Near-Infrared Spectroscopy: A One-Stop-Shop for Mosquito Epidemiological Monitoring?

Lead Research Organisation: Imperial College London
Department Name: School of Public Health

Abstract

Mosquito borne diseases such as malaria, dengue, chikungunya and zika cause huge suffering in tropical regions of the world. One of the main approaches to controlling these diseases is to use insecticides to kill mosquitoes and prevent them from transmitting the infection from person to person. Millions of pounds are spent on mosquito control each year though surprisingly there is no simple method for evaluating the ability of these interventions to kill mosquitoes or prevent them from transmitting disease. The number of biting mosquitoes in an area fluctuates substantially from day to day due to local weather patterns so the number of mosquitoes caught in traps is a poor predictor of the size of the population. More importantly the number of mosquitoes in itself is not a good predictor of risk as many diseases take several days to develop inside the mosquito and find their way to the mouthparts. This means that only older mosquitoes can pass on the infection. Mosquito age is therefore very important for assessing the effectiveness of anti-mosquito interventions but currently, there is no easy, accurate way of assessing the age of a mosquito population.

Near-Infrared Spectroscopy (NIRS) is a new age-grading and species identification technique that has been developed in the laboratory. It predicts the age of the mosquito by measuring how a beam of light is reflected differently from the bodies of mosquitoes as they get older. Unlike other methods NIRS doesn't require costly chemicals or procedures and it can be carried out by anybody with minimal training. This makes it feasible for use as a routine method for monitoring mosquito age in the field. Currently NIRS cannot predict the age of an individual mosquito very accurately and tests have only been done on mosquitoes reared in the laboratory which are likely to be more uniform (and therefore give more accurate results) than those caught in the wild. However, for disease control it is more important to know the average age of the mosquito population than the age of individuals. Our preliminary work suggests that if we change the way we analyse NIRS outputs we can generate highly precise predictions of the average age of the mosquito population. The project intends to take NIRS from the laboratory to the field and test whether it is good enough to be able to be used in the routine monitoring of mosquito populations. The project will use semi-field and field data to operationalise the technique and outline how many mosquitoes need to be caught (and over how many days) to generate estimates accurate enough to guide the deployment of mosquito control.

The work will concentrate on the two most important mosquito borne infections: malaria (which kills 438,000 people in 2015) and dengue (which infects 400 million people annually). However the technique developed here can be applied to other diseases and mosquito species. NIRS can also be used to differentiate closely-related mosquito species that are indistinguishable by eye. That is important, as not all of these mosquitoes have the same ability to transmit disease and are affected by control interventions differently. Similarly to age-grading, the capacity of NIRS to differentiate species needs to be more rigorously tested in the field. There is also evidence to suggest that NIRS might be able to detect whether a mosquito is infected with the virus that causes dengue disease. This will be tested for malaria, first in the laboratory in Burkina Faso and then in the field. Currently mosquito species, age and infection status are estimated using a variety of laborious and costly procedures that preclude their use as routine monitoring tools in poorer parts of the world. A single, inexpensive method for doing all three tests simultaneously would have significant public health impact: we could describe the risks of disease transmission and evaluate the efficacy of control programs far more cheaply and quickly.

Technical Summary

Mosquito control through the use of bednets, residual sprays or fumigation remains the most effective tool for preventing malaria and dengue though there is no easy to use entomological methods for directly assessing its efficacy. The rise of insecticide resistant mosquitoes exacerbates the need to understand how well interventions are working as it unclear whether control programmes should invest in more expensive insecticides. Mosquito age is the most informative method for evaluating the efficacy of adulticiding techniques though there are still no easy way of measuring it in the field.

Near-Infrared Spectroscopy (NIRS) has been shown in the laboratory to be a promising, potentially high-throughput method that can both age mosquitoes and differentiate between sibling species though it has never been evaluated in the field. NIRS has relatively high individual mosquito measurement error though preliminary evidence suggests that precise mean estimates of the age of the population can be made by improving the machine learning methods converting spectral data into age and by fitting parametric models to groups of mosquitoes.

This project proposes to rigorously test the ability of NIRS to monitor wild caught Anopheline and Aedes mosquito populations in semi-field and field sites. It shall use mathematical models to determine whether the mean age is sufficiently accurate to guide the use of vector control. The sampling requirements needed to estimate the effect size of an intervention will be defined and the methods tested in a malaria indoor-residual spraying programme in Africa. Evidence suggests that NIRS is also able to identify mosquitoes infected with dengue virus. This work will be extended to malaria to determine whether NIRS can differentiate uninfected, infected and infectious mosquitoes. Overall the proposal aims to generate the body of evidence needed to determine whether NIRS can be used to routinely monitor mosquito population in the field.

Planned Impact

People Living and Visiting Areas with Vector-Borne Diseases

The main beneficiaries of the proposed research should it be successful would be people living in areas endemic for vector-borne diseases. A new method for evaluating vector control could be rolled out within a 5 year period and would allow mosquito control to be optimised, improving public health and lowering unnecessary environmental exposure to insecticides. Many UK residence visit the tropics each year on holiday and business and they would also benefit from improved mosquito control.

Optimise Delivery of UK Aid

Each year the UK spends a considerable amount of money combatting vector borne diseases. For example, malaria is one of UK Aid's top priorities with a tripling of it's funding to combat the disease between 2008-2015. This makes the UK the second largest government donor to malaria programmes and the majority of this money is spent on vector control. Improved entomological metrics to evaluate mosquito control interventions would enable this money to be spent more efficiently and improve the cost effectiveness of UK Aid.

National Policy Makers

Currently national vector control policy makers have insufficient tools to determine what type of interventions they should use in a particular location. This problem has been exacerbated by the rise of insecticide resistance. As there is no easy to use method of evaluating the efficacy of an intervention it is unclear whether control programmes should invest in more expensive products (and therefore lower their intervention coverage) or persist with current interventions which may be less effective. More accurate entomological metrics would dramatically facilitate the decision making process.

International Policy Makers

The wide number of novel vector control tools under development means that international policy makers such as the World Health Organisation (WHO) need to be able to decide quickly whether to endorse a new product to ensure they can be adopted in a timely manner, saving lives. The problem of insecticide resistance exacerbates the urgency as resistance can spread quickly rendering previous methods ineffective. A direct measure of intervention efficacy would expedite the process and provide the evidence-base for prompt policy decisions. The last few years have seen major international outbreaks of diseases transmitted by mosquitoes such as chikungunya and zika. Other novel mosquito-borne pathogens are likely to follow. The routine monitoring of mosquito age would allow the risk of such outbreaks to be assessed, supporting their control and helping national and international containment.

Insecticide and Biological Control Industry

The agro-chemical industry is an important employer in the UK and would benefit should the proposed research be successful. Equally the UK is a world leader in the development of genetically modified mosquitoes with British companies such as Oxitec (who are currently commercially releasing mosquitoes in South America) being at the forefront of the nascent industry. The majority of the development of new insecticides and vector control products are undertaken by industrial partners though it is unclear what the minimum data requirements are to ensure novel products are endorsed by policy makers such as the WHO. This uncertainty is creating delays and dissuading industry from innovation. Currently, in malaria the WHO requires new paradigms in vector control to show an impact on clinical disease in randomised control trials, in part because of the poor predictive power of entomological methods. These trials are very expensive and time consuming and are complicated by human immunity/movement and the fact that insecticide resistance cannot be randomly allocated between sites. An improved entomological measure of intervention efficacy would speed up the process and make it easier for industry to justify products with greater efficacy but higher unit cost.
 
Description Participation in expert scientific advisory committee (New Paradigms in Vector Control)
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
Impact Investment in most appropriate tools for killing mosquitoes
URL http://www.ivcc.com
 
Description WHO spread of pyrethroid resistant mosquitoes across Africa.
Geographic Reach Africa 
Policy Influence Type Participation in a advisory committee
Impact Collaboration with the World Health Organisation (WHO) Global Malaria Programme to understand the spread of pyrethroid resistant mosquitoes across Africa and how this influences the effectiveness of insecticide treated bednets used to control malaria. Though this has not led to any specific policy recommendations the work was presented in a WHO document (World Malaria Report 2019, Global report on insecticide resistance in malaria vectors: 2010-2016, accessed https://www.who.int/malaria/publications/atoz/9789241514057/en/ ) and on a live WHO webinar (https://apps.who.int/iris/bitstream/handle/10665/274556/WHO-CDS-GMP-2018.17-eng.pdf?ua=1). This work has supported the development of online threat maps for insecticide resistance status (https://www.who.int/malaria/maps/threats-about/en/).
URL https://www.who.int/malaria/publications/atoz/9789241514057/en/
 
Title Experiments for detection of Plasmodium berghei infected Anopheles stephensi mosquitoes using near-infrared spectroscopy 
Description Spectra from uninfected, indected and infectious mosquitoes 
Type Of Material Database/Collection of data 
Year Produced 2018 
Provided To Others? Yes  
Impact None currently 
URL https://doi.org/10.5281/zenodo.1001720
 
Title Experiments for determination of species of field-collected lab-rared mosquitoes using near-infrared spectroscopy (A1T1) 
Description Experiments for determination of species of field-collected lab-rared mosquitoes using near-infrared spectroscopy (A1T1) This dataset contains near-infrared spectroscopy (NIRS) measurements on mosquitoes of different species ( Anopheles arabiensis, Anopheles coluzzii, Anopheles gambiae) collected from different locations in Burkina Faso (Dioulassoba, Klesso, Longo) at larval stage, and reared in the lab together with colony mosquitoes of the same species. For further details on the experimental setup see: P.M. Esperança, A.M. Blagborough, D.F. Da, F.E. Dowell, T.S. Churcher (2018) "Detection of Plasmodium berghei infected Anopheles stephensi using near-infrared spectroscopy". Parasites and Vector, 11:377. https://doi.org/10.1186/s13071-018-2960-z. The structure of the data file is as follows: column 1 ( Scan_ID): scan identifier column 2 ( Mosquito_ID): mosquito identifier column 3 ( Position): scanning position identifier (1,2,3,4) column 4 ( Location): collection location ("Dioulassoba", "Klesso", "Longo") column 5 ( Generation): generation type ("Lab", "F0", "F1") column 6 ( Species): mosquitoes species ("arabiensis", "coluzzii", "gambiae") columns 7 to 2157 ( x350 to x2500): NIRS absorbance measurements for wavelengths in the range 350 to 2500 nanometers 
Type Of Material Database/Collection of data 
Year Produced 2019 
Provided To Others? Yes  
 
Description Dr. Kounbobr Roch Dabiré of IRSS (Burkina Faso) 
Organisation Research Institute for Health Sciences (IRSS)
Country Burkina Faso 
Sector Public 
PI Contribution We have provided training in the use of spectroscopy and the alalytical methods needed to interpret the results.
Collaborator Contribution Dr Dabiré leads a research team which is extending the methods we have developed to mosquito vectors of malaria in Africa.
Impact Project meeting in London (UK) and Bobo Dioulasso (Burkina Faso).
Start Year 2017
 
Description Floyd Dowell of United States Department of Agriculture 
Organisation U.S. Department of Agriculture USDA
Department Agricultural Research Service
Country United States 
Sector Public 
PI Contribution We have developed new analytical methods to understand how mosquito age, species and infection status (with the malaria parasite) changes the light being measured by a spectrometer
Collaborator Contribution Dr Dowell is a Research Agricultural Engineer who has pioneered work using Near Infrared Spectroscopy to investigate the age of mosquitoes. Dr Dowell provided training and technical advice to scientists from Imperial College London and our partners
Impact Training of UK, Burkinabe and Australian Scientists in the use of spectrometer
Start Year 2017
 
Description Greg Devine at QIMR Berghofer (Brisbane, Australia) 
Organisation QIMR Berghofer Medical Research Institute
Country Australia 
Sector Academic/University 
PI Contribution Provide funding to run experiments in Australia on local Aedes mosquito populations
Collaborator Contribution Partner running experiments in Australia on local Aedes mosquito populations
Impact None yet
Start Year 2017
 
Description Testing of Near-Infrared Spectroscopy in Africa - Brian Foy 
Organisation Colorado State University
Country United States 
Sector Academic/University 
PI Contribution There is a clinical trial of a new systemic insecticide ivermectin in Burkina Faso designed to test whether repeated mass drug administrations can suppress the local mosquito population. RIMDAMAL II (https://clinicaltrials.gov/ct2/show/NCT03967054) is a double-blind, cluster randomized trial and we are using Near-Infrared Spectroscopy to determine whether we can detect a difference in the age of the mosquito population in the different arms of the trial.
Collaborator Contribution The work is being lead by Professor Brian Foy of Colorado State University who will provide spectra from mosquitoes from different arms of the randomised control trial. Our estimates of age will be compared to other methods conducted on the same mosquitoes.
Impact The project is highly multidisciplinary including epidemiologists, entomologists, clinicians and computer scientists.
Start Year 2019
 
Description The population dynamics of malaria within the mosquito and how this is influenced by temperature 
Organisation Penn State University
Country United States 
Sector Academic/University 
PI Contribution Provided Modelling expertise and data analysis
Collaborator Contribution Provided raw data from experimental infections of mosquitoes
Impact Manuscript accepted in Nature Ecology and Evolution Data provided by collaborator forms the basis of a PhD chapter.
Start Year 2019
 
Description Use of NIRS in ivermectin clinical trial 
Organisation Colorado State University
Country United States 
Sector Academic/University 
PI Contribution We have been evaluating the ability of spectroscopy to detech changes in the avaerage age of the mosquito population using data collected as part of a cluster-randomised control trial of repeat ivermectin mass drug administrations for control of malaria (RIMDAMAL).
Collaborator Contribution Spectroscopy data from wild caught mosquitoes
Impact Analyses of data collected by medical entomologists to help explain the epidemiological impact of the intervention.
Start Year 2020
 
Description WHO - Assessing spread of pyrethorid resistance across Africa 
Organisation World Health Organization (WHO)
Department Global Malaria Programme
Country Switzerland 
Sector Charity/Non Profit 
PI Contribution Collaboration with the World Health Organisation (WHO) Global Malaria Programme to understand the spread of pyrethroid resistant mosquitoes across Africa and how this influences the effectiveness of insecticide treated bednets used to control malaria.
Collaborator Contribution Provided data on impact of insecticide on wild caught mosquitoes.
Impact The work was presented in a WHO document (World Malaria Report 2019, Global report on insecticide resistance in malaria vectors: 2010-2016, accessed https://www.who.int/malaria/publications/atoz/9789241514057/en/ ) and on a live WHO webinar (https://apps.who.int/iris/bitstream/handle/10665/274556/WHO-CDS-GMP-2018.17-eng.pdf?ua=1). This work has supported the development of online threat maps for insecticide resistance status (https://www.who.int/malaria/maps/threats-about/en/). Attended WHO meetings resulting in policy recommendations and guideline changes. Meetings attended: (1) WHO consultation meeting, 15-18 December 2020 - WHO consultation to review results of the multi-centre study on determination of insecticide discriminating concentrations for monitoring of resistance in mosquitoes (2) Revision of Test procedures for IR monitoring in malaria vectors https://www.who.int/malaria/publications/atoz/9789241511575/en/
Start Year 2018
 
Description Malaria no more campaign 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Public health campaign related to eradication of malaria. Starring David Beckham and other high profile celebrities
Year(s) Of Engagement Activity 2007,2020
URL https://malarianomore.org.uk/
 
Description Present Research at Innovative Vector Control Consortium (IVCC) Expert Scientific Advisory Group, 8th March 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Policymakers/politicians
Results and Impact Presented to funders (Bill & Melinda Gates Foundation, IVCC) and policy makers (members of the WHO Malaria Programme Advisory Committee) at the expert meeting looking into new tools for targeting mosquitoes biting outside. Outlined the benefits and flaws with the spectroscopy method.
Year(s) Of Engagement Activity 2018