The dry season is a major challenge for Plasmodium falciparum parasites in many malaria endemic regions, where water availability limits mosquitoes to only part of the year. How P. falciparum bridges two transmission seasons months apart, without being cleared by the host or compromising host survival is poorly understood. Here we show that low levels of P. falciparum parasites persist in the blood of asymptomatic Malian individuals during the 5-to 6-month dry season, rarely causing symptoms and minimally affecting the host immune response. Parasites isolated during the dry season are transcriptionally distinct from those of subjects with febrile malaria in the transmission season, reflecting longer circulation within each replicative cycle, of parasitized erythrocytes without adhering to the vascular endothelium. Low parasite levels during the dry season are not due to impaired replication, but rather increased splenic clearance of longer-circulating infected erythrocytes. We propose that P. falciparum virulence in areas of seasonal malaria transmission is regulated so that the parasite decreases its endothelial binding capacity, allowing increased splenic clearance and enabling several months of subclinical parasite persistence.
BackgroundNew frontier settlements across the Amazon Basin pose a major challenge for malaria elimination in Brazil. Here we describe the epidemiology of malaria during the early phases of occupation of farming settlements in Remansinho area, Brazilian Amazonia. We examine the relative contribution of low-density and asymptomatic parasitemias to the overall Plasmodium vivax burden over a period of declining transmission and discuss potential hurdles for malaria elimination in Remansinho and similar settings.MethodsEight community-wide cross-sectional surveys, involving 584 subjects, were carried out in Remansinho over 3 years and complemented by active and passive surveillance of febrile illnesses between the surveys. We used quantitative PCR to detect low-density asexual parasitemias and gametocytemias missed by conventional microscopy. Mixed-effects multiple logistic regression models were used to characterize independent risk factors for P. vivax infection and disease.Principal Findings/Conclusions P. vivax prevalence decreased from 23.8% (March–April 2010) to 3.0% (April–May 2013), with no P. falciparum infections diagnosed after March–April 2011. Although migrants from malaria-free areas were at increased risk of malaria, their odds of having P. vivax infection and disease decreased by 2–3% with each year of residence in Amazonia. Several findings indicate that low-density and asymptomatic P. vivax parasitemias may complicate residual malaria elimination in Remansinho: (a) the proportion of subpatent infections (i.e. missed by microscopy) increased from 43.8% to 73.1% as P. vivax transmission declined; (b) most (56.6%) P. vivax infections were asymptomatic and 32.8% of them were both subpatent and asymptomatic; (c) asymptomatic parasite carriers accounted for 54.4% of the total P. vivax biomass in the host population; (d) over 90% subpatent and asymptomatic P. vivax had PCR-detectable gametocytemias; and (e) few (17.0%) asymptomatic and subpatent P. vivax infections that were left untreated progressed to clinical disease over 6 weeks of follow-up and became detectable by routine malaria surveillance.
BackgroundThe Americas were the last continent colonized by humans carrying malaria parasites. Plasmodium falciparum from the New World shows very little genetic diversity and greater linkage disequilibrium, compared with its African counterparts, and is clearly subdivided into local, highly divergent populations. However, limited available data have revealed extensive genetic diversity in American populations of another major human malaria parasite, P. vivax.MethodsWe used an improved sample preparation strategy and next-generation sequencing to characterize 9 high-quality P. vivax genome sequences from northwestern Brazil. These new data were compared with publicly available sequences from recently sampled clinical P. vivax isolates from Brazil (BRA, total n = 11 sequences), Peru (PER, n = 23), Colombia (COL, n = 31), and Mexico (MEX, n = 19).Principal findings/ConclusionsWe found that New World populations of P. vivax are as diverse (nucleotide diversity π between 5.2 × 10−4 and 6.2 × 10−4) as P. vivax populations from Southeast Asia, where malaria transmission is substantially more intense. They display several non-synonymous nucleotide substitutions (some of them previously undescribed) in genes known or suspected to be involved in antimalarial drug resistance, such as dhfr, dhps, mdr1, mrp1, and mrp-2, but not in the chloroquine resistance transporter ortholog (crt-o) gene. Moreover, P. vivax in the Americas is much less geographically substructured than local P. falciparum populations, with relatively little between-population genome-wide differentiation (pairwise FST values ranging between 0.025 and 0.092). Finally, P. vivax populations show a rapid decline in linkage disequilibrium with increasing distance between pairs of polymorphic sites, consistent with very frequent outcrossing. We hypothesize that the high diversity of present-day P. vivax lineages in the Americas originated from successive migratory waves and subsequent admixture between parasite lineages from geographically diverse sites. Further genome-wide analyses are required to test the demographic scenario suggested by our data.
Mansonella ozzardi (Nematoda: Onchocercidae) is an understudied filarial nematode, originally described by Patrick Manson in 1897, that can be transmitted by two families of dipteran vectors, biting midges (most of them members of the genus Culicoides) and black flies (genus Simulium). With a patchy geographic distribution from southern Mexico to northwestern Argentina, human infection with M. ozzardi is highly prevalent in some of the Caribbean islands, along riverine communities in the Amazon Basin, and on both sides of the border between Bolivia and Argentina. There is no clinical entity unequivocally associated with M. ozzardi infection, although fever, arthralgia, headache, cold lower extremities, and itchy cutaneous rashes are occasionally mentioned in case report series. More recently, ocular manifestations (especially keratitis) have been associated with mansonelliasis, opening an important area of investigation. Here, we briefly review the biology, epidemiology, pathogenesis, and clinical aspects of M. ozzardi infection and point to some existing knowledge gaps, aiming to stimulate a research agenda to help filling them. IntroductionMansonella ozzardi (Nematoda: Onchocercidae) is one of the several filarial nematodes that infect humans. This relatively unknown parasite has a patchy geographic distribution across Latin America and the Caribbean, from southern Mexico to northwestern Argentina. Most infected people, regardless of the parasite density, are asymptomatic or have few symptoms. As a consequence, infections with M. ozzardi usually remain undiagnosed and untreated. Ill-defined and unspecific symptoms such as fever, arthralgia, headache, cold lower extremities, and itchy cutaneous rashes are occasionally reported by patients, but whether they are caused by M. ozzardi infection remains to be determined. Nevertheless, ocular manifestations potentially associated with mansonelliasis, especially keratitis, have attracted substantial interest from ophthalmologists in recent years. Here, we summarize key biological, epidemiological, and clinical aspects of M. ozzardi infection. We explore recent developments in pathogenesis, laboratory diagnosis, and chemotherapy and discuss the potential public health impact of this highly prevalent but largely neglected New World parasite. Biological featuresThree filarial nematodes of the genus Mansonella are known to cause human mansonelliasis: Mansonella streptocerca, which is endemic to Africa; Mansonella perstans, which is commonly found in Africa but also occurs in South America; and M. ozzardi, which is found exclusively in the Americas and the Caribbean islands.1 Only humans appear to be naturally infected with M. ozzardi; African patas monkeys (Erythrocebus patas), but not chimpanzees, rhesus, capuchin, or squirrel monkeys, are susceptible to experimental infection with this nematode. 4 Several decades later, Orihel and Eberhard described the elusive adult male and female worms recovered from experimentally infected patas monkeys. 2Natural infection with M. ...
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