Tag: Malaria

Why The Malaria Vaccine Quickly Loses its Effectiveness

Image source: Ekamalev at Unsplash

More than 600 000 people worldwide still die from malaria every year, according to the WHO. The vast majority of fatal cases of malaria are caused by the single-celled pathogen Plasmodium falciparum, which so far has only one approved vaccine against it, and its efficacy, which is already rather low, is also short-lived. A new study in Science Immunology may have the explanation: a lack of cross-reactivity in T helper cells.

The vaccine targets CSP, the quantitatively dominant protein on the surface of the “sporozoites”. Sporozoites are the stage of the malaria pathogen which is transmitted with the bite of the mosquito and enters human blood. “To improve the vaccine, we need to understand which protective antibodies are induced by the immunisation. But the production of such antibodies depends to a large extent on help from the so-called follicular T helper cells,” explained Dr Hedda Wardemann, immunologist and senior author of the study. “They ensure that B cells transform into antibody-producing plasma cells and memory B cells.”

To study the T helper cell response against CSP in detail, Dr Wardemann’s team examined the blood of volunteers infected with killed P. falciparum sporozoites from the vaccine strain. The volunteers were of European descent and had no prior contact with malaria pathogens. The researchers analysed the induced Plasmodium-specific follicular T helper cells at the single cell level. They focused on which sequences of CSP are recognised by the T helper cells’ receptors.

The analyses revealed that the T-cell receptors mainly targeted amino acids 311 to 333 of the CSP. But the researchers were stunned by another finding: there was virtually no cross-reactivity between the individual T-cell clones. “The receptors highly specifically bind only the CSP epitopes of the vaccine strain used. Even deviations of only a single amino acid component were not tolerated in some cases,” Dr Wardemann explained.

The immunologist points out that in the natural population of P. falciparum, sequence polymorphisms occur to a high degree in this region of the CSP. “The specificity of the T-cell clones prevents the constantly recurring natural infections with the pathogen from acting as a natural ‘booster.’ This could possibly explain why the protective effect of the malaria vaccine wears off so quickly,” Dr Wardemann said. The researcher recommends that further development of the vaccine should test whether inducing a broader spectrum of T helper cells could generate longer-lasting immune protection.

Source: German Cancer Research Centre

Rollout of World’s First Malaria Vaccine in Sub-Saharan Africa

Mosquito, a malaria parasite vector
Photo by Егор Камелев on Unsplash

The world’s first malaria vaccine will soon be available across sub-Saharan Africa, according to PATH, partners of the vaccine developers, as positive results from the pioneering jab pile up.

The vaccine, known as RTS,S/AS01E and commercialised under the brand name Mosquirix, targets children as over three quarters of malaria deaths occur in under-five-year olds, according to the latest report from the WHO.

Findings from a WHO pilot held in Ghana, Kenya and Malawi, showed that the pioneering vaccine caused a significant reduction in severe malaria and hospitalisation among vaccinated children.

It means more countries in sub-Saharan Africa will soon receive the vaccine, says John Bawa, Africa lead for vaccine implementation at Program for Appropriate Technology in Health (PATH).

These findings pave the way for an expanded distribution scheme that will see countries like Mozambique, Nigeria and Zambia receive the vaccines, said Bawa during a webinar held in commemoration of World Malaria Day.

“The next is to deploy the vaccine to other endemic countries. Countries that are interested in the vaccine are expected to apply to GAVI from June to September,” he said at the webinar organised by the African Media and Malaria Research Network (AMMREN), PATH and Kintampo Health Research Centre (KHRC).

“Countries like Mozambique, Uganda, Zambia and Nigeria have already written officially to express interest for the vaccine,” Bawa said.

He said malaria vaccine coverage in Malawi was at 88% in 2020 and 93% in 2021. In Ghana, it was 71% in 2020 and 76% in 2021 and in Kenya, it was 69% in 2020 and 83% in 2021.

“These numbers indicate strong community demand and capacity of childhood vaccination platforms to effectively deliver the vaccine to children,” said Bawa.

Currently, 1 million children in Ghana, Kenya and Malawi have received at least one dose of the first malaria vaccine.

These vaccines were distributed in a pilot scheme organized by WHO. The organisation has now recommended the vaccine for use among children in areas with moderate to high transmission rate of malaria.

“This vaccine is not just a scientific breakthrough, it is life-changing for families across Africa. It demonstrates the power of science and innovation for health,” WHO Director-General Dr Tedros Adhanom Ghebreyesus said.

Vaccine procurement

In an arrangement to boost vaccine supply and coverage, GlaxoSmithKline, producers of the RTS,S vaccine, will transfer technology and patent to Bharat Biotech in India to manufacture the vaccines.

The WHO, in a press release, said more than US$155 million has been secured from to support the introduction, procurement and delivery of the malaria vaccine for Gavi-eligible countries in sub-Saharan Africa.

The organisation said it would provide guidance for countries that are considering the use of vaccines for the reduction childhood illnesses and deaths from malaria.

“For some countries, Gavi is paying about 80% [of the] cost of the vaccine, while it is expected that the country’s government would pay the [remaining] 20%,” Bawa said.

Wellington Oyibo, director of the Centre for Malaria Diagnosis, Research, Capacity Building and Policy at the University of Lagos, urged African leaders to ensure that their counterpart funds are available to purchase the vaccine.

He said the Nigerian government and the Prince Ned Nwoko Foundation malaria eradication project have applied to purchase the vaccine for Nigerian children.

Oyibo said while the initial rollout of the vaccine may not go around the country, the Nigerian government selected states with the highest malaria burden to begin with.

Reproduced under a Creative Commons Attribution License.

Source: SciDev.Net

Malaria’s Growing Resistance Requires New Insight

Mosquito, a malaria parasite vector
Photo by Егор Камелев on Unsplash

To deal with malaria’s growing resistance to existing drugs, researchers are exploring new areas of the deadly parasite’s life cycle. Research published in PLOS Pathogens has identified key processes the malaria parasite uses to remodel blood cells it hides inside.

Senior author Paul Gilson, an associate professor at Burney University, said the growing resistance to antimalarial medicines needs to be addressed soon to avoid serious treatment failures in the future.

“It’s only a matter of time before resistance becomes so bad that current measures perhaps become worthless,” he said.

“Current drugs tend to target very similar things. By discovering new targets and developing drugs to these, we can hopefully overcome resistance.

“Our research identifies processes in the parasites that are essential for its survival. And the more we understand about those processes, the better position we’re in to develop new treatments to block those processes.”

The research, A/Prof Gilson explains, looked into the nature of malaria parasites, particularly their need to renovate their host blood cells to grow rapidly and to escape the immune system.

The dynamic is analogous to an international arrivals terminal in need of better security.

“The renovations are carried out by special exported proteins made by the parasite that are only allowed to travel into the blood cell if they have the right passport,” he said.

“We used to think that gateways around the parasite called PTEX acted like immigration officers at the airport only allowing exported proteins with the right passports to pass through.

“What this study now shows is that the immigration officers appear to leave the airport and travel inside the parasites to check the exported protein passports not long after they are first made.

“The officers then pair up with their exported proteins and take them to the airport to let them go straight through into the blood cells.”

A/Prof Gilson said that hopefully, a greater understanding of the ways parasite proteins enter and modify blood cells could result in new drugs that block exported proteins from carrying out essential renovations to their blood cells.

The COVID pandemic has disrupted and set back malaria elimination programs in several countries, making the need for new drug developments to combat the disease all the more vital.

“Many countries only have very limited resources, and it’s estimated that there’s been quite a big increase in the number of malaria cases around the world because so much effort has been diverted to combat COVID,” he said.

Even though COVID has taken the global spotlight, A/Prof Gilson said that malaria is still a major issue. In 2020 there were an estimated 241 million cases of malaria worldwide, with an estimated 627 000 deaths, according to World Health Organization figures.

A/Prof Gilson said that over recent years significant inroads have been made in eliminating malaria, pointing out that annual death rates were in the millions at the start of the 21st century.

“We can’t let COVID undermine all the great work that’s been achieved over the years, as we aim to one day totally eliminate malaria.”

“Research into new drugs to combat malaria parasites, which are becoming resistant to existing drugs, is a crucial part of these efforts.”

Source: Burnet Institute

Paracetamol May Protect Against Kidney Damage in Malaria

Anatomic model of a kidney
Photo by Robina Weermeijer on Unsplash

Paracetamol may help protect against kidney damage in patients with malaria, according to a study recently published in Clinical Infectious Diseases.

The study found that for patients with severe malaria caused by the malaria parasite Plasmodium knowlesi (the most common cause of malaria in Malaysia), taking paracetamol regularly for 3 days led to improvements in kidney function when tested one week later.

The findings are important because they will help provide the best possible treatment to patients with severe malaria, said study leader Dr Daniel Cooper.

“Even minor kidney injury can have long-term effects, so anything we can do to minimise kidney injury from malaria will be beneficial for these patients’ long-term outcomes,” Dr Cooper said.

In collaboration with international partners, the study involved 396 people with knowlesi malaria in Sabah, Malaysia.

Assistant Professor Bridget Barber said that in severe malaria, red blood cells can rupture, releasing haemoglobin which can have a toxic impact on kidneys, and it is now believed that paracetamol can help to mitigate these toxic effects.

“These results are consistent with other studies conducted in patients with other forms of malaria, including in adults in Bangladesh, and in children in Africa. Importantly, these findings also suggest that paracetamol may help to protect the kidneys in other conditions that are also associated with rupture of red blood cells,” A/Prof Barber said.

Source: MedicalXpress

NICD Warns of Malaria Being Misdiagnosed as COVID

Photo by Егор Камелев on Unsplash

The National Institute for Communicable Diseases has warned that, as South Africa enters its peak malaria season, cases of malaria are being misdiagnosed as COVID. Both malaria and COVID have similar non-specific early symptoms such as fever, chills, headaches, fatigue and muscle pain. Undiagnosed and untreated malaria rapidly progresses to severe illness and can be fatal.

Speaking at a media briefing on Wednesday, principal NICD medical scientist Dr Jaishree Raman said that Gauteng has seen a slight increase of malaria cases recently. 

Dr Raman noted that COVID “has pulled resources from the malaria programmes, reducing active surveillance and case investigation, which is reducing the ability [to] classify cases accurately.”

However, the NICD does not know the exact source of the malaria. “Data cleaning and case classification is ongoing, so at the moment, we cannot say whether the uptick in cases is due to locally-acquired or imported malaria,” she said.

The NICD advises that any individual that prevents with fever or ‘flu-like illness, if they reside in a malaria-risk area in Limpopo, KwaZulu-Natal and Mpumalanga or have travelled to a malaria-risk area, especially Mozambique, in the past six weeks, must be tested for malaria by blood smear microscopy or malaria rapid diagnostic test. If they test positive for malaria, the patient must be started on malaria treatment, immediately.

The NICD also advises patients to remember to inform their healthcare provider of their recent travel, especially to neighbouring countries and malaria risk areas in South Africa.  

‘Taxi malaria’, transmitted by hitch-hiking mosquitoes, should be considered in a patient with unexplained fever who has not travelled to a malaria-endemic area, but is getting progressively sicker, with a low platelet count.

Source: NICD

World-first Malaria Vaccine Receives WHO Recommendation

Photo by Егор Камелев on Unsplash

The World Health Organization (WHO) is recommending widespread use of a new malaria vaccine among children in sub-Saharan Africa and in other regions with moderate to high P. falciparum malaria transmission. The vaccine, known as the RTS,S/AS01 (RTS,S or Mosquirix), has been trialled in three countries in a pilot programme involving 800 000 children.

Though the vaccine only offers moderate protection against malaria, with 36% protection against malaria cases among children. One study estimated that even with realistic vaccine coverage, at a constraint of 30 million doses, 5.3 million cases and 24 000 deaths could be prevented among children under five, .

“This is a historic moment. The long-awaited malaria vaccine for children is a breakthrough for science, child health and malaria control,” said WHO Director-General Dr Tedros Adhanom Ghebreyesus. “Using this vaccine on top of existing tools to prevent malaria could save tens of thousands of young lives each year.”

This comes amid stagnation in progress in recent years against the deadly disease. In sub-Saharan Africa, malaria remains a primary cause of childhood illness and death. More than 260 000 African children under the age of five die from malaria annually.

“For centuries, malaria has stalked sub-Saharan Africa, causing immense personal suffering,” said Dr Matshidiso Moeti, WHO Regional Director for Africa. “We have long hoped for an effective malaria vaccine and now for the first time ever, we have such a vaccine recommended for widespread use. Today’s recommendation offers a glimmer of hope for the continent which shoulders the heaviest burden of the disease and we expect many more African children to be protected from malaria and grow into healthy adults.”

The WHO recommends that in the context of comprehensive malaria control the RTS,S malaria vaccine be used for the prevention of P. falciparum malaria in children living in regions with moderate to high transmission as defined by the WHO. This vaccine should be provided in a schedule of 4 doses in children from 5 months of age for the reduction of malaria disease and burden.

The outcome of the pilots informed the recommendation based on data and insights generated from two years of vaccination in child health clinics in Ghana, Kenya and Malawi. Findings include:

  • Vaccine introduction is feasible, improves health and saves lives, with good and equitable coverage of RTS,S seen through routine immunization systems. This occurred even in the context of the COVID pandemic.
  • RTS,S enhances equity in access to malaria prevention.
  • Data from the pilot programme showed that more than two-thirds of children in the 3 countries who are not sleeping under a bednet are benefitting from the RTS,S vaccine.
  • Layering of tools results in over 90% of children benefitting from at least one preventive intervention (insecticide treated bednets or the malaria vaccine).
  • Strong safety profile: To date, more than 2.3 million doses of the vaccine have been administered in 3 African countries – the vaccine has a favorable safety profile.
  • No negative impact on uptake of bednets, other childhood vaccinations, or health seeking behavior for febrile illness. In areas where the vaccine has been introduced, there has been no decrease in the use of insecticide-treated nets, uptake of other childhood vaccinations or health seeking behavior for febrile illness.
  • High impact in real-life childhood vaccination settings: Significant reduction (30%) in deadly severe malaria, even when introduced in areas where insecticide-treated nets are widely used and there is good access to diagnosis and treatment.
  • Highly cost-effective: Modelling estimates that the vaccine is cost effective in areas of moderate to high malaria transmission.

Next steps for the WHO-recommended malaria vaccine will include funding decisions from the global health community for broader rollout, and country decision-making on whether to adopt the vaccine as part of national malaria control strategies.

The pilot programme was financed through collaboration between Gavi, the Vaccine Alliance; the Global Fund to Fight AIDS, Tuberculosis and Malaria; and Unitaid.

Source: WHO

Azithromycin Protects Pregnancies in Countries with Malaria

Photo by Hush Naidoo on Unsplash

A review has found that the common antibiotic azithromycin taken during pregnancy reduces low birth weight and premature births in countries where malaria is endemic.

The systematic review of 14 studies in African and Asia, published in The Lancet EClinicalMedicine, found that azithromycin, reduced low birth weight and prematurity but didn’t lower infant deaths, infections and hospital admissions.

Azithromycin, an inexpensive antibiotic widely used to treat chest and ear infections, has been specifically used in the past in pregnancy to treat STIs and, alongside other antimalarial drugs, to prevent adverse consequences of malaria on maternal and foetal outcomes and caesarean wound infections.

Murdoch Children’s Research Institute (MCRI) researcher Dr Maeve Hume-Nixon said it was not clear whether azithromycin would improve perinatal and neonatal outcomes in non-malaria endemic settings, and the potential harm on stillbirth rates needed further investigation.

Dr Hume-Nixon said these findings emphasised the importance of similar MCRI-led research currently being done in Fiji.

“This review found that there was uncertainty about the potential benefits of this intervention on neonatal deaths, admissions and infections, and potential harmful effects on stillbirth despite biological reasons why this intervention may have benefits for these outcomes,” she said.

“Therefore, results from studies like ours underway in Fiji will help to better understand the effect of this intervention on these outcomes.”

The Bulabula MaPei study is a randomised controlled clinical trial testing if azithromycin given to women in labour, prevents maternal and infant infections.

Globally, infections account for 21% of 2.4 million neonatal deaths per year and 52% of all under-five deaths, disproportionately occurring in low- and middle-income countries.

About five million cases of pregnancy-related infections occur in mothers each year as well, resulting in 75 000 maternal deaths.

MCRI Professor Fiona Russell said the large clinical trials in Africa and Asia, along with the MCRI-led trial in Fiji, were likely to inform global policy related to maternal child health and hopefully benefit infants and mothers around the world.

“Administration of azithromycin during labour may be a cheap and simple intervention that could be used to improve neonatal death rates in low and middle-income countries, alongside strengthening of maternal child health services,” she said. “This study, together with other large clinical trials, will add to evidence for the consideration of new international maternal and child health guidelines.”

Source: Murdoch Childrens Research Institute

New Antimalarial Compound Traps Parasites in Cells

Photo by Егор Камелев on Unsplash

To combat the growing resistance of malaria to current treatments, researchers at the Francis Crick Institute and the Latvian Institute of Organic Synthesis have designed a new antimalarial compound which interrupts the malaria parasite life cycle by trapping them in their host cells.

While drugs and mosquito control have reduced levels of malaria over recent decades, with malaria being effectively wiped out in North America by the 1950s, the parasite still kills over 400 000 people every year, 90% of whom live in sub-Saharan Africa. It has now developed resistance to many existing antimalarial drugs, meaning new treatments that work in different ways are urgently needed.

If we can effectively trap malaria in the cell by blocking the parasite’s exit route, we could stop the disease in its tracks and halt its devastating cycle of invading cells.
Mike Blackman

The researchers developed an array of compounds designed to prevent the parasites bursting out of blood cells, a vital replication step. One compound in particular was found to be very effective in human cell tests.

“Malaria parasites invade red blood cells where they replicate many times, before bursting out into the bloodstream to repeat the process. It’s this cycle and build-up of infected red blood cells which causes the symptoms and sometimes fatal effects of the disease,” says Mike Blackman, lead author and group leader of the Malaria Biochemistry Laboratory at the Crick.  

“If we can effectively trap malaria in the cell by blocking the parasite’s exit route, we could stop the disease in its tracks and halt its devastating cycle of invading cells.”

Blocking the parasite’s emergence

The compound works by blocking an enzyme called SUB1, needed for them to burst out of cells. Current antimalarials kill the parasite within the cell, so the researchers hope this alternative drug action will overcome the resistance the parasite has acquired.

The compound can penetrate both the cell wall and the compartment within where the parasites reside.

The researchers are further refining the compound making it smaller and more potent. Further tests are needed before it can be trialled in humans.

Study author Chrislaine Withers-Martinez and researcher in the Malaria Biochemistry Laboratory, said: “Many existing antimalarial drugs are plant derived and while they’re incredibly effective, we don’t know the precise mechanisms behind how they work. Our decades of research have helped us identify and understand pathways crucial to the malaria life cycle allowing us to rationally design new drug compounds based on the structure and mechanism of critical enzymes like SUB1.

“This approach, which has already been highly successful at finding new treatments for diseases including HIV and Hepatitis C, could be key to sustained and effective malaria control for many years to come.” 

Source: Francis Crick Institute

Novel Magnetic Technique Detects Malaria in Blood

A new magnetic method has been developed that can detect malaria, leading to faster, accurate and cheap diagnosis of the deadly disease.

An international study field-tested this new tool in Papua New-Guinea, in the hopes of helping the fight against this disease, which had 229 million reported cases in 2019, with 700 000 deaths a year.

“Malaria is easily treated but it is actually hard to diagnose, and because of that there can be over-treatment, which we have seen can lead to the spread of drug-resistant malaria,” said Dr Stephan Karl, a Senior Research Fellow in Malaria and Vector Biology at James Cook University’s Australian Institute of Tropical Health and Medicine.

“Improving malaria diagnosis, especially through the development of practical methods for resource-limited places, is important and timely,” he said.

An international team including the University of Augsburg’s Professor Istvan Kezsmarki, with the PNG Institute of Medical Research and the Burnet Institute, came up with the magnetic detection method, called rotating-crystal magneto-optical detection (RMOD).

When malaria parasites break down blood, the haeme molecules are aggregated by the parasites into biocrystals called haemezoin, which contain magnetic iron. This iron can is detectable by the RMOD method.

“I’ve studied the magnetic properties of malaria infected blood since 2006, and we engaged with Professor Kezsmarki’s team in 2013 to demonstrate the sensitivity of this test using human malaria parasites,” Dr Karl said.

A field study was successfully conducted, involving almost 1000 suspected malaria patients in a high-transmission area of Papua New-Guinea.

“After years of in-lab optimisation of the device, in collaboration with Dr. Karl we demonstrated the great potential of RMOD in fast and reliable malaria field tests performed in Papua New-Guinea,” Prof Kezsmarki said.

“We showed that RMOD performs well in comparison to the most reliable existing method..It’s very promising, as RMOD testing can be conducted after a short training session and provides test results within 10 minutes. From a funding perspective the cost is very low since no expensive reagents are used,” said Dr Karl.

Dr Karl said the aim was to refine the design until a test could be done by a simple button push.

Source: Medical Xpress

Journal information: L. Arndt et al, Magneto-optical diagnosis of symptomatic malaria in Papua New Guinea, Nature Communications (2021). DOI: 10.1038/s41467-021-21110-w

Africa has 94% of All Malaria Cases

On November 30, the World Health Organization released this year’s World Malaria Report. Providing an up-to-date overview of the current global malaria disease burden, it also tracks investment, innovation and research against malaria.

Globally, malaria deaths have steadily declined over the years 2000–2019, from 736 000 in 2000 to 409 000 in 2019. The percentage of total malaria deaths that were children under 5 years of age was 84% in 2000 and 67% in 2019.

Six African countries accounted for 51% of global cases, with Nigeria (27%) contributing more than the other five countries combined. Partly this is due to its large relative population size compared to the rest of Africa, having over 200 million citizens.

Elsewhere, great progress is being made, The largest reduction in cases in the WHO South-East Asia Region was seen by India, from about 20 million cases in 2000 down to approximately 5.6 million in 2019.  Sri Lanka has been certified malaria free since 2015.

Source: Outbreak News Today