Malaria is a severe life-threatening disease caused by the bites of parasite-infected female Anopheles mosquitoes. It remains a significant problem for the most vulnerable children and women. Recent research has helped establish the relationship between microRNAs (miRNAs) and many other diseases. MiRNAs are the class of small non-coding RNAs consisting of 18–23 nucleotides in length that are evolutionarily conserved and regulate gene expression at a post-transcriptional level and play a significant role in various molecular mechanisms such as cell survival, cell proliferation, and differentiation. MiRNAs can help detect malaria infection as the malaria parasite could alter the miRNA expression of the host. These alterations can be diagnosed by the molecular diagnostic tool that can indicate disease. We summarize the current understanding of miRNA during malaria infection. miRNAs can also be used as biomarkers, and initial research has unearthed their potential in diagnosing and managing various diseases such as malaria.

Plasmodium spp. parasites, the causative agents of malaria, survive and replicate in human hosts by modulating host protective immune responses. In a rodent model, malaria manifests as a severe splenomegaly, with infiltration of cells and lympho‐proliferation as major contributing factors of the immunopathology. However, the cellular contents and the functions of these cells have not been well studied. Here, we report that Plasmodium berghei infection of mice leads to massive recruitment of mesen‐chymal stem cells (MSCs) in secondary lymphoid organs. Infusion of these cells into naïve mice was able to confer host resistance against malaria. Furthermore, MSCs augmented interleukin (IL)‐12 production but suppressed IL‐10 production in recipient animals. In addition, we observed dramatic reductions of regulatory T (Treg) cells in animals that received MSCs. Taken together, our findings have identified recruitment of MSCs as a novel host protective mechanism adopted by the host to combat malaria by modulating Treg‐cell responses.

Understanding naturally acquired immune responses to Plasmodium in India is key to improving malaria surveillance and diagnostic tools. Here we describe serological profiling of immune responses at three sites in India by probing protein microarrays consisting of 515 Plasmodium vivax and 500 Plasmodium falciparum proteins with 353 plasma samples. A total of 236 malaria-positive (symptomatic and asymptomatic) plasma samples and 117 malaria-negative samples were collected at three field sites in Raurkela, Nadiad, and Chennai. Indian samples showed significant seroreactivity to 265 P. vivax and 373 P. falciparum antigens, but overall seroreactivity to P. vivax antigens was lower compared to P. falciparum antigens. We identified the most immunogenic antigens of both Plasmodium species that were recognized at all three sites in India, as well as P. falciparum antigens that were associated with asymptomatic malaria. This is the first genome-scale analysis of serological responses to the two major species of malaria parasite in India. The range of immune responses characterized in different endemic settings argues for targeted surveillance approaches tailored to the diverse epidemiology of malaria across the world. Although malaria deaths have fallen by 60% worldwide since 2000, the disease remains a significant public health problem. India has the highest burden of malaria in the South-East Asia Region, where Plasmodium vivax and Plasmodium falciparum are its main causes. While the two major malaria parasite species co-occur in India, their proportion varies across the country. Antibodies in an individual indicate current or past Plasmodium infection, and can be used to identify suitable vaccine candidates, as well as develop novel tools for malaria surveillance. We present the results of a pilot study undertaking the first large-scale characterization of antibody responses to ~1000 Plasmodium antigens at three field sites in India using high-throughput protein microarray technology. Individuals from the eco-epidemiologically diverse sites showed reactivity to 265 P. vivax and 373 P. falciparum antigens, regardless of infection status. Further comparison of individuals with symptomatic and asymptomatic malaria revealed the most immunogenic Plasmodium antigens, as well as antigens that were recognized with greater intensity in individuals that were asymptomatic at the point of sample collection. These results are a valuable addition to existing data from other malaria endemic regions, and will help to expand our understanding of host immunity against the disease.

Introduction In low- and middle-income countries, children experience multiple risks for delayed development. We evaluated a multicomponent, group-based early child development intervention including behavioural recommendations on responsive stimulation, nutrition, water, sanitation, hygiene, mental health and lead exposure prevention. Methods We conducted a 9-month, parallel, multiarm, cluster-randomised controlled trial in 31 rural villages in Kishoreganj District, Bangladesh. Villages were randomly allocated to: group sessions (‘group’); alternating groups and home visits (‘combined’); or a passive control arm. Sessions were delivered fortnightly by trained community members. The primary outcome was child stimulation (Family Care Indicators); the secondary outcome was child development (Ages and Stages Questionnaire Inventory, ASQi). Other outcomes included dietary diversity, latrine status, use of a child potty, handwashing infrastructure, caregiver mental health and knowledge of lead. Analyses were intention to treat. Data collectors were independent from implementers. Results In July–August 2017, 621 pregnant women and primary caregivers of children<15 months were enrolled (group n=160, combined n=160, control n=301). At endline, immediately following intervention completion (July–August 2018), 574 participants were assessed (group n=144, combined n=149, control n=281). Primary caregivers in both intervention arms participated in more play activities than control caregivers (age-adjusted means: group 4.22, 95% CI 3.97 to 4.47; combined 4.77, 4.60 to 4.96; control 3.24, 3.05 to 3.39), and provided a larger variety of play materials (age-adjusted means: group 3.63, 3.31 to 3.96; combined 3.81, 3.62 to 3.99; control 2.48, 2.34 to 2.59). Compared with the control arm, children in the group arm had higher total ASQi scores (adjusted mean difference in standardised scores: 0.39, 0.15 to 0.64), while in the combined arm scores were not significantly different from the control (0.25, –0.07 to 0.54). Conclusion Our findings suggest that group-based, multicomponent interventions can be effective at improving child development outcomes in rural Bangladesh, and that they have the potential to be delivered at scale. Trial registration number The trial is registered in ISRCTN (ISRCTN16001234).

Background: Malaria, caused by Plasmodium parasites, remains a leading global health concern, impacting millions of people globally. Splenic macrophages are specialized immune cells that reside in the spleen and play a pivotal role in the pathogenesis and immune response during malaria. These cells are fundamental to the body's defense against Plasmodium due to their multifaceted roles in parasite clearance, antigen presentation, and immune regulation. They participate in the early immune response by phagocytosing infected red blood cells, producing cytokines, and interacting with other immune cells to modulate both pro‐inflammatory and anti‐inflammatory responses. Aim: This review highlights the evolving understanding of splenic macrophages in malaria pathogenesis and immunity and underscores their importance in the development of novel therapeutic interventions. Method: The search strategy included retrieving relevant studies from PubMed Central and Google Scholar spanning between 1955–2025. Articles were screened based on relevance to malaria immunology, macrophage biology, and therapeutic interventions. Both experimental and clinical studies were considered, and references from selected articles were also cross‐checked to identify additional relevant literature. Priority was given to peer‐reviewed articles, systematic reviews, and original research that provided insights into the immunological role of splenic macrophages in malaria. Result: Splenic macrophages play a dual role in disease progression and severity. They have a specialized ability to polarize into different functional states under different microenvironments. Notably, macrophage polarization during Plasmodium infection is not strictly dichotomous but exists along a continuum, with macrophages exhibiting both M1 and M2 characteristics, facilitating dynamic immune modulation. This continuum of polarization is essential for balancing immune responses and ensuring effective immunity while avoiding excessive inflammation. Emerging evidence suggests that splenic macrophages significantly influence malaria severity and clinical outcomes, positioning them as key targets for therapeutic strategies. Conclusion: Optimizing macrophage‐mediated immunity by targeting specific macrophage functions and biomarkers could hold promise for improving vaccine development, diagnostics, prognosis, and treatment strategies, thereby enhancing clinical outcomes for malaria patients.

Various immune cells are known to participate in combating infection. Regulatory B cells represent a subset of B cells that take part in immunomodulation and control inflammation. The immunoregulatory function of regulatory B cells has been shown in various murine models of several disorders. In this study, a comparable IL-10 competent B-10 cell subset (regulatory B cells) was characterized during lethal and non-lethal infection with malaria parasites using the mouse model. We observed that infection of Balb/c mice with P. yoelii I 7XL was lethal, and a rapid increase in dynamics of IL-10 producing B220⁺CD5⁺CD1d⁺ regulatory B cells over the course of infection was observed. However, animals infected with a less virulent strain of the parasite P. yoelii I7XNL attained complete resistance. It was observed that there is an increase in the population of regulatory B cells with an increase of parasitemia; however, a sudden drop in the frequency of these cells was observed with parasite clearance. Adoptive transfer of regulatory B cells to naïve mice followed by infection results in slow parasite growth and enhancement of survival in P. yoelii 17XL (lethal) infected animals. Adoptively transferred regulatory B cells also resulted in decreased production of pro-inflammatory cytokine (IFN-γ) and enhanced production of anti-inflammatory cytokine (IL-10). It infers that these regulatory B cells may contribute in immune protection by preventing the inflammation associated with disease and inhibiting the parasite growth.