Plasmodium vivax: who cares?

More attention is being focused on malaria today than any time since the world's last efforts to achieve eradication over 40 years ago. The global community is now discussing strategies aimed at dramatically reducing malarial disease burden and the eventual eradication of all types of malaria, everywhere. As a consequence, Plasmodium vivax, which has long been neglected and mistakenly considered inconsequential, is now entering into the strategic debates taking place on malaria epidemiology and control, drug resistance, pathogenesis and vaccines. Thus, contrary to the past, the malaria research community is becoming more aware and concerned about the widespread spectrum of illness and death caused by up to a couple of hundred million cases of vivax malaria each year. This review brings these issues to light and provides an overview of P. vivax vaccine development, then and now. Progress had been slow, given inherent research challenges and minimal support in the past, but prospects are looking better for making headway in the next few years. P. vivax, known to invade the youngest red blood cells, the reticulocytes, presents a strong challenge towards developing a reliable long-term culture system to facilitate needed research. The P. vivax genome was published recently, and vivax researchers now need to coordinate efforts to discover new vaccine candidates, establish new vaccine approaches, capitalize on non-human primate models for testing, and investigate the unique biological features of P. vivax, including the elusive P. vivax hypnozoites. Comparative studies on both P. falciparum and P. vivax in many areas of research will be essential to eradicate malaria. And to this end, the education and training of future generations of dedicated "malariologists" to advance our knowledge, understanding and the development of new interventions against each of the malaria species infecting humans also will be essential

The Role of Animal Models for Research on Severe Malaria

In light of the recent controversies over the role of animal models for research into the development of new treatments for severe malaria, particularly cerebral disease, a group of scientists came together to discuss the relative merits of a range of animal models and their overlap with the complex clinical syndromes of human disease. While it was not possible to fully resolve differences over the utility of the Plasmodium berghei ANKA model of experimental cerebral malaria, the meeting did bring the two research communities closer together to identify further work to provide information needed to validate the model and revitalise the development of other animal models displaying features of human pathology. The driving force behind this was the desire to ensure better translation of experimental findings into effective treatments for severe malaria

Preliminary Results from the CHOMPTT Laser Time-Transfer Mission

CubeSat Handling of Multisystem Precision Time Transfer (CHOMPTT) is a demonstration of precision ground-to-space time-transfer using a laser link to an orbiting CubeSat. The University of Florida-led mission is a collaboration with the NASA Ames Research Center. The 1U optical time-transfer payload was designed and built by the Precision Space Systems Lab at the University of Florida. The payload was integrated with a NASA Ames NOdeS-derived spacecraft bus to form a 3U spacecraft. The CHOMPTT satellite was successfully launched into low Earth orbit on 16 December 2018 on NASA’s ELaNa XIX mission using the Rocket Lab USA Electron vehicle. Here we describe the mission and report on the status of this unique technology demonstration. We use two satellite laser ranging facilities located at the Kennedy Space Center and Mount Stromlo, Australia to transmit nanosecond, 1064 nm laser pulses to the CHOMPTT CubeSat. These pulses are timed with an atomic clock on the ground and are detected by an avalanche photodetector on CHOMPTT. An event timer records the arrival time with respect to one of the two on-board chip-scale atomic clocks with an accuracy of 200 ps (6cm light-travel time). At the same time, a retroreflector returns the transmitted beam back to the ground. By comparing the transmitted and received times on the ground and the arrival time of the pulses at the CubeSat, the time difference between the ground and space clocks can be measured. This compact, power efficient and secure synchronization technology will enable advanced space navigation, communications, networking, and distributed aperture telescopes in the future

An assessment of false positive rates for malaria rapid diagnostic tests caused by non-Plasmodium infectious agents and immunological factors.

BACKGROUND: Malaria rapid diagnostic tests (RDTs) can produce false positive (FP) results in patients with human African trypanosomiasis and rheumatoid factor (RF), but specificity against other infectious agents and immunological factors is largely unknown. Low diagnostic specificity caused by cross-reactivity may lead to over-estimates of the number of malaria cases and over-use of antimalarial drugs, at the cost of not diagnosing and treating the true underlying condition. METHODS: Data from the WHO Malaria RDT Product Testing Programme was analysed to assess FP rates of 221 RDTs against four infectious agents (Chagas, dengue, Leishmaniasis and Schistosomiasis) and four immunological factors (anti-nuclear antibody, human anti-mouse antibody (HAMA), RF and rapid plasma regain). Only RDTs with a FP rate against clean negative samples less than 10% were included. Paired t-tests were used to compare product-specific FP rates on clean negative samples and samples containing non-Plasmodium infectious agents and immunological factors. RESULTS: Forty (18%) RDTs showed no FP results against any tested infectious agent or immunological factor. In the remaining RDTs significant and clinically relevant increases in FP rates were observed for samples containing HAMA and RF (P<0.001). There were significant correlations between product-matched FP rates for RF and HAMA on all RDT test bands (P<0.001), and FP rates for each infectious agent and immunological factor were also correlated between test bands of combination RDTs (P≤0.002). CONCLUSIONS: False positive results against non-Plasmodium infectious agents and immunological factors does not appear to be a universal property of malaria RDTs. However, since many malaria RDTs have elevated FP rates against HAMA and RF positive samples practitioners may need to consider the possibility of false positive results for malaria in patients with conditions that stimulate HAMA or RF

Comparison of the human immune responses to recombinant proteins representing three distinct surface proteins of Plasmodium vivax merozoites

Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Departamento de Microbiologia, Imunologia e ParasitologiaUniversidade Federal do Pará Departamento de PatologiaCenters for Disease Control and Prevention Division of Parasitic DiseasesInstituto Evandro ChagasUniversidade Federal de Minas Gerais Departamento de ParasitologiaUNIFESP, EPM, Depto. de Microbiologia, Imunologia e ParasitologiaSciEL

A Large Proportion of P. falciparum Isolates in the Amazon Region of Peru Lack pfhrp2 and pfhrp3: Implications for Malaria Rapid Diagnostic Tests

Background: Malaria rapid diagnostic tests (RDTs) offer significant potential to improve the diagnosis of malaria, and are playing an increasing role in malaria case management, control and elimination. Peru, along with other South American countries, is moving to introduce malaria RDTs as components of malaria control programmes supported by the Global Fund for AIDS, TB and malaria. The selection of the most suitable malaria RDTs is critical to the success of the programmes. Methods: Eight of nine microscopy positive P. falciparum samples collected in Iquitos, Peru tested negative or weak positive using HRP2-detecting RDTs. These samples were tested for the presence of pfhrp2 and pfhrp3 and their flanking genes by PCR, as well as the presence of HRP proteins by ELISA. To investigate for geographic extent of HRP-deleted parasites and their temporal occurrence a retrospective study was undertaken on 148 microscopy positive P. falciparum samples collected in different areas of the Amazon region of Peru. Findings: Eight of the nine isolates lacked the pfhrp2 and/or pfhrp3 genes and one or both flanking genes, and the absence of HRP was confirmed by ELISA. The retrospective study showed that 61 (41%) and 103 (70%) of the 148 samples lacked the pfhrp2 or pfhrp3 genes respectively, with 32 (21.6%) samples lacking both hrp genes. Conclusions: This is the first documentation of P. falciparum field isolates lacking pfhrp2 and/or pfhrp3. The high frequency and wide distribution of different parasites lacking pfhrp2 and/or pfhrp3 in widely dispersed areas in the Peruvian Amazon implies that malaria RDTs targeting HRP2 will fail to detect a high proportion of P. falciparum in malaria-endemic areas of Peru and should not be used. RDTs detecting parasite LDH or aldolase and quality microscopy should be use for malaria diagnosis in this region. There is an urgent need for investigation of the abundance and geographic distribution of these parasites in Peru and neighbouring countries

Two nonrecombining sympatric forms of the human malaria parasite Plasmodium ovale occur globally.

BACKGROUND: Malaria in humans is caused by apicomplexan parasites belonging to 5 species of the genus Plasmodium. Infections with Plasmodium ovale are widely distributed but rarely investigated, and the resulting burden of disease is not known. Dimorphism in defined genes has led to P. ovale parasites being divided into classic and variant types. We hypothesized that these dimorphs represent distinct parasite species. METHODS: Multilocus sequence analysis of 6 genetic characters was carried out among 55 isolates from 12 African and 3 Asia-Pacific countries. RESULTS: Each genetic character displayed complete dimorphism and segregated perfectly between the 2 types. Both types were identified in samples from Ghana, Nigeria, São Tomé, Sierra Leone, and Uganda and have been described previously in Myanmar. Splitting of the 2 lineages is estimated to have occurred between 1.0 and 3.5 million years ago in hominid hosts. CONCLUSIONS: We propose that P. ovale comprises 2 nonrecombining species that are sympatric in Africa and Asia. We speculate on possible scenarios that could have led to this speciation. Furthermore, the relatively high frequency of imported cases of symptomatic P. ovale infection in the United Kingdom suggests that the morbidity caused by ovale malaria has been underestimated

A Systems-Based Analysis of Plasmodium vivax Lifecycle Transcription from Human to Mosquito

Most of the 250 million malaria cases outside of Africa are caused by the parasite Plasmodium vivax. Although drugs can be used to treat P. vivax malaria, drug resistance is spreading and there is no available vaccine. Because this species cannot be readily grown in the laboratory there are added challenges to understanding the function of the many hypothetical genes in the genome. We isolated transcriptional messages from parasites growing in human blood and in mosquitoes, labeled the messages and measured how their levels for different parasite growth conditions. The data for 5,419 parasite genes shows extensive changes as the parasite moves between human and mosquito and reveals highly expressed genes whose proteins might represent new therapeutic targets for experimental vaccines. We discover sets of genes that are likely to play a role in the earliest stages of hepatocyte infection. We find intriguing differences in the expression patterns of different blood stage parasites that may be related to host-response status