On Friday 21^st August, APLMA will hold the second of its Malaria Gamechangers roundtable series. It focusses this time on vector control and is co-sponsored by IVCC and RBM Partnership to End Malaria. The roundtable aims to engage senior policy-makers across the Indo-Pacific in exploring some of the new and existing vector control products that will be vital to achieving malaria elimination in the region by 2030.

The panel will also focus on the regulatory hurdles, as outlined in IVCC’s Regulatory Landscape Report, that must be negotiated swiftly if these products are to have the desired impact. Vasanthan John Paul, the author of the report and IVCC’s regulatory consultant, will join the panel to speak on regulatory issues and opportunities for improved access to vector control solutions.

On the panel, there will also be a number of representatives from companies that IVCC has enjoyed successful partnerships with for many years, such as Bayer Cropscience and Sumitomo Chemical Company. There will also be speakers from organisations and countries with whom it is important we strengthen our relationships in order to maximise the impact of our work in the region. Our co-sponsoring of the roundtable is itself also a small example of where we have been forging new relationships and collaborations, as we seek to strengthen our network in support of the Indo-Pacific Initiative (IPI), funded by the Australian Government’s Department of Foreign Affairs and Trade.

IPI’s overall aim is to develop a vector control toolbox for the Indo-Pacific region. We are approaching this by focussing primarily on tools for malaria control in Papua New Guinea and Cambodia. In PNG, we are working with the PNG Institute of Medical Research, Burnet Institute and James Cook University, to develop the capacity in PNG for testing new tools, build a national vector control stakeholder network and test products in the community. The priority product categories for testing in PNG are Indoor Residual Spraying (including eaves and verandas), Spatial Repellents and Larvicides. In Cambodia and Thailand, we are working with a partnership led by University of California, San Francisco-Malaria Elimination Initiative, involving CNM, AFRIMS and Kasetsart University amongst others, to evaluate Forest Packs as a means of delivering effective bite prevention tools (Insecticide Treated Clothing, Spatial Repellent and Topical Repellent) to forest-going populations. To support these two main areas of work, we are also partnering with Imperial College London to model the potential impact of new new tools on malaria in the region.

IPI is guided by an Advisory Group of experts based in the region or with significant experience therein. The Advisory Group is based on the principle of delivering through robust partnerships, and draws from IVCC’s trademark model for external expert engagement and scrutiny: the External Scientific Advisory Committee (ESAC). IPI sits under Objective 7 of the IVCC strategy, which aims ‘to capitalise on knowledge and innovation to address malaria and other vector borne diseases outside sub-Saharan Africa in order to maximise the impact of our work and the products being developed’. Now more than ever, if we are to expand our activity into new geographies with little ‘on the ground’ presence, we are reliant on networking and forging strong partnerships. Add the myriad ramifications of Covid-19 into the mix- not least restricted travel- and it becomes even more important to have trusted collaborations through which to deliver.

As IPI ramps up, IVCC further explicates its strategic approach to the Indo-Pacific region and new opportunities arise elsewhere, we will need to continue to think realistically about what IVCC can deliver and what is best done by partners. We are fortunate in these considerations that IVCC has always recognised the importance of delivering through strong partnerships and that this is built into the way that we operate.

If IVCC is to achieve its vision of ‘saving lives, protecting health and increasing prosperity by preventing insect-borne disease’, and if success is to be seen more widely across the vector control community in the fight against insect-borne disease, it is clear that success will depend on the strength of working with the right people, at the right time and via the right kind of collaborations.

“I am very pleased that together we achieved our goal of establishing a sustainable, growing and competitive market for third generation, longer lasting and resistance-breaking insecticides for Indoor Residual Spraying (IRS).”

On December 31st, 2019, the Unitaid funded NgenIRS project came to an end. The NgenIRS team, led by IVCC and made up of colleagues from PATH and Abt Associates, worked in partnership with 16 malaria control and elimination programmes across Africa, the US President’s Malaria Initiative (PMI), the Global Fund and three insecticide manufacturers.

The downward trend in IRS use was reversed and the resulting expansion of use has resulted in significant public health impact, savings in commodity costs and new evidence showing the cost-effectiveness of third generation IRS (3GIRS). What’s more, the foundation has been laid to sustain and expand on these successes, providing malaria programmes with more options for rotation and ultimately more lives saved on the path towards malaria elimination.

Today we launch a collection of evidence materials, consisting of a video, a project overview and evidence slides (available in both English and French). These materials are available for free download on the NgenIRS web page and IVCC resource library. These materials have been prepared to show the impact of the NgenIRS project and are intended for use by partners and stakeholders who need to communicate the contribution of 3GIRS products to the reduction of malaria. We hope that these are useful to you and advice on use can be found within the materials.

I would like to extend my heartfelt thanks to the NgenIRS team and our many other partners who worked tirelessly and selflessly to make this project such a huge success. Although we have achieved great things together, we must maintain this commitment to enhancing and smartly deploying the vector control toolbox if we are to reach our shared goal of malaria eradication.

View all evidence materials > 

The subject for this blog is one of my favourites, which is exactly why I decided to go down this tortuous route: Gene Drive! It is based on a pre-print by Vanessa Macias et al. from the laboratory of Jason Rasgon at Pennsylvania State University. Tony James from the University of California, Irvine is also an author. It is interesting to know that both of these authors have been willing to take original and different directions from the mainstream. Dr. Rasgon provided some great insights into the mechanisms that Wolbachia cause in mosquitoes to inhibit or promote pathogens and Dr. James has been a bit of a competitor to Imperial College’s efforts on gene drive led so ably by Dr. Austen Burt.

If you have no time to read further, then this sentence from the pre-print summarizes the technique featured in the article:

“P2C-Cas9 and P2C-EGFP proteins were expressed for pET228a-P2C-Cas9and pRSET-P2C-EGFP respectively by recombinant BL21 E. coli (NEB) as described previously…”

Need I say more?

Let’s back up just a tad so that everyone knows what I am talking about. The famous CRISPR-Cas9 technique, controversially Nobel-prizeless so far, basically edits genes at precise locations on BOTH CHROMOSOMES OF A PAIR. The result is 100% expression of the modified genome, rather than the catch-and-catch-can insertion of genes and subsequent back-crossing of previous techniques. Hurray! We can make mosquitoes do or die whatever we want. Not so fast, gene jockey.

The process of getting those bits of DNA and RNA into the mosquito so that genes are permanently modified throughout the bug and all its offspring just isn’t that simple. The standard has been to inject embryos in the egg at just the right moment, using very fine glass needles and crazy-sensitive injection systems. Many embryos die, many don’t integrate the genetic material and the bottom line is that many, many eggs have to be injected and reared to get the candidate mosquitoes. Believe me when I say it takes a special sort of stamina for technicians to do this work.

What Dr. Macias and co-workers describe is a technique to inject the mother mosquito (in this case Anopheles stephensi) with the material. Such injections really have become standard for virus and other studies, sticking a fine (but less fine than to get into an egg) glass needle into the thorax of the mosquito. They showed that they could use Drosophila melanogaster egg yolk proteins mixed with the genetic components to target the entire ovaries of the mother mosquitoes. The experiment showed that they could knock out one of two fluorescent proteins that had been transgenically inserted into that strain of Anopheles stephensi. Kind of a reverse whammy. In any event, using this technique, they got about 1.5% of the offspring in the condition they intended. That doesn’t sound like much, but it would go much faster than injecting eggs and would require MUCH less skill. The authors hope that this will bring gene drive to a much wider group of laboratories.

In an ironic twist to this ultra-high-tech story, one of the essential ingredients of their brew was crude extract of Quallaja bark, a source of saponins. That doesn’t bring this work down to the common level of date syrup in ATSB, but at least it shows that a bit of alchemy is sometimes needed even in advanced genetic engineering.

As the world grapples with the COVID-19 pandemic, there is a renewed awareness of the devastating effects of infectious diseases and the need for robust health and surveillance systems. COVID-19 is testing the resilience of these systems around the world and is now moving into resource-limited settings, where its impact could be even more devastating. Malaria-endemic countries across the globe have reported cases of COVID-19 and 37 countries in Africa (which carries more than 90% of the global malaria burden) had reported cases by 5^th April 2020. Efforts to limit the spread of COVID-19 are necessary to allow health care systems to continue to serve their communities during this crisis.

At the same time, these efforts must not compromise access to life-saving malaria prevention, diagnosis and treatment services or threaten to reverse decades of hard-fought progress against malaria. Experience from previous disease outbreaks has shown the disruptive effect on health service delivery and the consequences for already vulnerable populations. COVID-19 is not the first reminder of the potentially delicate balance of global health challenges (Swine influenza in 2009, Ebola in 2014 and Zika virus in 2015) and it won’t be the last, although somehow it seems we forget and move on so quickly. Recognising this balance, the World Health Organization (WHO) has underlined the critical importance of continuing malaria prevention at this time. Ensuring access to vector control tools and products is an important strategy for reducing the strain on health systems. These vital tools include insecticide-treated nets (ITNs) and Indoor Residual Spraying (IRS) – which have been responsible for more than three quarters of averted clinical cases of malaria in the past 18 years.

In recent days, there have been reports of the suspension of vector control programmes in several African countries due to COVID-19. The WHO strongly encourages countries not to suspend the planning for or implementation of vector control activities, whilst, of course, taking all necessary precautions against spreading infection. There are also disruptions in the supply chains of essential vector control interventions, resulting from lockdowns and from a suspension of the importation and exportation of goods in response to COVID-19. Coordinated action is required to ensure the availability of these tools for the people who need them most and we are committed to contributing our expertise and networks to this end.

At IVCC, our vision is a world free of insect-borne disease, where lives are saved, and prosperity increased. Our strategy to reach this goal is to deliver a comprehensive toolbox of resistance-breaking vector control tools and to maximise their impact through market access interventions. During this time, we will continue to work in partnership with colleagues across the global health community to see this happen. The COVID-19 pandemic has demonstrated once again that we do not have all the tools needed to tackle infectious diseases and so, if anything, more innovation than ever is essential. Current investments in malaria are saving hundreds of thousands of lives and preventing millions of cases per year. This is significant progress but too many people continue to suffer and die. In 2018, there were an estimated 228 million cases of malaria worldwide and an estimated 405,000 deaths – of which two thirds were children under five in Africa. As long as malaria exists, it threatens the poorest and most vulnerable and has the potential to resurge in times of public health crises – like the one we are facing now.

Against the backdrop of COVID-19 it could be easy for malaria to be forgotten by the international community and for vital resource allocation to suffer, so we are incredibly grateful for the continued support, guidance and work of all our funders and partners. In recognition of the importance of not taking our foot off the pedal with malaria eradication, our funders have encouraged us to continue to support partners through the challenges of COVID-19. It is difficult to apply blanket rules but we are taking a flexible and pragmatic approach to adjusting workplans and contracts to ensure the continuation of delivery of programs; supporting reasonable costs to ensure that essential resources and expertise remain in place; and considering, in good faith, requests to re-profile and revise project budgets, timelines and milestones. It is due to this commitment by us all to stay the course, even in these unprecedented times, that we will reach a malaria-free world.

Our thoughts remain, always, with people in malaria-endemic countries, our partners globally and our colleagues – we hope that you stay safe and well, and remain committed to playing our part in that.

Breakthroughs in disease control have arisen through leaps in understanding and completely new methods of control. For example, the discovery by Sir Ronald Ross in 1897 that malaria is transmitted by mosquitoes and the subsequent use of insecticides to control them. Incremental improvements in tackling mosquitoes have involved many smaller innovations, for example the introduction of control flow valves for compression sprayers which enable walls to be sprayed more accurately and consistently with insecticide to maximise the impact on mosquitoes that transmit malaria.

IVCC keeps watch for new ideas in vector control and receives many innovative proposals for development and testing of new products. There is a need to choose those most likely to have a strong impact on disease transmission, short time to deployment, low cost of development, high probability of success and good fit with IVCC’s priorities for vector control. Once these innovations have been selected, IVCC’s role is to test, guide and accelerate them towards adoption and to help maximise the benefits from their use.

An example of this is IVCC’s contribution to the U.S. Agency for International Development (USAID) ‘Grand Challenge for Zika and Future Threats’, which ran from 2017 – 2019. In this case, USAID issued a call for proposals and selected 26 innovations from over 900 submissions. IVCC helped manage 9 of these projects relating to vector control, vector surveillance and Zika virus transmission prevention. IVCC’s role was to support the projects to develop and test their technologies to tackle the principal vector of Zika virus, the mosquito Aedes aegypti. An IVCC Programme Manager, who worked closely with the projects and with USAID’s ‘Center for Accelerating Innovation and Impact’, set up a Zika External Scientific Advisory Committee (ESAC) with experts drawn from existing IVCC ESACs and supplemented by experts on Aedes aegypti. Meetings of the Zika ESAC were held at approximately 6 monthly intervals, for project updates and ESAC guidance. In addition to this, specialists were appointed to help the projects understand, evaluate and resolve their specific technical, regulatory, production and commercialisation challenges.

The diagram below shows the 12 areas in which IVCC added value to the Zika Grand Challenge projects.

IVCC’s work on Target Product Profiles (TPPs) formed the core of the guidance to the projects to help them to develop products that would combat Zika virus and future threats most effectively and to demonstrate that their innovations would be successful. These profiles define the performance criteria that eventually need to be met and hence gave the research teams a clear vision of what to aim towards.

IVCC also monitored the progress and prospects of each of the projects, regularly evaluating their Strengths, Weaknesses, Opportunities, Threats (SWOT), risks and issues. This helped with determining needs for further funding to address additional aspects of the TPPs and opportunities for development and cross-over of relevant technologies into malaria vector control.

Several projects were successful in achieving their milestones including a spatial repellent product from Sumitomo and a novel automated mosquito trap.

The spatial repellent is impregnated in a small device which can be hung from the ceiling to protect people inside the room from being bitten by mosquitoes. In a project led by QIMR Berghofer Medical Research Institute and involving Emory University and the Autonomous University of Yucatan, two seasons of trials on the mosquito Aedes aegypti in Mexico’s Yucatan peninsula demonstrated very good results, suggesting that the product could protect the population from viruses transmitted by this vector (dengue, Zika virus, yellow fever etc.). A significant and important results was that the spatial repellent was effective even in the presence of insecticide resistant mosquitoes. Further work is now funded to investigate cost effectiveness and optimum deployment.

Johns Hopkins University developed a mosquito monitoring trap that incorporates a novel system for recognition, identification and counting of the mosquitoes it catches, as well as automatic transmission of this information via a wireless network. Tests demonstrated a very high level of accuracy in identification, enabling more rapid and accurate monitoring and reduction in labour costs associated with visiting conventional traps and manually identifying their catches.

Innovation is vital to succeeding in the fight against vector-borne diseases and in collaboration with its funders and partners, IVCC is accelerating vector control innovations to save lives.