Associate Editor
Medical Research Council The Gambia Unit (MRC)
Francis Okot, Norman Aweno, Ebenezer C. Ikechukwu, Abubaker Rom, Gerald Kabuye, Jamshed Khan, Anthony Kirabira, Atemthi Dhieu Dau, Amanya Jacob, Ezbon WApary, Simon Peter Katongole, Denis Mubiru, Chukwudi A. Nnaji
Rakesh Padhan, Jatin Kumar, Bharti Goyal, Ram Das, Vikas Kumar, Soumyaranjan Pradhan, Kailash C. Pandey, Tarun Kumar Vats, Bhuvan Dixit
Insecticide resistance in mosquitoes has created a severe bottleneck, undermining global public health initiatives targeting vector-borne pathogens such as Plasmodium, dengue, and Zika viruses. Using a comprehensive narrative review methodology, this article maps the shifting evolutionary landscapes of vector control across four primary, universally recognized resistance mechanisms: target-site insensitivity (kdr, ace-1, and Rdl pore transformations), metabolic detoxification (cytochrome P450s, carboxylesterases, and glutathione S-transferases), cuticular thickening, and behavioral avoidance. Beyond these classical frameworks, this review addresses important contemporary discoveries, highlighting the functional role of the commensal midgut microbiota in the escalation of phenotypic pyrethroid resistance and underscoring novel extracellular metabolic markers such as the CSDIR protein. To counteract these adaptation networks, public health programs are undergoing a paradigm shift away from traditional neurotoxic monotherapies. The review touches upon the operational efficacy of next-generation, World Health Organization-prequalified interventions designed to circumvent legacy cross-resistance, focusing on neonicotinoids (clothianidin), pyrroles (chlorfenapyr), novel meta-diamides (broflanilide), and biorational insect growth regulators (pyriproxyfen). Finally, this review contextualizes these dynamics within the geographically and epidemiologically diverse landscape of India. The review points to specific Indian evidence, including the mapped multi-insecticide resistance profiles of primary rural (Anopheles culicifacies) and urban (Anopheles stephensi) vectors, PCR-based target-site genotyping (L1014F/S and V1010L alleles) from the national sentinel networks of the NCVBDC and ICMR-NIMR, and localized evaluations of novel allosteric chemistries. By bridging India’s field surveillance data with international resistance management frameworks, this review outlines integrated strategies to delay the selection of multi-resistant phenotypes and safeguard sustainable vector elimination targets worldwide.
Anthony Pilorget, Sospeter Ngoci Njeru, Damaris Matoke-Muhia, Christophe Loizel
Malaria remains one of the most devastating infectious diseases globally, causing an estimated 282 million cases and 610,000 deaths in 2024, predominantly among children in sub-Saharan Africa. While the WHO approval of the RTS,S/AS01 and R21/Matrix-M vaccines represents a historic milestone, these first-generation tools exhibit partial and waning efficacy and face severe manufacturing and deployment bottlenecks. Current biological production systems rely on highly centralized, capital-intensive cell culture facilities predominantly located in the Global North, perpetuating a structural geography of dependence for low- and middle-income countries (LMICs). The convergence of artificial intelligence (AI) and novel whole-insect biomanufacturing platforms offers a transformative solution to these scientific and structural challenges. AI is revolutionizing malaria therapeutics through reverse vaccinology, structural antigen design, and the optimization of potent, broadly neutralizing monoclonal antibodies (mAbs). However, translating these in silico designs into physical vaccines and therapeutics requires overcoming critical production bottlenecks. This perspective paper examines the Bombyx mori (silkworm) baculovirus expression vector system (BEVS) as a highly scalable, decentralizable platform uniquely suited for LMICs. We highlight the silkworm platform’s capacity to produce both complex multi-epitope vaccine antigens and functional IgG monoclonal antibodies at a fraction of the cost of mammalian cell culture. By proposing a farm-to-GMP supply chain model, in which African silkworm farms supply healthy larvae to centralized GMP facilities for baculovirus infection and protein purification, we demonstrate how the integration of AI and the silkworm platform can directly support the Partnerships for African Vaccine Manufacturing (PAVM) framework, providing a sustainable pathway to achieving the African Union’s 2040 local manufacturing targets.
Francis Okot, Norman Aweno, Ebenezer C. Ikechukwu, Abubaker Rom, Gerald Kabuye, Jamshed Khan, Anthony Kirabira, Atemthi Dhieu Dau, Amanya Jacob, Ezbon WApary, Simon Peter Katongole, Denis Mubiru, Chukwudi A. Nnaji
Health interventions that require multi-dose regimens are most effective when all doses are taken. Adherence to a full three-day course of Sulfadoxine-pyrimethamine plus amodiaquine (SPAQ) in all planned cycles of the annual seasonal malaria chemoprevention (SMC) round (cohort retention) is essential for maximizing the intervention’s impact. For this study cohort retention refers to eligible children completing the full three-day course of SPAQ during all planned 5 cycles of the annual SMC round. This s tudy aimed to assess the extent of cohort retention across SMC cycles and to identify factors associated with retention among eligible children in Northern Bahr el Ghazal, South Sudan. In November 2024, a household survey was conducted in Aweil West and Aweil South counties, South Sudan, one month after the completion of the fifth cycle of SMC distribution. A multi-stage random sampling was utilized to select 1,500 child-caregiver pairs across 75 clusters (40 in Aweil West and 35 in Aweil South). Data were collected using a structured questionnaire administered using SurveyCTO. Mixed-effects modified Poisson regression modeling was employed, with statistical significance set at p < 0.05. Of the 1,500 eligible children sampled, 66.9% (95% CI: 64.4 – 69.2) were retained. Caregivers that were knowledgeable about purpose of SMC medicines (adjusted prevalence ratio (aPR):2.04; 95%CI: 1.34-3.11; P = 0.001), perceived SMC medicines as effective (aPR:4.85; 95%CI: 1.25-18.9; P = 0.023), and caregivers that had paid work (aPR: 1.28; 95%CI:1.01-1.62; P = 0.04) were significantly associated with retention. SMC cohort retention in Aweil South and West counties is strongly associated with caregivers’ trust in and knowledge of the intervention. Strengthening community engagement and increasing awareness is vital for improving retention, enhancing the intervention’s effectiveness and ultimately reducing malaria morbidity and mortality among children.
Suresh Thangudu, Karthik Nuthalapati, Chiranjib Patra, Ganesh Kamble, Chiranjeevi Korupalli, Ganesh Gollavelli
Malaria is still one of the world’s most devastating infectious diseases, even with significant progress in treatment, mosquito control, and vaccines. The rise of drug-resistant Plasmodium parasites and insecticide-resistant Anopheles mosquitoes, along with limitations in traditional diagnosis and treatment methods, continue to hinder efforts to eliminate malaria globally. Nanotechnology has emerged as a valuable approach to address these issues. It offers highly sensitive diagnosis, targeted drug delivery, controlled drug release, vaccine development, and better mosquito management. This review critically highlights the latest advancements in nanotheranostics of malaria based on metal, metal oxides, carbon-based, polymeric, lipid-based, and other hybrid nanomaterials for malaria vaccine delivery and vector control, along with theranostics. The review also highlights key challenges such as nanotoxicity, safety for the environment, manufacturing challenges, consistency, and regulatory issues, along with recent advancements in nanomedicine and artificial-intelligence-based malaria diagnosis systems. Overall, this review underscores the growing potential of innovative nanomaterials to advance malaria diagnosis, treatment, and prevention while pointing out essential research areas needed for successful clinical use.
