The insects are coming. But the world is unprepared.

Several countries in Asia are grappling with thousands of dengue cases this year, and one of the potential culprits is climate change. Factors contributing to surges in dengue cases include increased vector density due to gradual increases in temperatures, erratic rainfall, and urbanization — all of which have links to climate change, said Neelika Malavige, head of the dengue global program and scientific affairs, India, at the Drugs for Neglected Diseases initiative, or DNDi. But it’s not just dengue. Overall malaria transmission in Africa, which accounts for 96% of all malaria deaths globally, is “likely” to increase due to climate change, putting an additional 76 million people in southern and eastern Africa at risk of malaria by 2080, the latest U.N. Intergovernmental Panel on Climate Change report states. And diseases, such as the human African trypanosomiasis, or HAT, known as sleeping sickness, could put an additional 46-77 million people at risk by 2090, according to one study. But despite these gloomy projections, the tools to protect populations from these diseases, as well as funding on climate change’s impact on many of them are limited, according to Julie Archer, senior manager of scientific and public health communications at DNDi. “[O]ne of the challenges of evaluating the impact of climate change on [neglected tropical diseases] is the lack of funding for this research – that’s where the N in NTDs comes in – neglected! Some NTDs have little to no research on the impact of climate change, and HAT/sleeping sickness doesn’t have loads,” she told Devex via email. “If money was pumped into dengue like COVID, we would have several treatments right now for dengue.” --— Neelika Malavige, head of the dengue global program and scientific affairs (India), Drugs for Neglected Diseases initiative Within the United Nations Framework Convention on Climate Change discussions, health is also “very rarely mentioned,” said Rachael Crockett, DNDi policy advocacy manager. Innovations to tackle climate-sensitive diseases are not included in discussions at this year’s 27th U.N. Climate Change Conference, or COP 27, she added. There are side events dedicated to health at the upcoming conference, but experts don’t expect it to be part of main negotiations, despite the close links between health and climate. The health community however is working to ensure health is “reflected in government positions on existing agenda items” at COP 27, Jess Beagley, policy lead at the Global Climate and Health Alliance, wrote in an email to Devex. "While health side events at COP have grown significantly in number from year to year, not least on account of a dedicated health pavilion hosted by the World Health Organization, there is no negotiation stream focused exclusively on health,” she said. Neglecting the neglected There’s a dearth of tools to combat many of these climate-sensitive diseases. One example is dengue. According to a Lancet report in 2020, changes in climate for the past eight decades have led to an increase in dengue transmission, and this is likely to further increase over time. And per the IPCC report, an additional 2.25 billion people in the world could be at risk of dengue by 2080 if temperatures rise to 2.6 degrees Celsius. Although the majority of infections are mild, some can still suffer from a severe disease, which can lead to serious illness and death. However, there are no treatments for dengue, and only a limited number of vaccines is available. Dengvaxia, the first vaccine to be approved for use, is only recommended for people who have had dengue before and it’s not used in many countries, such as in the Philippines where it faced controversy over alleged links to deaths due to immunization, which led to vaccine hesitancy. A new vaccine, Qdenga, developed by Japanese pharmaceutical company Takeda, meanwhile, has so far only been approved in Indonesia. “If money was pumped into dengue like COVID, we would have several treatments right now for dengue,” Malavige said. Another example is leishmaniasis, a parasitic disease spread by infected female phlebotomine sand flies that some scientists have warned of spreading in more areas in the U.S. There are several forms of leishmaniasis, the most severe form being visceral leishmaniasis, which can be fatal when left untreated, according to the World Health Organization. There are several treatment options for leishmaniasis, but it varies by form and region, and access can be difficult in some countries. In eastern Africa, where there are frequent outbreaks of visceral leishmaniasis, the current standard treatment includes a combination of paromomycin, an injectable antibiotic, and sodium stibogluconate, which is administered via injection or intravenously. But this is not ideal, as patients may suffer from rare but heavy side effects such as damage to the heart and liver, and inflammation of the pancreas associated with sodium stibogluconate. This treatment is also difficult to administer, as it requires patients to endure two injections every day for 17 days, said Archer. “[W]hat works in India doesn’t necessarily work in Kenya. This is due to the many different species of the parasite in the different regions, which respond to treatment very differently. The Indian sub-continent has an extremely successful elimination programme and numbers have been dropping every year in India, Bangladesh, and Nepal. However, Eastern Africa can only dream of that, for the moment,” she said. Miltefosine, the only approved oral drug for leishmaniasis, can be expensive and supply challenges can occur due to the limited number of manufacturers. It’s also not recommended for pregnant women because of its potential to cause fetal harm. DNDi is hopeful that a combination of miltefosine and paromomycin would allow patients to spend less time in the hospital for visceral leishmaniasis treatment and reduce side effects associated with sodium stibogluconate. According to results of a phase three clinical trial conducted in eastern Africa and released in late September, the combination therapy is over 91% effective in treating visceral leishmaniasis, and lowers the risk of dermal leishmaniasis, a common complication. Apart from this, DNDi has six new chemical entities in its research and development pipeline that Archer said holds “great promise for future short-course oral regimens.” Many of these diseases are already not getting enough investments in the biomedical market. “There's no market incentive. Pharmaceutical companies aren't going to get rich necessarily off of developing drugs for these diseases,” Archer said. But observed and predicted increases in the incidence and transmission of some of these diseases in high-income countries could spur investments and innovations. However, Crockett is concerned that equity will become another challenge, as seen with COVID-19 and monkeypox. “The biomedical [research & development] system is already failing these neglected populations,” Archer said. “Without changes to the policies that shape this R&D system, we're going to continue to see this issue [where] innovation will almost be … a privilege of the rich, while these populations in already burdened countries, particularly in the global south, will be the hardest hit by these climate sensitive infectious diseases,” she said. R&D as climate adaptation tools Diagnostics and medicines aren’t always thought of as climate adaptation tools. But DNDi thinks they should be, especially with the threat of climate-sensitive diseases becoming more widespread, and reaching new regions and areas where existing tools might not be available, or work. The key question however for organizations like DNDi is how to get the global attention needed for a set of diseases that have been neglected for so long. Some of them have very low cases worldwide, like sleeping sickness, which only had 980 cases in 2019. But that’s still far from elimination, and the world needs to prepare for when cases start appearing in places where health care practitioners may not be aware of them, have never seen a patient sick with one, and don’t have the tools to test and treat them. According to a study published in 2021, sleeping sickness has already been observed to shift its geographical distribution in Kenya, increasing in highland areas. A 2018 study on the vector population of sleeping sickness in Mana Pools National Park in Zimbabwe suggests that temperature increases have resulted in decreases in local populations of tsetse flies, but that may have made some higher, cooler parts of the country more suitable to the vector population. Other infectious diseases too — not just those spread by insects — could spread in other areas due to climate-driven migration. “This is exactly what the team that I'm in is looking at — how to … frame this in a way that makes people kind of understand what is coming and what then needs to be done now to be able to address that,” Crockett said. That will need to reach high-income countries that aren’t as affected now as lower-income countries but could experience more cases in the coming years and decades. “Until something threatens you, although it's a threat to somebody else, people don't seem to sort of get it,” Malavige said.