Indoles as therapeutics of interest in medicinal chemistry: Bird's eye view.

In spite of significant progress towards malaria control and elimination achieved in South America in the 2000s, this mosquito-transmitted tropical disease remains an important public health concern in the region. Most malaria cases in South America come from Amazon rain forest areas in northern countries, where more than half of malaria is caused by Plasmodium vivax, while Plasmodium falciparum malaria incidence has decreased in recent years. This review discusses current malaria data, policies and challenges in four South American Amazon countries: Brazil, Colombia, Peru and the Bolivarian Republic of Venezuela. Challenges to continuing efforts to further decrease malaria incidence in this region include: a significant increase in malaria cases in recent years in Venezuela, evidence of submicroscopic and asymptomatic infections, peri-urban malaria, gold mining-related malaria, malaria in pregnancy, glucose-6-phosphate dehydrogenase (G6PD) deficiency and primaquine use, and possible under-detection of Plasmodium malariae. Some of these challenges underscore the need to implement appropriate tools and procedures in specific regions, such as a field-compatible molecular malaria test, a P. malariae-specific test, malaria diagnosis and appropriate treatment as part of regular antenatal care visits, G6PD test before primaquine administration for P. vivax cases (with weekly primaquine regimen for G6PD deficient individuals), single low dose of primaquine for P. falciparum malaria in Colombia, and national and regional efforts to contain malaria spread in Venezuela urgently needed especially in mining areas. Joint efforts and commitment towards malaria control and elimination should be strategized based on examples of successful regional malaria fighting initiatives, such as PAMAFRO and RAVREDA/AMI.

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Malaria in Brazil, Colombia, Peru and Venezuela: current challenges in malaria control and elimination

Translating genomic technologies into healthcare applications for the malaria parasite Plasmodium falciparum has been limited by the technical and logistical difficulties of obtaining high quality clinical samples from the field. Sampling by dried blood spot (DBS) finger-pricks can be performed safely and efficiently with minimal resource and storage requirements compared with venous blood (VB). Here, the use of selective whole genome amplification (sWGA) to sequence the P. falciparum genome from clinical DBS samples was evaluated, and the results compared with current methods that use leucodepleted VB. Parasite DNA with high (>95%) human DNA contamination was selectively amplified by Phi29 polymerase using short oligonucleotide probes of 8–12 mers as primers. These primers were selected on the basis of their differential frequency of binding the desired (P. falciparum DNA) and contaminating (human) genomes. Using sWGA method, clinical samples from 156 malaria patients, including 120 paired samples for head-to-head comparison of DBS and leucodepleted VB were sequenced. Greater than 18-fold enrichment of P. falciparum DNA was achieved from DBS extracts. The parasitaemia threshold to achieve >5× coverage for 50% of the genome was 0.03% (40 parasites per 200 white blood cells). Over 99% SNP concordance between VB and DBS samples was achieved after excluding missing calls. The sWGA methods described here provide a reliable and scalable way of generating P. falciparum genome sequence data from DBS samples. The current data indicate that it will be possible to get good quality sequence on most if not all drug resistance loci from the majority of symptomatic malaria patients. This technique overcomes a major limiting factor in P. falciparum genome sequencing from field samples, and paves the way for large-scale epidemiological applications.

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Whole genome sequencing of Plasmodium falciparum from dried blood spots using selective whole genome amplification

Nucleic acid testing (NAT) has been studied extensively in paper-based diagnostics, presenting a substantially higher sensitivity and specificity than immunoassays Paper-based NAT provides an alternative to laborious, expensive and time-consuming conventional NAT Recent advances in paper fabrication and modification technologies have made it possible to integrate all key steps of NAT (ie, sample preparation, nucleic acid amplification and amplicon detection) into one single paper-based device, and are hence suitable for resource-poor settings However, multiple challenges are yet to be addressed to translate the technologies into practical applications In the present review, we discuss the current status and challenges in accomplishing each key step of NAT using low-cost paper substrates We highlight the most recent advances, challenges and possible solutions in integrating all these steps into a compact paper-based device We also review the latest progress towards commercialization and future perspectives on the development of an ideal sample-in-answer-out device

Advances and challenges of fully integrated paper-based point-of-care nucleic acid testing

Macroscopic descriptions of populations commonly assume that encounters between individuals are well mixed; ie each individual has an equal chance of coming into contact with any other individual Relaxing this assumption can be challenging though, due to the difficulty of acquiring detailed knowledge about the non-random nature of encounters Here, we fitted a mathematical model of dengue virus transmission to spatial time-series data from Pakistan and compared maximum-likelihood estimates of 'mixing parameters' when disaggregating data across an urban-rural gradient We show that dynamics across this gradient are subject not only to differing transmission intensities but also to differing strengths of nonlinearity due to differences in mixing Accounting for differences in mobility by incorporating two fine-scale, density-dependent covariate layers eliminates differences in mixing but results in a doubling of the estimated transmission potential of the large urban district of Lahore We furthermore show that neglecting spatial variation in mixing can lead to substantial underestimates of the level of effort needed to control a pathogen with vaccines or other interventions We complement this analysis with estimates of the relationships between dengue transmission intensity and other putative environmental drivers thereof

https://royalsocietypublishing.org/doi/pdf/10.1098/rsif.2015.0468

Big city, small world: density, contact rates, and transmission of dengue across Pakistan.

The Asia Pacific Malaria Elimination Network (APMEN) is a collaboration of 18 country partners committed to eliminating malaria from within their borders. Over the past 5 years, APMEN has helped to build the knowledge, tools and in-country technical expertise required to attain this goal. At its inaugural meeting in Brisbane in 2009, Plasmodium vivax infections were identified across the region as a common threat to this ambitious programme; the APMEN Vivax Working Group was established to tackle specifically this issue. The Working Group developed a four-stage strategy to identify knowledge gaps, build regional consensus on shared priorities, generate evidence and change practice to optimize malaria elimination activities. This case study describes the issues faced and the solutions found in developing this robust strategic partnership between national programmes and research partners within the Working Group. The success of the approach adopted by the group may facilitate similar applications in other regions seeking to deploy evidence-based policy and practice.

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P Grewal-Daumerie

Papers

Targeting vivax malaria in the Asia Pacific: The Asia Pacific Malaria Elimination Network Vivax Working Group