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 Plasmodium falciparum increases its investment in gametocytes in the wet season in asymptomatic individuals

2020 ◽  
Author(s):  
Colins O. Oduma ◽  
Sidney Ogolla ◽  
Harrysone Atieli ◽  
Bartholomew N. Ondigo ◽  
Ming-Chieh Lee ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Parasite Prevalence ◽  
Dry Season ◽  
Wet Season ◽  
Western Kenya ◽  
Gametocyte Carriage ◽  
Vector Abundance ◽  
Asymptomatic Individuals

AbstractIn many regions, malaria transmission is seasonal, but it is not well understood whether P. falciparum modulates its investment in transmission in response to seasonal vector abundance. In two sites in western Kenya (Chulaimbo and Homa Bay), we sampled 1116 asymptomatic individuals in the wet season, when vectors are abundant, and 1743 in the dry season. We screened for P. falciparum by qPCR, and gametocytes by pfs25 RT-qPCR. Parasite prevalence in Chulaimbo and Homa Bay was 27.1% and 9.4% in the dry season, and 48.2% and 7.8% in the wet season respectively. Mean parasite densities did not differ between seasons (P=0.562). A contrasting pattern of gametocyte carriage was observed. In the wet season, fewer infections harbored gametocytes (22.3% vs. 33.8%, P=0.009), but densities were 3-fold higher (P<0.001). Thus, in the wet season, among gametocyte positive individuals, higher proportion of all parasites were gametocytes, reflecting an increased investment in transmission.

scholarly journals Long-distance transmission patterns modelled from SNP barcodes of Plasmodium falciparum infections in The Gambia

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Alfred Amambua-Ngwa ◽  
David Jeffries ◽  
Julia Mwesigwa ◽  
Aminata Seedy-Jawara ◽  
Joseph Okebe ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Genetic Relatedness ◽  
Malaria Prevalence ◽  
The Gambia ◽  
Long Distance ◽  
Travel History ◽  
Transmission Season ◽  
Malaria Transmission Season ◽  
Likelihood Model

Abstract Malaria has declined significantly in The Gambia and determining transmission dynamics of Plasmodium falciparum can help targeting control interventions towards elimination. This can be inferred from genetic similarity between parasite isolates from different sites and timepoints. Here, we imposed a P. falciparum life cycle time on a genetic distance likelihood model to determine transmission paths from a 54 SNP barcode of 355 isolates. Samples were collected monthly during the 2013 malaria season from six pairs of villages spanning 300 km from western to eastern Gambia. There was spatial and temporal hierarchy in pairwise genetic relatedness, with the most similar barcodes from isolates within the same households and village. Constrained by travel data, the model detected 60 directional transmission events, with 27% paths linking persons from different regions. We identified 13 infected individuals (4.2% of those genotyped) responsible for 2 to 8 subsequent infections within their communities. These super-infectors were mostly from high transmission villages. When considering paths between isolates from the most distant regions (west vs east) and travel history, there were 3 transmission paths from eastern to western Gambia, all at the peak (October) of the malaria transmission season. No paths with known travel originated from the extreme west to east. Although more than half of all paths were within-village, parasite flow from east to west may contribute to maintain transmission in western Gambia, where malaria transmission is already low. Therefore, interrupting malaria transmission in western Gambia would require targeting eastern Gambia, where malaria prevalence is substantially higher, with intensified malaria interventions.

scholarly journals Effect of 4 years of seasonal malaria chemoprevention on the acquisition of antibodies to Plasmodium falciparum antigens in Ouelessebougou, Mali

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Almahamoudou Mahamar ◽  
Djibrilla Issiaka ◽  
Ahamadou Youssouf ◽  
Sidi M. Niambele ◽  
Harouna M. Soumare ◽  
...  
Keyword(s):  
At Risk ◽  
Plasmodium Falciparum ◽  
Malaria Transmission ◽  
Confidence Intervals ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Transmission Season ◽  
Malaria Transmission Season ◽  
Seasonal Malaria Chemoprevention ◽  
Antibody Levels

Abstract Background More than 200 million people live in areas of highly seasonal malaria transmission where Seasonal Malaria Chemoprevention (SMC) with sulfadoxine-pyrimethamine (SP) and amodiaquine (AQ) was recommended in 2012 by WHO. This strategy is now implemented widely and protected more than 19 million children in 2018. It was previously reported that exposure to SMC reduced antibody levels to AMA1, MSP-142 and CSP, but the duration of exposure to SMC up to three 3 years, had no effect on antibody levels to MSP-142 and CSP. Methods In 2017, a cross-sectional survey was carried out 1 month after the last dose of SMC had been given to children aged 4–5 years randomly selected from areas where SMC had been given for 2 or 4 years during the malaria transmission season. A total of 461 children were enrolled, 242 children in areas where SMC had been implemented for 4 years and 219 children in areas where SMC had been implemented for 2 years. Antibody extracted from dry blood spots was used to measure IgG levels to the malaria antigens CSP, MSP-142 and AMA1 by ELISA. Results The prevalence of antibodies to MSP-142 was similar in children who had received SMC for 4 years compared to those who had received SMC for only 2 years (85.1 vs 86.0%, ajusted odd ratio (aOR) = 1.06, 95% confidence intervals (CI 0.62–1.80), p = 0.80). The prevalence of antibodies to AMA-1 and to CSP was not lower in children who received SMC for 4 years compared to those who had received SMC for only 2 years (95.3 vs 88.8%, aOR = 3.16, 95% CI 1.44–6.95, p = 0.004 for AMA-1; and 91.2 vs 81.9%, aOR = 3.14, 95% CI 1.70–5.76, p < 0.001 for CSP). Median antibody levels for anti-MSP-142 IgG were not significatively inferior in children who had received SMC for four rather than 2 years (0.88 (IQR: 0.64–1.15) and 0.95 ((0.68–1.15), respectively), anti-CSP (1.30 (1.00–1.56) and 1.17 (0.87–1.47)), and anti-AMA-1 (1.45 (1.24–1.68) and 1.41 (1.17–1.64)). Conclusion In an area of high seasonal malaria transmission, children who had received SMC for 4 years did not had lower seropositivity or antibody levels to AMA1, MSP-142 and CSP compared to children who had received SMC for only 2 years suggesting that children who have received SMC for 4 years may not be more at risk of malaria after the cessation of SMC than children who have received SMC for a shorter period.

scholarly journals Effect of naturally occurring Wolbachia in Anopheles gambiae s.l. mosquitoes from Mali on Plasmodium falciparum malaria transmission

2017 ◽  
Vol 114 (47) ◽  
pp. 12566-12571 ◽  
Author(s):  
Fabio M. Gomes ◽  
Bretta L. Hixson ◽  
Miles D. W. Tyner ◽  
Jose Luis Ramirez ◽  
Gaspar E. Canepa ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Anopheles Gambiae ◽  
Malaria Transmission ◽  
Deleterious Effect ◽  
Plasmodium Falciparum Malaria ◽  
Anopheles Coluzzii ◽  
Naturally Occurring ◽  
Anopheles Gambiae S.L ◽  
Cat Fleas ◽  
Sporozoite Infection

A naturally occurring Wolbachia strain (wAnga-Mali) was identified in mosquitoes of the Anopheles gambiae complex collected in the Malian villages of Dangassa and Kenieroba. Phylogenetic analysis of the nucleotide sequence of two 16S rRNA regions showed that wAnga-Mali clusters with Wolbachia strains from supergroup A and has the highest homology to a Wolbachia strain isolated from cat fleas (Ctenocephalides). wAnga-Mali is different from two Wolbachia strains previously reported in A. gambiae from Burkina Faso (wAnga_VK5_STP and wAnga_VK5_3.1a). Quantitative analysis of Wolbachia and Plasmodium sporozoite infection in field-collected mosquitoes indicates that the prevalence and intensity of Plasmodium falciparum sporozoite infection is significantly lower in Wolbachia-infected females. The presence of Wolbachia in females from a laboratory Anopheles coluzzii (A. gambiae, M form) colony experimentally infected with P. falciparum (NF54 strain) gametocyte cultures slightly enhanced oocyst infection. However, Wolbachia infection significantly reduced the prevalence and intensity of sporozoite infection, as observed in the field. This indicates that wAnga-Mali infection does not limit early stages of Plasmodium infection in the mosquito, but it has a strong deleterious effect on sporozoites and reduces malaria transmission.

scholarly journals 1241. PfSPZ Vaccine Administered by Direct Venous Inoculation to Prevent Plasmodium falciparum Malaria is as Safe as Normal Saline – a Meta-analysis of 12 Randomized Controlled Clinical Trials

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S639-S640
Author(s):  
L W Preston Church
Keyword(s):  
Plasmodium Falciparum ◽  
Random Effects ◽  
Normal Saline ◽  
Meta Analysis ◽  
Laboratory Data ◽  
Plasmodium Falciparum Malaria ◽  
Sub Saharan Africa ◽  
Sensitivity Analyses ◽  
Double Blind ◽  
Significant Difference

Abstract Background Sanaria’s PfSPZ Vaccine prevents Plasmodium falciparum (Pf) infection transmitted in the field and by controlled human malaria infection. Safety of PfSPZ Vaccine has been demonstrated in 12 randomized, double-blind, placebo-controlled trials (RCT) varying in regimen from 3 to 5 doses over 4 to 20 weeks and in size from 18 to 332 subjects in adults in the US and EU and 5-month to 65-year-olds in 5 countries in sub-Saharan Africa. This study was conducted to analyze solicited adverse event (AE) and laboratory data by random effects meta-analysis. Methods PfSPZ Vaccine is composed of radiation-attenuated, aseptic, purified, cryopreserved Pf sporozoites (SPZ) administered by direct venous inoculation (DVI). Normal saline (NS) is always the placebo. Data from all completed RCTs were included as either age &gt; 18 years (n=598) or age 5 months to 17 years (n=641). Any subject receiving at least one dose was included. A random-effects model was used to study vaccine safety and I2 to evaluate heterogeneity. Analysis was performed for any systemic solicited AE and for the most frequently observed AEs and laboratory abnormalities. Sensitivity analyses were performed by removal of trials with zero events to evaluate potential bias. Results When examined individually, only 1 trial had a significant difference between PfSPZ Vaccine and NS for any AE (myalgias in adults). In the adult meta-analysis, there was no difference in the random effects risk ratios (RR) for having any vaccine-related AEs (1.40, 95% confidence interval (CI) 0.88-2.28), or for fever (0.75, 0.24-2.35), headache (1.23, 0.74-2.02), fatigue (0.72, 0.19-2.54), or myalgia (1.09, 0.26-4.68). In the pediatric meta-analysis there was no difference between the RR for PfSPZ Vaccine and NS for any AE (0.84, 0.59-1.18) or for fever (1.09, 0.44-2.69). No significant differences in the most common grade 2 or higher laboratory abnormalities – declines in hemoglobin, neutrophil or platelet count – were detected. Sensitivity analysis did not change the results. Conclusion There was no difference in risk for AEs or lab abnormalities between PfSPZ Vaccine and NS, indicating that PfSPZ Vaccine administered by DVI was extremely safe and well tolerated in 5-month- to 65-year-olds. Disclosures LW Preston Church, MD, FIDSA, Sanaria Inc. (Employee)

scholarly journals Influence of Cytochrome P450 (CYP) 2C8 Polymorphisms on the Efficacy and Tolerability of Artesunate-Amodiaquine Treatment of Uncomplicated Plasmodium Falciparum Malaria in Zanzibar

2020 ◽  
Author(s):  
Leyre Pernaute-Lau ◽  
Ulrika Morris ◽  
Mwinyi Msellem ◽  
Andreas Mårtensson ◽  
Anders Björkman ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Cytochrome P450 ◽  
Randomized Clinical Trials ◽  
Plasmodium Falciparum Malaria ◽  
Serious Adverse Events ◽  
Cytochrome P450 2C8 ◽  
Significant Difference ◽  
Minor Alleles ◽  
Long Acting ◽  
Parasitological Response

Abstract Background The antimalarial drug amodiaquine, a commonly used long acting partner drug in artemisinin-based combination therapy, is metabolized to active desethyl-amodiaquine (DEAQ) by cytochrome P450 2C8 (CYP2C8). The CYP2C8 gene carries several polymorphisms including the more frequent minor alleles CYP2C8*2 and CYP2C8*3. These minor alleles have been associated with decreased enzymatic activity, slowing the amodiaquine biotransformation towards DEAQ. This study aimed to assess the influence of CYP2C8 polymorphisms on the efficacy and tolerability of artesunate-amodiaquine treatment for uncomplicated Plasmodium falciparum malaria in Zanzibar.Methods We analysed data from 618 children <5 years with uncomplicated P. falciparum malaria enrolled in two randomized clinical trials comparing artesunate-amodiaquine and artemether-lumefantrine in 2002-2005 in Zanzibar. CYP2C8*2 and CYP2C8*3 genotypes were determined by PCR-restriction fragment length polymorphism and assessed in relation to clinical data on treatment outcome and tolerance. Results The allele frequencies of CYP2C8*2 and CYP2C8*3 were 17.5% (95% CI 15.4-19.7%) and 2.7% (95% CI 1.8-3.7%), respectively. There was no significant difference in the proportion of subjects carrying either CYP2C8*2 or CYP2C8*3 alleles amongst those with reinfections (44.1 %; 95% CI 33.8-54.8) or those with recrudescent infections (48.3%; 95% CI 29.4-67.5), compared to those with adequate clinical and parasitological response (36.7 %; 95% CI 30.0-43.9) (P = 0.25 and P = 0.31, respectively). However, patients carrying either the CYP2C8*2 or CYP2C8*3 allele were significantly associated with increased occurrence of non-serious adverse events compare with CYP2C8 *1/*1 wildtype homozygotes (44.9%; 95% CI 36.1-54.0 versus 28.1%; 95% CI 21.9-35.0, respectively; P = 0.003). Conclusions CYP2C8 genotypes did not influence treatment efficacy directly, but the tolerability to ASAQ may be reduced in subjects carrying the CYP2C8*3 and CYP2C8*2 alleles. The importance of this non-negligible association with regards to amodiaquine-based malaria chemotherapy warrants further investigation.

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