Tag: Malaria

Categories : Diseases, Syndromes and ConditionsTags :

Resistance to Artemisinin Found in African Children with Severe Malaria

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Indiana University School of Medicine researchers, in collaboration with colleagues at Makerere University in Uganda, have uncovered evidence of partial resistance to artemisinin derivatives – the primary treatment for malaria – in young children with severe, or “complicated,” malaria. 

Earlier studies have shown partial resistance to artemisinin in children with uncomplicated malaria, but the new study, published in the Journal of the American Medical Association (JAMA), is the first to document such resistance in African children with well-defined signs of severe disease from malaria. 

“Artemisinin-based therapies have been quintessential in the fight against malaria for the past 20 years,” said corresponding author Chandy C. John, MD, the professor of paediatrics at the IU School of Medicine. “Growing evidence of artemisinin partial resistance in African children with uncomplicated malaria has led to concerns that new therapies, like triple artemisinin combination therapies, may be needed in uncomplicated malaria. The findings of artemisinin partial resistance in children with severe or complicated malaria, as well as the findings of a high rate of recurrent malaria with current standard treatment in these areas raise the question of whether new treatments are needed for severe malaria as well.”

Led by John and co-authors Ruth Namazzi, MBChB, MMEd, and Robert Opoka, MD, MPH, of Makerere University; Ryan Henrici, MD, PhD, of the University of Pennsylvania; and Colin Sutherland, PhD, MPH, of the London School of Tropical Medicine and Hygiene, the study examined 100 Ugandan children aged 6 months to 12 years who were undergoing treatment for severe malaria complications caused by Plasmodium falciparum, the deadly malaria parasite transmitted by mosquitos. 

In the study, 10 children had parasites with genetic mutations previously associated with artemisinin partial resistance. The most common mutation, which was seen in eight of these children, was associated with a longer parasite clearance half-life — the time it takes the parasite’s burden in the body to reach half of its initial level. The study also showed that 10% of children returned within 28 days of treatment with an infection from the same malaria strain they had during their original admission. These were all children who had received complete intravenous and then oral treatment for severe malaria, and all had cleared the parasite by microscopic examination. John said these findings suggest that the standard intravenous and oral treatment lowers the parasite level to where it cannot be detected by microscopy, but it does not completely eliminate the parasite in some children.   

Reports of artemisinin resistance first surfaced in Southeast Asia in 2008 before emerging in East Africa, a trend the IU research team unexpectedly observed through their ongoing work in Uganda. While studying why severe malaria develops in children, the researchers noticed slower responses to artemisinin in some of their Ugandan study participants, prompting the present study. 

“The study findings point to a need for more data on artemisinin resistance and recurrence of clinical malaria in children with severe malaria,” John said. “If our study findings are confirmed in other areas, that would suggest that treatment guidelines for severe malaria may require revision.”  

John presented the study’s results at the Annual Meeting of the American Society of Tropical Medicine and Hygiene on Nov. 14 in New Orleans, Louisiana.

Source: Indiana University

Categories : Paediatrics VaccinesTags :

Maternal Antibodies in Infants Interfere with Malaria Vaccine Responses

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Maternal antibodies passed across the placenta can interfere with the response to the malaria vaccine, which would explain its lower efficacy in infants under five months of age, according to research led by the Barcelona Institute for Global Health (ISGlobal), in collaboration with seven African centers (CISM-Mozambique, IHI-Tanzania, CRUN-Burkina Faso, KHRC-Ghana, NNIMR-Ghana, CERMEL-Gabon, KEMRI-Kenya).

The findings, published in Lancet Infectious Diseases, suggest that children younger than currently recommended by the WHO may benefit from the RTS,S and R21 malaria vaccines if they live in areas with low malaria transmission, where mothers have less antibodies to the parasite.

The world has reached an incredible milestone: the deployment of the first two malaria vaccines –RTS,S/AS01E and the more recent R21/Matrix-M– to protect African children against malaria caused by Plasmodium falciparum. Both vaccines target a portion of the parasite protein called circumsporozoite (CSP) and are recommended for children aged 5 months or more at the moment of the first dose.

“We know that the RTS,S/AS01E malaria vaccine is less effective in infants under five months of age, but the reason for this difference is still debated,” says Carlota Dobaño, who leads the Malaria Immunology group at ISGlobal, a centre supported by “la Caixa” Foundation. 

To investigate this, Dobaño and her team analysed blood samples from more than 600 children (age 5-17 months) and infants (age 6-12 weeks) who participated in the phase 3 clinical trial of RTS,S/AS01E. Using protein microarrays, they measured antibodies against 1000 P. falciparum antigens before vaccination to determine if and how malaria exposure and age affected IgG antibody responses to the malaria vaccine.

“This microarray approach allowed us to accurately measure malaria exposure at the individual level, including maternal exposure for infants and past infections for older children,” says Didac Maciá, ISGlobal researcher and first author of the study. 

The role of maternal antibodies

The analysis of antibodies to P. falciparum in children who had received a control vaccine instead of RTS,S/AS01E revealed a typical “exposure” signature, with high levels in the first three months of life due to the passive transfer of maternal antibodies through the placenta, a decline during the first year of life, and then a gradual increase as a result of naturally acquired infections.

In children vaccinated with RTS,S/AS01E, antibodies induced by natural infections did not affect the vaccine response. However, in infants, high levels of antibodies to P. falciparum, presumably passed from their mothers during pregnancy, correlated with reduced vaccine responses. This effect was particularly strong for maternal anti-CSP antibodies targeting the central region of the protein. Conversely, infants with very low or undetectable maternal anti-CSP IgGs exhibited similar vaccine responses as those observed in children.

The molecular mechanisms underlying this interference by maternal antibodies are not fully understood, but the same phenomenon has been observed with other vaccines such as measles. 

Overall, these findings confirm something that was already suspected but not clearly demonstrated: despite their protective function, maternal anti-CSP antibodies, which decline within the first three to six months of life, may interfere with vaccine effectiveness. The higher the level of malaria transmission, the more maternal antibodies are transmitted to the baby, resulting in lower vaccine effectiveness. These findings further suggest that infants below five months of age may benefit from RTS,S or R21 vaccination in low malaria transmission settings, during outbreaks in malaria-free regions, or in populations migrating from low to high transmission settings.

“Our study highlights the need to consider timing and maternal malaria antibody levels to improve vaccine efficacy for the youngest and most vulnerable infants,” says Gemma Moncunill, ISGlobal researcher and co-senior author of the study, together with Dobaño.

Source: Barcelona Institute for Global Health (ISGlobal)

Categories : Diseases, Syndromes and ConditionsTags :

What Time at Night a Malaria Mosquito Bites Impacts Infection

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Researchers have discovered that what time of the night a malaria-bearing mosquito bites may have significant effect on the subsequent infection’s severity.

When mice are infected in the middle of the night with the parasites causing cerebral malaria, the symptoms of the disease are less severe than for those inflected during the day, and the spread of the parasites within the hosts is more limited, research teams from McGill University, the Douglas Research Centre and the Research Institute of the McGill University Health Centre have discovered.

Malaria is a mosquito-borne infectious disease that affects hundreds of millions of people worldwide. It kills more than half a million people each year, most of them children. Cerebral malaria is the deadliest form of the disease.

The researchers’ findings, published in the journals iScience and ImmunoHorizons, have the potential to lead to new treatment practices based on aligning medication with our circadian rhythms.

How circadian rhythms of host and parasite interact

Circadian rhythms are defined as physiological and behavioral oscillations with cycles of approximately 24 hours, matching the Earth’s rotation, that persist in the absence of environmental timing cues. These rhythms are regulated by a master clock in the brain, as well as by clocks located in most other organs and cell types throughout the organism.

“We explored how the circadian rhythms of both the host and the malaria parasite interact to affect the severity of the disease and the host’s ability to fight off the parasite,” said Priscilla Carvalho Cabral, a recent McGill PhD graduate who carried out the experiments described in two recent studies on the subject.

Nicolas Cermakian, Director of the Laboratory of Molecular Chronobiology, and the corresponding author of the two studies, noted, “The difference in a host’s response to infection depending on the time of day suggests that their circadian rhythms could be influencing the progression of the disease. How such immune clocks impact malaria has not been looked at before.”

An important advance in knowledge

In parasites and their animal hosts, as well as in most living organisms, many bodily functions are under circadian control. It is known, for instance, that the replication of malaria parasites inside the red blood cells of a host follows a daily rhythm. Previous work from the same team has already shown that another serious parasitic disease, leishmaniasis, is affected by host clocks: the time of infection influences the replication of the parasite as well as the immune response to it. In the new studies, the same was found to be true for cerebral malaria.

“Our results represent an important advance in knowledge since many of the mechanisms driving the rhythms in susceptibility to diseases, especially parasitic diseases, remain largely unknown,” says Martin Olivier, Director of the Laboratory for the Study of Host-Parasite Interaction, a professor in McGill’s Department of Microbiology and Immunology and co-author of the two studies.

Source: McGill University

Categories : GeneticsTags :

First DNA Study of Ancient Eastern Arabians Reveals Malaria Adaptation

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Photo by MJ RAHNAMA

People living in ancient Eastern Arabia appear to have developed resistance to malaria following the appearance of agriculture in the region around five thousand years ago, a new study published its in Cell Genomics reveals.

DNA analysis of the remains of four individuals from Tylos-period Bahrain (300 BCE to 600 CE) – the first ancient genomes from Eastern Arabia – revealed the malaria-protective G6PD Mediterranean mutation in three samples.

The discovery of the G6PD Mediterranean mutation in ancient Bahrainis suggests that many people in the region’s ancient populations may have enjoyed protection from malaria.

In the present day, among the populations examined, the G6PD mutation is detected at its peak frequency in the Emirates, the study indicates.

Researchers discovered that the ancestry of Tylos-period inhabitants of Bahrain comprises sources related to ancient groups from Anatolia, the Levant and Caucasus/Iran.

The four Bahrain individuals were genetically more like present-day populations from the Levant and Iraq than to Arabians.

Experts from Liverpool John Moores University, the University of Birmingham Dubai, and the University of Cambridge worked with the Bahrain Authority for Culture and Antiquities and other Arabian institutes such as the Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, as well as research centres in Europe.

Lead researcher Rui Martiniano, from Liverpool John Moores University, commented: “According to our estimates, the G6PD Mediterranean mutation rose in frequency around five-to-six thousand years ago — coinciding with the onset of agriculture in the region, which would have created ideal conditions for the proliferation of malaria.”

Due to poor ancient DNA preservation in hot and humid climates, no ancient DNA from Arabia has been sequenced until now — preventing the direct examination of the genetic ancestry of its past populations.

Marc Haber, from the University of Birmingham Dubai, commented: “By obtaining the first ancient genomes from Eastern Arabia, we provide unprecedented insights into human history and disease progression in this region. This knowledge goes beyond historical understanding, providing predictive capabilities for disease susceptibility, spread, and treatment, thus promoting better health outcomes.”

“The rich population history of Bahrain, and more generally of Arabia, has been severely understudied from a genetic perspective. We provide the first genetic snapshot of past Arabian populations – obtaining important insights about malaria adaptation, which was historically endemic in the region,” commented Fatima Aloraifi, from the Mersey and West Lancashire NHS Trust.

Salman Almahari, Director of Antiquities and Museums at the Bahrain Authority for Culture and Antiquities, states, “Our study also paves the way for future research that will shed light on human population movements in Arabia and other regions with harsh climates where it is difficult to find well-preserved sources of DNA.”

Data gathered from the analysis of the four individuals’ remains allowed researchers to characterise the genetic composition of the region’s pre-Islamic inhabitants – insights that could only have been obtained by directly examining ancient DNA sequences.

Researchers collected ancient human remains from archaeological collections stored at the Bahrain National Museum, gathering DNA from 25 of them. Only four samples were sequenced to higher coverage due to poor preservation.

The finding of malaria adaptation agrees with archaeological and textual evidence that suggested malaria was historically endemic in Eastern Arabia, whilst the DNA ancestry of Tylos-period inhabitants of Bahrain corroborates archaeological evidence of interactions between Bahrain and neighbouring regions.

Source: University of Birmingham

Categories : Immune SystemTags :

‘Junk Cells’ Actually Have a Powerful Role against Malaria

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Red blood cell Infected with malaria parasites. Colourised scanning electron micrograph of red blood cell infected with malaria parasites (teal). The small bumps on the infected cell show how the parasite remodels its host cell by forming protrusions called ‘knobs’ on the surface, enabling it to avoid destruction and cause inflammation. Uninfected cells (red) have smoother surfaces. Credit: NIAID

Researchers from The Australian National University (ANU) have discovered a previously unknown ability of a group of immune system cells, known as Atypical B cells (ABCs), to fight infectious diseases such as malaria.

The discovery, published in Science Immunology, provides new insight into how the immune system fights infections and brings scientists a step closer to harnessing the body’s natural defences to combat malaria.

The scientists say ABCs could also be key to developing new treatments for chronic autoimmune conditions such as lupus. According to the researchers, ABCs have long been associated with malaria, as malaria patients have more of these cells in their system compared to the general population.

“In this study, we wanted to understand the mechanisms that drive the creation of ABCs in the immune system, but also find out whether these cells are good or bad for us when it comes to fighting infection,” lead author Dr Xin Gao, from ANU, said.

“Although ABCs are known to contribute to chronic inflammatory diseases and autoimmunity, we’ve discovered a previously unknown ability of these cells to fight disease. In this sense, ABCs are like a double-edged sword.

“Contrary to past belief, ABCs are not junk cells; they are more important than we thought.

“Our research found that ABCs are also instrumental in developing T follicular helper cells. These helper cells generate powerful antibodies that help the body fight malaria parasites.

“Antibodies can block parasites in the blood as they travel from the site of the infectious mosquito bite to the liver, where the infection is first established.”

In 2022, malaria killed more than 600 000 people worldwide. Although the disease is preventable and curable, scientists face an uphill battle to find long-lasting treatments as malaria parasites continue to find new ways to build resistance to current therapies.

Using gene-editing technology on mice, the ANU researchers discovered a gene called Zeb2 is crucial to the production of ABCs.

“We found that manipulating the Zeb2 gene disrupted the creation of ABCs in the immune system,” study co-author Professor Ian Cockburn, from The ANU John Curtin School of Medical Research, said.

“Importantly, we found that mice without the Zeb2 gene were unable to control malaria infection.

“Therefore, the findings show that ABCs play a crucial role in fighting malaria infections.”

The researchers say targeting ABCs could also pave the way for new treatments for certain autoimmune diseases such as lupus.

“ABCs also appear in large numbers in many autoimmune diseases, including lupus, which can be life-threating in severe cases,” Professor Cockburn said.

“By developing a better understanding of the role of ABCs in the immune system and the cells’ role in fighting disease, it could bring us a step closer to one day developing new and more effective therapies.”

Source: Australian National University

Categories : Diseases, Syndromes and Conditions New Compounds and TreatmentsTags :

Autofluorescent Compound Paints a Bright Future for Antimalarial Research

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Red Blood Cell Infected with Malaria Parasites Colourised scanning electron micrograph of red blood cell infected with malaria parasites (teal). The small bumps on the infected cell show how the parasite remodels its host cell by forming protrusions called ‘knobs’ on the surface, enabling it to avoid destruction and cause inflammation. Uninfected cells (red) have smoother surfaces. Credit: NIAID

New compounds are continuously required due to the risk of malaria parasites becoming resistant to the medicines currently used. A team of researchers at Friedrich-Alexander-Universität Erlangen-Nürnberg (FAU) combined the anti-malaria drug artemisinin with coumarin, and developed a compound from both bioactive plant-derived substances. This compound is also autofluorescent, making it particularly useful as it can be used for imaging in live cells.

The working group, led by Prof Dr Svetlana B. Tsogoeva, also discovered that the autofluorescent artemisinin-coumarin hybrids are able to destroy a certain drug-resistant malaria pathogen called Plasmodium palcifarum. They published their findings in the journal Chemical Science.

Artemisinin is a highly-effective and common ingredient for the manufacture of malaria medication gained from a plant called sweet wormwood (Artemisia annua L.). Coumarin is a secondary plant compound found in various plants.

In the development of drugs against malaria, active substances such as artemisinin are labelled with fluorescent substances in order to identify how they act against malaria pathogens in precise chronological order using imaging techniques.

Combining substances to achieve autofluorescence

A significant disadvantage of labeling with fluorescent substances is the fact that they alter how the medication works.

For example, this means that in certain circumstances cells infected with malaria absorb a drug like artemisinin differently after fluorescent marking than previously.

The solubility of the drug can also change. This was avoided by the development of autofluorescent hybrids, which are compounds made of two or more basic compounds that are inherently fluorescent and whose mode of action can be precisely observed using imaging techniques.

Active agent with special skills

The team decided to combine artemisinin with bioactive coumarins because coumarin derivatives also possess anti-malaria properties. They can also be easily chemically altered so that they become extremely fluorescent.

The researchers discovered that it was not only possible to observe the mode of action of this first autofluorescent artemisinin-coumarin hybrid in living red blood cells infected with P. falciparum.

In conjunction with Prof. Barbara Kappes (Department of Chemical and Biological Engineering, FAU) and Dr. Diogo R. M. Moreira (Instituto Gonçalo Moniz, Fiocruz Bahia, Brazil), they also discovered that the active agent was highly effective against P. falciparum strains in vitro that are resistant to chloroquin and other malaria drugs.

Above all, however, the new compound also proved highly effective against the malaria pathogens in vivo in mouse models.

With the creation of the first autofluorescent artemisinin-coumarin hybrid, the FAU researchers hope that they have laid the foundation for the development of further autofluorescent agents for treating malaria and have made significant process in overcoming multi-drug resistance in the treatment of malaria.

Source: Friedrich-Alexander-Universität Erlangen-Nürnberg

Categories : Diseases, Syndromes and Conditions General InterestTags :

H3D’s Pioneering Research Adds Hope to the Fight against Malaria 

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Members of the University of Cape Town’s Holistic Drug Discovery and Development Centre H3D

A formidable disease that has plagued humanity for centuries, malaria has exacted a heavy toll on human lives, disrupting communities and hindering socio-economic progress across some of the most vulnerable regions of the world, particularly the African continent.  

With its stealthy transmission through the bites of infected mosquitoes, malaria has earned the dubious reputation of being one of the deadliest vector-borne diseases on the planet. So much so that the World Health Organization’s World Malaria Report reveals that malaria cases are on the rise, with instances rising from 245 million cases in 2020 to over 247 million a year later1. 

With an estimated 619,000 people succumbing to the disease in 20211, it remains a defining challenge for global healthcare systems. However, through the unyielding persistence and spirit of medical innovation and scientific ingenuity exemplified by research facilities such as the University of Cape Town’s Holistic Drug Discovery and Development Centre (H3D), solutions to mitigate the severity of malaria are on the horizon.  

“As the first and only integrated drug discovery platform on the African continent, H3D’s mission is to discover and develop innovative life-saving medicines for diseases that predominantly affect African patients,” explains Bada Pharasi, CEO of the Innovative Pharmaceutical Association of South Africa (IPASA).

H3D’s focus on building Africa-specific models aims to improve treatment outcomes in African patients and to educate and train a critical mass of skilled African-based drug discovery scientists. H3D’s scientific output and research model includes attracting international investment in local innovative pharmaceutical research and development (R&D) across the African continent to address the disproportionately high global disease burden. Importantly, H3D targets critical infectious diseases, including tuberculosis, antibiotic-resistant microbial diseases, and malaria. 

“Given the vulnerability of many of the African populations, the continent accounted for 95% of malaria cases and 96% of malaria deaths in 20211. Accordingly, continued antimalarial drug research and development, such as the studies conducted by H3D, is important to prevent and treat the millions of cases that arise each year, all of which have consequences on both the health and socioeconomic development of the continent,” adds Pharasi.

Since the official launch of H3D’s programs in April 2011, there have been notable advances in innovative drug discovery projects. The centre has demonstrated a strong track record with multiple chemical series discovered and being progressed at H3D in each stage of the drug development pipeline.

A significant achievement reached by H3D was the discovery of the malaria clinical candidate, MMV390048, which reached phase II human trials in African patients. This was the first ever small molecule clinical candidate, for any disease, researched on African soil by an African drug discovery research unit. 

According to Dr Candice Soares de Melo, Chief Investigator at H3D, the centre’s current anti-malarial programmes will focus on the identification of quality leads suitable for optimisation and candidate selection as potential agents for the treatment of uncomplicated Plasmodium falciparum malaria, ideally with additional activity against liver-stage parasites to offer protection and prevent relapses (in case of malaria caused by the species Plasmodium vivax), as well as blocking the transmission of the disease. 

“A critical component of the research conducted at H3D is to develop medicines that are safe and sufficiently tolerated to be given to the widest range of recipients, including infants and pregnant women,” says Soares de Melo.

Besides the potential benefits of providing a new cure for malaria, H3D serves as a catalyst for training scientists in infectious disease research and influencing the R&D environment in Africa.  As part of its partnership with the South African Medical Research Council, H3D has worked to mentor and develop scientists at other African universities, including those at Historically Disadvantaged Institutions (HDIs) within South Africa. 

Furthermore, apart from strengthening drug discovery innovation at UCT, the centre has also taken a lead role in partnership with the Bill & Melinda Gates Foundation in catalysing drug discovery across sub-Saharan Africa, with upwards of 16 university research groups working on malaria and tuberculosis drug discovery. 

“An example of this is the Phase 1 clinical trial for the H3D clinical candidate MMV390048, which was carried out at the UCT Division of Clinical Pharmacology,” adds Soares de Melo. 

Another is the MATRIX independent special project, which has the potential to transform local drug manufacturing across the continent. Funded by the United States Agency for International Development (USAID), the project aims to pilot cost-effective local manufacture of antiretroviral Active Pharmaceutical Ingredients using flow reactor technology.

“Should Africa intend on a path to self-sufficiency, it’s important to drive continued investment in health innovations developed for and by Africa.

“We support the research efforts of H3D, and strongly believe that now is the time to take a deliberate and systematic approach to develop new capabilities, transfer technologies, leverage partnerships and networks, and train scientists, all while delivering on drug discovery projects to help address the continent’s, and the world’s, greatest health challenges,” concludes Pharasi.

For more information, visit https://h3d.uct.ac.za/ or contact Candice Soares de Melo at candice.soaresdemelo@uct.ac.za.

Categories : Skeletal SystemTags :

AI Finds that an Antimalarial Drug might Treat Osteoporosis Too

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Using a deep learning algorithm, which is a kind of artificial intelligence (AI), researchers reporting have found that dihydroartemisinin (DHA), an antimalarial drug and derivative of a traditional Chinese medicine, could treat osteoporosis as well. Publishing their findings in ACS Central Science, the team showed that in mice, DHA effectively reversed osteoporosis-related bone loss.

In healthy people, there is a balance between the osteoblasts that build new bone and osteoclasts that break it down. Current treatments for osteoporosis primarily focus on slowing the activity of the ‘wrecking crew’ of osteoclasts. But osteoblasts, or more specifically, their precursors known as bone marrow mesenchymal stem cells (BMMSCs), could be the basis for a different approach. During osteoporosis, these multipotent cells tend to turn into fat-creating cells instead, but they could be reprogrammed to help treat the disease. Previously, Zhengwei Xie and colleagues developed a deep learning algorithm that could predict how effectively certain small-molecule drugs reversed changes to gene expression associated with the disease. This time, joined by Yan Liu and Weiran Li, they wanted to use the algorithm to find a new treatment strategy for osteoporosis that focused on BMMSCs.

The team ran their program on a profile of differently expressed genes in newborn and adult mice. One of the top-ranked compounds identified was DHA, a derivative of artemisinin and a key component of malaria treatments. Administering DHA extract for six weeks to mice with induced osteoporosis significantly reduced bone loss in their femurs and nearly completely preserved bone structure. To improve delivery, the team designed a more robust system using injected, DHA-loaded nanoparticles. Bones of mice with osteoporosis that received the treatment were similar to those of the control group, and the treatment showed no evidence of toxicity. In further tests, the team determined that DHA interacted with BMMSCs to maintain their stemness and ultimately produce more osteoblasts. The researchers say that this work demonstrates that DHA is a promising therapeutic agent for osteoporosis.

Source: American Chemical Society

Categories : Environmental Effects GeneticsTags :

Scientists Abuzz over a Genetic Way to Deafen Mosquitoes

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Specific receptors in the ears of mosquitoes have been revealed to modulate their hearing, finds a new study led by researchers at UCL and University of Oldenburg. Since male mosquitoes need to hear female mosquitoes is a crucial factor in their reproduction, this discovery could help develop new insecticides and control the spread of harmful diseases, such as malaria, dengue, and yellow fever.

In the study, published in Nature Communications, the researchers focused on a signalling pathway involving a molecule called octopamine. They demonstrated that it is key for mosquito hearing and mating partner detection, and so is a potential new target for mosquito control.

Male mosquitoes acoustically detect the buzz generated by females within large swarms that form transiently at dusk.

As swarms are potentially noisy, mosquitoes have developed highly sophisticated ears to detect the faint flight tone of females amid hundreds of mosquitoes flying together.

However, the molecular mechanisms by which mosquito males ‘sharpen their ears’ to respond to female flight tones during swarm time have been largely unknown.

The researchers looked at the expression of genes in the mosquito ear and found that an octopamine receptor specifically peaks in the male mosquito ear when mosquitoes swarm.

The study found that octopamine affects mosquito hearing on multiple levels. It modulates the frequency tuning and stiffness of the sound receiver in the male ear, and also controls other mechanical changes to boost the detection of the female.

The researchers demonstrated that the octopaminergic system in the mosquito ear can be targeted by insecticides. Mosquito mating is a bottleneck for mosquito survival, so identifying new targets to disrupt it is key to controlling disease-transmitting mosquito populations.

Source: University College London

Categories : Diseases, Syndromes and ConditionsTags :

Inflammation Impedes the Development of Malaria Parasites

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Researchers have found that inflammation can slow down the development of malaria parasites in the bloodstream, which may lead to a new strategy for preventing or limiting severe disease.

The malaria-causing Plasmodium parasites invade and multiply within red blood cells. Studies have shown that the parasites can rapidly sense and respond to conditions within the host by intimately syncing with their internal body clocks. While it is known that the body’s nutrient levels and daily circadian rhythms affect the parasites’ development, little was known about the impact of host inflammation on the parasites.

This animal-model study, led by the Peter Doherty Institute for Infection and Immunity (Doherty Institute) and the Kirby Institute and published in the journal mBio, reveals that when the body’s immune system responds to inflammation it alters the plasma’s chemical composition, directly impeding the maturation of the Plasmodium parasites in the bloodstream.

University of Melbourne’s Associate Professor Ashraful Haque, a senior author of the paper, said this work highlights the captivating dynamic of the host-parasite relationship.

“First, we discovered that inflammation in the body prevented the early stage of the parasites from maturing. We also noticed that inflammation triggered significant changes in the composition of the plasma – we were actually quite surprised by the magnitude of these changes,” said Associate Professor Haque.

“As we dug deeper, we found substances in the altered plasma that, we believe, are what may inhibit parasite growth in the body. This work reveals a new mechanism that slows down the malaria parasite’s development in the bloodstream. Our research was done using animal models, so it would be really interesting to study if such inhibitory mechanisms occur in humans too.”

Dr David Khoury, co-senior author of the paper, said the scientists found a remarkable response by the parasites to the changes in their environment.

“Parasites residing in red blood cells rapidly sense and respond to their new environment, showing fascinating adaptability. Using cutting-edge genome sequencing technology, we observed that even after just four hours in this changed plasma, the parasites adjusted their genetic and protein activity, resulting in slower maturation within red blood cells. It’s almost like the parasites actively sense an inhospitable host environment, and as a result trigger a coping mechanism,” said Dr Khoury.

“We believe this is the first study to show that inflammation can change how individual parasites behave genetically in the body.”

Professor Miles Davenport, co-senior author of the paper, said this work on the interaction between systemic host inflammation and malaria parasite maturation offers several potential benefits.

“This study, while based on animal models, broadens our understanding of malaria. It provides a foundation for further investigations into the specific mechanisms involved in the modulation of parasite maturation by inflammation, and opens avenues for future studies to explore the identified inhibitory factors, genetic changes and their implications for malaria development,” said Professor Davenport.

Source: The Peter Doherty Institute for Infection and Immunity