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Background: The continued spread of insecticide resistance in mosquito vectors of malaria and arboviral diseases may lead to operational failure of insecticide-based interventions if resistance is not monitored and managed efficiently. This study aimed to develop and validate a new WHO glass bottle bioassay method as an alternative to the WHO standard insecticide tube test to monitor mosquito susceptibility to new public health insecticides with particular modes of action, physical properties or both., Methods: A multi-centre study involving 21 laboratories worldwide generated data on the susceptibility of seven mosquito species (Aedes aegypti, Aedes albopictus, Anopheles gambiae sensu stricto [An. gambiae s.s.], Anopheles funestus, Anopheles stephensi, Anopheles minimus and Anopheles albimanus) to seven public health insecticides in five classes, including pyrethroids (metofluthrin, prallethrin and transfluthrin), neonicotinoids (clothianidin), pyrroles (chlorfenapyr), juvenile hormone mimics (pyriproxyfen) and butenolides (flupyradifurone), in glass bottle assays. The data were analysed using a Bayesian binomial model to determine the concentration-response curves for each insecticide-species combination and to assess the within-bioassay variability in the susceptibility endpoints, namely the concentration that kills 50% and 99% of the test population (LC 50 and LC 99 , respectively) and the concentration that inhibits oviposition of the test population by 50% and 99% (OI 50 and OI 99 ), to measure mortality and the sterilizing effect, respectively., Results: Overall, about 200,000 mosquitoes were tested with the new bottle bioassay, and LC 50 /LC 99 or OI 50 /OI 99 values were determined for all insecticides. Variation was seen between laboratories in estimates for some mosquito species-insecticide combinations, while other test results were consistent. The variation was generally greater with transfluthrin and flupyradifurone than with the other compounds tested, especially against Anopheles species. Overall, the mean within-bioassay variability in mortality and oviposition inhibition were < 10% for most mosquito species-insecticide combinations., Conclusion: Our findings, based on the largest susceptibility dataset ever produced on mosquitoes, showed that the new WHO bottle bioassay is adequate for evaluating mosquito susceptibility to new and promising public health insecticides currently deployed for vector control. The datasets presented in this study have been used recently by the WHO to establish 17 new insecticide discriminating concentrations (DCs) for either Aedes spp. or Anopheles spp. The bottle bioassay and DCs can now be widely used to monitor baseline insecticide susceptibility of wild populations of vectors of malaria and Aedes-borne diseases worldwide., (© 2023. World Health Organization.)

Background: Long-lasting insecticide nets (LLINs) are a core malaria intervention. LLINs should retain efficacy against mosquito vectors for a minimum of three years. Efficacy and durability of Olyset ® Plus, a permethrin and piperonyl butoxide (PBO) treated LLIN, was evaluated versus permethrin treated Olyset ® Net. In the absence of WHO guidelines of how to evaluate PBO nets, and considering the manufacturer's product claim, Olyset ® Plus was evaluated as a pyrethroid LLIN., Methods: This was a household randomized controlled trial in a malaria endemic rice cultivation zone of Kirinyaga County, Kenya between 2014 and 2017. Cone bioassays and tunnel tests were done against Anopheles gambiae Kisumu. The chemical content, fabric integrity and LLIN survivorship were monitored. Comparisons between nets were tested for significance using the Chi-square test. Exact binomial distribution with 95% confidence intervals (95% CI) was used for percentages. The WHO efficacy criteria used were ≥ 95% knockdown and/or ≥ 80% mortality rate in cone bioassays and ≥ 80% mortality and/or ≥ 90% blood-feeding inhibition in tunnel tests., Results: At 36 months, Olyset ® Plus lost 52% permethrin and 87% PBO content; Olyset ® Net lost 24% permethrin. Over 80% of Olyset ® Plus and Olyset ® Net passed the WHO efficacy criteria for LLINs up to 18 and 12 months, respectively. At month 36, 91.2% Olyset ® Plus and 86.4% Olyset ® Net survived, while 72% and 63% developed at least one hole. The proportionate Hole Index (pHI) values representing nets in good, serviceable and torn condition were 49.6%, 27.1% and 23.2%, respectively for Olyset ® Plus, and 44.9%, 32.8% and 22.2%, respectively for Olyset ® Net but were not significantly different., Conclusions: Olyset ® Plus retained efficacy above or close to the WHO efficacy criteria for about 2 years than Olyset ® Net (1-1.5 years). Both nets did not meet the 3-year WHO efficacy criteria, and showed little attrition, comparable physical durability and survivorship, with 50% of Olyset ® Plus having good and serviceable condition after 3 years. Better community education on appropriate use and upkeep of LLINs is essential to ensure effectiveness of LLIN based malaria interventions., (© 2021. The Author(s).)

Background: Through a nationally representative household survey in Afghanistan, we conducted an operational study in two relatively secure provinces comparing effectiveness of computer-aided personal interviewing (CAPI) with paper-and-pencil interviewing (PAPI)., Methods: In Panjshir and Parwan provinces, household survey data were collected using paper questionnaires in 15 clusters, and OpenDataKit (ODK) software on electronic tablets in 15 other clusters. Added value was evaluated from three perspectives: efficient implementation, data quality, and acceptability. Efficiency was measured through financial expenditures and time stamped data. Data quality was measured by examining completeness. Acceptability was studied through focus group discussions with survey staff., Results: Survey costs were 68% more expensive in CAPI clusters compared to PAPI clusters, due primarily to the upfront one-time investment for survey programming. Enumerators spent significantly less time administering surveys in CAPI cluster households (248 min survey time) compared to PAPI (289 min), for an average savings of 41 min per household (95% CI 25-55). CAPI offered a savings of 87 days for data management over PAPI. Among 49 tracer variables (meaning responses were required from all respondents), small differences were observed between PAPI and CAPI. 2.2% of the cleaned dataset's tracer data points were missing in CAPI surveys (1216/ 56,073 data points), compared to 3.2% in PAPI surveys (1953/ 60,675 data points). In pre-cleaned datasets, 3.9% of tracer data points were missing in CAPI surveys (2151/ 55,092 data points) compared to 3.2% in PAPI surveys (1924/ 60,113 data points). Enumerators from Panjsher and Parwan preferred CAPI over PAPI due to time savings, user-friendliness, improved data security, and less conspicuity when traveling; however approximately half of enumerators trained from all 34 provinces reported feeling unsafe due to Taliban presence. Community and household respondent skepticism could be resolved by enumerator reassurance. Enumerators shared that in the future, they prefer collecting data using CAPI when possible., Conclusions: CAPI offers clear gains in efficiency over PAPI for data collection and management time, although costs are relatively comparable even without the programming investment. However, serious field staff concerns around Taliban threats and general insecurity mean that CAPI should only be conducted in relatively secure areas., (© 2021. The Author(s).)

Background: Vector control plays a critical role in the prevention, control and elimination of vector-borne diseases, and interventions of vector control continue to depend largely on the action of chemical insecticides. A global survey was conducted on the management practices of vector control insecticides at country level to identify gaps to inform future strategies on pesticide management, seeking to improve efficacy of interventions and reduce the side-effects of chemicals used on health and the environment., Methods: A survey by questionnaire on the management practices of vector control insecticides was disseminated among all WHO Member States. Data were analysed using descriptive statistics in MS Excel., Results: Responses were received from 94 countries, or a 48% response rate. Capacity for insecticide resistance monitoring was established in 68-80% of the countries in most regions, often with external support; however, this capacity was largely lacking from the European & Others Region (i.e. Western & Eastern Europe, North America, Australia and New Zealand). Procurement of vector control insecticides was in 50-75% of countries taking place by agencies other than the central-level procuring agency, over which the central authorities lacked control, for example, to select the product or assure its quality, highlighting the importance of post-market monitoring. Moreover, some countries experienced problems with estimating the correct amounts for procurement, especially for emergency purposes. Large fractions (29-78%) of countries across regions showed shortcomings in worker safety, pesticide storage practices and pesticide waste disposal. Shortcomings were most pronounced in countries of the European & Others Region, which has long been relatively free from mosquito-borne diseases but has recently faced challenges of re-emerging vector-borne diseases., Conclusions: Critical shortcomings in the management of vector control insecticides are common in countries across regions, with risks of adverse pesticide effects on health and the environment. Advocacy and resource mobilization are needed at regional and country levels to address these challenges.

In the publication of this article [1], there is an error in the name of one of the contributing authors.

Background: Atrial myxoma remains a rare clinical entity with an incidence of surgically resected cases of 0.5-0.7 per million population and prevalence of < 5 per 10,000. It typically manifests in woman after third decade of life; symptoms vary greatly and may present with arrhythmia, intracardiac flow obstruction, embolic phenomenon, and associated constitutional symptoms. Neurological complications associated with atrial myxoma most frequently include cerebral infarct due to embolus. Cerebellar involvement is very rare and only a few cases have been reported in the literature., Case Presentation: A 55-year-old Brahmin man with no history of diabetes mellitus and hypertension, presented with complaints of dizziness, headache, vomiting, double vision, and unsteadiness of gait for 2 weeks. His headache was sudden in onset, of a pulsating type and localized on left temporal side. Vomiting was projectile and bilious. Double vision was present in all directions of gaze and he had uncoordinated movement of his body and tilting to the left side. On examination, his cerebellar functions were impaired. He was thoroughly investigated for the cause of stroke after abnormal magnetic resonance imaging results with normal computed tomography angiography of his brain. Echocardiography and computed tomography of his chest showed a mass attached to intra-atrial septum and prolapsing through mitral valve, which was suggestive of left atrial myxoma. Five days following admission, he developed abdominal pain due to thromboembolism causing splenic and renal infarct., Conclusion: Although rare, atrial myxoma has to be considered a cause of stroke and other embolic phenomenon causing multiorgan infarctions. Early and timely diagnosis of the condition can prevent further recurrence and inappropriate anticoagulant therapy. It would be pertinent to have echocardiography done in patients who present with a stroke, arrhythmias, and other constitutional symptoms. The tumor once detected must be removed surgically as early as possible, which not only reduces serious thromboembolic complications but can be potentially curative.

Background: Visceral leishmaniasis, commonly known as kala-azar in India, is a global public health problem. In Southeast Asia, Bangladesh, Bhutan, India, Nepal, Sri Lanka and Thailand are endemic for visceral leishmaniasis. The role of sandflies as the vector of kala-azar was first confirmed in 1942 in India. Insecticide resistance in Phlebotomus argentipes Annandale and Brunetti, the vector of kala-azar in the Indian subcontinent, was first reported in 1987 in Bihar, India. This article provides a scoping review of the studies undertaken from 1959 to 2015 on insecticide resistance in P. argentipes and P. papatasi (Scopoli), the vectors of visceral and cutaneous leishmaniasis respectively, in Southeast Asia, mainly in Bangladesh, India, Nepal and Sri Lanka., Results: Studies undertaken in areas of Bihar and West Bengal in India where kala-azar is endemic have reported resistance of P. argentipes to DDT, while in non-endemic areas it has been reported to be susceptible. In areas of Nepal bordering India, there are indications of resistance to DDT; biochemical resistance has been reported in Sri Lanka. No laboratory studies have been undertaken in Bangladesh; however, the sandfly vector is reported to be still susceptible to pyrethroids in all kala-azar endemic areas in the aforementioned countries., Conclusions: Studies are needed to determine the resistance of sandfly vectors to all available classes of potential insecticides in kala-azar endemic areas. There is a need to assess the impact of indoor residual spraying with DDT and pyrethroids on the incidence of kala-azar in India where 54 districts remain endemic for the disease, strengthen entomological surveillance capacity, and develop and implement an insecticide management plan. Alpha-cypermethrin indoor residual spraying has been introduced in 33 kala-azar endemic districts in Bihar State of India in a pilot trial; the outcomes should be used to inform decisions on expanding coverage with alpha-cypermethrin in all remaining endemic districts to achieve the revised goal of elimination of visceral leishmaniasis by 2020.

Background: Fast development of pyrethroid resistance in malaria vectors prompted the development of new vector control tools including combination of insecticides with different modes of action as part of resistance management strategies. Olyset Plus® is a new long-lasting insecticidal net, in which, permethrin and a synergist, piperonyl butoxide (PBO), are incorporated into filaments. Mixture nets such as this may have application against resistant mosquitoes, particularly those whose resistance is based on oxidative metabolism. There may also be enhanced activity against susceptible mosquitoes since mixed function oxidases are involved in a many metabolic activities including activation to form bioactive compounds., Methods: Bio-efficacy of Olyset Plus was evaluated against susceptible malaria vector, Anopheles fluviatilis in experimental huts. Deterrence, blood feeding inhibition, induced exophily and killing effect were measured to assess the bio-efficacy. The results were compared with Olyset Net®, a polyethylene permethrin-incorporated LLIN and a conventionally treated polyester net (with permethrin) washed to just before exhaustion., Results: Results showed significant reduction in entry (treatment: 0.4-0.8; control: 4.2 per trap-night) and increase in exit (56.3-82.9 % and 44.2 %) rates of Anopheles fluviatilis in the treatment arms compared to control (P < 0.05). While blood feeding rates declined in treatment arms (18.8-30.6 %), it increased in control (77.6 %) (P < 0.05). This was further evident from the blood-feeding inhibition rates in treatment arms (60.6-90.6 %). Total mortality was significantly higher in all treatment arms (96.3-100 %) compared to control arm (2 %) (P < 0.05). Chemical analysis for active ingredient (AI) showed retention of 75 and 88 % in Olyset plus and Olyset net respectively after 20 washes. Performance of Olyset Plus washed 20 times was equal to the CTN and Olyset Net against the susceptible malaria vector An. fluviatilis, fulfilling the WHO efficacy criteria of Phase II evaluation for LLIN. However, the benefit of incorporating PBO and permethrin together in a long-lasting treatment could not be demonstrated in the current study as the target vector species was fully susceptible to pyrethroids., Conclusion: Olyset Plus, with its intrinsic bio-efficacy could be an effective vector control tool to prevent transmission of malaria by susceptible vectors like An. fluviatilis. However, the results of the current study need to be further supported by testing the net at village level (Phase III) for community acceptability. Before taking the net to village level, it needs to be verified whether the net is better than pyrethroid nets in terms of bio-efficacy against resistant An. culicifacies, another malaria vector that has developed resistance to synthetic pyrethroids in India.

Background: Public health pesticides has been the mainstay control of vectors of malaria and other diseases, and public health pests, but there is increasing concern over how these pesticides are being managed. Poor pesticide management could lead to risks to human health and the environment, or diminish the effectiveness of interventions. Strategies for strengthening the management of public health pesticides, from manufacture to disposal, should be evaluated to propose future directions., Methods: The process and outcomes of three strategies were studied in five regions of the WHO (African Region, Eastern Mediterranean Region, South-East Asia Region, Western Pacific Region, and American Region) and 13 selected countries. These strategies are: regional policy development, in-depth country support and thematic support across countries., Results: Consensus, frameworks and action plans on public health pesticide management were developed at regional level. Country support for situation analysis and national action planning highlighted weaknesses over the entire spectrum of pesticide management practices, mainly related to malaria control. The thematic support on pesticide quality control contributed to structural improvements on a priority issue for malaria control across countries., Conclusions: The three strategies showed promising and complementary results, but guidelines and tools for implementation of the strategies should be further improved. Increased national and international priority should be given to support the development of policy, legislation and capacity that are necessary for sound management of public health pesticides.

Background: Identification of genes underlying drought tolerance (DT) quantitative trait loci (QTLs) will facilitate understanding of molecular mechanisms of drought tolerance, and also will accelerate genetic improvement of pearl millet through marker-assisted selection. We report a map based on genes with assigned functional roles in plant adaptation to drought and other abiotic stresses and demonstrate its use in identifying candidate genes underlying a major DT-QTL., Results: Seventy five single nucleotide polymorphism (SNP) and conserved intron spanning primer (CISP) markers were developed from available expressed sequence tags (ESTs) using four genotypes, H 77/833-2, PRLT 2/89-33, ICMR 01029 and ICMR 01004, representing parents of two mapping populations. A total of 228 SNPs were obtained from 30.5 kb sequenced region resulting in a SNP frequency of 1/134 bp. The positions of major pearl millet linkage group (LG) 2 DT-QTLs (reported from crosses H 77/833-2 × PRLT 2/89-33 and 841B × 863B) were added to the present consensus function map which identified 18 genes, coding for PSI reaction center subunit III, PHYC, actin, alanine glyoxylate aminotransferase, uridylate kinase, acyl-CoA oxidase, dipeptidyl peptidase IV, MADS-box, serine/threonine protein kinase, ubiquitin conjugating enzyme, zinc finger C- × 8-C × 5-C × 3-H type, Hd3, acetyl CoA carboxylase, chlorophyll a/b binding protein, photolyase, protein phosphatase1 regulatory subunit SDS22 and two hypothetical proteins, co-mapping in this DT-QTL interval. Many of these candidate genes were found to have significant association with QTLs of grain yield, flowering time and leaf rolling under drought stress conditions., Conclusions: We have exploited available pearl millet EST sequences to generate a mapped resource of seventy five new gene-based markers for pearl millet and demonstrated its use in identifying candidate genes underlying a major DT-QTL in this species. The reported gene-based markers represent an important resource for identification of candidate genes for other mapped abiotic stress QTLs in pearl millet. They also provide a resource for initiating association studies using candidate genes and also for comparing the structure and function of distantly related plant genomes such as other Poaceae members.

Background: It is critical that vector control pesticides are used for their acceptable purpose without causing adverse effects on health and the environment. This paper provides a global overview of the current status of pesticides management in the practice of vector control., Methods: A questionnaire was distributed to WHO member states and completed either by the director of the vector-borne disease control programme or by the national manager for vector control. In all, 113 countries responded to the questionnaire (80% response rate), representing 94% of the total population of the countries targeted., Results: Major gaps were evident in countries in pesticide procurement practices, training on vector control decision making, certification and quality control of pesticide application, monitoring of worker safety, public awareness programmes, and safe disposal of pesticide-related waste. Nevertheless, basic conditions of policy and coordination have been established in many countries through which the management of vector control pesticides could potentially be improved. Most countries responded that they have adopted relevant recommendations by the WHO., Conclusions: Given the deficiencies identified in this first global survey on public health pesticide management and the recent rise in pesticide use for malaria control, the effectiveness and safety of pesticide use are being compromised. This highlights the urgent need for countries to strengthen their capacity on pesticide management and evidence-based decision making within the context of an integrated vector management approach.

Background: Genetic polymorphism is an inevitable component of a complex organism especially in multistage infectious organisms such as malaria parasites. Understanding the population genetic structure of the parasites would provide valuable information for effective malaria control strategies. Recently, the development of molecular tools like PCR has made analysis of field samples possible and easier and research on Plasmodium vivax has also been strengthened. Not many reports are available on the genetic polymorphism of P. vivax from the Indian sub-continent. This study evaluates the extent of diversity in field isolates of India with respect to Pvgam-1., Methods: A study was designed to assess the diversity of Pvgam-1 among field isolates from India, using a nested PCR assay. Field isolates were collected from different regions of the country and the observed variability was confirmed by sequencing data., Results: Both Belem and Chesson type alleles were present either exclusively or in mixed form among isolates of all 10 study sites. The Belem type allele was predominant, occurring in 67% of isolates. The proportion of isolates showing the mixed form (both Belem and Chesson type alleles occurring together in the same isolate) was about 13 overall (up to 38.5% in some isolates). Sequencing of the PCR-amplified Belem and Chesson type alleles confirmed the PCR results. Among the 10 study sequences, 11 polymorphic sites and four singleton variations were observed. All the nucleotide substitutions were non-synonymous., Conclusion: Study shows limited diversity of Pvgam-1 marker in Indian isolates with well representation of both Belem and Chesson type alleles.