Recent gains in reducing the global burden of malaria are threatened by the emergence of Plasmodium falciparum resistance to artemisinins. The discovery that mutations in portions of a P. falciparum gene encoding kelch (K13)–propeller domains are the major determinant of resistance has provided opportunities for monitoring such resistance on a global scale. We analyzed the K13-propeller sequence polymorphism in 14,037 samples collected in 59 countries in which malaria is endemic. Most of the samples (84.5%) were obtained from patients who were treated at sentinel sites used for nationwide surveillance of antimalarial resistance. We evaluated the emergence and dissemination of mutations by haplotyping neighboring loci. We identified 108 nonsynonymous K13 mutations, which showed marked geographic disparity in their frequency and distribution. In Asia, 36.5% of the K13 mutations were distributed within two areas — one in Cambodia, Vietnam, and Laos and the other in western Thailand, Myanmar, and China — with no overlap. In Africa, we observed a broad array of rare nonsynonymous mutations that were not associated with delayed parasite clearance. The gene-edited Dd2 transgenic line with the A578S mutation, which expresses the most frequently observed African allele, was found to be susceptible to artemisinin in vitro on a ring-stage survival assay. No evidence of artemisinin resistance was found outside Southeast Asia and China, where resistance-associated K13 mutations were confined. The common African A578S allele was not associated with clinical or in vitro resistance to artemisinin, and many African mutations appear to be neutral. (Funded by Institut Pasteur Paris and others.)

Additive manufacturing (AM), an enabler of Industry 4.0, recently opened limitless possibilities in various sectors covering personal, industrial, medical, aviation and even extra-terrestrial applications. Although significant research thrust is prevalent on this topic, a detailed review covering the impact, status, and prospects of artificial intelligence (AI) in the manufacturing sector has been ignored in the literature. Therefore, this review provides comprehensive information on smart mechanisms and systems emphasizing additive, subtractive and/or hybrid manufacturing processes in a collaborative, predictive, decisive, and intelligent environment. Relevant electronic databases were searched, and 248 articles were selected for qualitative synthesis. Our review suggests that significant improvements are required in connectivity, data sensing, and collection to enhance both subtractive and additive technologies, though the pervasive use of AI by machines and software helps to automate processes. An intelligent system is highly recommended in both conventional and non-conventional subtractive manufacturing (SM) methods to monitor and inspect the workpiece conditions for defect detection and to control the machining strategies in response to instantaneous output. Similarly, AM product quality can be improved through the online monitoring of melt pool and defect formation using suitable sensing devices followed by process control using machine learning (ML) algorithms. Challenges in implementing intelligent additive and subtractive manufacturing systems are also discussed in the article. The challenges comprise difficulty in self-optimizing CNC systems considering real-time material property and tool condition, defect detections by in-situ AM process monitoring, issues of overfitting and underfitting data in ML models and expensive and complicated set-ups in hybrid manufacturing processes.

Serostudies are needed to answer generalizable questions on disease risk. However, recruitment is usually biased by age or location. We present a nationally-representative study for dengue from 70 communities in Bangladesh. We collected data on risk factors, trapped mosquitoes and tested serum for IgG. Out of 5866 individuals, 24% had evidence of historic infection, ranging from 3% in the north to >80% in Dhaka. Being male (aOR:1.8, [95%CI:1.5–2.0]) and recent travel (aOR:1.3, [1.1–1.8]) were linked to seropositivity. We estimate that 40 million [34.3–47.2] people have been infected nationally, with 2.4 million ([1.3–4.5]) annual infections. Had we visited only 20 communities, seropositivity estimates would have ranged from 13% to 37%, highlighting the lack of representativeness generated by small numbers of communities. Our findings have implications for both the design of serosurveys and tackling dengue in Bangladesh.

Bangladesh is a malaria hypo-endemic country sharing borders with India and Myanmar. Artemisinin combination therapy (ACT) remains successful in Bangladesh. An increase of artemisinin-resistant malaria parasites on the Thai-Cambodia and Thai-Myanmar borders is worrisome. K13 propeller gene (PF3D7_1343700 or PF13_0238) mutations have been linked to both in vitro artemisinin resistance and in vivo slow parasite clearance rates. This group undertook to evaluate if mutations seen in Cambodia have emerged in Bangladesh where ACT use is now standard for a decade. Samples were obtained from Plasmodium falciparum-infected malaria patients from Upazila health complexes (UHC) between 2009 and 2013 in seven endemic districts of Bangladesh. These districts included Khagrachari (Matiranga UHC), Rangamati (Rajasthali UHC), Cox’s Bazar (Ramu and Ukhia UHC), Bandarban (Lama UHC), Mymensingh (Haluaghat UHC), Netrokona (Durgapur and Kalmakanda UHC), and Moulvibazar (Sreemangal and Kamalganj UHC). Out of 296 microscopically positive P. falciparum samples, 271 (91.6%) were confirmed as mono-infections by both real-time PCR and nested PCR. The K13 propeller gene from 253 (93.4%) samples was sequenced bi-directionally. One non-synonymous mutation (A578S) was found in Bangladeshi clinical isolates. The A578S mutation was confirmed and lies adjacent to the C580Y mutation, the major mutation causing delayed parasite clearance in Cambodia. Based on computational modeling A578S should have a significant effect on tertiary structure of the protein. The data suggest that P. falciparum in Bangladesh remains free of the C580Y mutation linked to delayed parasite clearance. However, the mutation A578S is present and based on structural analysis could affect K13 gene function. Further in vivo clinical studies are required to validate the effect of this mutation.

Information related to malaria vectors is very limited in Bangladesh. In the changing environment and various Anopheles species may be incriminated and play role in the transmission cycle. This study was designed with an intention to identify anopheline species and possible malaria vectors in the border belt areas, where the malaria is endemic in Bangladesh.

The delivery of safe and effective radical cure for Plasmodium vivax is one of the greatest challenges for achieving malaria elimination from the Asia–Pacific by 2030. During the annual meeting of the Asia Pacific Malaria Elimination Network Vivax Working Group in October 2016, a round table discussion was held to discuss the programmatic issues hindering the widespread use of primaquine (PQ) radical cure. Participants included 73 representatives from 16 partner countries and 33 institutional partners and other research institutes. In this meeting report, the key discussion points are presented and grouped into five themes: (i) current barriers for glucose-6-phosphate deficiency (G6PD) testing prior to PQ radical cure, (ii) necessary properties of G6PD tests for wide scale deployment, (iii) the promotion of G6PD testing, (iv) improving adherence to PQ regimens and (v) the challenges for future tafenoquine (TQ) roll out. Robust point of care (PoC) G6PD tests are needed, which are suitable and cost-effective for clinical settings with limited infrastructure. An affordable and competitive test price is needed, accompanied by sustainable funding for the product with appropriate training of healthcare staff, and robust quality control and assurance processes. In the absence of quantitative PoC G6PD tests, G6PD status can be gauged with qualitative diagnostics, however none of the available tests is currently sensitive enough to guide TQ treatment. TQ introduction will require overcoming additional challenges including the management of severely and intermediately G6PD deficient individuals. Robust strategies are needed to ensure that effective treatment practices can be deployed widely, and these should ensure that the caveats are outweighed by the benefits of radical cure for both the patients and the community. Widespread access to quality controlled G6PD testing will be critical.