateb H, Flynn C, Filipiak W, Khalid T, et al. A review of the volatiles from the healthy human body. J Breath Res. 2014;8(1):014001.

    Google Scholar 

  2. Jiang R, Cudjoe E, Bojko B, Abaffy T, Pawliszyn J. A non-invasive method for in vivo skin volatile compounds sampling. Anal Chim Acta. 2013;804:111–9.

    CAS  PubMed  Google Scholar 

  3. Filipiak W, Mochalski P, Filipiak A, Ager C, Cumeras R, E Davis C, et al. A compendium of volatile organic compounds (VOCs) released by human cell lines. Curr Med Chem. 2016;23(20):2112–31.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Belinato JR, Silva E, de Souza DS, Março PH, Valderrama P, do Prado RM, et al. Rapid discrimination of fungal strains isolated from human skin based on microbial volatile organic profiles. J Chromatogr B. 2019;1110:9–14.

    Google Scholar 

  5. Zwiebel L, Takken W. Olfactory regulation of mosquito–host interactions. Insect Biochem Mol Biol. 2004;34(7):645–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Verhulst NO, Weldegergis BT, Menger D, Takken W. Attractiveness of volatiles from different body parts to the malaria mosquito Anopheles coluzzii is affected by deodorant compounds. Sci Rep. 2016;6:27141.

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Nyasembe VO, Tchouassi DP, Kirwa HK, Foster WA, Teal PEA, Borgemeister C, et al. Development and assessment of plant-based synthetic odor baits for surveillance and control of malaria vectors. PLoS One. 2014;9(2):e89818.

    PubMed  PubMed Central  Google Scholar 

  8. Barreaux P, Barreaux AM, Sternberg ED, Suh E, Waite JL, Whitehead SA, et al. Priorities for broadening the malaria vector control tool kit. Trends Parasitol. 2017;33(10):763–74.

    PubMed  PubMed Central  Google Scholar 

  9. Verhulst NO, Umanets A, Weldegergis BT, Maas JP, Visser TM, Dicke M, et al. Do apes smell like humans? The role of skin bacteria and volatiles of primates in mosquito host selection. J Exp Biol. 2018;221(22):jeb185959.

    PubMed  Google Scholar 

  10. Takken W, Knols BG. Odor-mediated behavior of Afrotropical malaria mosquitoes. Annu Rev Entomol. 1999;44(1):131–57.

    CAS  PubMed  Google Scholar 

  11. Hallem EA, Nicole Fox A, Zwiebel LJ, Carlson JR. Olfaction: mosquito receptor for human-sweat odorant. Nature. 2004;427(6971):212–3.

    CAS  PubMed  Google Scholar 

  12. Verhulst NO, Qiu YT, Beijleveld H, Maliepaard C, Knights D, Schulz S, et al. Composition of human skin microbiota affects attractiveness to malaria mosquitoes. PLoS One. 2011;6(12):e28991.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Takken W, Verhulst NO. Chemical signaling in mosquito–host interactions: the role of human skin microbiota. Curr Opin Insect Sci. 2017;20:68–74.

    PubMed  Google Scholar 

  14. Paluch G, Bartholomay L, Coats J. Mosquito repellents: a review of chemical structure diversity and olfaction. Pest Manag Sci. 2010;66(9):925–35.

    CAS  PubMed  Google Scholar 

  15. Dormont L, Bessière J-M, Cohuet A. Human skin volatiles: a review. J Chem Ecol. 2013;39(5):569–78.

    CAS  PubMed  Google Scholar 

  16. Soini HA, Bruce KE, Wiesler D, David F, Sandra P, Novotny MV. Stir bar sorptive extraction: a new quantitative and comprehensive sampling technique for determination of chemical signal profiles from biological media. J Chem Ecol. 2005;31(2):377–92.

    CAS  PubMed  Google Scholar 

  17. Roodt AP, Naudé Y, Stoltz A, Rohwer E. Human skin volatiles: passive sampling and GC× GC-ToFMS analysis as a tool to investigate the skin microbiome and interactions with anthropophilic mosquito disease vectors. J Chromatogr B. 2018;1097:83–93.

    Google Scholar 

  18. Mochalski P, Wiesenhofer H, Allers M, Zimmermann S, Güntner AT, Pineau NJ, et al. Monitoring of selected skin-and breath-borne volatile organic compounds emitted from the human body using gas chromatography ion mobility spectrometry (GC-IMS). J Chromatogr B. 2018;1076:29–34.

    CAS  Google Scholar 

  19. Robinson A, Busula AO, Voets MA, Beshir KB, Caulfield JC, Powers SJ, et al. Plasmodium-associated changes in human odor attract mosquitoes. Proc Natl Acad Sci U S A. 2018;115(18):E4209–E18.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Bernier UR, Kline DL, Schreck CE, Yost RA, Barnard DR. Chemical analysis of human skin emanations: comparison of volatiles from humans that differ in attraction of Aedes aegypti (Diptera: Culicidae). J Am Mosq Control Assoc. 2002;8(3):186–95.

    Google Scholar 

  21. Martin HJ, Turner MA, Bandelow S, Edwards L, Riazanskaia S, Thomas C. Volatile organic compound markers of psychological stress in skin: a pilot study. J Breath Res. 2016;10(4):046012.

    CAS  PubMed  Google Scholar 

  22. Riazanskaia S, Blackburn G, Harker M, Taylor D, Thomas C. The analytical utility of thermally desorbed polydimethylsilicone membranes for in-vivo sampling of volatile organic compounds in and on human skin. Analyst. 2008;133(8):1020–7.

    CAS  PubMed  Google Scholar 

  23. Martin HJ, Reynolds JC, Riazanskaia S, Thomas CP. High throughput volatile fatty acid skin metabolite profiling by thermal desorption secondary electrospray ionisation mass spectrometry. Analyst. 2014;139(17):4279–86.

    CAS  PubMed  Google Scholar 

  24. Baltussen E, Cramers C, Sandra P. Sorptive sample preparation – a review. Anal Bioanal Chem. 2002;373(1):3–22.

    CAS  PubMed  Google Scholar 

  25. Clements AN. The biology of mosquitoes: sensory reception and behaviour. Cambridge: Cambridge University Press; 1999.

    Google Scholar 

  26. Braack L, Hunt R, Koekemoer LL, Gericke A, Munhenga G, Haddow AD, et al. Biting behaviour of African malaria vectors: 1. Where do the main vector species bite on the human body? Parasit Vectors. 2015;8(1):76.

    PubMed  PubMed Central  Google Scholar 

  27. Dekker T, Takken W, Knols BG, Bouman E, Laak S, Bever A, et al. Selection of biting sites on a human host by Anopheles gambiae ss, An. arabiensis and An. quadriannulatus. Entomol Exp Appl. 1998;87(3):295–300.

    Google Scholar 

  28. Naudé Y, Gorst-Allman P, Rohwer E. A cheap and simple passive sampler using silicone rubber for the analysis of surface water by gas chromatography-time of flight mass spectrometry. Water SA: WISA 2014-Water Innovations Special Edition. 2015;41(2):182–8.

  29. Naudé Y, Rohwer ER. Two multidimensional chromatographic methods for enantiomeric analysis of o, p′-DDT and o, p′-DDD in contaminated soil and air in a malaria area of South Africa. Anal Chim Acta. 2012;730:120–6.

    PubMed  Google Scholar 

  30. Naudé Y, Van Rooyen MW, Rohwer ER. Evidence for a geochemical origin of the mysterious circles in the Pro-Namib desert. J Arid Environ. 2011;75(5):446–56.

    Google Scholar 

  31. Wooding M, Rohwer ER, Naudé Y. Comparison of a disposable sorptive sampler with thermal desorption in a gas chromatographic inlet, or in a dedicated thermal desorber, to conventional stir bar sorptive extraction-thermal desorption for the determination of micropollutants in water. Anal Chim Acta. 2017;107–115.

  32. Wooding M, Rohwer ER, Naudé Y. Determination of endocrine disrupting chemicals and antiretroviral compounds in surface water: a disposable sorptive sampler with comprehensive gas chromatography–time-of-flight mass spectrometry and large volume injection with ultra-high performance liquid chromatography–tandem mass spectrometry. J Chromatogr A. 2017;1496:122–32.

    CAS  PubMed  Google Scholar 

  33. Triñanes S, Pena MT, Casais MC, Mejuto MC. Development of a new sorptive extraction method based on simultaneous direct and headspace sampling modes for the screening of polycyclic aromatic hydrocarbons in water samples. Talanta. 2015;132(0):433–42.

    PubMed  Google Scholar 

  34. Wooding M, Rohwer ER, Naudé Y. Non-invasive sorptive extraction with GC×GC-TOFMS for the separation of human skin surface chemicals: a mosquito-host biting site investigation. In prep, submitted to J Sep Sci. 2020 (under review).

  35. Van den Dool H, Kratz P. A generalization of the retention index system including linear temperature programmed gas—liquid partition chromatography. J Chromatogr A. 1963;11:463–71.

    Google Scholar 

  36. Mochalski P, King J, Unterkofler K, Hinterhuber H, Amann A. Emission rates of selected volatile organic compounds from skin of healthy volunteers. J Chromatogr B. 2014;959:62–70.

    CAS  Google Scholar 

  37. Verhulst NO, Beijleveld H, Qiu YT, Maliepaard C, Verduyn W, Haasnoot GW, et al. Relation between HLA genes, human skin volatiles and attractiveness of humans to malaria mosquitoes. Infect Genet Evol. 2013;18:87–93.

    CAS  PubMed  Google Scholar 

  38. Qiu YT, Smallegange RC, Hoppe S, van Loon JJ, Bakker EJ, Takken W. Behavioural and electrophysiological responses of the malaria mosquito Anopheles gambiae Giles sensu stricto (Diptera: Culicidae) to human skin emanations. Med Vet Entomol. 2004;18(4)429–38.

  39. Logan JG, Birkett MA, Clark SJ, Powers S, Seal NJ, Wadhams LJ, et al. Identification of human-derived volatile chemicals that interfere with attraction of Aedes aegypti mosquitoes. J Chem Ecol. 2008;34(3):308.

    CAS  PubMed  Google Scholar 

  40. Smallegange RC, Bukovinszkiné-Kiss G, Otieno B, Mbadi PA, Takken W, Mukabana WR, et al. Identification of candidate volatiles that affect the behavioural response of the malaria mosquito Anopheles gambiae sensu stricto to an active kairomone blend: laboratory and semi-field assays. Physiol Entomol. 2012;37(1):60–71.

  41. Tauxe GM, MacWilliam D, Boyle SM, Guda T, Ray A. Targeting a dual detector of skin and CO2 to modify mosquito host seeking. Cell. 2013;155(6):1365–79.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Smallegange RC, Qiu YT, van Loon JA, Takken W. Synergism between ammonia, lactic acid and carboxylic acids as kairomones in the host-seeking behaviour of the malaria mosquito Anopheles gambiae sensu stricto (Diptera: Culicidae). Chem Senses. 2005;30(2):145–52.

    CAS  PubMed  Google Scholar 

  43. Knols BG, van Loon JJ, Cork A, Robinson RD, Adam W, Meijerink J, et al. Behavioural and electrophysiological responses of the female malaria mosquito Anopheles gambiae (Diptera: Culicidae) to Limburger cheese volatiles. Bull Entomol Res. 1997;87(2):151–9.

    CAS  Google Scholar 

  44. Qiu YT, Van Loon JJ, Takken W, Meijerink J, Smid HM. Olfactory coding in antennal neurons of the malaria mosquito, Anopheles gambiae. Chem Senses. 2006;31(9):845–63.

    CAS  PubMed  Google Scholar 

  45. Smallegange RC, Qiu YT, Bukovinszkiné-Kiss G, Van Loon JJ, Takken W. The effect of aliphatic carboxylic acids on olfaction-based host-seeking of the malaria mosquito Anopheles gambiae sensu stricto. J Chem Ecol. 2009;35(8):933.

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Okumu FO, Killeen GF, Ogoma S, Biswaro L, Smallegange RC, Mbeyela E, et al. Development and field evaluation of a synthetic mosquito lure that is more attractive than humans. PLoS One. 2010;5(1):e8951.

    PubMed  PubMed Central  Google Scholar 

  47. Jawara M, Awolola TS, Pinder M, Jeffries D, Smallegange RC, Takken W, et al. Field testing of different chemical combinations as odour baits for trapping wild mosquitoes in the Gambia. PLoS One. 2011;6(5):e19676.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Menger DJ, van Loon JJ, Takken W. Assessing the efficacy of candidate mosquito repellents against the background of an attractive source that mimics a human host. Med Vet Entomol. 2014;28(4):407–13.

    CAS  PubMed  Google Scholar 

  49. Mweresa CK, Mukabana WR, Omusula P, Otieno B, Van Loon JJ, Takken W. Enhancing attraction of African malaria vectors to a synthetic odor blend. J Chem Ecol. 2016;42(6):508–16.

    CAS  PubMed  Google Scholar 

  50. Hiscox A, Otieno B, Kibet A, Mweresa CK, Omusula P, Geier M, Rose A, Mukabana WR, Takken W. Development and optimization of the Suna trap as a tool for mosquito monitoring and control. Malar J. 2014;13(1):257.

  51. Van Loon JJ, Smallegange RC, Bukovinszkiné-Kiss G, Jacobs F, De Rijk M, Mukabana WR, et al. Mosquito attraction: crucial role of carbon dioxide in formulation of a five-component blend of human-derived volatiles. J Chem Ecol. 2015;41(6):567–73.

    PubMed  PubMed Central  Google Scholar 

  52. Busula AO, Takken W, Loy DE, Hahn BH, Mukabana WR, Verhulst NO. Mosquito host preferences affect their response to synthetic and natural odour blends. Malar J. 2015;14(1):1.

    CAS  Google Scholar 

  53. Nyasembe VO, Torto B. Volatile phytochemicals as mosquito semiochemicals. Phytochem Lett. 2014;8:196–201.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Cuzuel V, Sizun A, Cognon G, Rivals I, Heulard F, Thiébaut D, et al. Human odor and forensics. Optimization of a comprehensive two-dimensional gas chromatography method based on orthogonality: how not to choose between criteria. J Chromatogr A. 2017;1536:58–66.

  55. Lemfack MC, Ravella SR, Lorenz N, Kai M, Jung K, Schulz S, et al. Novel volatiles of skin-borne bacteria inhibit the growth of Gram-positive bacteria and affect quorum-sensing controlled phenotypes of Gram-negative bacteria. Syst Appl Microbiol. 2016;39(8):503–15.

    CAS  PubMed  Google Scholar 

  56. Jhumur US, Dötterl S, Jürgens A. Floral odors of Silene otites: their variability and attractiveness to mosquitoes. J Chem Ecol. 2007;34(1):14–25.

    PubMed  Google Scholar 

  57. Ding X, Lin S, Weng H, Liang J. Separation and determination of the enantiomers of lactic acid and 2-hydroxyglutaric acid by chiral derivatization combined with gas chromatography and mass spectrometry. J Sep Sci. 2018;41(12):2576–84.

    CAS  PubMed  Google Scholar 

  58. Ganesan K, Mendki MJ, Suryanarayana MV, Prakash S, Malhotra RC. Studies of Aedes aegypti (Diptera: Culicidae) ovipositional responses to newly identified semiochemicals from conspecific eggs. Aust J Entomol. 2006;45(1):75–80.

    Google Scholar 

  59. National Center for Biotechnology Information, PubChem Database, Propoxur, CID=4944. https://pubchem.ncbi.nlm.nih.gov/compound/Propoxur. Accessed 6 April 2020.

  60. Braack L, Coetzee M, Hunt R, Biggs H, Cornel A, Gericke A. Biting pattern and host-seeking behavior of Anopheles arabiensis (Diptera: Culicidae) in northeastern South Africa. J Med Entomol. 1994;31(3):333–9.

    CAS  PubMed  Google Scholar 

  61. Govere J, Braack L, Durrheim D, Hunt R, Coetzee M. Repellent effects on Anopheles arabiensis biting humans in Kruger Park, South Africa. Med Vet Entomol. 2001;15(3):287–92.

    CAS  PubMed  Google Scholar 

  62. Verhulst NO, Beijleveld H, Knols BG, Takken W, Schraa G, Bouwmeester HJ, Smallegange RC. Cultured skin microbiota attracts malaria mosquitoes. Malar J. 2009;8(1):302.

  63. Cooperband MF, McElfresh JS, Millar JG, Cardé RT. Attraction of female Culex quinquefasciatus Say (Diptera: Culicidae) to odors from chicken feces. J Insect Physiol. 2008;54(7):1184–92.

    CAS  PubMed  Google Scholar 

  64. Afify A, Galizia CG. Chemosensory cues for mosquito oviposition site selection. J Med Entomol. 2015;52(2):120–30.

    CAS  PubMed  Google Scholar 

  65. Meijerink J, Braks M, Brack A, Adam W, Dekker T, Posthumus M, Van Beek TA, Van Loon JJA. Identification of olfactory stimulants for Anopheles gambiae from human sweat samples. J Chem Ecol. 2000;26(6):1367–82.

  66. Mweresa CK, Omusula P, Otieno B, Loon JJA, Takken W, Mukabana WR. Molasses as a source of carbon dioxide for attracting the malaria mosquitoes Anopheles gambiae and Anopheles funestus. Malar J. 2014;13(160).

  67. Wooding M, Naudé Y, Rohwer E, Bouwer M. Controlling mosquitoes with semiochemicals: a review. Parasit Vectors. 2020;13(1):1–20.

    Google Scholar 

  68. Kline DL, Bernier UR, Posey KH, Barnard DR. Olfactometric evaluation of spatial repellents for Aedes aegypti. J Med Entomol. 2003;40(4):463–7.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We wish to thank David Masemula for assembling the PDMS loops, the University of Pretoria Institute for Sustainable Malaria Control (UP ISMC), Dr. Hubert Mandery for partial financial support in his private capacity, and as well as L’Oréal-UNESCO For Women in Science sub-Saharan African Programme for partial financial support.

Funding

This study was partially funded by a donation from a philanthropist, Dr. Hubert Mandery, in his private capacity in support of malaria research.

Author information

Authors and Affiliations

Authors

Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analyses were performed by Madelien Wooding with contributions from Yvette Naudé. The first draft of the manuscript was written by Madelien Wooding and all authors contributed to working versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Yvette Naudé.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

The study protocol was approved by the ethics committee of the Faculty of Natural and Agricultural Sciences at the University of Pretoria, South Africa (Reference number EC171109-159).

Consent to participate

Informed consent was obtained prior to collection of the samples.

Consent for publication

Informed consent was obtained prior to collection of the samples.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic supplementary material

ESM 1

(PDF 217 kb).

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Wooding, M., Rohwer, E.R. & Naudé, Y. Chemical profiling of the human skin surface for malaria vector control via a non-invasive sorptive sampler with GC×GC-TOFMS. Anal Bioanal Chem 412, 5759–5777 (2020). https://doi.org/10.1007/s00216-020-02799-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-020-02799-y

Keywords

Navigation