scholarly journals The prevalence and density of asymptomatic Plasmodium falciparum infections among children and adults in three communities of western Kenya

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Christina Salgado ◽  
George Ayodo ◽  
Michael D. Macklin ◽  
Meetha P. Gould ◽  
Srinivas Nallandhighal ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Malaria Incidence ◽  
Experimental Studies ◽  
Low Density ◽  
Healthy Children ◽  
Cross Sectional Survey ◽  
Western Kenya ◽  
Transcriptional Pattern ◽  
Asymptomatic Infections

Abstract Background Further reductions in malaria incidence as more countries approach malaria elimination require the identification and treatment of asymptomatic individuals who carry mosquito-infective Plasmodium gametocytes that are responsible for furthering malaria transmission. Assessing the relationship between total parasitaemia and gametocytaemia in field surveys can provide insight as to whether detection of low-density, asymptomatic Plasmodium falciparum infections with sensitive molecular methods can adequately detect the majority of infected individuals who are potentially capable of onward transmission. Methods In a cross-sectional survey of 1354 healthy children and adults in three communities in western Kenya across a gradient of malaria transmission (Ajigo, Webuye, and Kapsisywa–Kipsamoite), asymptomatic P. falciparum infections were screened by rapid diagnostic tests, blood smear, and quantitative PCR of dried blood spots targeting the varATS gene in genomic DNA. A multiplex quantitative reverse-transcriptase PCR assay targeting female and male gametocyte genes (pfs25, pfs230p), a gene with a transcriptional pattern restricted to asexual blood stages (piesp2), and human GAPDH was also developed to determine total parasite and gametocyte densities among parasitaemic individuals. Results The prevalence of varATS-detectable asymptomatic infections was greatest in Ajigo (42%), followed by Webuye (10%). Only two infections were detected in Kapsisywa. No infections were detected in Kipsamoite. Across all communities, children aged 11–15 years account for the greatest proportion total and sub-microscopic asymptomatic infections. In younger age groups, the majority of infections were detectable by microscopy, while 68% of asymptomatically infected adults (> 21 years old) had sub-microscopic parasitaemia. Piesp2-derived parasite densities correlated poorly with microscopy-determined parasite densities in patent infections relative to varATS-based detection. In general, both male and female gametocytaemia increased with increasing varATS-derived total parasitaemia. A substantial proportion (41.7%) of individuals with potential for onward transmission had qPCR-estimated parasite densities below the limit of microscopic detection, but above the detectable limit of varATS qPCR. Conclusions This assessment of parasitaemia and gametocytaemia in three communities with different transmission intensities revealed evidence of a substantial sub-patent infectious reservoir among asymptomatic carriers of P. falciparum. Experimental studies are needed to definitively determine whether the low-density infections in communities such as Ajigo and Webuye contribute significantly to malaria transmission.

scholarly journals The prevalence and density of asymptomatic Plasmodium falciparum infections among children and adults in three communities of western Kenya

2021 ◽  
Author(s):  
Christina Salgado ◽  
George Ayodo ◽  
Michael D. Macklin ◽  
Meetha P. Gould ◽  
Srinivas Nallandhighal ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Malaria Incidence ◽  
Experimental Studies ◽  
Low Density ◽  
Healthy Children ◽  
Cross Sectional Survey ◽  
Western Kenya ◽  
Transcriptional Pattern ◽  
Asymptomatic Infections

Background: Further reductions in malaria incidence as more countries approach malaria elimination require the identification and treatment of asymptomatic individuals who carry mosquito-infective Plasmodium gametocytes that are responsible for furthering malaria transmission. Assessing the relationship between total parasitemia and gametocytemia in field surveys can provide insight as to whether detection of low-density, asymptomatic Plasmodium falciparum infections using sensitive molecular methods can sufficiently detect the majority of infected individuals who are potentially capable of onward transmission. Methods: In a cross-sectional survey of 1,354 healthy children and adults in three communities in western Kenya across a gradient of malaria transmission (Ajigo, Webuye, and Kapsisywa-Kipsamoite), we screened for asymptomatic P. falciparum infections by rapid diagnostic tests, blood smear, and quantitative PCR of dried blood spots targeting the varATS gene in genomic DNA. A multiplex quantitative reverse-transcriptase PCR assay targeting female and male gametocyte genes (pfs25, pfs230p), a gene with a transcriptional pattern restricted to asexual blood-stages (piesp2), and human GAPDH was also developed to determine total parasite and gametocyte densities among parasitemic individuals. Results: The prevalence of varATS-detectable asymptomatic infections was greatest in Ajigo (42%), followed by Webuye (10%). Only two infections were detected in Kapsisywa. No infections were detected in Kipsamoite. Across all communities, children aged 11-15 years account for the greatest proportion total and sub-microscopic asymptomatic infections. In younger age groups, the majority of infections were detectable by microscopy, while 68% of asymptomatically infected adults (>21 years old) had sub-microscopic parasitemia. Piesp2-derived parasite densities correlated poorly with microscopy-determined parasite densities in patent infections relative to varATS-based detection. In general, both male and female gametocytemia increased with increasing varATS-derived total parasitemia. A substantial proportion (41.7%) of individuals with potential for onward transmission had qPCR-estimated parasite densities below the limit of microscopic detection but above the detectable limit of varATS qPCR. Conclusions: This assessment of parasitemia and gametocytemia in three communities with different transmission intensities revealed evidence of a substantial sub-patent infectious reservoir among asymptomatic carriers of P. falciparum. Experimental studies are needed to definitively determine whether the low-density infections in communities such as Ajigo and Webuye contribute significantly to malaria transmission.

scholarly journals Genotyping cognate Plasmodium falciparum in humans and mosquitoes to estimate onward transmission of asymptomatic infections

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kelsey M. Sumner ◽  
Elizabeth Freedman ◽  
Lucy Abel ◽  
Andrew Obala ◽  
Brian W. Pence ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Odds Ratio ◽  
Asymptomatic Malaria ◽  
Major Contributor ◽  
Western Kenya ◽  
High Transmission ◽  
Transmission Reduction ◽  
Asymptomatic Infections ◽  
Infection Types ◽  
Natural Settings

AbstractMalaria control may be enhanced by targeting reservoirs of Plasmodium falciparum transmission. One putative reservoir is asymptomatic malaria infections and the scale of their contribution to transmission in natural settings is not known. We assess the contribution of asymptomatic malaria to onward transmission using a 14-month longitudinal cohort of 239 participants in a high transmission site in Western Kenya. We identify P. falciparum in asymptomatically- and symptomatically-infected participants and naturally-fed mosquitoes from their households, genotype all parasites using deep sequencing of the parasite genes pfama1 and pfcsp, and use haplotypes to infer participant-to-mosquito transmission through a probabilistic model. In 1,242 infections (1,039 in people and 203 in mosquitoes), we observe 229 (pfcsp) and 348 (pfama1) unique parasite haplotypes. Using these to link human and mosquito infections, compared with symptomatic infections, asymptomatic infections more than double the odds of transmission to a mosquito among people with both infection types (Odds Ratio: 2.56; 95% Confidence Interval (CI): 1.36–4.81) and among all participants (OR 2.66; 95% CI: 2.05–3.47). Overall, 94.6% (95% CI: 93.1–95.8%) of mosquito infections likely resulted from asymptomatic infections. In high transmission areas, asymptomatic infections are the major contributor to mosquito infections and may be targeted as a component of transmission reduction.

scholarly journals Gametocyte clearance in children, from western Kenya, with uncomplicated Plasmodium falciparum malaria after artemether–lumefantrine or dihydroartemisinin–piperaquine treatment

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Protus Omondi ◽  
Marion Burugu ◽  
Damaris Matoke-Muhia ◽  
Edwin Too ◽  
Eva A. Nambati ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Plasmodium Falciparum Malaria ◽  
Western Kenya ◽  
Transmission Season ◽  
Gametocyte Carriage ◽  
Qrt Pcr ◽  
Malaria Transmission Season ◽  
Significant Difference ◽  
Blocking Malaria Transmission

Abstract Background The efficacy and safety of artemether–lumefantrine (AL) and dihydroartemisinin–piperaquine (DP) against asexual parasites population has been documented. However, the effect of these anti-malarials on sexual parasites is still less clear. Gametocyte clearance following treatment is essential for malaria control and elimination efforts; therefore, the study sought to determine trends in gametocyte clearance after AL or DP treatment in children from a malaria-endemic site in Kenya. Methods Children aged between 0.5 and 12 years from Busia, western Kenya with uncomplicated Plasmodium falciparum malaria were assigned randomly to AL or DP treatment. A total of 334 children were enrolled, and dried blood spot samples were collected for up to 6 weeks after treatment during the peak malaria transmission season in 2016 and preserved. Plasmodium falciparum gametocytes were detected by qRT-PCR and gametocyte prevalence, density and mean duration of gametocyte carriage were determined. Results At baseline, all the 334 children had positive asexual parasites by microscopy, 12% (40/334) had detectable gametocyte by microscopy, and 83.7% (253/302) children had gametocytes by RT-qPCR. Gametocyte prevalence by RT-qPCR decreased from 85.1% (126/148) at day 0 to 7.04% (5/71) at day 42 in AL group and from 82.4% (127/154) at day 0 to 14.5% (11/74) at day 42 in DP group. The average duration of gametocyte carriage as estimated by qRT-PCR was slightly shorter in the AL group (4.5 days) than in the DP group (5.1 days) but not significantly different (p = 0.301). Conclusion The study identifies no significant difference between AL and DP in gametocyte clearance. Gametocytes persisted up to 42 days post treatment in minority of individuals in both treatment arms. A gametocytocidal drug, in combination with artemisinin-based combination therapy, will be useful in blocking malaria transmission more efficiently.

scholarly journals PO 8419 SPATIO-TEMPORAL MAPPING OF ASYMPTOMATIC AND CLINICAL MALARIA INFECTIONS REVEALS FOCI OF MALARIA TRANSMISSION FOR TARGETED CONTROL INTERVENTIONS

2019 ◽  
Vol 4 (Suppl 3) ◽  
pp. A35.2-A35
Author(s):  
Makhtar Niang ◽  
Cheikh Talla ◽  
Nafissatou Diagne ◽  
Fatoutama Diene-Sarr ◽  
Cheikh Sokhna
Keyword(s):  
Malaria Transmission ◽  
Malaria Incidence ◽  
Clinical Malaria ◽  
Asymptomatic Malaria ◽  
Design Strategies ◽  
Cross Sectional ◽  
Asymptomatic Infections ◽  
Spatio Temporal ◽  
Malaria Episodes

BackgroundThe global decline of malaria incidence over the past decade has led to the thought that elimination could be achieved. This has resulted in an increased interest to design strategies to target the hidden reservoir of asymptomatic infections among populations and interrupt on-going residual local malaria transmission. This study explored the reservoir of asymptomatic Plasmodium infections and its relationship with subsequent clinical malaria infections in low-transmission areas in Senegal.MethodsCross-sectional surveys were carried out in 2013, 2014, 2015, and 2016 and combined with longitudinal follow-up to determine and geolocalise both asymptomatic and clinical malaria episodes in Dielmo and Ndiop, Senegal. The prevalence of asymptomatic Plasmodium carriage in the community was investigated by real-time PCR while clinical malaria attacks were identified at health facilities during the transmission season. All households were georeferenced to spatially map asymptomatic and clinical infections.ResultsThe study revealed substantial asymptomatic infections with average parasite carriage of 8.11% and 7% in Dielmo and Ndiop, respectively. P. falciparum accounted for most asymptomatic infections (more than 90%). In Dielmo, 95% of asymptomatic infections clustered within the same geographical areas while infections were disparate in Ndiop. Preliminary fine-scale mapping of asymptomatic and clinical malaria infections identified clusters of higher malaria incidence interpreted as foci of transmission across the four-year study period with 95%–98% of clinical infections occurring in households where an asymptomatic malaria infection existed.ConclusionThis study revealed substantial asymptomatic Plasmodium infections in both settings throughout the four-year study period and spatial clusters of malaria infections at the microepidemiological level. Together, these findings could offer a feasible approach for a rational targeting of malaria control interventions to achieve elimination.

scholarly journals Within-household clustering of genetically related Plasmodium falciparum infections in a moderate transmission area of Uganda

2021 ◽  
Author(s):  
Jessica Briggs ◽  
Alison Kuchta ◽  
Max Murphy ◽  
Sofonias Tessema ◽  
Emmanuel Arinaitwe ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Genetic Relatedness ◽  
Malaria Incidence ◽  
Spatial Scales ◽  
Genetic Data ◽  
Fine Scale ◽  
Lower Elevation ◽  
Significant Difference

Abstract Background Evaluation of genetic relatedness of malaria parasites is a useful tool for understanding transmission patterns, but patterns are not easily detectable in areas with moderate to high malaria transmission. To evaluate the feasibility of detecting genetic relatedness in a moderate malaria transmission setting, relatedness of Plasmodium falciparum infections was measured in cohort participants from randomly selected households in the Kihihi sub-county of Uganda (annual entomological inoculation rate of 27 infectious bites per person). Methods All infections detected via microscopy or Plasmodium-specific loop mediated isothermal amplification from passive and active case detection during August 2011-March 2012 were genotyped at 26 microsatellite loci, providing data for 349 samples from 230 participants living in 80 households. Pairwise genetic relatedness was calculated using identity by state (IBS).Results As expected, genetic diversity was high (mean heterozygosity [He]=0.73), and the majority (76.5%) of samples were polyclonal. Despite the high genetic diversity, fine-scale population structure was detectable, with significant spatiotemporal clustering of highly related infections. Although the difference in malaria incidence between households at higher (mean 1127 metres) versus lower elevation (mean 1015 metres) was modest (1.4 malaria cases per person-year versus 1.9 per person-year, respectively), there was a significant difference in multiplicity of infection (2.2 versus 2.6, p = 0.008) and, more strikingly, a higher proportion of highly related infections within households (6.3% vs 0.9%, p = 0.0005) at higher elevation compared to lower elevation. Conclusions Genetic data from a relatively small number of diverse, multiallelic loci reflected fine scale patterns of malaria transmission. Given the increasing interest in applying genetic data to augment malaria surveillance, this study provides evidence that genetic data can be used to inform transmission patterns at local spatial scales even in moderate transmission areas.

scholarly journals Impact of asymptomatic Plasmodium falciparum infection on the risk of subsequent symptomatic malaria in a longitudinal cohort in Kenya

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Kelsey M Sumner ◽  
Judith N Mangeni ◽  
Andrew A Obala ◽  
Elizabeth Freedman ◽  
Lucy Abel ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Sub Saharan Africa ◽  
Cox Models ◽  
Western Kenya ◽  
Symptomatic Malaria ◽  
Transmission Setting ◽  
Asymptomatic Infections ◽  
Sub Saharan ◽  
Children Under 5

Background:Asymptomatic Plasmodium falciparum infections are common in sub-Saharan Africa, but their effect on subsequent symptomaticity is incompletely understood.Methods:In a 29-month cohort of 268 people in Western Kenya, we investigated the association between asymptomatic P. falciparum and subsequent symptomatic malaria with frailty Cox models.Results:Compared to being uninfected, asymptomatic infections were associated with an increased 1-month likelihood of symptomatic malaria [adjusted Hazard Ratio (aHR):2.61, 95%CI:2.05-3.33], and this association was modified by sex, with females [aHR:3.71, 95%CI:2.62-5.24] at higher risk for symptomaticity than males [aHR:1.76, 95%CI:1.24-2.50]. This increased symptomatic malaria risk was observed for asymptomatic infections of all densities and in people of all ages. Long-term risk was attenuated but still present in children under 5 [29-month aHR:1.38, 95%CI:1.05-1.81].Conclusions:In this high-transmission setting, asymptomatic P. falciparum can be quickly followed by symptoms and may be targeted to reduce the incidence of symptomatic illness.Funding:This work was supported by the National Institute of Allergy and Infectious Diseases (R21AI126024 to WPO, R01AI146849 to WPO and SMT).

scholarly journals Increased investment in gametocytes in asymptomatic Plasmodium falciparum infections in the wet season

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Colins O. Oduma ◽  
Sidney Ogolla ◽  
Harrysone Atieli ◽  
Bartholomew N. Ondigo ◽  
Ming-Chieh Lee ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Limit Of Detection ◽  
Parasite Prevalence ◽  
Dry Season ◽  
Control Measures ◽  
Wet Season ◽  
Western Kenya ◽  
Vector Abundance ◽  
Asymptomatic Infections ◽  
Asymptomatic Individuals

Abstract Background Transmission stemming from asymptomatic infections is increasingly being recognized as a threat to malaria elimination. In many regions, malaria transmission is seasonal. It is not well understood whether Plasmodium falciparum modulates its investment in transmission to coincide with seasonal vector abundance. Methods We sampled 1116 asymptomatic individuals in the wet season, when vectors are abundant, and 1743 in the dry season, in two sites in western Kenya, representing different transmission intensities (Chulaimbo, moderate transmission, and Homa Bay, low transmission). Blood samples were screened for P. falciparum by qPCR, and gametocytes by pfs25 RT-qPCR. Results Parasite prevalence by qPCR was 27.1% (Chulaimbo, dry), 48.2% (Chulaimbo, wet), 9.4% (Homabay, dry), and 7.8% (Homabay, wet). Mean parasite densities did not differ between seasons (P = 0.562). pfs25 transcripts were detected in 119/456 (26.1%) of infections. In the wet season, fewer infections harbored detectable gametocytes (22.3% vs. 33.8%, P = 0.009), but densities were 3-fold higher (wet: 3.46 transcripts/uL, dry: 1.05 transcripts/uL, P < 0.001). In the dry season, 4.0% of infections carried gametocytes at moderate-to-high densities likely infective (> 1 gametocyte per 2 uL blood), compared to 7.9% in the wet season. Children aged 5–15 years harbored 76.7% of infections with gametocytes at moderate-to-high densities. Conclusions Parasites increase their investment in transmission in the wet season, reflected by higher gametocyte densities. Despite increased gametocyte densities, parasite density remained similar across seasons and were often below the limit of detection of microscopy or rapid diagnostic test, thus a large proportion of infective infections would escape population screening in the wet season. Seasonal changes of gametocytemia in asymptomatic infections need to be considered when designing malaria control measures.

scholarly journals Within‐household clustering of genetically related Plasmodium falciparum infections in a moderate transmission area of Uganda

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Jessica Briggs ◽  
Alison Kuchta ◽  
Max Murphy ◽  
Sofonias Tessema ◽  
Emmanuel Arinaitwe ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Genetic Relatedness ◽  
Malaria Incidence ◽  
Spatial Scales ◽  
Genetic Data ◽  
Fine Scale ◽  
Lower Elevation ◽  
Significant Difference

Abstract Background Evaluation of genetic relatedness of malaria parasites is a useful tool for understanding transmission patterns, but patterns are not easily detectable in areas with moderate to high malaria transmission. To evaluate the feasibility of detecting genetic relatedness in a moderate malaria transmission setting, relatedness of Plasmodium falciparum infections was measured in cohort participants from randomly selected households in the Kihihi sub-county of Uganda (annual entomological inoculation rate of 27 infectious bites per person). Methods All infections detected via microscopy or Plasmodium-specific loop mediated isothermal amplification from passive and active case detection during August 2011-March 2012 were genotyped at 26 microsatellite loci, providing data for 349 samples from 230 participants living in 80 households. Pairwise genetic relatedness was calculated using identity by state (IBS). Results As expected, genetic diversity was high (mean heterozygosity [He] = 0.73), and the majority (76.5 %) of samples were polyclonal. Despite the high genetic diversity, fine-scale population structure was detectable, with significant spatiotemporal clustering of highly related infections. Although the difference in malaria incidence between households at higher (mean 1127 metres) versus lower elevation (mean 1015 metres) was modest (1.4 malaria cases per person-year vs. 1.9 per person-year, respectively), there was a significant difference in multiplicity of infection (2.2 vs. 2.6, p = 0.008) and, more strikingly, a higher proportion of highly related infections within households (6.3 % vs. 0.9 %, p = 0.0005) at higher elevation compared to lower elevation. Conclusions Genetic data from a relatively small number of diverse, multiallelic loci reflected fine scale patterns of malaria transmission. Given the increasing interest in applying genetic data to augment malaria surveillance, this study provides evidence that genetic data can be used to inform transmission patterns at local spatial scales even in moderate transmission areas.

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