What is the current status of the malaria epidemic? A conversation with Dr James Kelley from WHO’s Regional Office for the Western Pacific

Our guest this week is Dr James Kelley, Team Lead for Malaria and Vector-borne Diseases in the World Health Organization’s Western Pacific Regional Office. In honour of World Malaria Day 2023, Dr Kelley describes the status of the epidemic globally and in the Indo-Pacific Region. 

We also discuss:

• Getting the Global Technical Strategy target of reducing global malaria incidence and mortality rates by at least 90% by 2030 back on track.
• Recent developments in malaria prevention technologies, including new insecticide-treated nets and malaria vaccines.
• The potential impact of increased urbanisation on malaria risk.
• Progress on antimalarial drug resistance in the Greater Mekong subregion.

You can read more about the Global Technical Strategy here and the latest World Malaria Report here. We encourage you to join the conversation on Twitter at @CentreHealthSec. You can follow Dr Kelley on @JFKWPRO. 

Transcript

Please note: We provide transcripts for information purposes only. Anyone accessing our transcripts undertake responsibility for assessing the relevance and accuracy of the content. Before using the material contained in a transcript, the permission of the relevant presenter should be obtained.   

The views presented in this podcast are the views of the host and guests. They do not necessarily represent the views or the official position of the Australian Government. 

Camilla Burkot 00:26

Welcome to Contain This. I’m Camilla Burkot, senior technical adviser in the Australian Government’s Indo-Pacific Centre for Health Security. Every year since 2008, the 25th of April has been recognised by the global health community as World Malaria Day. The objective of the day is to raise awareness and galvanise partners to maintain momentum in the fight against a disease which still affects too many lives. The official theme of World Malaria Day 2023 is “time to deliver zero malaria: invest, innovate, implement”. Australia works with partner governments in our region to support malaria elimination, in addition to investing in regional and global malaria initiatives, such as the Asia Pacific Leaders Malaria Alliance, the Global Fund to Fight AIDS, TB and Malaria and efforts led by the World Health Organization. In line with this theme, on today’s episode we take a look at the current shape of the malaria epidemic globally and in the Indo-Pacific Region, and progress on issues such as antimalarial drug resistance in the Greater Mekong Subregion. We also consider some of the recent developments in malaria prevention technologies, including new insecticide-treated nets and malaria vaccines, and the potential impact of increased urbanization on malaria risk. To talk about what it might take to reach zero malaria, I’m joined by Dr James Kelley, Team Lead for Malaria and Vector-borne Diseases in the World Health Organization’s Regional Office for the Western Pacific.

Thanks for joining us today, James. Could you describe what your role is in the WHO regional office for the Western Pacific?

Dr James Kelley 01:52

So I'm happy to be here. Thanks for inviting me. My name is James Kelley. I am the current team leader for malaria and vector borne diseases, including dengue and other arboviruses. Here at the WHO regional office for the Western Pacific, based in in Manila, Philippines. I've been here around six years, two years as team lead, and working to support countries on developing strategies to meet targets of the global technical strategy of WHO and their national strategies to eliminate malaria and other vector borne diseases. And also, a big part of our work is working with countries to develop and disseminate global guidance, guidelines, technical strategies, and normative basically normal normative guidance role and partner coordination, funding mobilisation for countries through global fund and things like that. This is the year for Global Fund renewal. So we're quite busy supporting countries on their global fund development process, funding requests. So that's, that's who I am kind of what I've been doing here at the region.

Camilla Burkot 03:11

The reason we're recording this podcast now, part of the reason is, we've just had World Malaria Day, on the 25th of April. So wanted to sort of take the opportunity to really dive into what's happening in relation to malaria in our region. So I wanted to start off by asking you a little bit about the epidemiological trajectory, the World Malaria Report, which is published in December every year, last year reported, there were an estimated 247 million cases of malaria globally in 2021. And that is an increase on in 2020 245 232 million and in 2019. So I guess the question is, what should we conclude is the global fight against malaria going in the wrong or the right direction?

Dr James Kelley 04:01

Yeah, in brief, I would say wrong direction. But I want to add some content and context around that. I mean, when we look at the data from 2019 to 2020, in a very short time period, we see that there has been an increase, obviously, in the number of malaria cases over the past few years. This trend is certainly a cause for concern, as obviously malaria remains a significant public health issue, particularly in countries with limited resources. So globally speaking, when we look at trends over a longer period of time, to see if we are actually going in the right direction in terms of eliminating malaria controlling disease reducing burden. We can look at some of longer-term cases, maybe from a decade ago, comparing from 2021. And we actually see more of a marked reduction in overall morbidity and mortality. For example, from 20, from 2000 to 2015 globally, there was a pretty good trend with a steady decrease from around I think, 245 million to 230 million in the 108 endemic countries in 2000. So unfortunately, since 2015, starting in 2016, cases increased. And the largest increase that was observed or reported, was around 13 million cases between 2019 and 2020. And this was coincided of course, with COVID-19 pandemic. This increase, you know, between this period was, was obviously high, and then the year after the increase was considerably smaller, with 2 million additional cases increasing. So overall, this, you know, we attribute to around 13 million cases to the pandemic and that trend, obviously, it's only two years, but that trend, which was so high at the beginning of the pandemic is now coming down. So overall, there has been significant progress in reducing malaria related deaths globally, and that's a positive note. And that's sort of a proxy for health systems improving and more timely reporting, more timely diagnosis and treatment and other preventive strategies. But this number was around 620,000 in 2010, globally, and it's reduced to around 465 or so in 2021. So this is about a 25% reduction in malaria related deaths over the last decade. And if we look at the numbers more broadly, we're about midway. And in relation to the global technical strategy, the WHO global technical strategy for malaria, which in which has an end date of 2030, we're now about midway between 2016 and 2030. And much as much of the effort remains to meet the global targets, strategies, targets of at least 90% reduction in global mortality and morbidity while eliminating malaria from 35 countries. So there's still a lot to do. And at this point, data and modelling that are reported in the World Malaria report point to being significantly off track to meet the GTS targets. So some of the drivers leading to the current status include challenged health systems access in different degrees of quality of care, and really imperfect tools and biological threats, which we can talk about limited financing and increasing costs globally, and other disruptions such as health emergencies, political unrest, and climate change. So there's, again, as I mentioned, there's a lot to be done. I think, overall, the focus to get back on track, will be really political leadership, that translates into action and resources, maximising the impact of available financing and interventions, such as sub national tailoring of activities, and really identifying the most vulnerable and hard to reach populations that can show impact and really reduce cases. And these people are really being missed. So one of the efforts are really needed to overcome the barriers that they face, also affected partnership at all levels, including implementers, donors, partners, and innovation and researchers and new tools and the ability to address biological threats. So that's sort of, in summary, not doing great in terms of the GTS targets, I think we are off track. But I think now that we are post pandemic, efforts are being made to sort of reverse those trends and get back on track.

Camilla Burkot 08:57

So that's, that's a really helpful summary of the status of at the global level. And what about at the regional level in the Asia Pacific is, as is it broadly, does that sort of reflect the global trends or what have we seen in in this sub region?

Dr James Kelley 09:12

Sure, yeah. So Malaria is endemic in nine countries in the Western Pacific region. And I'll focus on Western Pacific because obviously, that's where I am, who also has Southeast Asia Regional Office, which is sort of subdividing Asia Pacific region in Western Asia, but Western Pacific region are accounting for nine endemic countries and the number of cases across the region, it's been relatively stable with the slight reduction in the near term. So in 2021, there were roughly 1.5 million confirmed malaria cases, which is down from about 1.7 reported in 2020. Still, as reported in the recent World Malaria Report, the region did not achieve the GTS 2020 milestones for morbidity or mortality, and in 2021 case incidents and the mortality rate were off target quite significantly. So, when we look, you know, say for example, between 2015 and 2021 region, why the case incidents increased 10% and mortality rate by 4%. So at the current trajectory, malaria cases and deaths in the region are predicted to reduce by 12% and 24%, respectively by 2023. But this is well short of the targets of 90%. So, yeah, there's still work to be done. But I would like to emphasise in our region, the lack of reduction in cases and deaths is primarily due to an increased trend in Papua New Guinea, which accounts for about 87% of the malaria burden in the region. And we also saw an increase in case incidents in the Solomon Islands since 2015 by more than 40%, which also accounts for around 10% Of all the cases in the region. But on a positive note, China was certified malaria free by who in 2021 and Malaysia reported zero malaria cases for the fourth consecutive year in 2020. Of course, this doesn't count for the zoonotic malaria Plasmodium knowlesi, which Malaysia is reporting over 2.5 to 3000 cases of zoonotic malaria year but decreases in case incidents of more than 40% was reported in all other countries in the region except Vanuatu, in 2021, compared with the GTS 2015 baseline, but I must note that in Vanuatu, it was affected by several tropical storms in 2015. And more recently, last year, that I think people are aware of and this severely disrupted malaria diagnostic services and treatment seeking options. So I think it's likely that cases have been underestimated in Vanuatu. If we look at Cambodia in the Greater Mekong sub region, which is also part of our mandate in the Western Pacific, Cambodia, and Lao PDR, and Vietnam, was supported the WHO Mekong malaria elimination programme have demonstrated massive gains towards the elimination of falciparum malaria. And this was an effort put out to really prevent anti-malarial drug resistance, which in the Greater Mekong sub region is a primary concern. Cases have decreased year over year in some areas in the GMS by more than 80%, which is a phenomenal achievement by the countries. I think, overall, we see pretty good trend, there's still a lot of work, but it depends on where you're looking at also in the region, as I mentioned in the Pacific is more challenging, we're seeing more increase in incidents, whereas in the GMS. In the Greater Mekong, we see a decrease in incidence. So overall data suggest progress has been made, there's still a lot of work to do, while accelerating intensification strategies and other countries to reach malaria elimination.

Camilla Burkot 13:17

Yes, actually a lot of variability. And, and it's a good reminder, you mentioned Vanuatu, we're always, you know, increasingly conscious of the impacts of these weather events and climate change, affecting, affecting progress, as well as all those health systems and governance and politics and financing issues. I want to turn to talk a little bit about prevention and some of the tools that are that are available and are coming online. You know, historically, insecticide treated nets have been one of one of the most powerful or impactful tools that we've seen for malaria prevention, and the Global Malaria programme, who recently recommended the use of some new dual active ingredient nets. Can you tell us a little bit about those? What are some of the key opportunities or the potential challenges that they're having these new nets available might present? 

Dr James Kelley 14:12

So insecticide treated nets, as you mentioned, or what we call long-lasting insecticide treated nets, LLINs, or ITNs, indeed, have been one of the most effective tools in preventing malaria cases, particularly and high burden areas where transmission is high. The use of ITNs can significantly reduce malaria incidence among vulnerable populations, such as pregnant women and children. And as you mentioned, who has recently recommended the use of new dual active ingredient nets. And these nets contain two insecticides, which sort of act together synergistically or together to prevent the spread of malaria. And some of the chemicals used the one being what's known as pyrethroid is the most common insecticide in ITNs. It works to kill adult mosquitoes that come in contact with the nets. And then there's another chemical pyriproxyfen. It's an insecticide growth factor that targets larvae of the mosquito preventing them from developing into adult mosquitoes that can transmit malaria. So, the combination of these two insecticides is expected to provide greater protection against malaria transmission, rather than using pyrethroid alone. And as pyrethroid resistance becomes more widespread, and increases in intensity nets with new chemistries are really needed. Fortunately, there has been progress in this area. So an example of one of these nets is pyrethroid together with piperonyl butoxide or PBO. And this has led to the development of pyrethroid PPO ITNs which have been shown to have a higher efficacy than pyrethroid only nets and these nets these PBO nets are now recommended by who they are two other pyrethroid combination ITNs under evaluation by who alpha–cypermethrin and pyriproxyfen ITNs and alpha–cypermethrin chlorfenapyr ITNs. Chlorfenapyr targets the mosquitoes mitochondria, stopping respiration at the cellular level and thus killing the mosquito. So there was a recent trial done in Tanzania comparing the effectiveness of pyrethroid only nets with these other types of pyrethroid combination nets, and it showed that overall the combination ITNs performed better at preventing malaria infections in children. However, the difference was only statistically significant for the chlorfenapyr combination. Obviously, one of the key opportunities presented by these new dual active ingredient nets is the potential for greater protection against malaria. The use of pyriproxyfen can also help reduce the number of adult mosquitoes in the environment, which can help reduce obviously, forward malaria transmission. And as mentioned, the use of dual active ingredient nets may help reduce development of insecticide resistance, which is a significant challenge in many endemic areas. Still, the use of these nets may present some potential challenges. One main concern is the cost, which is often higher than traditional ITNs. And this may limit their availability and use particularly in areas with limited resources. There may also be some logistical challenges in distributing these new nets to remote areas with limited infrastructure and resources. But really, this is the same for traditional LLINs or ITN so the distribution challenges aren't new. So really, but but one thing worth noting, I think, is the importance to continue to monitor and evaluate the effectiveness of these new dual use nets as they are being rolled out to to really determine to know if they're effective and worth, sort of the bang for the buck in terms of the costing and impact of use.

Camilla Burkot 18:25

Another new technology that seems to be coming onto the scene is the potential for vaccines against malaria. We know there's a there's a one vaccine that has received a WHO recommendation, I believe in 2021, the RTSS vaccine. There are also a couple of national regulators that have approved use of the R21 vaccine that doesn't yet have a WHO recommendation. Interested to know, what you see is potentially the role that that malaria vaccines might play alongside, you know, ITNs and all these other tools that that already exist.

Dr James Kelley 19:11

Yeah, so this is it's a very interesting topic. And it's created a lot of buzz in the malaria world. Obviously, any vaccine, which could be considered sort of a silver bullet, is it's very welcomed. But it's worth noting and highlighting that these vaccines that are being developed, although very good, innovative tools that can be used, shouldn't be necessarily perceived as a silver bullet. So the deployment, the development and deployment of the vaccines against malaria, obviously, it's really important and to eliminate the disease. And as you mentioned the most the two most recent vaccines, receiving the most attention are the RTSS in the R21. The RTSS with the AS 01 adjuvant is it's received a recommendation for the use in countries from who for use in young children and highly endemic countries or high endemic countries. It's undergone already extensive clinical trials; it's been shown to be effective in preventing malaria reducing the incidence by almost 40% over a four-year period in young children. The R21 with the matrix M adjuvant is it's a promising vaccine candidate that is currently being developed by a team of researchers from University of Oxford and the Serum Institute of India. The vaccine is the R21 is a virus like particle. It's a protein-based vaccine and it targets the circumsporozoite protein or CSP of the of the malaria parasite, which is found on the surface of the sporozoites which are the parasites that are injected sporozoites are injected into the human body by infected mosquitoes. So in 2021, the results from the phase two trial two B trial of the R21 were published in The Lancet journal, and it involved over 400 children in Burkina Faso, and it showed that the vaccine had an efficacy rate of 77% After 12 month follow up. So that's good. And the trial also showed that the R21 vaccine was well tolerated and had no safety concerns. So following these promising results, the R21 is now moving into phase three, which will involve almost 5000 children across four African countries. And the trial will be conducted by who and the vaccines developers who hope to have the vaccine approved by us by 2024. So as you mentioned there, Ghana and Nigeria have their national regulatory authorities have approved the use of the R21. Although who has not seen the dossier submitted to the regulatory agencies for approval, but still, ultimately, the role of the malaria vaccines will play that they will play in conjunction with other tools, including ITNs and IRS, it will really depend on a number of factors including the efficacy and safety of the vaccines, the cost, and the availability by the manufacturers of the vaccines as well as the other interventions. So, you know, the deployment of the vaccines against malaria is an important step forward in the global effort to control and eventually eliminate the disease. But I just want to emphasise again that the vaccines are definitely not 100% effective. And additional measures and tools as mentioned, ITNs and IRS, bed nets they are still required really to control malaria. The vaccines are just one tool in the toolkit, and will not be the silver bullet to eliminate malaria. All other tools will be needed in conduct in conjunction with the vaccine particularly strong case management, tools for vector control and surveillance to detect treat and prevent all malaria cases.

Camilla Burkot 23:13

You mentioned vector control just then and then I went to the turn to entomology, a brief foray into entomology. You know, another thing that the world malaria report flagged was the incursion of anopheles stephensi, into Africa. And wondered if you tell us a little bit about that development and what makes that development potentially problematic?

Dr James Kelley 23:40

Sure, yeah anopheles stephensi is a species of mosquito that is known to transmit malaria, primarily in Asia and the Middle East. It's a highly adaptive and resilient species of mosquito, and it's well adapted to urban environments. As you mentioned, the 2022 World Malaria report described the incursion of stephensi into Africa, which is problematic for several reasons. Firstly, anopheles stephensi as I mentioned, is highly efficient. It transmits both plasmodium vivax and Plasmodium falciparum species, which are the two malaria species, obviously, that infect humans, the incursion of stephensi into Africa could lead to an increase of transmission in urban areas. And this this could be difficult, difficult to control because it's new, it's not something that necessarily the governments or malaria programmes have had to encounter and control. Secondly, anopheles stephensi is well adapted as I mentioned, to urban environments, and this in itself could facilitate its spread and the spread of malaria. Unlike other species of mosquitoes that tend to breed in rural or semi-rural areas. Anopheles stephensi is capable of breeding in small stagnant water bodies that are commonly found in urban environments, such as discarded containers, flower pots and gutters more like the 80 species that transmit other vector borne diseases such as dengue. This measure really means that the mosquito could rapidly spread in urban areas and make it very difficult to control. And thirdly, anopheles stephensi resistance to some of the insecticides that are commonly used to control mosquitoes. This resistance has been observed in several parts of Asia, and there is concern that it could spread to Africa further complicating efforts to control the spread of the mosquito. So overall, the incursion of anopheles stephensi into Africa is a cause for concern as it could lead to an increase in transmission of malaria in urban areas. And this really highlights the need for increased vector surveillance and control measures in these urban areas as well as the development of new tools, insecticides and strategies to control the spread of the mosquito. And in terms of the effort in in the relevance to the Western Pacific region, I mean, yes, there is a threat of urban malaria in some areas and we need to be concerned about that in the region. Although malaria is typically associated with rural areas, as we know in our region as well urbanisation itself in the migration of populations into urban areas, this creates new opportunities for malaria transmission. anopheles stephensi, as I mentioned, it's very adaptable, and it can thrive in these urban environments and doesn't need a lot of you know, traditionally known breeding sites that are typically used in vector control for malaria. So, it breeds quite easily in these urban areas. So, yeah, so I think in several factors that contribute to the emergence and spread in the region, really or anywhere really is this what I mentioned urbanisation, but also for housing and sanitation conditions, some issues around climate change that increase the breeding sites or might affect the breeding sites in urban areas, and the emergence of drug resistance malaria strains. So, urbanisation has led to the growth of more slums and informal settlements, and they lack maybe adequate sanitation are prone to water logging, or other areas, other activities that could, you know, induce or promote the spread of the mosquito. So, so yeah, to address the threat of, of sort of urban malaria in the in the Western Pacific region, I think it's going to take a comprehensive approach. Combining strategies such as, you know, like I mentioned, improved vector surveillance, diagnosis and vector control and access to effective treatment. And this should also be improved with improved living conditions in urban areas trying to support economic development and improve sanitation and housing, and address underlying social and economic factors really, that contribute to the spread of malaria. So more taking a holistic approach, we can reduce the threat of urban malaria and improve the health and well-being of communities in the region. Currently, WHO strategies including the global vector control response strategy, and other integrated vector management strategies tried to address this, who currently recommends that countries increase vector surveillance and delineate the geographical spread of anopheles stephensi and use data to implement interventions aimed at preventing its further spread, especially into urban and Peri urban areas. Also important, I think research institutions and implementers implementing partners, of course, are encouraged to immediately report any detection of anopheles stephensi to ministries of health and to who and inform a national and global response effort. And I think for listeners, if you're interested in this there, there is plenty of documentation and guidance on anopheles stephensi and other topics that we've talked about provided online, through WHO websites, there's WHO vector documentation and online resources.

Camilla Burkot 29:38

Thanks, James, I think you know, one of the things the world of malaria, there's so many different technical aspects, right? Like there's this the entomology, the vector control, the insecticides, the treatments, the diagnostics, there's so much to get into, what I really appreciate that you've brought out there too, is also that we are, we need to always be keeping in mind the social and the structural determinants of health that's really underpinning people's risk for malaria, and also a huge part of of how we're going to be able to continue to move towards better control and eventually elimination or eradication of malaria. The concerns around anti-malarial drug resistance really emerge out of the greater Meek Kong, can you give us a bit of an update on what's happening there, in terms of anti-malarial drug resistance and progress towards eliminating falciparum malaria.

Dr James Kelley 30:36

It’s a very important point anti-malarial drug resistance. And it's something that has justified a lot of attention to eliminate falciparum malaria from the Greater Mekong sub region, because the falciparum parasite is the parasite that is showing genetic mutations that are able to resist the current first line and second line anti-malarial drugs in some cases in some countries, and who supports country to monitor drug resistance through therapeutic efficacy studies. And what it does is it follows certain signal sites to track number of cases throughout the year to detect the number of parasites after they are given treatment. And they're followed up every day, or certain number of time points after treatment to determine parasite load. And what we've seen as over time is that you know, drug resistance has become a problem for first line in some cases, up to three first line drugs and second line drugs have become resistance in certain countries and in the Greater Mekong. So, fortunately, what has been done is active effort to eliminate falciparum from the Greater Mekong sub region, through intensified aggressive approaches, including active surveillance, active case detection and treatment, active fever screening, and really being active in the intensified strategies that countries are doing to reach the unreached or targeted populations where malaria transmission is occurring. And what we found and what countries have determined is that most of the transmission in the Greater Mekong sub region is found in people that travelled to the forest to harvest or to work or farm, they will live in these camps and work for several weeks and come back to their villages. And then transmission might happen within the villages. So countries in the sub region have really taken measures and develop intensified strategies with support of who in the Mekong malaria elimination programme to develop strategies to really target these populations, map them understand where they are, identify them, and then outreach activities for training for education, as well as vector control, distribution, active case detection and treatment, and so on. So I think it's just worth mentioning that this is a success that we've seen in the region, and we've really seen a reduction in incidence in these countries from these efforts. And the side benefit is that even though the target parasite has been falciparum malaria we've seen In a also quite a substantial reduction in the other species of malaria. So it just shows that with intensified effort. Malaria can be eliminated or impact can be shown. So I just wanted to highlight that point.

Camilla Burkot 34:00

That concludes today’s episode of Contain This, recorded in honour of World Malaria Day 2023. You’ve been listening to Dr James Kelley, Team Lead for Malaria and Vector-borne Diseases in the WHO Western Pacific Regional Office. Dr Kelley described the status of the epidemic globally as well as in the Indo-Pacific Region specifically. He also discussed the impact of increased urbanisation on malaria risk, recent developments in prevention technologies, progress on drug resistance in the Greater Mekong Subregion, and getting the Global Technical Strategy target of reducing incidence and mortality rates back on track. I’m Camilla Burkot from the Indo-Pacific Centre for Health Security. Thanks for listening. 

Contain This is produced by the Indo Pacific Centre for Health Security. We acknowledge the Traditional Owners and Custodians of Country throughout Australia and the Indo Pacific region. We recognise their continuing connection to land, waters, and community and pay our respects to Elders past and present. You can follow us on Twitter @centrehealthsec.