“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.