Latest news with #Plasmodiumfalciparum
The Hindu
5 days ago
- Health
- The Hindu
Major study says malaria reinfection creates special immune cells
In a groundbreaking discovery that could reshape our understanding of the immune system and pave the way for revolutionary new vaccines and drugs, scientists have characterised a previously less-understood immune cell with powerful regulatory functions. They have found that immune cells called T R 1 cells play a dominant role in mounting an immune response to malaria. The implications of the study, published in the journal Science Immunologyon April 25, are far-reaching, potentially opening new pathways to conquer not only malaria but many other 'difficult' infections for which we currently lack effective vaccines. Lines of defence The human immune system has a complex multi-layered defence against infections. Its arsenal of weapons includes numerous components and subcomponents with precisely defined tasks to execute. They must also coordinate with each other to ensure the response is effective and minimises self-harm. When an infectious agent breaches the first layers of defence (skin and mucosae), specialised arms of the immune system respond. The first among them is innate immunity: it acts against any threat non-specifically, while activating other arms of the system, which are collectively called adaptive immunity. In addition to acting against a threat, adaptive immunity stores a record of the molecular signature of the threat, or antigen, with help from the memory cells. Every antigen has specific memory cells. When they recognise an antigen they've encountered before, they accelerate and enhance the immune response. This adaptive immunity has two important subcomponents. Antibody-mediated humoral immunity is mediated chiefly by B-cells while cell-mediated immunity involves the T-cells. The real heroes The new study, led by Jason Nideffer of Stanford University, focused on a subtype of T-cells called CD4+ cells. They are also called helper cells because they help activate B-cells, T-cells, and immune cells like macrophages during an immune response. The team examined helper cells in children and adults who have suffered malaria multiple times. One subset of helper cells are the type-1 regulatory T-cells, or T R 1 cells. Another subset of helper cells are the T H 1 cells. The study was conducted in eastern Uganda, where the malaria parasite Plasmodium falciparum (Pf for short) is perennially transmitted. Ugandan children under 5 years of age often suffer three to five episodes of malaria every year. After multiple episodes, they become clinically immune by about 10 years of age: i.e., they don't develop symptoms despite getting infected by Pf again. The researchers have surmised that Pf-specific helper cells play a crucial role in developing this clinical immunity. Specifically, for many years, malaria textbooks said that the human body responded to a Pf infection by mounting a 'classic' immune response mediated by CD4+ T H 1 cells. But by sequencing more than 500,000 single CD4⁺ T-cells and tracking their genetic barcodes, the researchers found that T R 1 cells are the real heroes. While they make up only around 3% of resting CD4⁺ cells, they account for almost 90 % of all Pf-specific helper cells. This forces us to rethink what an effective anti-malarial T-cell response looks like. Technique that turned tables The research team took advantage of an ongoing three-year study called Malaria in Uganda Systems Biology and Computational Approaches study (MUSICAL). The study is trying to understand malaria in Uganda using advanced systems biology and computational approaches. Investigators follow the participants with regular surveillance, including blood smear, quantitative PCR tests, peripheral blood mononuclear cell sampling. In the new study, the researchers tracked helper-cell clones through multiple infections in humans to assess their long-term stability and the efficiency with which they could facilitate an immune response inside the body over hundreds of days. (Helper cells that respond to the same antigen are said to be clones of each other.) The first unique feature of the study was its longitudinal nature. All previous studies on the subject have been cross-sectional, i.e. studying a population at one point in time. Longitudinal studies are more challenging since they require repeated biological sampling, active case-finding, and long-term follow-ups of participants. The researchers used an advanced technique called single-cell RNA and T-cell receptor (TCR) sequencing to track the relative proliferation of different CD4+ T-cell clonotypes (clones derived from the same ancestor cell), their changes afterwards, and whether they multiplied in the same ways after every infection. Together, these data connote the cells' memory potential (how well they remember) and clonal fidelity (how well they make copies of themselves). This was the second unique feature of this study. Previous studies on the CD4+ T-cell response to malaria were based on characterising them using enzyme-linked immunosorbent spot assays or flow cytometry-based approaches, which have many inherent limitations. As a result, researchers have thus far had trouble confirming whether the T R 1 cells induced by malaria were a bona fide class of helper cells distinct from other T H 1 cells. Follow the barcode By sequencing memory CD4+ T-cells before, during, and multiple times after repeated episodes of malaria, the researchers acquired an unbiased picture of CD4+ T-cells' memory in the body. To perform its specific functions, each cell needs specific proteins. The sequencing technique reveals which proteins a cell is making. Call it a genetic barcode that the sequencing reads to reveal the cell's current state. The team found that nearly all clonotypes displayed a strong preference for one of seven subsets of CD4+ T-cells. This finding was made possible by the team's use of single-cell genomics in vivo. Perhaps the biggest finding was that the T R 1 cells also displayed high average clonal fidelity. The study also identified T R 1 cells as the dominant CD4+ T-cell subset induced after paediatric malaria and that they are capable of long-term memory with clonal fidelity upon reinfection. Sequence samples in the same individuals also revealed many clonotypes at multiple time points that retained their fidelity for hundreds of days. The researchers used each T-cell's barcode TCR sequence to keep track of 'who was who' as the cells went from a calm, resting state to a revved-up, activated state. The technique let them see — without any guess-work — which genes flipped on universally and which flipped on only in, say, T R 1 cells. It revealed the presence of fresh subset-specific genes. It also showed that while helper cells 'shouted' by expressing the TNF and IL-2 genes, regulator cells hit the brakes by expressing the FAS gene. The researchers also conducted another test that likened the seven CD4⁺ T-cells subsets to an army with seven regiments. When they blew a loud horn, every soldier charged forward. But when they waved a specific enemy flag — in this case, Pf-infected red blood cells — only one regiment, the T R 1 peacekeepers, stepped forward. These T R 1 troops are normally a small minority yet almost all malaria-recognising T-cell badges belonged to them. In other words, people who have never fought malaria don't have that regiment, so nothing much happens when their cells see the specific flag. In sum., the researchers were able to verify that T R 1 cells mounted a focused, antigen-specific response to blood-stage malaria and not a broad, nonspecific reaction. With longitudinal follow-ups, researchers found that T R 1 cells' abundance increased with every infection — even when the second infection occurred hundreds of days from the first — and more than tripled after a few infections. The abundance also correlated with the frequency of Pf parasites in the blood, suggesting that the T R 1 cell response depends on the antigen load. Although the abundance also dropped a bit from the peak once an individual recovered from an infection, it still maintained higher baseline levels in clinically immune individuals. In fact, even though a subset of helper cells called T H 1 cells also clonally expanded after a symptomatic infection, they didn't expand upon reinfection — whereas the T R 1 helper cells did. This suggested that the T H 1 cells are likely not Pf-specific and that their expansion after the first infection was unrelated to the infection being malaria. The finding is important because it almost completely negates a suggestion from previous studies that malaria primarily induces a T H 1 response. The researchers also found some preliminary evidence to suggest that the T R 1 cell response is encoded epigenetically, meaning the response is controlled in a way that is independent of the genes. Gene-expression studies of T R 1 cells showed that there are distinct subgroups of these cells: naïve-like T R 1 cells, effector T R 1 cells and memory T R 1 cells. The expansion and contraction of these subpopulations during and after symptomatic infections proved that these are functionally distinct entities and validated the memory potential of individual Pf-specific T R 1 clones. Tuning the immune system These insights into the immune response against malaria are likely to be game-changers: in approaches to prevent or manage malaria infections as well as in terms of opening new avenues to interrogate certain diseases and how our bodies respond to them. For example, by proving that T R 1 cells are the ones to follow during a malaria reinfection, the study offers new ways to develop effective vaccines against malaria. If T R 1 cells take centrestage, and given how they work, they may be helping the body carry Pf parasites without falling severely ill. Their specific role also opens the door to host-directed therapies, i.e. improving treatment outcomes by 'tuning' the immune system rather than targeting the pathogen itself. The findings may also open new avenues of research into the immunology of other infectious diseases and new ways to conquer them. Puneet Kumar is a clinician, Kumar Child Clinic, New Delhi.
IOL News
5 days ago
- Health
- IOL News
University of Cape Town leads regional action plan against drug-resistant malaria in East Africa
UCT is part of a research consortium that has played a pivotal role in developing the first regional action plan to combat drug-resistant malaria in East Africa. Image: Pexels/Jimmy Chan A research consortium led by the University of Cape Town (UCT) has played a pivotal role in developing the first regional action plan to combat drug-resistant malaria in East Africa. Endorsed by health ministers from across the region, the plan represents a major step forward in preserving the efficacy of life-saving antimalarial treatments. The Regional Detailed Action Plan for Responding to Antimalarial Drug Resistance in East Africa was officially endorsed in May 2025 at the 25th Ordinary Meeting of the East African Community (EAC) Sectoral Council of Ministers of Health. Developed through a partnership between UCT's Mitigating Antimalarial Resistance Consortium in South-East Africa (MARC SE-Africa) and the EAC Roll Back Malaria Secretariat, the plan unites national malaria programmes and global health stakeholders behind a common goal: safeguarding effective malaria treatment amid growing resistance and tightening global funding. Senior researcher at UCT and technical advisor within the consortium, Dr Stephanie van Wyk, said: 'This is a landmark achievement. This endorsement reflects the potential realised when scientific evidence, political will and regional solidarity converge. UCT remains committed to fostering solutions that not only assist our East African neighbours but also provide a template for responses to drug resistant malaria in other African regions. By enhancing case management and proactively addressing resistance challenges through regional collaboration, we contribute to safeguarding the effectiveness of antimalarial treatments throughout the endemic regions of Southern Africa.' The action plan targets drug-resistant Plasmodium falciparum, especially resistance to artemisinin-based combination therapies (ACTs) – the frontline treatment for malaria.– the frontline treatment for malaria. The plan outlines a roadmap for optimised treatment protocols, improved supply chain management and strengthened regional cooperation by integrating the latest research and surveillance data. It also identifies evidence-based short- and medium-term interventions to address resistance before it undermines decades of progress in malaria control. Video Player is loading. Play Video Play Unmute Current Time 0:00 / Duration -:- Loaded : 0% Stream Type LIVE Seek to live, currently behind live LIVE Remaining Time - 0:00 This is a modal window. Beginning of dialog window. Escape will cancel and close the window. Text Color White Black Red Green Blue Yellow Magenta Cyan Transparency Opaque Semi-Transparent Background Color Black White Red Green Blue Yellow Magenta Cyan Transparency Opaque Semi-Transparent Transparent Window Color Black White Red Green Blue Yellow Magenta Cyan Transparency Transparent Semi-Transparent Opaque Font Size 50% 75% 100% 125% 150% 175% 200% 300% 400% Text Edge Style None Raised Depressed Uniform Dropshadow Font Family Proportional Sans-Serif Monospace Sans-Serif Proportional Serif Monospace Serif Casual Script Small Caps Reset restore all settings to the default values Done Close Modal Dialog End of dialog window. Advertisement Next Stay Close ✕ The plan's development involved intensive collaboration with leading national and international health partners, including the Global Fund, the President's Malaria Initiative, the Clinton Health Access Initiative, the African Leaders Malaria Alliance and Medicines for Malaria Venture. The EAC Roll Back Malaria Secretariat, led by Dr Michael Katende, played a central coordinating role in aligning partner countries and institutions behind a shared vision. 'Malaria knows no borders, and neither should our response. This consensus-based regional action plan demonstrates the power of multinational collaboration in tackling drug-resistant malaria. Now is the critical moment for East African nations and international partners to commit to sustained action and ensure effective malaria treatment remains available for millions at risk,' said Professor Karen Barnes, lead of MARC SE-Africa and coordinator of the initiative at UCT. With more than 300 million people – over 80% of the EAC population – living at risk of malaria, the plan arrives at a critical juncture. Resistance is rising, and funding shortfalls threaten to reverse hard-won gains. The coordinated approach signals a shift toward African-led, research-driven and politically unified responses to one of the continent's most pressing public health threats. Through this regional initiative, East Africa sets a new precedent for protecting the impact of ACTs, reinforcing its commitment to collective action, and demonstrating leadership in global health innovation.
The Hindu
25-05-2025
- Health
- The Hindu
Antimalarial agents sidestep insecticide resistance by fighting parasite
Researchers reported in Nature on May 22 that they had identified compounds that could target the deadly malaria-causing parasite Plasmodium falciparum during its developmental stages in Anopheles mosquitoes, potentially enhancing efforts to control malaria in an affordable way in the resource-poor areas where it is often endemic. Per the World Health Organisation (WHO), there were 263 million malaria cases in 2023, up 4.3% from 2022. About 94% of all cases and 95% of all deaths in that year were reported in African countries. Last year, India's Health Ministry said the country had exited the WHO's High Burden to High Impact group in 2024, meaning it longer needs to mount intensive efforts to fight the disease. Even so, the National Vector Borne Diseases Control has estimated that 'about 95%' of India's population 'resides in malaria endemic areas'. While the fight against malaria was boosted by the rollout of the WHO-recommended malaria vaccines RTS,S and R21, an important, cost-effective method to stave off malaria infections is to use nets sprayed with insecticide. But according to the new paper, the nets' impact often levels off when mosquitoes acquire resistance. To this end, the study has thrown up a suite of specific compounds that can be sprayed on the nets and which the researchers have said will confer both long-lasting and resistance-proof protection against P. falciparum. The root of this effort is the idea that rather than killing mosquitoes, killing the parasites could be more effective. The researchers have done this by embedding potent, mosquito-stage antiplasmodial drugs in the same polymer fibres that currently carry insecticide. Because these compounds act on P. falciparum, they 'avoid potential development of resistance by the vector' and can block transmission even when the insecticide on the net no longer works. The researchers screened 81 compounds with known antimalarial properties, targeting the early developmental stages of P. falciparum within mosquitoes. These compounds were applied to the bodies of female Anopheles gambiae mosquitoes before they ingested an infected blood meal. Then the researchers assessed the mosquitoes' parasite burden a week later by counting the number of oocysts, an important phase of the P. falciparum lifecycle when it proliferates into its infectious form. They shortlisted 22 compounds that mitigated parasite infection, including endochin-like quinolones (ELQs) — antimicrobial agents known for their potent action against many human parasites. ELQ-456 in particular completely blocked parasite infections while ELQ-331 tamped down the infection's spread. When mosquitoes landed momentarily on surfaces treated with these compounds, ELQ-456 emerged as the most promising candidate. They also found that when mosquitoes briefly contacted a combination of ELQ-453 and ELQ-613, P. falciparum infections in their bodies were kept to a significant degree from maturing to their infectious forms. Next, the researchers evaluated ELQ compounds by incorporating them into polyethylene films like those used in insecticide-treated nets. Reportedly, the films effectively inhibited parasite development in both standard and insecticide-resistant mosquito strains even after they were stored for a year in the open. Finally, the team assessed the potential for these agents to induce antimicrobial resistance in the parasite. Team members found ELQ compounds with similar mechanisms of action didn't induce resistance across pathways other than their own (a.k.a. cross-resistance). They also raised mutated parasite strains that could resist the agents and reported even their transmissibility was significantly impaired. The team concluded in its paper that the agents' 'straightforward synthesis is a promising indication of cost-effectiveness, and … with additional process chemistry optimisation, manufacturing-scale synthesis, and bulk net production and procurement, these compounds will be an affordable and effective addition to bed nets even in the current highly competitive market.'
India Today
21-05-2025
- Health
- India Today
Myths about Malaria that could be dangerous
Malaria is a disease transmitted by mosquitoes and caused by Plasmodium parasites. It continues to be a significant public health issue in many tropical and subtropical substantial progress in raising awareness and improving treatment, myths and misconceptions about malaria persist. These misunderstandings can lead to delayed diagnoses, inappropriate prevention measures, and preventable complications. As we work towards eliminating malaria, it is essential to distinguish between fact and fiction. All you need to know from the expert Dr. Rajib Paul, Senior Consultant in Internal Medicine at Apollo Hospitals, Jubilee Hills, 1: MALARIA SPREADS FROM PERSON TO PERSON Truth: Malaria is not contagious. You cannot catch malaria by touching, kissing, or sharing food with someone who is infected. It is transmitted exclusively through the bite of an infected Anopheles mosquito. In rare cases, malaria can be transmitted through blood transfusion, organ transplants, or from mother to foetus, but direct person-to-person transmission does not 2: YOU CAN ONLY GET MALARIA IN RURAL OR FORESTED AREASTruth: While rural and forested regions may have higher mosquito density, urban areas are not immune. Poor drainage, stagnant water, and unplanned urban development provide ideal breeding grounds for mosquitoes even in cities. With a changing climate and increased travel, malaria transmission is becoming more unpredictable, crossing urban-rural 3: MALARIA IS NOT A SERIOUS DISEASE AND CAN BE TREATED AT HOMEadvertisementTruth: Malaria is potentially life-threatening if not diagnosed and treated promptly. Certain types of malaria, especially Plasmodium falciparum, can cause severe complications such as cerebral malaria, kidney failure, or even death. Self-medication without proper diagnosis can be dangerous, and relying on herbal remedies or over-the-counter drugs may delay effective 4: ONCE YOU GET MALARIA, YOU'RE IMMUNE FOR LIFETruth: Immunity to malaria is not lifelong. Any immunity acquired through previous exposure can wane over time, especially in people who leave endemic areas. Even those who have had malaria multiple times can get reinfected. No one is completely immune, and preventive measures should never be 5: MOSQUITOES BITE ONLY AT NIGHT, SO YOU'RE SAFE DURING THE DAYTruth: The Anopheles mosquito that transmits malaria typically bites between dusk and dawn, but activity can vary. Relying solely on the time of day to determine risk is risky. Protecting yourself during the evening and at night with bed nets, repellents, and covered clothing remains 6: ANTIMALARIAL DRUGS ARE DANGEROUS AND UNNECESSARYTruth: Modern antimalarial medications are safe when prescribed by healthcare professionals. Side effects are generally mild and manageable. In malaria-prone areas or while travelling, prophylactic drugs can significantly reduce the risk of infection. Avoiding them out of fear or misinformation could result in preventable 7: ONLY CHILDREN AND THE ELDERLY ARE AT RISKTruth: While children under five, pregnant women, and the elderly are more vulnerable to severe forms of malaria, anyone can contract the disease regardless of age. Travellers from non-endemic regions are especially at risk due to a lack of THE FOG: WHAT WORKSTo effectively protect against malaria, it's important to follow evidence-based prevention strategies:Use insecticide-treated bed nets, especially while sleeping. Apply mosquito repellent on exposed skin. Eliminate standing water where mosquitoes breed. Take prescribed antimalarial medication when travelling to high-risk areas. Seek medical help promptly at the first sign of fever, chills, or flu-like campaigns and public health interventions have significantly reduced malaria cases in recent years. However, busting persistent myths is equally important to sustaining this progress and empowering individuals with correct conclusion, combating malaria is not just about medication — it's about mindset. Dispelling myths, embracing science, and promoting accurate information will be vital in our fight to make malaria history.
Time of India
20-05-2025
- Health
- Time of India
46 malaria fatalities since 2020: Officials
Aizawl: In Mizoram, malaria has resulted in 46 fatalities over the past five years since 2020. However, among the 873 cases identified during January - March this year, no deaths were reported, officials of state health department's National Vector Borne Disease Control Programme (NVBDCP) said on Tuesday. Last year's data revealed that out of 3,07,468 blood samples analysed, 16,899 individuals tested positive for malaria, with seven fatalities. The cases comprised 8,950 Plasmodium falciparum (Pf) infections and 7,949 Plasmodium vivax (Pv) infections. In 2024, Lawngtlai district in South Mizoram, which shares borders with Myanmar and Bangladesh, recorded the highest malaria occurrence with 8,067 cases and five deaths. The district also registered the highest annual parasite incidence (API) at 56.70 cases per 1,000 population and led in test positivity rate (TPR) at 16.60 per 100 tests. Following Lawngtlai are Lunglei and Mamit districts, both adjacent to Bangladesh, reporting 3,775 and 3,299 cases respectively, with one death in Mamit. Lunglei recorded an API of 21.63, while Mamit showed 32.44. Siaha district, bordering Myanmar, ranked fourth with 1,607 cases during the same period. by Taboola by Taboola Sponsored Links Sponsored Links Promoted Links Promoted Links You May Like [Click Here] 2025 Best Luxury Hotel Prices Expertinspector Learn More Undo From 2020 to 2024, the total number of malaria cases reached 59,119, with 46 deaths. The highest mortality was recorded in 2023 with 13 deaths, followed by 10 deaths each in 2021 and 2022. The year 2020 saw six fatalities, while seven deaths occurred during the previous year.
