Outdoor malaria transmission in forested villages of Cambodia

Durnez, Lies; Sokny, Mao; Denis, Leen; Roelants, Patricia; Sochantha, Tho; Coosemans, Marc

doi:10.1186/1475-2875-12-329

Cited by 118 publications

(126 citation statements)

References 33 publications

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“…In P. vivax, a strong New World vs. Old World divide correlates with genetic variation in pvs47, the ortholog of pfs47, which has been associated with differential infectivity in different mosquito species (63,64). However, both Anopheles dirus s.s. and Anopheles minimus s.s., the main malaria vectors in Cambodia, are adept at transmitting both P. falciparum and P. vivax (65,66). Therefore we do not think that the species-specific differences observed in population structure and signatures of selection are attributable solely to unmeasured mosquito factors.…”

Section: Discussionmentioning

confidence: 99%

Selective sweep suggests transcriptional regulation may underlie Plasmodium vivax resilience to malaria control measures in Cambodia

Parobek

Lin

Saunders

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Cambodia, in which both Plasmodium vivax and Plasmodium falciparum are endemic, has been the focus of numerous malaria-control interventions, resulting in a marked decline in overall malaria incidence. Despite this decline, the number of P. vivax cases has actually increased. To understand better the factors underlying this resilience, we compared the genetic responses of the two species to recent selective pressures. We sequenced and studied the genomes of 70 P. vivax and 80 P. falciparum isolates collected between 2009 and 2013. We found that although P. falciparum has undergone population fracturing, the coendemic P. vivax population has grown undisrupted, resulting in a larger effective population size, no discernable population structure, and frequent multiclonal infections. Signatures of selection suggest recent, species-specific evolutionary differences. Particularly, in contrast to P. falciparum, P. vivax transcription factors, chromatin modifiers, and histone deacetylases have undergone strong directional selection, including a particularly strong selective sweep at an AP2 transcription factor. Together, our findings point to different population-level adaptive mechanisms used by P. vivax and P. falciparum parasites. Although population substructuring in P. falciparum has resulted in clonal outgrowths of resistant parasites, P. vivax may use a nuanced transcriptional regulatory approach to population maintenance, enabling it to preserve a larger, more diverse population better suited to facing selective threats. We conclude that transcriptional control may underlie P. vivax's resilience to malaria control measures. Novel strategies to target such processes are likely required to eradicate P. vivax and achieve malaria elimination.D uring the last decade, western Cambodia has been the focus of numerous and multimodal interventions to control the spread of artemisinin-resistant Plasmodium falciparum (1, 2). Such interventions, including increased vector control, increased surveillance, and improved access to quality artemisinin-combination therapy (ACT), would be expected to curtail coendemic Plasmodium vivax as well. However, even as P. falciparum infections in Cambodia decreased by 81% between 2009 and 2013, P. vivax cases have increased, making it the predominant species in the Mekong region (3-6). This scenario, repeated in Brazil and other areas of coendemicity, has led to growing awareness that P. vivax, although infecting the same populations and transmitted by the same mosquito vectors, will likely be the more challenging species to eradicate (6-9). In this study, we use population genomics to gain insight into the evolutionary factors underlying P. vivax's resilience to malaria control measures.Population genetic studies have previously hinted at the resilience of P. vivax populations in comparison with P. falciparum. Studies of microsatellites and highly variable antigens of sympatric P. vivax and P. falciparum populations in Southeast Asia and the Southwest Pacific have consistently shown P. viv...

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Section: Discussionmentioning

confidence: 99%

Selective sweep suggests transcriptional regulation may underlie Plasmodium vivax resilience to malaria control measures in Cambodia

Parobek

Lin

Saunders

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…Strategies to protect high-risk individuals from contracting malaria need to be developed, taking into account that the two main forest-related vectors, Anopheles dirus and Anopheles minumus are outdoor biting mosquitoes. 22,32 Surprisingly, the PCR failed to detect 18 infections (0.23%) found positive by microscopy (five P. falciparum, 12 P. vivax, and one mixed P. falciparum/P. vivax).…”

Section: 29mentioning

confidence: 99%

National Malaria Prevalence in Cambodia: Microscopy Versus Polymerase Chain Reaction Estimates

Lek¹,

Popovici²,

Ariey³

et al. 2016

The American Society of Tropical Medicine and Hygiene

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Abstract. Accurate information regarding malaria prevalence at national level is required to design and assess malaria control/elimination efforts. Although many comparisons of microscopy and polymerase chain reaction (PCR)-based methods have been conducted, there is little published literature covering such comparisons in southeast Asia especially at the national level. Both microscopic examination and PCR detection were performed on blood films and dried blood spots samples collected from 8,067 individuals enrolled in a nationwide, stratified, multistage, cluster sampling malaria prevalence survey conducted in Cambodia in 2007. The overall malaria prevalence and prevalence rates of Plasmodium falciparum, Plasmodium vivax, and Plasmodium malariae infections estimated by microscopy (N ¼ 8,067) were 2.74% (95% confidence interval [CI]: 2.39-3.12%), 1.81% (95% CI: 1.53-2.13%), 1.14% (95% CI: 0.92-1.40%), and 0.01% (95% CI: 0.003-0.07%), respectively. The overall malaria prevalence based on PCR detection (N ¼ 7,718) was almost 2.5-fold higher (6.31%, 95% CI: 5.76-6.89%, P < 0.00001). This difference was significantly more pronounced for P. falciparum (4.40%, 95% CI: 3.95-4.90%, P < 0.00001) compared with P. vivax (1.89%, 95% CI: 1.60-2.22%, P < 0.001) and P. malariae infections (0.22%, 95% CI: 0.13-0.35%, P < 0.0001). The significant proportion of microscopy-negative but PCR-positive individuals (289/7,491, 3.85%) suggest microscopic examination frequently underestimated malaria infections and that active case detection based on microscopy may miss a significant reservoir of infection, especially in low-transmission settings. BACKGROUND

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“…mosquitoes are active (23)(24)(25)(26). Therefore, the quest to develop malaria vaccines continues apace (3,6).…”

mentioning

confidence: 99%

Synergistic and antagonistic interactions between bednets and vaccines in the control of malaria

Artzy‐Randrup

Dobson

Pascual

2015

Proc. Natl. Acad. Sci. U.S.A.

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It is extremely likely that the malaria vaccines currently in development will be used in conjunction with treated bednets and other forms of malaria control. The interaction of different intervention methods is at present poorly understood in a disease such as malaria where immunity is more complex than for other pathogens that have been successfully controlled by vaccination. Here we develop a general mathematical model of malaria transmission to examine the interaction between vaccination and bednets. Counterintuitively, we find that the frailty of malaria immunity will potentially cause both synergistic and antagonistic interactions between vaccination and the use of bednets. We explore the conditions that create these tensions, and outline strategies that minimize their detrimental impact. Our analysis specifically considers the three leading vaccine classes currently in development: preerythrocytic (PEV), blood stage (BSV), and transmission blocking (TBV). We find that the combination of BSV with treated bednets can lead to increased morbidity with no added value in terms of elimination; the interaction is clearly antagonistic. In contrast, there is strong synergy between PEV and treated bednets that may facilitate elimination, although transient stages are likely to increase morbidity. The combination of TBV with treated bednets is synergistic, lowering both morbidity and elimination thresholds. Our results suggest that vaccines will not provide a straightforward solution to malaria control, and that future programs need to consider the synergistic and antagonistic interactions between vaccines and treated bednets.

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Outdoor malaria transmission in forested villages of Cambodia

Cited by 118 publications

References 33 publications

Selective sweep suggests transcriptional regulation may underlie Plasmodium vivax resilience to malaria control measures in Cambodia

Selective sweep suggests transcriptional regulation may underlie Plasmodium vivax resilience to malaria control measures in Cambodia

National Malaria Prevalence in Cambodia: Microscopy Versus Polymerase Chain Reaction Estimates

Synergistic and antagonistic interactions between bednets and vaccines in the control of malaria

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