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Abstract Plasmodium malariae parasites are widely observed across the tropics and sub-tropics. This slow-growing species, known to maintain chronic asymptomatic infections, has been associated with reduced antimalarial susceptibility. We analyse 251 P. malariae genomes from 28 countries, and leveraging 131,601 high-quality SNPs, demonstrate segregation of African and Asian isolates. Signals of recent evolutionary selection were identified in genes encoding putative surface proteins (pmmsp1) and putative erythrocyte invasion proteins (pmdpap3, pmrbp2, pmnif4). Amino acid substitutions were identified in orthologs of genes associated with antimalarial susceptibility including 2 amino acid substitutions in pmdhfr aligning with pyrimethamine resistance mutations in P. falciparum. Additionally, we characterise pmdhfr mutation F57L and demonstrate its involvement in reduced susceptibility to pyrimethamine in an in vitro parasite assay. We validate CRISPR-Cas9 mediated ortholog replacement in P. knowlesi parasites to determine the function of pmdhfr mutations and demonstrate that circulating pmdhfr genotypes are less susceptible to pyrimethamine.

Abstract Background Among 13 endemic districts, the Chittagong Hill Tracts bear more than 90% of Bangladesh’s malaria burden. Despite the private sector’s prominence in rural healthcare, its role in malaria management remains underutilized. This study aimed to strategize leveraging the for-profit private sector, such as diagnostic and treatment centers, to bolster national malaria surveillance and control, advancing Bangladesh toward malaria elimination by 2030. Methods This mixed-method study commenced with a questionnaire-based cross-sectional survey followed by selected focused group discussions (FGDs) among the participants. Three FGDs were held with the for-profit service providers so that further insights and qualitative viewpoints of them can be utilized in situation analysis. Based on the endemicity and strategic priorities, a comprehensive mapping of private for-profit facilities from the regions comprising 15 sub-districts across 8 chosen districts (7 malaria endemic districts and the rest non-endemic districts) was created. For the non-endemic zone, the sub-districts were selected based on their proximity to an area with high malaria transmission. Results Among the 104 representative participants, majority were male (n = 92, 88.5%), had a diploma in their respective fields (n = 53, 51%) and were involved either in laboratory work (n = 49, 47.1%) or as owners/managers of health centers (n = 41, 39.4%). The selected health facilities were close to the corresponding Upazila Health Complexes (mean distance 2.8 km), but were distantly located from the designated district hospitals (mean distance 48.9 km). The main sources of RDT kits (62.3%) and anti-malarial drugs (63.2%) were local wholesale markets. A large share of the corresponding facilities neither provided malaria treatment services (81.7%) nor worked with the NMEP (93.3%). Conclusions This study highlights challenges and recommendations for engaging private for-profit health facilities in Bangladesh’s malaria elimination efforts. The identified challenges include low-quality RDTs, staff shortages, and inadequate capacity building. Recommendations emphasize effective training, stakeholder interaction, and enhanced oversight for successful malaria control efforts.

BackgroundDengue, a viral infection transmitted by Aedes species mosquitoes, presents a substantial global public health concern, particularly in tropical regions. In Bangladesh, where dengue prevalence is noteworthy, accurately mapping the distribution of high-risk and low-risk areas and comprehending the clustering of dengue cases throughout the year is essential for the development of effective risk-based prevention and control strategies. Our objective was to identify dengue hotspots and temporal patterns over the years across Bangladesh in the years 2019-2023 excluding year 2020.MethodsA sequential spatial analysis was employed for each year to identify high-risk areas for dengue cases. Choropleth graphs were used to visualize the geographic distribution of dengue incidence rates per million population across the areas. Monthly distribution analysis was performed to identify temporal trends over the year 2022 and 2023. Additionally, the global Moran's I test was used to assess the overall geographical pattern. Subsequently, Anselin local Moran's I test was employed to identified clustering and hotspots of dengue incidences.ResultsDengue cases in Bangladesh exhibited a significant increase from 2019 to 2023 (excluding 2020 data), with a cumulative total of 513,344 reported cases. Dhaka city initially bore substantial burden, accounting for over half (51%) of the 101,354 cases in 2019. The case fatality rate also demonstrated a steadily rise, reaching 0.5% in 2023 with 321,179 cases (a five-fold increase compare to 2022). Interestingly, the proportion of cases in Dhaka city decreased from 51% in 2019 to 34% in 2023. Notably, the southeast and central regions of Bangladesh showed the highest dengue rates, persisting throughout the study period. Cases were concentrated in urban regions, with Dhaka exhibiting the highest caseload in most years, followed by Manikganj in 2023. A distinct temporal shift in dengue transmission was observed in 2023, when the peak incidence occurred three months earlier in July with complete geographic coverage (all the 64 districts) compared to the peak in October 2022 (covering 95%, 61 districts). Positive global autocorrelation analysis revealed spatial dependence, with more stable trends in 2023 compared to previous years. Several districts like, Bagerhat, Barisal, and Faridpur remained persistent hotspots or emerged as new hotspots in 2023. Conversely, districts like Dinajpur, Gaibandha, Nilphamari, Rangpur and Sylhet consistently exhibited low caseloads, categorized as dengue coldspots throughout most of the years. Jhalokati in 2019 and Gopalganj in 2022, both initially classified as low-incidence district surrounded by high-incidence districts, emerged as hotspots in 2023.ConclusionThis study sheds light on the spatiotemporal dynamics of dengue transmission in Bangladesh, particularly by identifying hotspots and clustering patterns. These insights offer valuable information for designing and implementing targeted public health interventions and control strategies. Furthermore, the observed trends highlight the need for adaptable strategies to address the region's evolving nature of dengue transmission effectively.

Autism Spectrum Disorder (ASD) is a developmental disorder that impacts social communication and conduct. ASD lacks standard treatment protocols or medication, thus early identification and proper intervention are the most effective procedures to treat this disorder. Artificial intelligence could be a very effective tool to be used in ASD diagnosis as this is free from human bias. This research examines the effect of face alignment for the early diagnosis of Autism Spectrum Disorder (ASD) using facial images with the possibility that face alignment can improve the prediction accuracy of deep learning algorithms. This work uses the SOTA deep learning-based face alignment algorithm MTCNN to preprocess the raw data. In addition, the impacts of facial alignment on ASD diagnosis using facial images are investigated using state-of-the-art CNN backbones such as ResNet50, Xception, and MobileNet. ResNet50V2 achieves the maximum prediction accuracy of 93.97% and AUC of 96.33% with the alignment of training samples, which is a substantial improvement over previous research. This research paves the way for a data-centric approach that can be applied to medical datasets in order to improve the efficacy of deep neural network algorithms used to develop smart medical devices for the benefit of mankind. ABSTRAK: Gangguan Spektrum Autisme (ASD) adalah gangguan perkembangan yang memberi kesan kepada komunikasi dan tingkah laku sosial. Kelemahan dalam rawatan ASD adalah ianya tidak mempunyai protokol rawatan standard atau ubat. Oleh itu pengenalan awal dan campur tangan betul merupakan prosedur paling berkesan bagi merawat gangguan ini. Kecerdasan buatan boleh menjadi alat berkesan bagi diagnosis ASD kerana bebas campur tangan manusia. Penyelidikan ini mengkaji kesan penjajaran muka bagi diagnosis awal ASD menggunakan imej muka dengan kebarangkalian penjajaran muka dapat meningkatkan ketepatan ramalan algoritma pembelajaran mendalam. Kajian ini menggunakan algoritma penjajaran muka MTCNN berasaskan pembelajaran mendalam SOTA bagi pra-proses data mentah. Selain itu, kesan penjajaran muka pada diagnosis ASD menggunakan imej muka disiasat menggunakan CNN terkini seperti ResNet50, Xception dan MobileNet. ResNet50V2 mencapai ketepatan ramalan maksimum sebanyak 93.97% dan AUC 96.33% dengan sampel penjajaran latihan, yang merupakan peningkatan ketara berbanding penyelidikan terdahulu. Kajian ini membuka jalan bagi pendekatan data berpusat yang boleh digunakan pada set data perubatan bagi meningkatkan keberkesanan algoritma rangkaian saraf mendalam dan membangunkan peranti perubatan pintar bermanfaat untuk manusia.

Background Culex (Cx.) tritaeniorhynchus is an invasive mosquito species with an extensive and expanding inter-continental distribution, currently reported across Asia, Africa, the Middle East, Europe and now Australia. It is an important vector of medical and veterinary pathogens which cause significant morbidity and mortality in human and animal populations. Across regions endemic for Japanese encephalitis virus (JEV), Cx. tritaeniorhynchus is considered the major vector and has also been shown to contribute to the transmission of several other zoonotic arboviruses including Rift Valley fever virus (RVFV) and West Nile virus (WNV). Methods In this study, we used laboratory vector competence experiments to determine if Cx. tritaeniorhynchus from a Southern European population were competent JEV vectors. We also obtained samples from multiple geographically dispersed Cx. tritaeniorhynchus populations from countries within Europe, Africa, Eurasia and Asia to perform phylogenetic analysis to measure the level of mitochondrial divergence using the cytochrome oxidase subunit 1 (CO1) gene. We also undertook bacterial 16S rRNA gene amplicon sequencing to determine microbial diversity and used multi-locus sequence typing (MLST) to determine any evidence for the presence of strains of the naturally occurring endosymbiotic bacterium Wolbachia. Results Cx. tritaeniorhynchus from a Greek population were shown be be competent vectors of JEV with high levels of virus present in saliva. We found a signficant level of mitochondrial genetic diversity using the mosquito CO1 gene between geographically dispersed populations. Furthermore, we report diverse microbiomes identified by 16S rRNA gene amplicon sequencing within and between geographical populations. Evidence for the detection of the endosymbiotic bacteria Wolbachia was confirmed using Wolbachia-specific PCR and MLST. Conclusions This study enhances our understanding of the diversity of Cx. tritaeniorhynchus and the associated microbiome across its inter-continental range and highlights the need for greater surveillance of this invasive vector species in Europe.

Abstract Background Joint efforts by government and non-government organizations have helped to reduce malaria in Bangladesh and set the country on a clear path to eventual malaria elimination. However, achieving that goal would be challenging without a comprehensive understanding of vector bionomics. Methods Targeted capturing of Anopheles mosquitoes over a rainy season, utilizing specific sampling methods, including human landing catches (HLCs), CDC-light traps (CDC-LTs), and pyrethrum spray catches (PSCs) were aimed to characterize entomological drivers of transmission in four sites of Bandarban, Bangladesh. Results Molecular characterization of a subset of 4637 mosquitoes has demonstrated the presence of at least 17 species whose capture rates were representative of the rainy season. Species compositions and bionomic traits did not vary between sites with Anopheles maculatus having the highest landing rate by HLCs and Anopheles vagus having the highest capture rate with CDC-LTs. Interestingly, Anopheles species compositions and capture rates varied significantly (p

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of the coronavirus disease 2019 (COVID-19), has recently posed a threat to global health by spreading at a high rate and taking millions of lives worldwide. Along with the respiratory symptoms, there are gastrointestinal manifestations and one of the most common gastrointestinal symptoms is diarrhea which is seen in a significant percentage of COVID-19 patients. Literature review: Several studies have shown the plausible correlation between overexpressed angiotensin converting enzyme 2 (ACE2) in enterocytes and SARS-CoV-2, as ACE2 is the only known receptor for the virus entry. Along with the dysregulated ACE2, there are other contributing factors such as gut microbiome dysbiosis, adverse effects of antiviral and antibiotics for treating infections and inflammatory response to SARS-CoV-2 which bring about increased permeability of gut cells and subsequent occurrence of diarrhea. Few studies found that the SARS-CoV-2 is capable of damaging liver cells too. No single effective treatment option is available. Limitations: Confirmed pathophysiology is still unavailable. Studies regarding global population are also insufficient. Conclusion: In this review, based on the previous works and literature, we summarized the putative molecular pathophysiology of COVID-19 associated diarrhea, concomitant complications and the standard practices of management of diarrhea and hepatic manifestations in international setups.

Background The optimal dosing of primaquine to prevent relapsing Plasmodium vivax malaria in South Asia remains unclear. We investigated the efficacy and safety of different primaquine regimens to prevent P. vivax relapse.Methods A systematic review identified P. vivax efficacy studies from South Asia published between 1 January 2000 and 23 August 2021. In a one-stage meta-analysis of available individual patient data, the cumulative risks of P. vivax recurrence at day 42 and 180 were assessed by primaquine total mg/kg dose and duration. The risk of recurrence by day 180 was also determined in a two-stage meta-analysis. Patients with a >25% drop in haemoglobin to 50 g/L between days 1 and 14 were categorised by daily mg/kg primaquine dose.Results In 791 patients from 7 studies in the one-stage meta-analysis, the day 180 cumulative risk of recurrence was 61.1% (95% CI 42.2% to 80.4%; 201 patients; 25 recurrences) after treatment without primaquine, 28.8% (95% CI 8.2% to 74.1%; 398 patients; 4 recurrences) following low total (2 to 25% drop in haemoglobin to

IntroductionScreening for G6PD deficiency can inform disease management including malaria. Treatment with the antimalarial drugs primaquine and tafenoquine can be guided by point-of-care testing for G6PD deficiency.Methods and findingsData from similar clinical studies evaluating the performance of the STANDARD G6PD Test (SD Biosensor, South Korea) conducted in Bangladesh, Brazil, Ethiopia, India, Thailand, the United Kingdom, and the United States were pooled. Test performance was assessed in a retrospective analysis on capillary and venous specimens. All study sites used spectrophotometry for reference G6PD testing, and either the HemoCue or complete blood count for reference hemoglobin measurement. The sensitivity of the STANDARD G6PD Test using the manufacturer thresholds for G6PD deficient and intermediate cases in capillary specimens from 4212 study participants was 100% (95% Confidence Interval (CI): 97.5%-100%) for G6PD deficient cases with 60% on the reference assay. The negative predictive value for females with G6PD activity >60% was 99.6% (95% CI 99.1%-99.8%) on capillary specimens. Sensitivity among 396 P. vivax malaria cases was 100% (69.2%-100.0%) for both deficient and intermediate cases. Across the full dataset, 37% of those classified as G6PD deficient or intermediate resulted from true normal cases. Despite this, over 95% of cases would receive correct treatment with primaquine, over 87% of cases would receive correct treatment with tafenoquine, and no true G6PD deficient cases would be treated inappropriately based on the result of the STANDARD G6PD Test.ConclusionsThe STANDARD G6PD Test enables safe access to drugs which are contraindicated for individuals with G6PD deficiency. Operational considerations will inform test uptake in specific settings.

Abstract Building up a map is essential for mobile robots to localize their position and perfect autonomous navigation which is known as Simultaneous Localization and Mapping (SLAM). The map has become very important when the weather is inappropriate for the robot. However, the map becomes inconsistent when the robot moves in the environment and detects errors in its detection accuracy. The robot had difficulty identifying its previously visited path, which is called loop-closure detection when the climate changed immensely e.g. seasonal changes. The main goal of this work is to apply Independent Component Analysis (ICA) and Auto-Encoder (Convolutional Auto-Encoder and Fundamental Auto-Encoder) to understand the route through the robot. During the operation of robots across a wide range of environmental changing conditions, the ICA has auspicious potential to extract descriptors of condition-invariant images. On the other hand, Auto-Encoder has the capability to differentiate condition variant and condition invariant characteristics of a site and identify the most possible route for the robot. In order to complete this work perfectly, we used three seasonal datasets, they are Summer–Fall, Spring–Fall, and Summer–Spring datasets. This work uses the baseline method with a precision-recall curve and evaluates the performance of our proposed algorithm, especially the ICA algorithm. In short, the proposed algorithm ICA showed a 91.05% accuracy rate which is better than the baseline algorithm.

Abstract Background Bangladesh has reduced malaria incidence and mortality by over 75% between 2010 and 2020. Widespread long-lasting insecticidal net (LLIN) distribution and use is one of the measures responsible for this success. Recalcitrant malaria hotspots within the Chittagong Hill Tracts districts suggest important drivers of malaria risk may remain uncharacterized. Methods Towards understanding how household-level human behaviour impacts exposure to mosquitoes, parallel human landing catches and human behavioural observations were conducted in four households for 6 months (May–October) over the rainy season in the Bandarban District. Analysis quantifies spatiotemporal human behaviour-adjusted exposure to Anopheles with and without LLINs. Results This small-scale operational study demonstrates that human spatial and temporal presence along with LLIN use drives exposure to Anopheles. Though the four households had both outdoor and indoor exposure, especially in the evening (1800–2000 h) and early morning (0400–0500 h), data points to household-based heterogeneity in malaria exposure even with similar LLIN access. Conclusion Incorporating human behaviour into exposure estimates can be used to understand the efficacy and limitations of local vector control strategies and identify gaps in protection, as well as where present intervention strategies may be optimized.

Summary: Climate change is one of several drivers of recurrent outbreaks and geographical range expansion of infectious diseases in Europe. We propose a framework for the co-production of policy-relevant indicators and decision-support tools that track past, present, and future climate-induced disease risks across hazard, exposure, and vulnerability domains at the animal, human, and environmental interface. This entails the co-development of early warning and response systems and tools to assess the costs and benefits of climate change adaptation and mitigation measures across sectors, to increase health system resilience at regional and local levels and reveal novel policy entry points and opportunities. Our approach involves multi-level engagement, innovative methodologies, and novel data streams. We take advantage of intelligence generated locally and empirically to quantify effects in areas experiencing rapid urban transformation and heterogeneous climate-induced disease threats. Our goal is to reduce the knowledge-to-action gap by developing an integrated One Health—Climate Risk framework.

Abstract Background Malaria remains endemic in Bangladesh, with the majority of cases occurring in forested, mountainous region in the Chittagong Hill Tracts (CHT). This area is home to Bengali and diverse groups of indigenous people (Pahari) residing largely in mono-ethnic villages. Methods 1002 individuals of the 9 most prominent Pahari and the Bengali population were randomly selected and screened by RDT and qPCR. Parasites were genotyped by msp2 and deep sequencing of 5 amplicons (ama1-D3, cpmp, cpp, csp, and msp7) for Plasmodium falciparum (n = 20), and by microsatellite (MS) typing of ten loci and amplicon sequencing of msp1 for Plasmodium vivax (n = 21). Population structure was analysed using STRUCTURE software. Identity-by-state (IBS) was calculated as a measure of parasite relatedness and used to generate relatedness networks. Results The prevalence of P. falciparum and P. vivax infection was 0.7% by RDT (P. falciparum 6/1002; P. vivax 0/1002, mixed: 1/1002) and 4% by qPCR (P. falciparum 21/1002; P. vivax 16/1002, mixed: 5/1002). Infections were highly clustered, with 64% (27/42) of infections occurring in only two Pahari groups, the Khumi and Mro. Diversity was high; expected heterozygosity was 0.93 for P. falciparum and 0.81 for P. vivax. 85.7% (18/21) of P. vivax and 25% (5/20) of P. falciparum infections were polyclonal. No population structure was evident for either species, suggesting high transmission and gene flow among Pahari groups. Conclusions High subclinical infection prevalence and genetic diversity mirror ongoing transmission. Control activities should be specifically directed to Pahari groups at greatest risk.

The early diagnosis of autism spectrum disorder (ASD) encounters challenges stemming from domain variations in facial image datasets. This study investigates the potential of active learning, particularly uncertainty-based sampling, for domain adaptation in early ASD diagnosis. Our focus is on improving model performance across diverse data sources. Utilizing the Kaggle ASD and YTUIA datasets, we meticulously analyze domain variations and assess transfer learning and active learning methodologies. Two state-of-the-art convolutional neural networks, Xception and ResNet50V2, pretrained on distinct datasets, demonstrate noteworthy accuracies of 95% on Kaggle ASD and 96% on YTUIA, respectively. However, combining datasets results in a modest decline in average accuracy, underscoring the necessity for effective domain adaptation techniques. We employ uncertainty-based active learning to address this, which significantly mitigates the accuracy drop. Xception and ResNet50V2 achieve 80% and 79% accuracy when pretrained on Kaggle ASD and applying active learning on YTUIA, respectively. Our findings highlight the efficacy of uncertainty-based active learning for domain adaptation, showcasing its potential to enhance accuracy and reduce annotation needs in early ASD diagnosis. This study contributes to the growing body of literature on ASD diagnosis methodologies. Future research should delve deeper into refining active learning strategies, ultimately paving the way for more robust and efficient ASD detection tools across diverse datasets.

Abstract Background Plasmodium vivax forms dormant liver stages that can reactivate weeks or months following an acute infection. Recurrent infections are often associated with a febrile illness and can cause a cumulative risk of severe anaemia, direct and indirect mortality, and onward transmission of the parasite. There is an increased risk of P. vivax parasitaemia following falciparum malaria suggesting a rationale for universal use of radically curative treatment in patients with P. falciparum malaria even in the absence of detectable P. vivax parasitaemia in areas that are co-endemic for both species. Methods This is a multicentre, health care facility-based, randomized, controlled, open-label trial in Bangladesh, Indonesia and Ethiopia. Patients with uncomplicated falciparum malaria, G6PD activity of ≥70% of the adjusted male median (AMM) and haemoglobin levels ≥8g/dl are recruited into the study and randomized to either receive standard schizonticidal treatment plus 7-day high dose primaquine (total dose 7mg/kg) or standard care in a 1:1 ratio. Patients are followed up weekly until day 63. The primary endpoint is the incidence risk of any P. vivax parasitemia on day 63. Secondary endpoints include incidence risk on day 63 of symptomatic P. vivax malaria and the risk of any P. falciparum parasitaemia. Secondary safety outcomes include the proportion of adverse events and serious adverse events, the incidence risk of severe anaemia (Hb

Solar geoengineering, an emergency climate intervention, could shift one billion people back into areas of malaria risk. Regional tradeoffs and potential adverse outcomes point to the need for health sector planning with Global South leadership.

Ensuring adherence to antimalarial treatment is crucial for achieving a radical cure and elimination of malaria, especially in hard-to-reach areas. We conducted this study to assess the current scenario of drug adherence in four endemic sub-districts of Bangladesh. Among 110 enrolled participants, 70% were mono-infected with Plasmodium falciparum and the remaining 30% with P. vivax. The overall treatment adherence frequency was 92.7% (95% CI: 83.0–96.3%). A total of eight participants were found to be nonadherent to treatment and all of them were from Bandarban. Level of nonadherence was equally observed in two age groups: 11–17 and 18+ years. However, male participants (n = 6) were found to be more nonadherent than females (n = 2). Among 7.3% with nonadherence to treatment, a single participant with P. falciparum mono-infection refused to take medication and became nonadherent. Remaining participants stated that they were feeling well and going to work, thus leaving treatment course uncompleted. Although overall compliance with malaria medication seems good, a gradual increase in noncompliance to P. vivax malaria treatment suggests that the National Malaria Elimination Program must be enhanced and monitored to fulfil the projected malaria elimination goal before 2030 from Bangladesh.

ABSTRACT Accurate and early diagnoses are prerequisites for prompt treatment. For coronavirus disease 2019 (COVID-19), it is even more crucial. Currently, choice of methods include rapid diagnostic tests and reverse transcription polymerase chain reaction (RT-PCR) using samples mostly of respiratory origin and sometimes saliva. We evaluated two rapid diagnostic tests with three specimen types using viral transport medium (VTM) containing naso-oropharyngeal (NOP) swabs, direct nasal and direct nasopharyngeal (NP) samples from 428 prospective patients. We also performed RT-PCR for 428 NOP VTM and 316 saliva samples to compare results. The sensitivity of the SD Biosensor Standard Q COVID-19 antigen (Ag) test kit drastically raised from an average of 65.55% (NOP VTM) to 85.25% (direct nasal samples), while RT-PCR was the gold standard. For the CareStart kit, the sensitivity was almost similar for direct NP swabs; the average was 84.57%. The specificities were ≥95% for both SD Biosensor Standard Q and CareStart COVID-19 Ag tests in all platforms. The kits were also able to detect patients with different variants as well. Alternatively, RT-PCR results from saliva and NOP VTM samples showed high sensitivities of 96.45% and 95.48% with respect to each other as standard. The overall results demonstrated high performance of the rapid tests, indicating the suitability for regular surveillance at clinical facilities when using direct nasal or direct NP samples rather than NOP VTM. Additionally, the analysis also signifies not showed that RT-PCR of saliva can be used as an choice of method to RT-PCR of NOP VTM, providing an easier, non-invasive sample collection method. IMPORTANCE There are several methods for the diagnosis of coronavirus disease 2019 (COVID-19), and the choice of methods depends mostly on the resources and level of sensitivity required by the user and health care providers. Still, reverse transcription polymerase chain reaction (RT-PCR) has been chosen as the best method using direct naso-oropharyngeal swabs. There are also other methods of fast detection, such as rapid diagnostic tests (RDTs), which offer result within 15 to 20 min and have become quite popular for self-testing and in the clinical setting. The major drawback of the currently used RT-PCR method is compliance, as it may cause irritation, and patients often refuse to test in such a way. RDTs, although inexpensive, suffer from low sensitivity due to technical issues. In this article, we propose saliva as a noninvasive source for RT-PCR samples and evaluate various specimen types at different times after infection for the best possible output from COVID-19 rapid tests.

The research describes an effective deep learning-based, data-centric approach for diagnosing autism spectrum disorder from facial images. To classify ASD and non-ASD subjects, this method requires training a convolutional neural network using the facial image dataset. As a part of the data-centric approach, this research applies pre-processing and synthesizing of the training dataset. The trained model is subsequently evaluated on an independent test set in order to assess the performance matrices of various data-centric approaches. The results reveal that the proposed method that simultaneously applies the pre-processing and augmentation approach on the training dataset outperforms the recent works, achieving excellent 98.9% prediction accuracy, sensitivity, and specificity while having 99.9% AUC. This work enhances the clarity and comprehensibility of the algorithm by integrating explainable AI techniques, providing clinicians with valuable and interpretable insights into the decision-making process of the ASD diagnosis model.

Abstract Background The radical cure of Plasmodium vivax requires treatment with an 8-aminoquinoline drug, such as primaquine and tafenoquine, to eradicate liver hypnozoite stages, which can reactivate to cause relapsing infections. Safe treatment regimens require prior screening of patients for glucose-6-phosphate dehydrogenase (G6PD) deficiency to avoid potential life-threatening drug induced haemolysis. Testing is rarely available in malaria endemic countries, but will be needed to support routine use of radical cure. This study investigates end-user perspectives in Bangladesh on the introduction of a quantitative G6PD test (SD Biosensor STANDARD™ G6PD analyser) to support malaria elimination. Methods The perspectives of users on the SD Biosensor test were analysed using semi-structured interviews and focus group discussions with health care providers and malaria programme officers in Bangladesh. Key emerging themes regarding the feasibility of introducing this test into routine practice, including perceived barriers, were analysed. Results In total 63 participants were interviewed. Participants emphasized the life-saving potential of the biosensor, but raised concerns including the impact of limited staff time, high workload and some technical aspects of the device. Participants highlighted that there are both too few and too many P. vivax patients to implement G6PD testing owing to challenges of funding, workload and complex testing infrastructure. Implementing the biosensor would require flexibility and improvisation to deal with remote sites, overcoming a low index of suspicion and mutual interplay of declining patient numbers and reluctance to test. This approach would generate new forms of evidence to justify introduction in policy and carefully consider questions of deployment given declining patient numbers. Conclusions The results of the study show that, in an elimination context, the importance of malaria needs to be maintained for both policy makers and the affected communities, in this case by ensuring P. vivax, PQ treatment, and G6PD deficiency remain visible. Availability of new technologies, such as the biosensor, will fuel ongoing debates about priorities for allocating resources that must be adapted to a constantly evolving target. Technical and logistical concerns regarding the biosensor should be addressed by future product designs, adequate training, strengthened supply chains, and careful planning of communication, advocacy and staff interactions at all health system levels.

Abstract Background Arboviral diseases, including dengue and chikungunya, are major public health concerns in Bangladesh where there have been unprecedented levels of transmission reported in recent years. The primary approach to control these diseases is to control the vector Aedes aegypti using pyrethroid insecticides. Although chemical control has long been practiced, no comprehensive analysis of Ae. aegypti susceptibility to insecticides has been conducted to date. The aim of this study was to determine the insecticide resistance status of Ae. aegypti in Bangladesh and investigate the role of detoxification enzymes and altered target site sensitivity as resistance mechanisms. Methods Eggs of Aedes mosquitoes were collected using ovitraps from five districts across Bangladesh and in eight neighborhoods of the capital city Dhaka, from August to November 2017. CDC bottle bioassays were conducted for permethrin, deltamethrin, malathion, and bendiocarb using 3- to 5-day-old F0–F2 non-blood-fed female mosquitoes. Biochemical assays were conducted to detect metabolic resistance mechanisms, and real-time PCR was performed to determine the frequencies of the knockdown resistance (kdr) mutations Gly1016, Cys1534, and Leu410. Results High levels of resistance to permethrin were detected in all Ae. aegypti populations, with mortality ranging from 0 to 14.8% at the diagnostic dose. Substantial resistance continued to be detected against higher (2×) doses of permethrin (5.1–44.4% mortality). Susceptibility to deltamethrin and malathion varied between populations while complete susceptibility to bendiocarb was observed in all populations. Significantly higher levels of esterase and oxidase activity were detected in most of the test populations as compared to the susceptible reference Rockefeller strain. A significant association was detected between permethrin resistance and the presence of Gly1016 and Cys1534 homozygotes. The frequency of kdr (knockdown resistance) alleles varied across the Dhaka Aedes populations. Leu410 was not detected in any of the tested populations. Conclusions The detection of widespread pyrethroid resistance and multiple resistance mechanisms highlights the urgency for implementing alternate Ae. aegypti control strategies. In addition, implementing routine monitoring of insecticide resistance in Ae. aegypti in Bangladesh will lead to a greater understanding of susceptibility trends over space and time, thereby enabling the development of improved control strategies.

Abstract Background Surveillance of low-density infections and of exposure to vectors is crucial to understand where malaria elimination might be feasible, and where the risk of outbreaks is high. Archived rapid diagnostic tests (RDTs), used by national malaria control and elimination programs for clinical diagnosis, present a valuable, yet rarely used resource for in-depth studies on malaria epidemiology. Methods 1022 RDTs from two sub-Districts in Bangladesh (Alikadam and Kamalganj) were screened by qPCR for low-density Plasmodium falciparum and Plasmodium vivax infections, and by ELISA for Anopheles salivary gland antibodies as a marker for exposure to vectors. Results Concordance between RDT and qPCR was moderate. qPCR detected 31/1022 infections compared to 36/1022 diagnosed by RDT. Exposure to Anopheles was significantly higher in Kamalganj despite low transmission, which could be explained by low bed net use. Conclusions Archived RDTs present a valuable source of antibodies for serological studies on exposure to vectors. In contrast, the benefit of screening archived RDTs to obtain a better estimate of clinical case numbers is moderate. Kamalganj could be prone to outbreaks.

Primaquine and tafenoquine are the only licensed drugs with activity against Plasmodium vivax hypnozoites but cause haemolysis in patients with glucose–6–phosphate dehydrogenase (G6PD) deficiency. Malaria also causes haemolysis, leading to the replacement of older erythrocytes with low G6PD activity by reticulocytes and young erythrocytes with higher activity. Aim of this study was to assess the impact of acute malaria on G6PD activity. Selected patients with uncomplicated malaria were recruited in Bangladesh (n = 87), Indonesia (n = 75), and Ethiopia (n = 173); G6PD activity was measured at the initial presentation with malaria and a median of 176 days later (range 140 to 998) in the absence of malaria. Among selected participants (deficient participants preferentially enrolled in Bangladesh but not at other sites) G6PD activity fell between malaria and follow up by 79.1% (95%CI: 40.4 to 117.8) in 6 participants classified as deficient (

This report describes the MalariaGEN Pv4 dataset, a new release of curated genome variation data on 1,895 samples of Plasmodium vivax collected at 88 worldwide locations between 2001 and 2017. It includes 1,370 new samples contributed by MalariaGEN and VivaxGEN partner studies in addition to previously published samples from these and other sources. We provide genotype calls at over 4.5 million variable positions including over 3 million single nucleotide polymorphisms (SNPs), as well as short indels and tandem duplications. This enlarged dataset highlights major compartments of parasite population structure, with clear differentiation between Africa, Latin America, Oceania, Western Asia and different parts of Southeast Asia. Each sample has been classified for drug resistance to sulfadoxine, pyrimethamine and mefloquine based on known markers at the dhfr, dhps and mdr1 loci. The prevalence of all of these resistance markers was much higher in Southeast Asia and Oceania than elsewhere. This open resource of analysis-ready genome variation data from the MalariaGEN and VivaxGEN networks is driven by our collective goal to advance research into the complex biology of P. vivax and to accelerate genomic surveillance for malaria control and elimination.

ABSTRACT Emerging resistance to artemisinin drugs threatens the elimination of malaria. Resistance is widespread in South East Asia (SEA) and Myanmar. Neighboring Bangladesh, where 90% of infections occur in the Chittagong Hill Tracts (CHTs), lacks recent assessment. We undertook a prospective study in the sole district-level hospital in Bandarban, a CHT district with low population densities but 60% of reported malaria cases. Thirty patients presented with malaria in 2018. An increase to 68 patients in 2019 correlated with the district-level rise in malaria, rainfall, humidity, and temperature. Twenty-four patients (7 in 2018 and 17 in 2019) with uncomplicated Plasmodium falciparum monoinfection were assessed for clearing parasites after starting artemisinin combination therapy (ACT). The median (range) time to clear half of the initial parasites was 5.6 (1.5 to 9.6) h, with 20% of patients showing a median of 8 h. There was no correlation between parasite clearance and initial parasitemia, blood cell counts, or mutations of P. falciparum gene Pfkelch13 (the molecular marker of artemisinin resistance [AR]). The in vitro ring-stage survival assay (RSA) revealed one (of four) culture-adapted strains with a quantifiable resistance of 2.01% ± 0.1% (mean ± standard error of the mean [SEM]). Regression analyses of in vivo and in vitro measurements of the four CHT strains and WHO-validated K13 resistance mutations yielded good correlation (R2 = 0.7; ρ = 0.9, P 90% of malaria in Bangladesh. We show the first establishment of capacity to assess clinical artemisinin resistance directly in patients in the hilltops and laboratory adaptation of Bangladeshi parasite strains from a remote, sparsely populated malaria frontier that is responsive to climate. Our study also provides a generalized model for comprehensive monitoring of drug resistance for countries where malaria is endemic.

Background The introduction of novel short course treatment regimens for the radical cure of Plasmodium vivax requires reliable point-of-care diagnosis that can identify glucose-6-phosphate dehydrogenase (G6PD) deficient individuals. While deficient males can be identified using a qualitative diagnostic test, the genetic make-up of females requires a quantitative measurement. SD Biosensor (Republic of Korea) has developed a handheld quantitative G6PD diagnostic (STANDARD G6PD test), that has approximately 90% accuracy in field studies for identifying individuals with intermediate or severe deficiency. The device can only be considered for routine care if precision of the assay is high. Methods and findings Commercial lyophilised controls (ACS Analytics, USA) with high, intermediate, and low G6PD activities were assessed 20 times on 10 Biosensor devices and compared to spectrophotometry (Pointe Scientific, USA). Each device was then dispatched to one of 10 different laboratories with a standard set of the controls. Each control was tested 40 times at each laboratory by a single user and compared to spectrophotometry results. When tested at one site, the mean coefficient of variation (CV) was 0.111, 0.172 and 0.260 for high, intermediate, and low controls across all devices respectively; combined G6PD Biosensor readings correlated well with spectrophotometry (rs = 0.859, pConclusions Repeatability and inter-laboratory reproducibility of the Biosensor were good; though the device did not reliably discriminate between intermediate and low G6PD activities of the lyophilized specimens. Clinical studies are now required to assess the devices performance in practice. Author summary Novel treatment regimens for the radical cure of P. vivax malaria are more effective than current options but require prior quantitative G6PD testing. The reference method for quantitative G6PD measurement is spectrophotometry but, due to its operational characteristics, is not suitable for routine use. Furthermore, poor inter-laboratory reproducibility of spectrophotometry has prevented quantitative global definitions of G6PD deficiency. SD Biosensor (ROK) have developed a novel handheld “Biosensor” device (G6PD STANDARD), which measures G6PD activity within two minutes and has operational characteristics suited to point of care diagnosis. Reported accuracy of the Biosensor against spectrophotometry is around 90%, but its reproducibility remains unknown. This article reports the reproducibility of the device. Standardized samples were tested in two phases, first by a single user on ten Biosensors and then by ten independent users. All users received a standardized one-hour online training. Measured G6PD activities did not differ significantly across all devices in either phase, demonstrating the capacity to provide user-independent results. If further studies under real life conditions generate comparable results, the Biosensor will allow global cut offs for G6PD deficiency to be defined and will greatly simplify the roll out of novel highly effective radical cure treatment regimens for P. vivax infections.

Abstract Background Malaria elimination requires diagnostic methods able to detect parasite levels well below what is currently possible with microscopy and rapid diagnostic tests. This is particularly true in surveillance of malaria at the population level that includes so-called “asymptomatic” individuals. Methods The development of the first ultrasensitive loop mediated amplification method capable of detecting malaria from both whole blood and dried blood spots (DBS) is described. The 18S rRNA and corresponding genes that remain stable on DBS for up to 5 months are targeted. Results In the case of Plasmodium falciparum, lower limits of detection of 25 parasite/mL and 50–100 parasite/mL from whole blood and DBS were obtained, respectively. A sensitivity of 97.0% (95% CI 82.5–99.8) and specificity of 99.1% (95% CI 97.6–99.7) was obtained for the detection of all species in asymptomatic individuals from Africa and Asia (n = 494). Conclusion This tool is ideally suited for low middle-income countries where malaria is endemic and ultrasensitive surveillance of malaria is highly desirable for elimination.

Amongst the multiple ways to diagnose coronavirus disease-2019 (COVID-19), reverse transcription polymerase chain reaction (RT-PCR) remains the reference gold standard, providing fast and accurate results. This study evaluated and compared the performance of three commercially available COVID-19 RT-PCR kits-Aridia® COVID-19 Real-Time PCR Test (CTK Biotech, Inc., Poway, CA, USA), Novel Coronavirus (2019-nCoV) Nucleic Acid Detection Kit (Sansure Biotech Inc., Changsha, China) and AllplexTM 2019-nCoV assay (Seegene Inc., Seoul, Republic of Korea) for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A total of 326 clinically suspected patients were enrolled for the study, and among them, 209 were diagnosed as positive and 117 as negative when tested with the reference method, US CDC 2019-Novel Coronavirus (2019-nCoV) Real Time RT-PCR Diagnostic Panel. The Aridia® kit showed total agreement with the reference test, with a sensitivity of 100% (95% CI: 98.25% to 100.0%) and a specificity of 100% (96.90% to 100.00%). The AllplexTM kit also showed 100% specificity (95% CI: 96.90% to 100.00%), but a lower sensitivity (98.09%, 95% CI: 95.17% to 99.48%). Among the three kits, the Novel Coronavirus (2019-nCoV) Nucleic Acid Detection Kit showed the worst performance, with a sensitivity of 98.6% (95% CI: 95.9% to 99.7%) and a specificity of 95.73, 95% (CI: 90.31% to 98.60%). While all these kits conform to the requirement for routine molecular diagnosis with high performances, the Aridia® COVID-19 Real-Time PCR Test showed the best performance among the three kits.

BackgroundGlucose-6-phosphate dehydrogenase (G6PD) activity is dependent upon G6PD genotype and age of the red blood cell (RBC) population, with younger RBCs having higher activity. Peripheral parasitemia with Plasmodium spp. induces hemolysis, replacing older RBCs with younger cells with higher G6PD activity. This study aimed to assess whether G6PD activity varies between individuals with and without malaria or a history of malaria.Methods and findingsIndividuals living in the Chittagong Hill Tracts of Bangladesh were enrolled into 3 complementary studies: (i) a prospective, single-arm clinical efficacy trial of patients (n = 175) with uncomplicated malaria done between 2014 and 2015, (ii) a cross-sectional survey done between 2015 and 2016 (n = 999), and (iii) a matched case-control study of aparasitemic individuals with and without a history of malaria done in 2020 (n = 506). G6PD activity was compared between individuals with and without malaria diagnosed by microscopy, rapid diagnostic test (RDT), or polymerase chain reaction (PCR), and in aparasitemic participants with and without a history of malaria. In the cross-sectional survey and clinical trial, 15.5% (182/1,174) of participants had peripheral parasitemia detected by microscopy or RDT, 3.1% (36/1,174) were positive by PCR only, and 81.4% (956/1,174) were aparasitemic. Aparasitemic individuals had significantly lower G6PD activity (median 6.9 U/g Hb, IQR 5.2-8.6) than those with peripheral parasitemia detected by microscopy or RDT (7.9 U/g Hb, IQR 6.6-9.8, p < 0.001), but G6PD activity similar to those with parasitemia detected by PCR alone (submicroscopic parasitemia) (6.1 U/g Hb, IQR 4.8-8.6, p = 0.312). In total, 7.7% (14/182) of patients with malaria had G6PD activity < 70% compared to 25.0% (248/992) of participants with submicroscopic or no parasitemia (odds ratio [OR] 0.25, 95% CI 0.14-0.44, p < 0.001). In the case-control study, the median G6PD activity was 10.3 U/g Hb (IQR 8.8-12.2) in 253 patients with a history of malaria and 10.2 U/g Hb (IQR 8.7-11.8) in 253 individuals without a history of malaria (p = 0.323). The proportion of individuals with G6PD activity < 70% was 11.5% (29/253) in the cases and 15.4% (39/253) in the controls (OR 0.7, 95% CI 0.41-1.23, p = 0.192). Limitations of the study included the non-contemporaneous nature of the clinical trial and cross-sectional survey.ConclusionsPatients with acute malaria had significantly higher G6PD activity than individuals without malaria, and this could not be accounted for by a protective effect of G6PD deficiency. G6PD-deficient patients with malaria may have higher than expected G6PD enzyme activity and an attenuated risk of primaquine-induced hemolysis compared to the risk when not infected.