Malaria Cases Rise as Insecticide Resistance Spreads

The World Health Organisation (WHO) has alerted to rise in malaria cases and the fears of resurgence as progress in the fight against a curable disease that kills hundreds of thousands of children has stalled.

The WHO, in a recent report, said the number of malaria cases rose in many countries in 2016, suggesting that progress has halted in the global fight against the disease.

The apex United Nations (UN) health agency found that globally, malaria infections increased by about five million from 2015 to 2016, for a total of 216 million, with apparent jumps in parts of Asia, Africa and South America and that the number of people who died from the disease remained relatively steady, at around 445,000.

According to the World Malaria Report released last week, Nigeria is one of the three African countries that recorded an increase in malaria cases of more than 500,000 in 2016, compared to 2015. The report also highlighted Nigeria’s leader position in percentage terms of global malaria cases (27 per cent) and malaria deaths (30 per cent) – more than double the percentage of the next highest ranked country, the Democratic Republic of the Congo.

However, what the report does not show is the looming crisis for Nigeria’s anti-malaria efforts: a US$582 million (N23 billion) funding gap for the National Malaria Strategy (NMS) 2018-2019, which will prevent 13 states from receiving malaria prevention, testing, and treatment services. Without these interventions and treatments, malaria deaths, which already are the number cause of deaths in Nigeria, could surge.

Consequently, Nigeria has been urged to prioritize malaria funding with the World Bank IDA18 loan request.

There is a short-term opportunity to fill this funding gap with US$300m in World Bank IDA18 financing. These funds, would help Nigeria meet the Global Fund’s co-financing requirement and unlock an additional US$38 million for malaria control, and would be co-invested alongside a US$275 million Global Fund grant (2018-2020) and an expected annual US$75 million to be invested by the U.S. President’s Malaria Initiative.

The allocation agreement between the World Bank and Nigeria is expected to occur on December 12.

Stakeholders are unanimous that the IDA funding is critical to help prevent a looming crisis for Nigeria’s anti-malaria efforts.

Although data on malaria is often inexact in countries with weak health-care systems, many researchers are concerned by the trends described in the WHO report, which the agency attributes to flat funding levels for anti-malaria programmes.

Director of the Global Malaria Programme at the WHO in Geneva, Switzerland, Pedro Alonso, said: “For the first time, we can confidently say that we have stopped making progress.” Alonso is worried that governments and donors have become complacent about malaria, given that deaths from the disease fell by an estimated 62 per cent between 2000 and 2015. “We know what happens when we stop applying pressure,” Alonso said. “Malaria comes back with a vengeance.”

Meanwhile, the largest ever-genetic study of mosquitoes reveals the movement of insecticide resistance between different regions of Africa and finds several rapidly evolving insecticide resistance genes.

According to the study published in the journal Nature, this genetic resource will be used to develop new tools for monitoring resistance and managing insecticide use, and for designing novel control methods.

Mosquitoes transmit malaria and rising resistance to insecticides is hampering efforts to control the disease. The study by researchers from the Wellcome Trust Sanger Institute and their collaborators also discovered that wild mosquitoes collected in Africa were genetically far more diverse than had been thought. This helps to explain how mosquitoes evolve insecticide resistance so quickly.

Earlier genetic analysis of mosquito populations in Africa showed that recent successes in controlling malaria through treated bednets has led to widespread insecticide resistance in mosquitoes.

The study led by Charles Wondji of the Liverpool School of Tropical Medicine, with Kayla Barnes, Gareth Weedall and colleagues was published in journal PLOS Genetics.

Also scientists at the Nigeria Institute of Medical Research (NIMR), Yaba, Lagos, had in June revealed that mosquitoes in 18 states in Nigeria have developed resistance to the LLIN insecticide nets, with Lagos, Ogun and Niger state having the highest incidence of cases.

Other states where the resistance were also detected include Jigawa, Katsina, Kebbi, Sokoto, Zamfara, Benue, Kwara, Nasarawa, Plateau, Anambra, Enugu, Rivers, Ondo, Osun and Oyo state, with the outcome of the study identified as a major threat to the eradication of malaria in Nigeria by 2030.

The Nigerian National statistics showed that malaria accounts for 60 per cent of hospital outpatients visits, 25 per cent infant deaths, 30 per cent of under-five deaths and 11 per cent of maternal mortality annually, although, currently, the prevalence of malaria in Nigeria is 27 per cent.

According to the WHO, more than 200 million people are infected with the malaria parasite worldwide each year, which is transmitted by blood-sucking Anopheles mosquitoes. Malaria caused the deaths of around 429,000 people in 2015 with the majority of cases in sub-Saharan Africa.

Public health measures in Africa such as insecticide-treated bed nets and insecticide-spraying have helped reduce the numbers of malaria cases since 2000, but many mosquitoes have evolved resistance to insecticides. This is now threatening to derail malaria control in Africa.

To understand how mosquitoes are evolving, researchers working with the Anopheles gambiae 1000 genomes project sequenced the Deoxy ribonucleic Acid (DNA)/genetic material of 765 wild Anopheles mosquitoes. These were taken from 15 locations across eight African countries, creating the largest data resource on natural genetic variation for any species of insect. They then examined each of the mosquito genomes.

The researchers revealed that the Anopheles gambie mosquitoes are extremely genetically diverse compared with most other animal species. High genetic diversity enables rapid evolution and the study found 52 million small differences amongst the mosquito genomes.

A corresponding author on the paper and Faculty at the Wellcome Trust Sanger Institute, Dr. Mara Lawniczak, said: “The diversity of mosquito genomes was far greater than we expected. Such high levels of genetic variation poise mosquito populations to rapidly evolve in response to our efforts to control them whether that be with insecticides or any other control measure, including gene drive.”

New strategies to control mosquitoes are being developed that use ‘gene drive’- using the latest Crispr/Cas 9 genetic tools to make mosquitoes infertile or unable to carry the malaria parasite. However, this technology requires an exact match with any targeted gene. The researchers found that gene drive is unlikely to work for most mosquito genes because they are too variable in nature, however they also used the data to highlight less variable targets that are potentially more suitable for gene drive based methods to control mosquitoes.

The mosquito genomes also revealed rapid evolution of several genes that had previously been implicated in insecticide resistance. Unexpectedly, the researchers discovered many previously unknown genetic variants within those genes that could be causing insecticide resistance. Worryingly, they showed that these genetic variants for insecticide resistance were not only emerging independently in different parts of Africa, but were also being spread across the continent by mosquito migration.

When governments listed malaria reduction as one of the United Nations’ Millennium Development Goals in 2000, billions of dollars in funding flowed in from the Global Fund to Fight AIDS, Tuberculosis and Malaria and other donors, and death rates began to drop. One of the strongest pushes involved getting the gold-standard cure for the disease — pills called artemisinin-combination therapies (ACTs) — to remote regions. Children are at particularly high risk of death if malarial fevers are not treated within a couple of weeks.

Strategies for lowering the cost of ACTs to less than a few dollars per treatment course and to distribute the drugs to health workers have been relatively successful over the past decade. The Global Fund estimates that the malaria-control programmes it has helped to fund have provided 668 million malaria treatments.

And the spread of rapid diagnostic tests for malaria have likely helped to delay the development of drug resistance, by limiting the number of children who are treated for suspected, but not confirmed, cases of the disease. The percentage of suspected cases tested in sub-Saharan Africa — the region hit hardest by malaria — increased from 36 per cent in 2010 to 87 percent in 2016.

That does not mean that everyone who needs treatment is getting it. Between 2014 and 2016, 39 per cent of African children under the age of five who developed fevers were not taken to a trained health-care provider, the WHO report says, citing household surveys. The percentage of children receiving care for fevers is often used as an indication of how many may have sought treatment for malaria, although it is an imperfect measure.

“If you ask me, the number-one priority must be to ensure that people stop dying of a disease that is entirely curable,” says Alonso.

The spread of drug-resistant malaria is also a worry. Strains of Plasmodium falciparum, the parasite that causes the most deadly form of the disease, have become resistant to artemisinin in Thailand, Cambodia, Myanmar, Laos and Vietnam.

Southeast Asia accounts for just three per cent of the world’s malaria cases. But if drug-resistant malaria spreads from Asia to Africa, where 90 per cent of P. falciparum cases occur, it would wreak havoc, says Nick White, a malariologist at the Mahidol Oxford Tropical Medicine Research Unit in Bangkok, Thailand. “There is a narrow window of opportunity to eliminate malaria in Southeast Asia before we lose the drugs, and it’s shutting,” White says. “Time is running out.”

Nonetheless, the money available for malaria-elimination programmes has been dropping. A review of 75 malaria resurgences between 1930 and 2011 found that most upticks in the disease followed funding disruptions that weakened malaria-control programmes. Other causes included conflict and natural disaster.