Contribution of Plasmodium immunomics: potential impact for serological testing and surveillance of malaria.

Introduction: Plasmodium vivax (Pv) and P. knowlesi account together for a considerable share of the global burden of malaria, along with P. falciparum (Pf). However, inaccurate diagnosis and undetectable asymptomatic/submicroscopic malaria infections remain very challenging. Blood-stage antigens involved in either invasion of red blood cells or sequestration/cytoadherence of parasitized erythrocytes have been immunomics-characterized, and are vital for the detection of malaria incidence. Areas covered: We review the recent advances in Plasmodium immunomics to discuss serological markers with potential for specific and sensitive diagnosis of malaria. Insights on alternative use of immunomics to assess malaria prevalence are also highlighted. Finally, we provide practical applications of serological markers as diagnostics, with an emphasis on dot immunogold filtration assay which holds promise for malaria diagnosis and epidemiological surveys. Expert commentary: The approach largely contributes to Pf and Pv research in identifying promising non-orthologous antigens able to detect malaria incidence and to differentiate between past and recent infections. However, further studies to profiling naturally acquired immune responses are expected in order to help discover/validate serological markers of no cross-seroreactivity and guide control interventions. More so, the application of immunomics to knowlesi infections would help validate the recently identified antigens and contribute to the discovery of additional biomarkers of exposure, immunity, or both.

Genome-wide scans for the identification of Plasmodium vivax genes under positive selection.

BACKGROUND: The current trend of Plasmodium vivax cases imported from Southeast Asia into China has sharply increased recently, especially from the China-Myanmar border (CMB) area. High recombination rates of P. vivax populations associated with varied transmission intensity might cause distinct local selective pressures. The information on the genetic variability of P. vivax in this area is scant. Hence, this study assessed the genetic diversity of P. vivax genome sequence in CMB area and aimed to provide information on the positive selection of new gene loci. RESULTS: This study reports a genome-wide survey of P. vivax in CMB area, using blood samples from local patients to identify population-specific selective processes. The result showed that considerable genetic diversity and mean pair-wise divergence among the sequenced P. vivax isolates were higher in some important gene families. Using the standardized integrated haplotype score (|iHS|) for all SNPs in chromosomal regions with SNPs above the top 1% distribution, it was observed that the top score locus involved 356 genes and most of them are associated with red blood cell invasion and immune evasion. The XP-EHH test was also applied and some important genes associated with anti-malarial drug resistance were observed in high positive scores list. This result suggests that P. vivax in CMB area is facing more pressure to survive than any other region and this has led to the strong positive selection of genes that are associated with host-parasite interactions. CONCLUSIONS: This study suggests that greater genetic diversity in P. vivax from CMB area and positive selection signals in invasion and drug resistance genes are consistent with the history of drug use during malaria elimination programme in CMB area. Furthermore, this result also demonstrates that haplotype-based detecting selection can assist the genome-wide methods to identify the determinants of P. vivax diversity.

Immunomic approaches for antigen discovery of human parasites.

INTRODUCTION: Genetics combined with proteomics allows for a better understanding of parasite-host interactions and host immune responses. Immunomics elucidates that antigens are targets of induced or naturally acquired immunity (NAI), a promising solution to the challenge of eradicating human infections. High-throughput protein microarrays enhance rapid antigen discovery for the development of serodiagnostic tests/vaccines. Areas covered: This review systematically analyzes the emergence of protein microarrays as a powerful technology for parasite antigen discovery and subsequently summarizes some of the attributes and disadvantages of these approaches. Major insights on novel/validated serological biomarkers or vaccine candidates against malaria and Neglected Tropical Diseases (NTDs) are highlighted. We conclude with a brief description of the processes involved in immunomic protein microarrays. Expert commentary: Interesting discoveries have been made using protein microarrays. However, there is a need to evaluate targets that elicit strong immunogenicity and correlates of protective efficacy to aid prioritization and guide further clinical development. The goal of parasitic disease elimination will be best achieved through an integrated strategy that will incorporate and implement the different control components.

A Molecular Investigation of Malaria Infections From High-Transmission Areas of Southern Togo Reveals Different Species of Plasmodium Parasites.

Malaria particularly burdens people in poor and neglected settings across the tropics of Africa. Meanwhile, a large proportion of the Togo population have poor understanding of malaria epidemiology and parasites. This study carried out a molecular survey of malaria cases in southern Togo during 2017-2019. We estimated Plasmodium species infection rates and microscopic examination compliance with nested PCR results. Sensitivity and specificity analyses were performed in conjunction with predictive values. Also, phylogenetic characterization of species of malaria parasites was assessed. Plasmodium genus-specific nested PCR identified 565 positive cases including 536/611 (87.8%) confirmed cases from the microscopy-positive group and 29/199 (14.6%) diagnosed malaria cases from the microscopy-negative group. Our findings revealed a disease prevalence (69.8%) higher than that reported (25.5-55.1%) for the country. The diagnostic test had 94.9% sensitivity and 69.4% specificity, i.e., it missed 120 of the people who had malaria and about one-third of the people tested positive for the disease, which they did not have, respectively. In conjunction, the test showed 87.7% positive predictive value and 85.4% negative predictive value, which, from a clinical perspective, indicates the chance that a person with a positive diagnostic test truly has the disease and the probability that a person with a negative test does not have the disease, respectively. Further species-specific nested PCR followed by analysis of gene sequences confirmed species of malaria parasites and indicated infection rates for Plasmodium falciparum (Pf), 95.5% (540/565); P. ovale (Po), 0.5% (3/565); and P. malariae (Pm), 0.4% (2/565). In addition, 20 cases were coinfection cases of Pf-Po (15/565) and Pf-Pm (5/565). This study publicly reports, for the first time, a molecular survey of malaria cases in Togo and reveals the presence of other malaria parasites (Po and Pm) other than Pf. These findings might provide answers to some basic questions on the malaria scenario and, knowledge gained could help with intervention deployment for effective malaria control in Togo.

Spatio-temporal distribution characteristics of cysticercosis from 2000 to 2014 in Dali, Yunnan province, China.

Cysticercosis remains a public health problem in China, with disease prevalence attributed to poor socio-economic and public health conditions. This parasitic food-borne disease was prioritized for effective control following implementation of the national surveys on parasitic diseases carried out in China. We predicted the cysticercosis distribution in Dali, Yunnan Province by assessing spatio-temporal distribution characteristics between 2000 and 2014 to better understand the trend of the disease incidence. A database of cysticercosis cases was provided by the clinical department at the Dali Prefectural Institute of Research and Control of Schistosomiasis. Describing the epidemiological features of cysticercosis and analyzing its spatiotemporal distribution of cases using mapping, scanning and spatial autocorrelation analysis, our findings found a total of 3,347 patients with cysticercosis infection, neurocysticercosis in particular. Cysticercosis prevalence was the highest among young and middle-aged male farmers, and also predominant among the Bai nationality. Three aggregation areas were identified during the period 2000-2014. Hotspot analysis implicated Dali City, Eryuan County and Yangbi County between 2000 and 2007, with areas gradually shifting towards the western and northern parts of the province. The hotspot map indicated that Eryuan County was a constant problem with respect to cysticercosis. The results indicated three cysticercosis clusters in Dali that could be attributed to environmental factors and unhealthy lifestyles. Multi-sectoral control initiatives are, therefore, recommended in these areas to effectively control and prevent cysticercosis among the population.

Intestinal microbiome profiles in Oncomelania hupensis in mainland China.

Oncomelania hupensis plays a significant role in the transmission of schistosomiasis japonica, which remains a major public health concern in China. Understanding the biological characteristics of O. hupensis is a prerequisite for its control; however, there are currently no studies investigating the intestinal microbiota of the O. hupensis snail. This study aimed to profile the intestinal microbiome of O. hupensis across different ecological landscapes in mainland China. DNA was extracted from the intestines of the collected snails and the bacterial communities were detected using 454 pyrosequencing. A total of 3,799 operational taxonomic units (OTUs) were obtained, and Proteobacteria, Firmicutes, and Actinobacteria were identified as the dominant bacterial taxa at the phylum level. Bacillus and Lactococcus were the most common genera in samples obtained from the four ecological landscapes. Snail specimens were clustered into three clades according to microbial community diversity, and thirty-seven genera that contributed to differential microbiota distributions were identified. Co-occurrence network analysis indicated a symbiotic relationship for the intestinal microbiota of O. hupensis, and PICRUSt analysis predicted forty-one metabolic functions in all snail samples, including membrane transport, amino acid metabolism, carbohydrate metabolism, replication and repair, energy metabolism, as well as xenobiotics biodegradation and metabolism. These findings improve our understanding of bacterial ecology in the O. hupensis intestine; further studies will focus on the relationship between O. hupensis intestinal microbiota and the microbiota in their specific ecological environments.

High-resolution remote sensing-based spatial modeling for the prediction of potential risk areas of schistosomiasis in the Dongting Lake area, China.

The geographical distribution of snail (i.e., the intermediate host of schistosomiasis) is consistent with that of endemic areas. The suitable snail habitus requires necessary environmental conditions for snail population. The high-resolution remote sensing provides an important tool for the spatio-temporal analysis of disease monitoring and prediction. This study conducted a typical schistosomiasis epidemic area in the marshland and lake regions along the Yangtze River, Yueyang City, Hunan Province of China. And three types of environmental factors, i.e., NDVI, soil moisture, and shortest distance to water body, associated with the geographical distribution of snail population, were extracted from the high-resolution remoting sensing data. The predicted distribution of snail habitus from the high-resolution environmental factors were compared with the data of annual program of snail survey. The results have shown that the application of high-resolution remote sensing can improve the accuracy of the modeled and predicted the potential risk areas of schistosomiasis, and may become an important tool for the ongoing national schistosomiasis control program.

High-resolution remote sensing-based spatial modeling for the prediction of potential risk areas of schistosomiasis in the Dongting Lake area, China.

The geographical distribution of snail (i.e., the intermediate host of schistosomiasis) is consistent with that of endemic areas. The suitable snail habitus requires necessary environmental conditions for snail population. The high-resolution remote sensing provides an important tool for the spatio-temporal analysis of disease monitoring and prediction. This study conducted a typical schistosomiasis epidemic area in the marshland and lake regions along the Yangtze River, Yueyang City, Hunan Province of China. And three types of environmental factors, i.e., NDVI, soil moisture, and shortest distance to water body, associated with the geographical distribution of snail population, were extracted from the high-resolution remoting sensing data. The predicted distribution of snail habitus from the high-resolution environmental factors were compared with the data of annual program of snail survey. The results have shown that the application of high-resolution remote sensing can improve the accuracy of the modeled and predicted the potential risk areas of schistosomiasis, and may become an important tool for the ongoing national schistosomiasis control program.

Integrating ecological approaches to interrupt schistosomiasis transmission: opportunities and challenges.

BACKGROUND: The development of agenda for global schistosomiasis elimination as a public health problem generates enthusiasms among global health communities, motivating great interests in both research and practice. Recent China-Africa schistosomiasis control initiatives, aiming to enhance collaboration on disease control in African countries, reflect in part that momentum. Yet there is a pressing need to know whether the Chinese experiences can be translated and applied in African settings. MAIN BODY: China's remarkable achievements in schistosomiasis control programme, associated experiences and lessons, have much to offer to those combating the disease. Central to the success of China's control programmes is a strategy termed "integrated control" - integrating environmental approaches (e.g. improved sanitation, agricultural and hydrological development and management), which target different phases of the parasite transmission system, to chemical-based drug treatment and mollusciciding. Yet, despite significant measurable public health benefits, such integration is usually based on field experience and remains largely uncharacterized in an ecological context. This has limited our knowledge on relative contributions of varying components of the integrated control programme to the suppression of disease transmission, making it challenging to generalize the strategy elsewhere. In this opinion article, we have described and discussed these challenges, along with opportunities and research needs to move forward. CONCLUSIONS: There is an urgent need to formalize an ecological framework for the integrated control programme that would allow research towards improved mechanistic understanding, quantification, and prediction of the control efforts.

Differentiating snail intermediate hosts of Schistosoma spp. using molecular approaches: fundamental to successful integrated control mechanism in Africa.

BACKGROUND: Snail intermediate hosts play active roles in the transmission of snail-borne trematode infections in Africa. A good knowledge of snail-borne diseases epidemiology particularly snail intermediate host populations would provide the necessary impetus to complementing existing control strategy. MAIN BODY: This review highlights the importance of molecular approaches in differentiating snail hosts population structure and the need to provide adequate information on snail host populations by updating snail hosts genome database for Africa, in order to equip different stakeholders with adequate information on the ecology of snail intermediate hosts and their roles in the transmission of different diseases. Also, we identify the gaps and areas where there is need for urgent intervention to facilitate effective integrated control of schistosomiasis and other snail-borne trematode infections. CONCLUSIONS: Prioritizing snail studies, especially snail differentiation using molecular tools will boost disease surveillance and also enhance efficient schistosomaisis control programme in Africa.