Characterization of Anopheles gambiae D7 salivary proteins as markers of human–mosquito bite contact

Background Malaria is transmitted when infected Anopheles mosquitoes take a blood meal. During this process, the mosquitoes inject a cocktail of bioactive proteins that elicit antibody responses in humans and could be used as biomarkers of exposure to mosquito bites. This study evaluated the utility of IgG responses to members of the Anopheles gambiae D7 protein family as serological markers of human–vector contact. Methods The D7L2, D7r1, D7r2, D7r3, D7r4 and SG6 salivary proteins from An. gambiae were expressed as recombinant antigens in Escherichia coli. Antibody responses to the salivary proteins were compared in Europeans with no prior exposure to malaria and lifelong residents of Junju in Kenya and Kitgum in Uganda where the intensity of malaria transmission is moderate and high, respectively. In addition, to evaluate the feasibility of using anti-D7 IgG responses as a tool to evaluate the impact of vector control interventions, we compared responses between individuals using insecticide-treated bednets to those who did not in Junju, Kenya where bednet data were available. Results We show that both the long and short forms of the D7 salivary gland antigens elicit a strong antibody response in humans. IgG responses against the D7 antigens reflected the transmission intensities of the three study areas, with the highest to lowest responses observed in Kitgum (northern Uganda), Junju (Kenya) and malaria-naïve Europeans, respectively. Specifically, the long form D7L2 induced an IgG antibody response that increased with age and that was lower in individuals who slept under a bednet, indicating its potential as a serological tool for estimating human–vector contact and monitoring the effectiveness of vector control interventions. Conclusions This study reveals that D7L2 salivary antigen has great potential as a biomarker of exposure to mosquito bites and as a tool for assessing the efficacy of vector control strategies such as bednet use. Graphical abstract

Part Three: Biomarker Changes in Cigarette Smokers Switched to Vuse Solo or Abstinence: A Randomized, Controlled Study

Biomarkers of exposure (BoE) can help evaluate exposure to combustion-related, tobacco-specific toxicants after smokers switch from cigarettes to potentially less-harmful products like electronic nicotine delivery systems (ENDS). This paper reports data for one (Vuse Solo Original) of three products evaluated in a randomized, controlled confinement study of BoE in smokers switched to ENDS. Subjects smoked their usual brand cigarette ad libitum for two days, then were randomized to one of three ENDS for a 7-day ad libitum use period, or to smoking abstinence. Thirteen BoE were assessed at baseline and Day 5, and percent change in mean values for each BoE was calculated. Biomarkers of potential harm (BoPH) linked to oxidative stress, platelet activation, and inflammation were also assessed. Levels decreased among subjects randomized to Vuse Solo versus Abstinence, respectively, for the following BoE: 42–96% vs. 52–97% (non-nicotine constituents); 51% vs. 55% (blood carboxyhemoglobin); and 29% vs. 96% (nicotine exposure). Significant decreases were observed in three BoPH: leukotriene E4, 11-dehydro-thromboxane B2, and 2,3-dinor thromboxane B2 on Day 7 in the Vuse Solo and Abstinence groups. These findings show that ENDS use results in substantially reduced exposure to toxicants compared to smoking, which may lead to reduced biological effects.

Systemic biomarkers of exposure associated with ENDS use: a scoping review

ObjectiveThis scoping review provides an overview of the existing literature on biomarkers of exposure from electronic nicotine delivery systems (ENDS) use and identifies gaps in existing knowledge.Data sourcesWe searched two international databases (PubMed and Web of Science) to identify relevant studies published from August 2013 to February 2021.Data selectionStudies were included if they assessed and compared biomarkers of exposure between exclusive ENDS users, non-users, exclusive cigarette smokers, dual users of ENDS and cigarettes or cigarette smokers who switch to ENDS.Data extraction and synthesisOf the 5074 studies identified, 188 studies met criteria and were selected for full-text screening. Of these, 27 studies were selected for inclusion and data extraction.ConclusionsConsistent, although limited, evidence shows that exclusive ENDS users have elevated levels of biomarkers of certain volatile organic compounds (VOCs; eg, acrylamide and acrylonitrile), metals (eg, cadmium and selenium) and propylene glycol compared with non-users; however, evidence for biomarkers of other toxicants (eg, acrolein, benzene and chromium) is mixed. Biomarkers of most VOCs are lower in ENDS users compared with cigarette smokers, and cigarette smokers who switch to ENDS consistently show reductions in VOC biomarkers. Evidence comparing metal exposures from exclusive ENDS use, cigarette smoking and dual use is mixed and depends on the metal. ENDS and e-liquid characteristics as well as use patterns may be associated with elevated exposure to VOCs and metals. Additional rigorous, controlled studies can assess biomarker exposures from ENDS use and inform the overall risk–benefit of ENDS use for different user populations.