scholarly journals Persistent malaria transmission from asymptomatic children despite highly effective malaria control in eastern Uganda

2021 ◽  
Author(s):  
Chiara Andolina ◽  
John C Rek ◽  
Jessica J Briggs ◽  
Joseph Okoth ◽  
Alex Musiime ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Parasite Prevalence ◽  
Gametocyte Density ◽  
Targeted Interventions ◽  
School Aged Children ◽  
Feeding Experiments ◽  
Asymptomatic Children ◽  
Membrane Feeding ◽  
Asymptomatic Infections ◽  
Eastern Uganda

Background. Persistent asymptomatic Plasmodium falciparum infections are common in malaria- endemic settings, but their contribution to transmission is poorly understood. Methods. A cohort of children and adults from Tororo, Uganda was closely followed for 24 months by continuous passive surveillance and routine assessments. P. falciparum parasite density, gametocyte density and genetic composition were determined molecularly; mosquito membrane feeding assays were performed on samples from participants with symptomatic and asymptomatic infections. Findings. From October 2017 to October 2019, we followed all 531 residents from 80 households. Parasite prevalence was 5.8% by microscopy and 17.3% by PCR at enrolment and declined thereafter. We conducted 538 mosquito feeding experiments on samples from 107 individuals. Mosquito infection rates were strongly associated with gametocyte densities of participants. Considering both transmissibility of infections and their relative frequency, the estimated human infectious reservoir was primarily asymptomatic microscopy-detected infections (83.8%), followed by asymptomatic submicroscopic (15.6%) and symptomatic (0.6%) infections. Over half of the infectious reservoir was children aged 5-15 years (56.8%); individuals <5 years (27.5%) and >16 years (15.7%) contributed less. Four children were responsible for 62.6% (279/446) of infected mosquitos and were infectious at multiple timepoints. Interpretation Individuals with asymptomatic infections were important drivers of malaria transmission. School-aged children were responsible for over half of all mosquito infections, with a small minority of asymptomatic children highly infectious. Demographically targeted interventions, aimed at school-aged children, could further reduce transmission in areas under effective vector control.

scholarly journals Optimization of Plasmodium vivax sporozoite production from Anopheles stephensi in South West India

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Ajeet Kumar Mohanty ◽  
Charles de Souza ◽  
Deepika Harjai ◽  
Prathamesh Ghavanalkar ◽  
Mezia Fernandes ◽  
...  
Keyword(s):  
South Asia ◽  
Plasmodium Vivax ◽  
Anopheles Stephensi ◽  
Parasite Development ◽  
Future Research ◽  
High Quality ◽  
Gametocyte Density ◽  
Feeding Experiments ◽  
South West ◽  
Membrane Feeding

Abstract Background Efforts to study the biology of Plasmodium vivax liver stages, particularly the latent hypnozoites, have been hampered by the limited availability of P. vivax sporozoites. Anopheles stephensi is a major urban malaria vector in Goa and elsewhere in South Asia. Using P. vivax patient blood samples, a series of standard membrane-feeding experiments were performed with An. stephensi under the US NIH International Center of Excellence for Malaria Research (ICEMR) for Malaria Evolution in South Asia (MESA). The goal was to understand the dynamics of parasite development in mosquitoes as well as the production of P. vivax sporozoites. To obtain a robust supply of P. vivax sporozoites, mosquito-rearing and mosquito membrane-feeding techniques were optimized, which are described here. Methods Membrane-feeding experiments were conducted using both wild and laboratory-colonized An. stephensi mosquitoes and patient-derived P. vivax collected at the Goa Medical College and Hospital. Parasite development to midgut oocysts and salivary gland sporozoites was assessed on days 7 and 14 post-feeding, respectively. The optimal conditions for mosquito rearing and feeding were evaluated to produce high-quality mosquitoes and to yield a high sporozoite rate, respectively. Results Laboratory-colonized mosquitoes could be starved for a shorter time before successful blood feeding compared with wild-caught mosquitoes. Optimizing the mosquito-rearing methods significantly increased mosquito survival. For mosquito feeding, replacing patient plasma with naïve serum increased sporozoite production > two-fold. With these changes, the sporozoite infection rate was high (> 85%) and resulted in an average of ~ 22,000 sporozoites per mosquito. Some mosquitoes reached up to 73,000 sporozoites. Sporozoite production could not be predicted from gametocyte density but could be predicted by measuring oocyst infection and oocyst load. Conclusions Optimized conditions for the production of high-quality P. vivax sporozoite-infected An. stephensi were established at a field site in South West India. This report describes techniques for producing a ready resource of P. vivax sporozoites. The improved protocols can help in future research on the biology of P. vivax liver stages, including hypnozoites, in India, as well as the development of anti-relapse interventions for vivax malaria.

scholarly journals PO 8562 SECRETED OOKINETE PROTEIN AS A MARKER OF INFECTIOUS BITES FOR ASSESSING TRANSMISSION DYNAMICS AT THE POPULATION LEVEL

2019 ◽  
Vol 4 (Suppl 3) ◽  
pp. A53.2-A53
Author(s):  
Kingsley Badu
Keyword(s):  
Malaria Transmission ◽  
Rainy Season ◽  
Parasite Prevalence ◽  
Transmission Intensity ◽  
Igg Antibody ◽  
Subtle Difference ◽  
Targeted Interventions ◽  
Malaria Transmission Intensity ◽  
Twofold Increase ◽  
Immunogenic Peptides

BackgroundAs malaria transmission intensity declines, the heterogeneity in infectious burden becomes pronounced. There is thus the need for more sensitive tools to identify micro-geographic areas of higher risk for targeted interventions. We sought to evaluate several immunogenic peptides of P. falciparum, secreted ookinete and sporozoite proteins (PSOP24) and possibly validate specific short sequence immunogenic peptides as an infectious bite marker for assessing malaria transmission intensity and dynamics.MethodsWe conducted four cross-sectional serological and parasitological surveys within one peri-urban and one rural community about 3 km apart, in South-western Ghana. The field surveys were conducted from November 2012 to July 2014 across dry and rainy seasons. Several bioinformatics models were used to predict the immunogenic epitopes of PSOP24 peptides. Total IgG antibody response were determined for three most promising peptides (PSOP24–374, PSOP24–375 and PSOP24–377), together with MSP119, CSP and salivary gland antigen. Alongside we determined parasite prevalence and density as well as the entomological inoculation rates.ResultsPeptide PSOP24-377 showed seasonal variation with a twofold increase in IgG response in the high-transmission rainy season. This collaborates with the twofold increase in IgG response to the mosquito salivary antigen gSG6-P1. Also, PSOP24-377 was able to show a subtle difference from Ayeigbekorpe to Odumase during the dry season and a high sero-prevalence between the two communities during the rainy season. This was in contrast with gSG6-P1 because, while PSOP24-377 measures sero-response to infectious bites, gSG6-P1 measure responses to only vector exposure. The immune response variation determined by PSOP24-377 correlated with parasite prevalence and the entomological inoculation rates.ConclusionThe preliminary data points to the potential of PSOP24-377 as an infectious bite marker. This may be exploited as a routine surveillance tool for monitoring malaria transmission at the community level.

scholarly journals Effect of seasonal malaria chemoprevention plus azithromycin on Plasmodium falciparum transmission: gametocyte infectivity and mosquito fitness

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Koudraogo Bienvenue Yaméogo ◽  
Rakiswendé Serge Yerbanga ◽  
Seydou Bienvenu Ouattara ◽  
Franck A. Yao ◽  
Thierry Lefèvre ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Life History Traits ◽  
Controlled Trial ◽  
Double Blind ◽  
Membrane Feeding ◽  
Seasonal Malaria Chemoprevention ◽  
Negative Effect ◽  
Transmission Period ◽  
Membrane Feeding Assay

Abstract Background Seasonal malaria chemoprevention (SMC) consists of administration of sulfadoxine-pyrimethamine (SP) + amodiaquine (AQ) at monthly intervals to children during the malaria transmission period. Whether the addition of azithromycin (AZ) to SMC could potentiate the benefit of the intervention was tested through a double-blind, randomized, placebo-controlled trial. The effect of SMC and the addition of AZ, on malaria transmission and on the life history traits of Anopheles gambiae mosquitoes have been investigated. Methods The study included 438 children randomly selected from among participants in the SMC + AZ trial and 198 children from the same area who did not receive chemoprevention. For each participant in the SMC + AZ trial, blood was collected 14 to 21 days post treatment, examined for the presence of malaria sexual and asexual stages and provided as a blood meal to An. gambiae females using a direct membrane-feeding assay. Results The SMC treatment, with or without AZ, significantly reduced the prevalence of asexual Plasmodium falciparum (LRT X22 = 69, P < 0.0001) and the gametocyte prevalence (LRT X22 = 54, P < 0.0001). In addition, the proportion of infectious feeds (LRT X22 = 61, P < 0.0001) and the prevalence of oocysts among exposed mosquitoes (LRT X22 = 22.8, P < 0.001) was reduced when mosquitoes were fed on blood from treated children compared to untreated controls. The addition of AZ to SPAQ was associated with an increased proportion of infectious feeds (LRT X21 = 5.2, P = 0.02), suggesting a significant effect of AZ on gametocyte infectivity. There was a slight negative effect of SPAQ and SPAQ + AZ on mosquito survival compared to mosquitoes fed with blood from control children (LRTX22 = 330, P < 0.0001). Conclusion This study demonstrates that SMC may contribute to a reduction in human to mosquito transmission of P. falciparum, and the reduced mosquito longevity observed for females fed on treated blood may increase the benefit of this intervention in control of malaria. The addition of AZ to SPAQ in SMC appeared to enhance the infectivity of gametocytes providing further evidence that this combination is not an appropriate intervention.

scholarly journals Community-based molecular and serological surveillance of subclinical malaria in Myanmar

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Katherine O’Flaherty ◽  
Win Han Oo ◽  
Sophie G. Zaloumis ◽  
Julia C. Cutts ◽  
Kyaw Zayar Aung ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Quantitative Polymerase Chain Reaction ◽  
Dried Blood Spots ◽  
Molecular Testing ◽  
Sample Collection ◽  
Malaria Surveillance ◽  
Surveillance Network ◽  
Targeted Interventions ◽  
Residual Malaria Transmission ◽  
Serological Surveillance

Abstract Background In the Greater Mekong Subregion (GMS), current malaria surveillance strategies rely on a network of village health volunteers (VHVs) reporting the results of rapid diagnostic tests (RDTs), known to miss many asymptomatic infections. Integration of more sensitive diagnostic molecular and serological measures into the VHV network may improve surveillance of residual malaria transmission in hard-to-reach areas in the region and inform targeted interventions and elimination responses. However, data on residual malaria transmission that would be captured by these measures in the VHV-led testing and treatment surveillance network in the GMS is unknown. Methods A total of 114 VHVs were trained to collect dried blood spots from villagers undergoing routine RDTs as part of VHV-led active and passive case detection from April 2015 to June 2016. Samples were subjected to molecular testing (quantitative polymerase chain reaction [qPCR]) to determine Plasmodium falciparum and P. vivax infection and serological testing (against P. falciparum and P. vivax antigens) to determine exposure to P. falciparum and P. vivax. Results Over 15 months, 114 VHVs performed 32,194 RDTs and collected samples for molecular (n = 13,157) and serological (n = 14,128) testing. The prevalence of molecular-detectable P. falciparum and P. vivax infection was 3.2% compared to the 0.16% prevalence of Plasmodium spp. by RDT, highlighting the large burden of infections undetected by standard surveillance. Peaks in anti-P. falciparum, but not P. vivax, merozoite IgG seroprevalence coincided with seasonal P. falciparum transmission peaks, even in those with no molecularly detectable parasites. At the individual level, antibody seropositivity was associated with reduced odds of contemporaneous P. falciparum (OR for PfCSP 0.51 [95%CI 0.35, 0.76], p = 0.001, PfAMA1 0.70 [95%CI 0.52, 0.93], p = 0.01, and PfMSP2 0.81 [95%CI 0.61, 1.08], p = 0.15), but not P. vivax infection (OR PvAMA1 1.02 [95%CI 0.73, 1.43], p = 0.89) indicating a potential role of immunity in protection against molecular-detectable P. falciparum parasitaemia. Conclusions We demonstrated that integration and implementation of sample collection for molecular and serological surveillance into networks of VHV servicing hard-to-reach populations in the GMS is feasible, can capture significant levels of ongoing undetected seasonal malaria transmission and has the potential to supplement current routine RDT testing. Improving malaria surveillance by advancing the integration of molecular and serological techniques, through centralised testing approaches or novel point-of-contact tests, will advance progress, and tracking, towards malaria elimination goals in the GMS.

scholarly journals Contribution of Asymptomatic Plasmodium Infections to the Transmission of Malaria in Kayin State, Myanmar

2018 ◽  
Vol 219 (9) ◽  
pp. 1499-1509 ◽  
Author(s):  
Victor Chaumeau ◽  
Ladda Kajeechiwa ◽  
Bénédicte Fustec ◽  
Jordi Landier ◽  
Saw Naw Nyo ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Entomological Inoculation Rate ◽  
Fold Increase ◽  
Estimating Equation ◽  
Malaria Prevalence ◽  
Pcr Analysis ◽  
Asymptomatic Malaria ◽  
Asymptomatic Infections ◽  
Greater Mekong Subregion ◽  
The Impact

Abstract Background The objective of mass antimalarial drug administration (MDA) is to eliminate malaria rapidly by eliminating the asymptomatic malaria parasite reservoirs and interrupting transmission. In the Greater Mekong Subregion, where artemisinin-resistant Plasmodium falciparum is now widespread, MDA has been proposed as an elimination accelerator, but the contribution of asymptomatic infections to malaria transmission has been questioned. The impact of MDA on entomological indices has not been characterized previously. Methods MDA was conducted in 4 villages in Kayin State (Myanmar). Malaria mosquito vectors were captured 3 months before, during, and 3 months after MDA, and their Plasmodium infections were detected by polymerase chain reaction (PCR) analysis. The relationship between the entomological inoculation rate, the malaria prevalence in humans determined by ultrasensitive PCR, and MDA was characterized by generalized estimating equation regression. Results Asymptomatic P. falciparum and Plasmodium vivax infections were cleared by MDA. The P. vivax entomological inoculation rate was reduced by 12.5-fold (95% confidence interval [CI], 1.6–100-fold), but the reservoir of asymptomatic P. vivax infections was reconstituted within 3 months, presumably because of relapses. This was coincident with a 5.3-fold (95% CI, 4.8–6.0-fold) increase in the vector infection rate. Conclusion Asymptomatic infections are a major source of malaria transmission in Southeast Asia.

scholarly journals Sex-based differences in clearance of chronic Plasmodium falciparum infection

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Jessica Briggs ◽  
Noam Teyssier ◽  
Joaniter I Nankabirwa ◽  
John Rek ◽  
Prasanna Jagannathan ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Host Response ◽  
Behavioral Risk ◽  
Biological Sex ◽  
Force Of Infection ◽  
Host Parasite Interactions ◽  
Infection Event ◽  
Asymptomatic Infections ◽  
Host Parasite ◽  
Eastern Uganda

Multiple studies have reported a male bias in incidence and/or prevalence of malaria infection in males compared to females. To test the hypothesis that sex-based differences in host-parasite interactions affect the epidemiology of malaria, we intensively followed Plasmodium falciparum infections in a cohort in a malaria endemic area of eastern Uganda and estimated both force of infection (FOI) and rate of clearance using amplicon deep-sequencing. We found no evidence of differences in behavioral risk factors, incidence of malaria, or FOI by sex. In contrast, females cleared asymptomatic infections at a faster rate than males (hazard ratio [HR]=1.82, 95% CI 1.20 to 2.75 by clone and HR = 2.07, 95% CI 1.24 to 3.47 by infection event) in multivariate models adjusted for age, timing of infection onset, and parasite density. These findings implicate biological sex-based differences as an important factor in the host response to this globally important pathogen.

scholarly journals Prevalence of asymptomatic P. falciparum gametocyte carriage among school children in Mbita, Western Kenya and assessment of the association between gametocyte density, multiplicity of infection and mosquito infection prevalence.

2021 ◽  
Vol 5 ◽  
pp. 259
Author(s):  
Abdoulie O. Touray ◽  
Victor A. Mobegi ◽  
Fred Wamunyokoli ◽  
Hellen Butungi ◽  
Jeremy K. Herren
Keyword(s):  
Infection Prevalence ◽  
Multiplicity Of Infection ◽  
Gametocyte Density ◽  
Western Kenya ◽  
Gametocyte Carriage ◽  
Membrane Feeding ◽  
Parasite Infections ◽  
Study Population ◽  
Associated Risk Factors ◽  
Mosquito Infection

Background: Asymptomatic Plasmodium falciparum gametocyte carriers are reservoirs for sustaining transmission in malaria endemic regions. Gametocyte presence in the host peripheral blood is a predictor of capacity to transmit malaria. However, it does not always directly translate to mosquito infectivity. Factors that affect mosquito infectivity include, gametocyte sex-ratio and density, multiplicity of infection (MOI), and host and vector anti-parasite immunity. We assess the prevalence of gametocyte carriage and some of its associated risk factors among asymptomatic schoolchildren in Western Kenya and to further analyse the association between gametocyte density, multiplicity of infection (MOI) and mosquito infection prevalence. Methods: P. falciparum parasite infections were detected by RDT (Rapid Diagnostic Test) and microscopy among schoolchildren (5-15 years old). Blood from 37 microscopy positive gametocyte carriers offered to laboratory reared An. gambiae s.l. mosquitoes. A total of 3395 fully fed mosquitoes were screened for Plasmodium sporozoites by ELISA. P. falciparum was genotyped using 10 polymorphic microsatellite markers. The association between MOI and gametocyte density and mosquito infection prevalence was investigated. Results: A significantly higher prevalence of P. falciparum infection was found in males 31.54% (764/2422) (p-value < 0.001) compared to females 26.72% (657/2459). The microscopic gametocyte prevalence among the study population was 2% (84/4881). Children aged 5-9 years have a higher prevalence of gametocyte carriage (odds ratios = 2.1 [95% CI = 1.3–3.4], P = 0.002) as compared to children aged 10-15 years. After offering gametocyte positive blood to An. gambiae s.l. by membrane feeding assay, our results indicated that 68.1% of the variation in mosquito infection prevalence was accounted for by gametocyte density and MOI (R-SQR. = 0.681, p < 0.001). Conclusions: We observed a higher risk of gametocyte carriage among the younger children (5-9 years). Gametocyte density and MOI significantly predicted mosquito infection prevalence.

scholarly journals Large Variations in Malaria Parasite Carriage by Afebrile School Children Living in Nearby Communities in the Central Region of Ghana

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Evans K. Obboh ◽  
Ruth E. Okonu ◽  
Linda E. Amoah
Keyword(s):  
Malaria Transmission ◽  
Central Region ◽  
Malaria Control ◽  
Filter Paper ◽  
Malaria Parasite ◽  
Molecular Evidence ◽  
Asymptomatic Malaria ◽  
Cape Coast ◽  
Malaria Parasites ◽  
Asymptomatic Infections

Background. Indicators of successful malaria control interventions include a reduction in the prevalence and densities of malaria parasites contained in both symptomatic and asymptomatic infections as well as a reduction in malaria transmission. Individuals harboring malaria parasites in asymptomatic infections serve as reservoirs for malaria transmission. This study determined the prevalence of asymptomatic malaria parasite carriage in afebrile children attending six different schools in two districts, the Cape Coast Metropolitan Assembly (CCMA) and the Komenda Edina Eguafo Abirem (KEEA) of the Central Region of Ghana. Methods. This cross sectional study recruited afebrile children aged between 3 and 15 years old from six randomly selected schools in the Central Region of Ghana. Finger-pricked blood was collected and used to prepare thick and thin blood smears as well as spot a strip of filter paper (Whatman #3). Nested PCR was used to identify Plasmodium falciparum, Plasmodium malariae, Plasmodium ovale, and Plasmodium vivax in DNA extracted from the filter paper spots. The multiplicity of P. falciparum infection was determined using merozoite surface protein 2 genotyping. Results. Out of the 528 children sampled, PCR identified 27.1% to harbor Plasmodium parasites in asymptomatic infections, whilst microscopy identified malaria parasites in 10.6% of the children. The overall PCR estimated prevalence of P. falciparum and P. malariae was 26.6% and 1.3%, respectively, with no P. ovale or P. vivax identified by PCR or microscopy. The RDT positivity rate ranged from 55.8% in Simiw to 4.5% in Kuful. Children from the Simiw Basic School accounted for 87.5% of all the asymptomatic infections. The multiplicity of P. falciparum infection was predominantly monoclonal and biclonal. Conclusions. The low prevalence of asymptomatic malaria parasite carriage by the children living in the Cape Coast Metropolis suggests that the malaria control interventions in place in CCMA are highly effective and that additional malaria control interventions are required for the KEEA district to reduce the prevalence of asymptomatic malaria parasite carriers. No molecular evidence of P. ovale and P. vivax was identified in the afebrile children sampled from the selected schools.

scholarly journals The Impact of 3 Years of Targeted Indoor Residual Spraying With Pirimiphos-Methyl on Malaria Parasite Prevalence in a High-Transmission Area of Northern Zambia

2019 ◽  
Vol 188 (12) ◽  
pp. 2120-2130 ◽  
Author(s):  
Marisa A Hast ◽  
Mike Chaponda ◽  
Mbanga Muleba ◽  
Jean-Bertin Kabuya ◽  
James Lupiya ◽  
...  
Keyword(s):  
Malaria Transmission ◽  
Malaria Control ◽  
Malaria Parasite ◽  
Control Measure ◽  
Indoor Residual Spraying ◽  
Parasite Prevalence ◽  
Organophosphate Insecticide ◽  
Malaria Burden ◽  
Pirimiphos Methyl ◽  
The Impact

Abstract Malaria transmission in northern Zambia has increased in the past decade, despite malaria control activities. Evidence-based intervention strategies are needed to effectively reduce malaria transmission. Zambia’s National Malaria Control Centre conducted targeted indoor residual spraying (IRS) in Nchelenge District, Luapula Province, from 2014 to 2016 using the organophosphate insecticide pirimiphos-methyl. An evaluation of the IRS campaign was conducted by the Southern Africa International Centers of Excellence for Malaria Research using actively detected malaria cases in bimonthly household surveys carried out from April 2012 to July 2017. Changes in malaria parasite prevalence after IRS were assessed by season using Poisson regression models with robust standard errors, controlling for clustering of participants in households and demographic, geographical, and climatological covariates. In targeted areas, parasite prevalence declined approximately 25% during the rainy season following IRS with pirimiphos-methyl but did not decline during the dry season or in the overall study area. Within targeted areas, parasite prevalence declined in unsprayed households, suggesting both direct and indirect effects of IRS. The moderate decrease in parasite prevalence within sprayed areas indicates that IRS with pirimiphos-methyl is an effective malaria control measure, but a more comprehensive package of interventions is needed to effectively reduce the malaria burden in this setting.

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