Repeated praziquantel treatments remodel the genetic and spatial landscape of schistosomiasis risk and transmission

Barbosa, Lúcio Macedo; Reis, Eliana A. G.; Santos, Cláudio R.A. dos; Costa, Jackson Maurício Lopes; Carmo, Theomira Mauadie Azevedo; Aminu, Peace T.; Pitanga, Thassila Nogueira; Ponce-Terashima, Rafael; Blank, Walter; Silva, Luciano K.; Reis, Mitermayer Galvão dos; Blanton, Ronald E.

doi:10.1016/j.ijpara.2016.01.007

Cited by 11 publications

(19 citation statements)

References 41 publications

(51 reference statements)

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“…For instance, in 2015 just over a third of the estimated 13.2 million people who required treatment in Uganda were reported to have received it . In addition, MDA programmes have no effect on recurrent reinfections in hotspots of transmission . More unsettlingly, there are reports of reduced efficacy of PZQ with multiple rounds of MDA .…”

Section: Introductionmentioning

confidence: 99%

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Schistosoma mansoni schistosomula antigens induce Th1/Pro‐inflammatory cytokine responses

Egesa

Lubyayi

Tukahebwa

et al. 2018

Parasite Immunology

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Summary Larvae of Schistosoma (schistosomula) are highly susceptible to host immune responses and are attractive prophylactic vaccine targets, although cellular immune responses against schistosomula antigens in endemic human populations are not well characterized. We collected blood and stool from 54 Schistosoma mansoni ‐infected Ugandans, isolated peripheral blood mononuclear cells and stimulated them for 24 hours with schistosome adult worm and soluble egg antigens ( AWA and SEA ), along with schistosomula recombinant proteins rSmKK7, Lymphocyte Antigen 6 isoforms (rSmLy6A and rSmLy6B), tetraspanin isoforms (rSmTSP6 and rSmTSP7). Cytokines, chemokines and growth factors were measured in the culture supernatants using a multiplex luminex assay, and infection intensity was determined before and at 1 year after praziquantel ( PZQ ) treatment using the Kato‐Katz method. Cellular responses were grouped and the relationship between groups of correlated cellular responses and infection intensity before and after PZQ treatment was investigated. AWA and SEA induced mainly Th2 responses. In contrast, rSmLy6B, rSmTSP6 and rSmTSP7 induced Th1/pro‐inflammatory responses. While recombinant antigens rSmKK7 and rSmLy6A did not induce a Th1/pro‐inflammatory response, they had an association with pre‐treatment infection intensity after adjusting for age and sex. Testing more schistosomula antigens using this approach could provide immune‐epidemiology identifiers necessary for prioritizing next generation schistosomiasis vaccine candidates.

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Section: Introductionmentioning

confidence: 99%

“…1 In addition, MDA programmes have no effect on recurrent reinfections in hotspots of transmission. 2 More unsettlingly, there are reports of reduced efficacy of PZQ with multiple rounds of MDA. 3,4 This suggests that MDA alone is insufficient to control morbidity and prevent schistosomiasis transmission.…”

Section: Introductionmentioning

confidence: 99%

Schistosoma mansoni schistosomula antigens induce Th1/Pro‐inflammatory cytokine responses

Egesa

Lubyayi

Tukahebwa

et al. 2018

Parasite Immunology

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“…in Senegal [ 16 ], or Kenya [ 17 ]) to clear effects of decreasing diversity and effective population size in response to treatment (e.g. in Brazil, [ 18 ]).…”

Section: Introductionmentioning

confidence: 99%

Phenotypic and genotypic monitoring of Schistosoma mansoni in Tanzanian schoolchildren five years into a preventative chemotherapy national control programme

et al. 2017

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Background Schistosoma mansoni is a parasite of profound medical importance. Current control focusses on mass praziquantel (PZQ) treatment of populations in endemic areas, termed Preventative Chemotherapy (PC). Large-scale PC programmes exert prolonged selection pressures on parasites with the potential for, direct and/or indirect, emergence of drug resistance. Molecular methods can help monitor genetic changes of schistosome populations over time and in response to drug treatment, as well as estimate adult worm burdens through parentage analysis. Furthermore, methods such as in vitro drug sensitivity assays help phenotype in vivo parasite genotypic drug efficacy.MethodsWe conducted combined in vitro PZQ efficacy testing with population genetic analyses of S. mansoni collected from children from two schools in 2010, five years after the introduction of a National Control Programme. Children at one school had received four annual PZQ treatments and the other school had received two mass treatments in total. We compared genetic differentiation, indices of genetic diversity, and estimated adult worm burden from parasites collected in 2010 with samples collected in 2005 (before the control programme began) and in 2006 (six months after the first PZQ treatment). Using 2010 larval samples, we also compared the genetic similarity of those with high and low in vitro sensitivity to PZQ.ResultsWe demonstrated that there were individual parasites with reduced PZQ susceptibility in the 2010 collections, as evidenced by our in vitro larval behavioural phenotypic assay. There was no evidence, however, that miracidia showing phenotypically reduced susceptibility clustered together genetically. Molecular analysis also demonstrated a significant reduction of adult worm load over time, despite little evidence of reduction in parasite infection intensity, as measured by egg output. Genetic diversity of infections did not reduce over time, despite changes in the genetic composition of the parasite populations.ConclusionsGenotypic and phenotypic monitoring did not indicate a selective sweep, as may be expected if PZQ treatment was selecting a small number of related “resistant” parasites, but there was evidence of genetic changes at the population level over time. Genetic data were used to estimate adult worm burdens, which unlike parasite infection intensity, showed reductions over time, suggesting the relaxation of negative density-dependent constraints on parasite fecundity with PZQ treatment. We thereby demonstrated that density-dependence in schistosome populations may complicate evaluation and monitoring of control programmes.Electronic supplementary materialThe online version of this article (10.1186/s13071-017-2533-6) contains supplementary material, which is available to authorized users.

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“…Between 2009 to 2013, two rural communities (Jenipapo and Volta do Rio) in the state of Bahia, Brazil were surveyed and treated twice for S. mansoni infections (Barbosa et al, 2016). These villages are 6 km apart on the Jiquiriçá River and have a total population of An average of 85% of the population participated in all three parasitological surveys where three stools were collected on different days, examined for infection and parasite eggs collected from all positive stools.…”

Section: Methodsmentioning

confidence: 99%

“…Our group has taken advantage of the naturally aggregated nature of fecal eggs to collect them from whole stools and determine allele frequencies directly based on this pool. This facilitated examination of every stool egg-positive individual in a small population of 849 in 2009 (Barbosa et al, 2016). With this approach, there is no question of how many eggs or miracidia to sample nor how many hosts.…”

Section: Introductionmentioning

confidence: 99%

The effect of sample size on estimates of genetic differentiation and effective population size for Schistosoma mansoni populations

Barbosa

Barros²,

Rodrigues

et al. 2018

International Journal for Parasitology

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Eradication or local extinction of the human parasite Schistosoma mansoni is a goal for many control programs. Population genetic analyses are helping to evaluate and guide these efforts, yet what to sample, how to sample and how densely to sample is not well established. We determined the S. mansoni allele frequency profile of nearly all infected inhabitants in two small Brazilian communities and created sub-samples representing 5–50% of all detected human infections (infrapopulations). Samples were selected at random with replacement, and each size class was replicated 100 times. Mean pairwise differentiation for all infrappopulations (Di) and the variance effective population size (Ne) were calculated for each sample. Prior to community-wide treatment, the true mean Di was moderate (0.095 – 0.123) and Ne large (>30,000). Most samples of <50% of those infected produced estimates outside of 5% of the true value. For estimates within 10%, sample sizes of >15% of all infrapopulations were required. At the 3 year follow-up after treatment, the Di increased and Ne was reduced by >15 fold. At this time sampling of >30–45% was needed to achieve the same accuracy. Following a second treatment and 4 years from baseline, the Di further increased and Ne decreased with little change in the sampling effort required. Extensive sampling is required for accurate estimates of these important population parameters. Characteristics such as population census size, infection prevalence, the community’s treatment history and the degree of infrapopulation differentiation should be taken into account. The intensity of infection was weakly correlated with the ability of a single infrapopulation to represent the component population (Dic), indicating a tendency toward random acquisition of parasite genotypes. This also suggests that targeted sampling from those most heavily infected will better represent the genetic diversity of the whole community than a random sample of infrapopulations.

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Repeated praziquantel treatments remodel the genetic and spatial landscape of schistosomiasis risk and transmission

Cited by 11 publications

References 41 publications

Schistosoma mansoni schistosomula antigens induce Th1/Pro‐inflammatory cytokine responses

Schistosoma mansoni schistosomula antigens induce Th1/Pro‐inflammatory cytokine responses

Phenotypic and genotypic monitoring of Schistosoma mansoni in Tanzanian schoolchildren five years into a preventative chemotherapy national control programme

The effect of sample size on estimates of genetic differentiation and effective population size for Schistosoma mansoni populations

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