Emerging Issues and New Tools to Fight Mosquito Borne Diseases in Africa

Ian MatthewsNews, News Around Global Health

EVENT TAKEAWAYS

Held in observance of World Mosquito Day 2020, this virtual event presented the state of mosquito-borne diseases in Africa; challenges and strategies for elimination; and the latest updates on new innovations, such as vector control tools to prevent and mitigate health risks associated with mosquito-borne diseases.

The webinar brought together over 140 participants from the private sector, international NGOs, academia, government organizations, and communities affected by mosquito-borne diseases. GBCHealth and CAMA partners, Aliko Dangote Foundation, Chevron, The Global Fund to Fight AIDS, TB and Malaria, Mylan, the National Malaria Elimination Programme (NMEP), the US Centers for Disease Control and Prevention (CDC), Sanofi, Sumitomo Chemical, Syngenta and Vestergaard, among others joined the conversation.

Key messages are summarized below, followed by an overview of the discussion and responses to some of the questions submitted by webinar attendees – but not answered – during the event.

SPEAKERS 

KEY MESSAGES

  • Mosquito-borne diseases such as malaria, lymphatic filariasis, chikungunya, dengue, yellow fever, Zika, and West Nile virus contribute significantly to the high burden of communicable diseases in Africa
  • Mosquito elimination requires a multi-sector and multifaceted approach, focused on diagnosis, treatment, supportive care, prevention and more
  • Despite all the recent successes in controlling mosquito-borne diseases, we still face a number of challenges including insecticide resistance (IR), residual malaria transmission, invasion of exotic species in the African region, sustainability of interventions, entomological surveillance & monitoring, environmental risk factors including climate change, lack of quality data, and tailoring of vector control interventions to crises such as the COVID-19 pandemic, which threatens prior gains
  • The comprehensive package of malaria control interventions needs to be sustained and scaled up, including indoor residual spraying (IRS), bed nets, larva source management, larvicide, and more
  • Scaling up and implementing initiatives / products correctly are as important as developing and identifying the right interventions
  • IR is a huge obstacle to the control of mosquito-borne diseases and new products, tools and innovative partnerships are key to addressing it
  • Community ownership and input into interventions is key for long-term success, and advocacy is an important part of any malaria control intervention
  • Designing and scaling up full-spectrum interventions for malaria and other mosquito-borne diseases requires multi-sector partnerships
  • Controlling, and ultimately eliminating, mosquito-borne diseases including malaria would bring tremendous health, social, and economic benefits to people in sub-Saharan Africa and around the globe

You can watch the full webinar at this link.


WEBINAR OVERVIEW

Ochuko Keyamo-Onyige, Nigeria Country Manager, GBCHealth/CAMA, opened the session and provided context for the discussion. She shared how global efforts to fight mosquito-borne diseases have saved millions of lives and prevented billions of cases of disease, and pointed out the remaining challenges such as the economic burden of malaria and other diseases. She also laid out the goals for the discussion, including sharing effective strategies for elimination, ways to mitigate and prevent diseases, and best practices with examples of successful tools and interventions.

Michael Steinberg, Team Lead, Global Public Health & Special Projects at Chevron Corporation, and Co-Chair, CAMA, then kicked off the discussion with welcome remarks. He emphasized the need to share tools, knowledge, and solutions. He highlighted that the threat of mosquito-borne diseases is especially great in Africa, and with regards to malaria, reiterating that COVID-19 is threatening prior gains.

He discussed Chevron’s decades of partnerships for control of malaria and other diseases, and said that partnerships like CAMA are necessary to fight these diseases. Because mosquito-borne diseases are a big public health threat, he said, fighting them is an important part of sustainable risk reduction which contributes to community prosperity and other goals. He highlighted CAMA’s efforts in sharing best practices, and facilitating multi-sector partnerships towards achieving these goals.

Dr. Emmanuel Chanda, Project Officer, Vector Control, WHO Regional Office for Africa, spoke about the threat of mosquito-borne diseases in Africa and the strategies to combat them. He explained that mosquitos contribute to a high percentage of communicable diseases in Africa, and the threat is high recently with recurrent outbreaks and epidemics. Malaria has a high burden in Africa, along with dengue and other mosquito-borne disease, and there are concurrent outbreaks of various diseases across Africa currently. Dr. Chanda then discussed the WHO’s work with member states implementing integrated vector management. He says these efforts have had a multiplicity of challenges, including IR, residual malaria transmission, the emergence of exotic species, sustainability, environment / climate, surveillance and monitoring, human resources, technical capacity, lack of evidence to tailor interventions, and ability to respond to crises like COVID-19. To achieve the SDGs, UHC and other goals, we need to beat these challenges, he explained.

He discussed the WHO’s global vector control risk response which aims to reinvigorate vector management through engaging communities, collaboration, integrating interventions, and monitoring / surveillance. He then talked about key available interventions, including IRS, nets, larva source management, larvicide, and highlighted the many innovations currently under evaluation. He said providing support to member states is key, including helping countries adopt and implement WHO guidance. The WHO framework was endorsed by Ministers across Africa. WHO helps countries with advocacy strategies too, as well as to develop capacity, bring in communities, and strengthen research and regulatory frameworks.

Dr. John Gimnig, Research Entomologist, Division of Parasitic Diseases, US CDC shared the CDC’s experience with malaria and other mosquito-borne diseases, including fighting IR. He highlighted the CDC’s work with the President’s Malaria Initiative (PMI), in partnership with the U.S. Agency for International Development, on regional programs. He mentioned partnering with The Global Fund and others on LLINs as well. He said this work is part of PMI’s mandate to scale up nets, IRS, diagnostics and other therapies in sub-Saharan Africa and elsewhere.

Dr. Gimnig also discussed the role of entomological monitoring, which is used to determine impact of interventions. The monitoring also extends to IR and especially pyrethroid resistance. He highlighted the importance of the obstacle of IR, giving examples of ways it has been addressed historically. He discussed switching to other interventions such as organophosphates, and mentioned that more products are being incorporated in recent years. He mentioned CDC’s and PMI’s partnerships with the private sector, research community, and others, highlighting their dependence on the private sector throughout the process from development of interventions to delivery through supply chain partnerships.

Melinda Hadi, Head Market Access, Vestergaard, shared insights on the company’s new tools and the evidence of their efficacy. She highlighted the evidence behind the use of bed nets, and the importance of making sure the nets are still being used during the pandemic. She discussed how Vestergaard’s products are being deployed widely, and how their R&D efforts work to make sure there are options that will be effective with wild mosquitos, highlighting products that can work in the context of pyrethroid and other resistances.

She focused on the importance of having a strategy to scale up interventions, and the important role of multilateral organizations in this regard. She mentioned the company’s IR mapper tool which uses publicly available data to be a resource for the community. She reiterated that it is not just malaria, but there are increasingly common outbreaks of dengue and other diseases, and it is important to work with partners to address these diseases and determine how to develop appropriate tools for each one. Finally, she emphasized the importance of scale, highlighting recent efforts to do implementation research and to think of new interventions holistically from product development to implementation and scale-up, which has many benefits including the ability to do better cost-effectiveness analysis with the bigger picture in mind.

Dr. Rose Peter, Commercial Head, Vector Control, Syngenta, discussed the role of IRS in malaria and the company’s perspective. She said IR is key, and that new tools have shown the ability to achieve high reduction in malaria in many African contexts despite the challenges posed by IR. She mentioned the importance of working with IRS users to help design IRS programs for their community’s specific needs. Overall, she encouragingly noted that as long as we rotate products, and follow recommendations from The Global Fund and others, we can achieve success against IR. She also discussed how to best measure impacts of IRS campaigns, and the importance of focusing on key malaria indicators such as the number of cases within a season. Finally, she discussed some of the challenges and opportunities for developing new tools, mentioning Syngenta’s work with the Innovative Vector Control Consortium (IVCC) and the Gates Foundation on IRS, the broadening of the company’s portfolio to larval source management and other fields, and ended by highlighting how much research goes into the development of each product.

Manuel F. Lluberas, Public Health Entomologist, Executive Director for Public Health, H. D. Hudson Manufacturing Company, gave the closing remarks. He summarized the discussion, highlighting challenges with the pandemic being paramount. Stay-at-home-measures can lead to outbreaks of various mosquito-borne diseases. With surveillance being one of the challenges, he highlighted potential new surveillance methods. He emphasized the need for older guidelines to be updated to the latest knowledge and best practices. He challenged the participants to think about vector control beyond just malaria control, by introducing a variety of interventions, including community engagement. He warned that vector control should be integral part of emergency crisis response, as the vector control community will be needed and tapped in this response due to flooding and other reasons. He added that as a continent, Africa has the capacity at a high level – ranging from the policy makers to decision makers – to win the war against the mosquito, but what is desperately needed are mid-level and field managers to drive implementation of interventions in countries, emphasizing the need to make that connection and bridge the gap.


SUPPLEMENTAL Q&A

Pyrethroid resistance seems to be the most concerning in the fight against malaria and mosquito-borne diseases in general. Recent publications show use that reverting to non-insecticide coated nets would help reverse the effects of this e.g. Paaijmans and Huijben (2020) and Okumu (2020). What is your take on that opinion?

One of the methods to mitigate IR is to use non-insecticide-based interventions. As such, non-insecticide coated nets would play a role when deployed alongside other interventions to reduce pyrethroid resistance selection pressure on the vectors. It should be noted that resistance management is better embarked upon when resistance has not been detected. -Dr. Emmanuel Chanda

While PMI recognizes the concerns of IR, we continue to support LLINs over untreated nets. First, modeling data suggests that approximately 50% of the effect of LLINs is due to the barrier and 50% is due to the insecticide. The importance of the insecticide has been highlighted in recent studies where PBO LLINs have been shown to be more effective than pyrethroid only LLINs, at least in the context of pyrethroid resistance where a pyrethroid only LLIN likely provides little additional benefit over an untreated net. In addition to providing some extra protection for users where nets become torn or damaged, high coverage with insecticide treated nets has been associated with a community effect whereby non-users receive some protection due to the overall impact on mosquito populations. Second, while some of the loss of insecticidal effects could be ameliorated by high coverage with more durable untreated nets, we have yet to observe a net product that will substantially improve physical durability and net longevity. An untreated net that has a few holes can revert from an excellent barrier to mosquito biting to an excellent tool to trap and collect mosquitoes that have entered the net. Until we see evidence of nets that are much more resistant to damage than the current polyester and polyethylene nets on the market and are not prohibitively expensive, PMI will continue to procure LLINs, likely with PBO or non-pyrethroid actives to address the increasing pyrethroid resistance among malaria vectors in Africa. -Dr. John Gimnig

Most large-scale IRS is funded by PMI and The Global Fund. How can we increase IRS intervention across Africa beyond GF and PMI funding?

Going forward governments need to find funding. A number of countries in the E8 have already set about finding funding for elimination and both Zambia and Swaziland have set up Malaria Elimination Councils which are doing this. These organizations raise funds independently of the government even though the government is also a stakeholder. Mozambique has also launched such a fund this week (National Malaria fund). I believe that private-public partnerships will also solve this problem much like the Tchau Tchau Malaria initiative in Mozambique (funded by GF and industry). -Dr. Rose Peter

IRS is an expensive intervention that requires substantial infrastructure to implement well. The ideal way to expand IRS would be to identify other sources of funding either through national or sub-national governments or with partnerships with the private sector. PMI is also interested in finding ways to make IRS less expensive. We have partnered with the Next Gen IRS project to begin scaling up new, non-pyrethroid insecticides in the hopes of priming the market to foster competition. With new formulations of insecticides becoming increasingly available, we hope that costs will eventually come down. PMI is also experimenting with novel ways to apply IRS from engaging community based spray operators to assessing the impact of partial sprays of a house that would both reduce the cost of IRS and increase the speed at which individual houses could be sprayed. -Dr. John Gimnig

Resistance management, what new insecticides are there or in the approval Pipeline? and when are these new innovations going to be made available for large scale use?

I know of at least 3 new insecticides in the pipeline. Some of these should come onto the market in 2022. For the time being we have to use what we have in strict rotation as little or no resistance has been recorded to the organophosphates or clothianidin. -Dr. Rose Peter

Two new products are in the pipeline for use on insecticide treated nets and are currently undergoing testing and piloting in a number of countries. These include chlorfenapyr which, along with alphacypermethrin, is one of the active ingredients on the Interceptor G2. Chlorfenapyr disrupts mitochondrial activity and respiration in insects. It is a slow acting insecticide although mosquitoes appear more susceptible if they are active and therefore respiring more. Experimental hut studies are promising but larger scale trials and pilots were recommended due to the slow acting nature of chlorfenapyr. Pyriproxyfen is an insect growth regulator incorporated into the Olyset Duo and the Royal Guard. Traditionally used as a larvicide, pyriproxyfen also has sublethal effects on the adult females. In particular, females tend to show high levels of sterility and possibly reduced blood feeding and longevity. Like the Interceptor G2, these nets are undergoing pilot implementation to confirm whether these non-lethal effects can result in reduced malaria transmission.

For IRS, there have been two new products (SumiShield & Fludora Fusion) that have a neonicatinoid as an active ingredient. These have come to market and are being implemented as part of PMI’s IRS activities. Another product in the pipeline is an IRS formulation of chlorfenapyr. Also, under development is a non-pyrethroid developed by Mitsui Chemical for use both in IRS and on LLINs (Tenebenal). Lastly, there have been some promising studies on a mechanical insecticide which can be applied as an IRS formulation (Imergard WP). -Dr. John Gimnig

Resistance management of the LLINs, what new nets are there or in the approval pipeline? 

Recently, two types of ITNs with two active ingredients have been prequalified by WHO. Interceptor® G2– a dual AI net treated with the pyrethroid alpha-cypermethrin and the pyrrole insecticide chlorfenapyr and Royal Guard®– a dual AI net containing the pyrethroid alpha-cypermethrin and the insect growth regulator pyriproxyfen. -Dr. Emmanuel Chanda

The objective of IR management is primarily to preserve the susceptibility of mosquito vectors to insecticides in order to maintain the effectiveness of insecticide-based vector control interventions. More research is required to determine the role LLINs could play in resistance management. Two pyrethroid-PBO LLINs, PermaNet® 3.0 and Olyset® Plus, have demonstrated efficacy against pyrethroid resistant mosquitoes and have been included in randomized control trials (RCTs) to assess their public health value. LLINs that combine a non-pyrethroid and a pyrethroid, Interceptor® G2 and Royal Guard®, are currently being assessed in RCTs and pilot deployments within the New Nets Project. Given the aims to address widespread pyrethroid resistance, it is essential that all PBO and dual active ingredient products have efficacy data to support their product claims.

More information on the new nets involved in the New Nets Project can be found on the IVCC website: https://www.ivcc.com/market-access/new-nets-project/

The list of currently WHO prequalified LLINs and other vector control products can be found here: https://www.who.int/pq-vector-control/prequalified-lists/en/ -Melinda Hadi

Is there a monitoring framework in place to ensure objectives are met by 2030?

The progress in implementation of the key activities of the Framework on the Global Vector Control Response (GVCR) in WHO [African region] will be monitored by mandatory reporting to the Regional Committee of the Ministers of Health from Member States every two years. -Dr. Emmanuel Chanda

Regarding new innovations on bed nets, when are these new innovations going to be made available for large scale use. It looks like mosquitoes are building resistance faster than new products being introduced into the toolbox for insecticide rotation

The development of resistance in mosquitoes is worrying and in order to not repeat the same situation we are finding ourselves in with the reliance on pyrethroids, innovation in LLINs, IRS, and other vector control interventions must be encouraged and supported. With widespread pyrethroid resistance, PBO LLINs and dual AI nets that are effective against pyrethroid resistant mosquitoes must be implemented now to minimize the impact of resistance on malaria. As new bed nets subsequently become available and prequalified in the future, the choice of products in the toolbox will ideally increase so that malaria control programs can select the optimal interventions given the epidemiological and entomological setting. -Melinda Hadi

We are experiencing misuse of treated bed nets. Do we dig deep on why there are misuse and prepare to mitigate it when we introduce the next generation bed net?

We, as the malaria community, should dig deeper to understand the types and causes of misuse. Thus far, the evidence on misuse of bed nets vary widely depending on the settings and environments where bed nets are deployed. Given the investment into next generation LLINs, ensuring they are acceptable and used by the community is essential to achieving reduction in malaria cases and deaths. -Melinda Hadi

Are there cultural and religious challenges encountered with the acceptability of ITNs in local communities in sub Saharan countries?

Cultural, social, and religious beliefs may have an impact on the acceptability and usage of ITNs across communities. With the support of effective education and social behavioral change communication (SBCC) conducted by the malaria control programs and partners, ITNs are generally an acceptable intervention in malaria endemic countries. -Melinda Hadi

Would we be able to cover breeding places of Anopheles mosquitoes using larvicides?

Covering all breeding places for Anopheles species whose breeding characteristics tend to be ubiquitous particularly in the rain season would not be feasible. It is recommended that larviciding be done during the dry season when the breeding sites are few, fixed and findable. In this regard, for Anopheles stephensi, larviciding would be feasible as this is an urban vector that breeds in artificial containers. -Dr. Emmanuel Chanda

Does WHO recommend the use of space spray insecticides for vector control in malaria campaigns?

Space spraying is not recommended for malaria vector control due to very-low certainty evidence for public health value and the risk of exacerbating selection of resistance in malaria vectors. When used in response to other mosquito-borne diseases such as dengue, caution should be taken and should be used in the context of IR management. -Dr. Emmanuel Chanda

Elaborate on the achievements made so far with respect to the GVCR since it was developed in 2017?

Countries are conducting Vector Control Needs Assessments (VCNAs) and updating their integrated vector management (IVM) strategies including IR management plans, established multi-sector collaboration and coordination, strengthening their surveillance, data management and incorporation of data into routine health information systems. WHO Prequalification Team for vector control is working with regulatory agencies in countries to ensure availability of quality vector control products. Countries are collaborating with the Innovation to Impact (I2I) to optimize registration of vector control products at country level. -Dr. Emmanuel Chanda

A recent paper in Nature Communications implied that in Papua New Guinea PermaNet had changed in their efficacy in the past 10 years (with a concomitant increase in malaria). As I understand it this might be due to the manner in which the WHO tests are conducted – these nets work in the tunnel test but not in standard bioassay. Is standard bioassay still a measure of efficacy or is the tunnel test now considered sufficient

The Guidelines for Laboratory and Field Testing of LLINS (WHO, 2013) describe the limitation of cone tests. Both cone and tunnel tests are considered standard WHO bioassays. -Melinda Hadi

What is PMI’s perspective on providing vector control to hard to reach areas, such as conflict zones and humanitarian crises? 

PMI does not specifically provide support in conflict zones or humanitarian crises other than what is routinely provided for malaria services in most countries. However, PMI generally has substantial flexibility in how money allocated to target countries can be used and in the event of a humanitarian crisis, PMI may be able to redirect resources in an emergency. For example, PMI has provided support for the Ebola response in West Africa to ensure that services for malaria prevention and control were not interrupted. In the recent outbreak in the Democratic Republic of Congo, PMI provided insecticide treated nets and mass drug administration to reduce the malaria case load experienced in clinics that were overburdened due to Ebola. In the aftermath of Cyclone Idai, PMI distributed insecticide treated nets to people who had lost their homes and mobile clinics were on hand to provide treatment services. -Dr. John Gimnig

Ian MatthewsEmerging Issues and New Tools to Fight Mosquito Borne Diseases in Africa