scholarly journals Plasmodium falciparum DHFR and DHPS Mutations Are Associated With HIV-1 Co-Infection and a Novel DHPS Mutation I504T Is Identified in Western Kenya

2020 ◽  
Vol 10 ◽  
Author(s):  
Brandi K. Torrevillas ◽  
Sarah M. Garrison ◽  
Alexander J. McKeeken ◽  
Dharmeshkumar Patel ◽  
James T. Van Leuven ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Haplotype Diversity ◽  
Plasmodium Malariae ◽  
Drug Binding ◽  
Cross Resistance ◽  
Asymptomatic Malaria ◽  
Newly Diagnosed ◽  
Cross Sectional ◽  
Antifolate Resistance ◽  
Hiv 1

Antifolate resistance is significant in Kenya and presumed to result from extensive use and cross-resistance between antifolate antimalarials and antibiotics, including cotrimoxazole/Bactrim used for HIV-1 chemotherapy. However, little is known about antifolate-resistant malaria in the context of newly diagnosed HIV-1 co-infection prior to administration of HIV-1 chemotherapy. Blood samples from a cross-sectional study of asymptomatic adult Kenyans enrolled during voluntary HIV testing were analyzed by PCR for Plasmodium spp. More than 95% of volunteers with identifiable parasite species (132 HIV-1 co-infected) were infected with Plasmodium falciparum alone or P. falciparum with Plasmodium ovale and/or Plasmodium malariae. Deep sequencing was used to screen for mutations in P. falciparum dihydrofolate reductase (dhfr) (N51I, C59R, S108N, I164L) and dihydropteroate synthase (dhps) (S436H, A437G, K540E, A581G) from 1133 volunteers. Individual mutations in DHPS but not DHFR correlated with HIV-1 status. DHFR haplotype diversity was significantly different among volunteers by gender and HIV-1 status. DHPS haplotype diversity by HIV-1 status was significantly different between volunteers paired by age and gender, indicating that patterns of resistance were independent of these variables. Molecular simulations for a novel DHPS mutation (I504T) suggested that the mutated protein has increased affinity for the endogenous ligand DHPPP and decreased affinity for drug binding. A sub-group of monoclonal infections revealed that age and parasitemia were not correlated and enabled identification of a rare septuple-mutant haplotype (IRNL-HGEA). In our study, adult Kenyans newly diagnosed with HIV-1 infection were predominantly infected with moderately resistant P. falciparum, with patterns of infecting parasite genotypes significantly associated with HIV-1 status. Together with the discovery of DHPS I504T, these data indicate that antifolate resistance continues to evolve in Kenya. Further, they highlight the need to understand the effects of associated mutations on both fitness and resistance of P. falciparum in the context of HIV-1 co-infection to better inform treatment for asymptomatic malaria.

scholarly journals Assessing Asymptomatic Malaria Carriage of Plasmodium falciparum and Non-falciparum Species in Children Resident in Nkolbisson, Yaoundé, Cameroon

Children ◽  
2021 ◽  
Vol 8 (11) ◽  
pp. 960
Author(s):  
Nji Mbuh Akindeh ◽  
Lesley Ngum Ngum ◽  
Peter Thelma Ngwa Niba ◽  
Innocent Mbulli Ali ◽  
Ornella Laetitia Oben Ayem ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Correct Diagnosis ◽  
Plasmodium Malariae ◽  
Cross Sectional Study ◽  
Malaria Prevalence ◽  
Asymptomatic Malaria ◽  
Cross Sectional ◽  
Predictive Values ◽  
Convenience Sampling ◽  
Polymerase Chain

Malaria is still a threat to public health as it remains the first endemic disease in the world. It is a pervasive parasitic disease in tropical and subtropical regions where asymptomatic malaria infection among humans serves as a significant reservoir for transmission. A rapid and correct diagnosis is considered to be an important strategy in the control of the disease especially in children, who are the most vulnerable group. This study assessed the prevalence of asymptomatic malaria in children at the Nkolbisson health area in Yaoundé, Cameroon. A cross-sectional study design and a convenience sampling plan were used. A total of 127 participants were recruited after informed and signed consent from parents and/or guardians. Blood samples were collected by finger-pricking and venipuncture from children aged 6 months to 10 years and then screened for asymptomatic parasitemia by a rapid diagnostic test (RDT), light microscopy (LM) staining with Giemsa and 18S rRNA polymerase chain reaction (PCR) for speciation. The data were analyzed using SPSS version 20 software. The study identified 85 children who were positive from the PCR, 95 positive from the RDT and 71 from the LM, revealing a malaria prevalence of 66.9%, 74.8% and 55.9%, respectively. The prevalence was not observed to be dependent on the sex and age group of the participants. Plasmodium falciparum was the predominant species followed by Plasmodium malariae and then Plasmodium ovale. The RDT and LM had the same sensitivity (90.6%) with a slight difference in their specificity (RDT: 57.1%; LM: 54.8%). The RDT also demonstrated higher positive and negative predictive values compared with those of the LM.

scholarly journals The epidemiology and detectability of asymptomatic Plasmodium vivax and Plasmodium falciparum infections in low, moderate and high transmission settings in Ethiopia

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Elifaged Hailemeskel ◽  
Surafel K Tebeje ◽  
Sinknesh W. Behaksra ◽  
Girma Shumie ◽  
Getasew Shitaye ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Vivax ◽  
Age Groups ◽  
Diagnostic Tools ◽  
Asymptomatic Malaria ◽  
Rapid Diagnostics ◽  
Cross Sectional ◽  
Low Transmission ◽  
High Transmission ◽  
Study Sites

Abstract Background As countries move to malaria elimination, detecting and targeting asymptomatic malaria infections might be needed. Here, the epidemiology and detectability of asymptomatic Plasmodium falciparum and Plasmodium vivax infections were investigated in different transmission settings in Ethiopia. Method: A total of 1093 dried blood spot (DBS) samples were collected from afebrile and apparently healthy individuals across ten study sites in Ethiopia from 2016 to 2020. Of these, 862 were from community and 231 from school based cross-sectional surveys. Malaria infection status was determined by microscopy or rapid diagnostics tests (RDT) and 18S rRNA-based nested PCR (nPCR). The annual parasite index (API) was used to classify endemicity as low (API > 0 and < 5), moderate (API ≥ 5 and < 100) and high transmission (API ≥ 100) and detectability of infections was assessed in these settings. Results In community surveys, the overall prevalence of asymptomatic Plasmodium infections by microscopy/RDT, nPCR and all methods combined was 12.2% (105/860), 21.6% (183/846) and 24.1% (208/862), respectively. The proportion of nPCR positive infections that was detectable by microscopy/RDT was 48.7% (73/150) for P. falciparum and 4.6% (2/44) for P. vivax. Compared to low transmission settings, the likelihood of detecting infections by microscopy/RDT was increased in moderate (Adjusted odds ratio [AOR]: 3.4; 95% confidence interval [95% CI] 1.6–7.2, P = 0.002) and high endemic settings (AOR = 5.1; 95% CI 2.6–9.9, P < 0.001). After adjustment for site and correlation between observations from the same survey, the likelihood of detecting asymptomatic infections by microscopy/RDT (AOR per year increase = 0.95, 95% CI 0.9–1.0, P = 0.013) declined with age. Conclusions Conventional diagnostics missed nearly half of the asymptomatic Plasmodium reservoir detected by nPCR. The detectability of infections was particularly low in older age groups and low transmission settings. These findings highlight the need for sensitive diagnostic tools to detect the entire parasite reservoir and potential infection transmitters.

scholarly journals The Epidemiology and Detectability of Asymptomatic Plasmodium Vivax and Plasmodium Falciparum Infections in Low, Moderate and High Transmission Settings in Ethiopia 

2020 ◽  
Author(s):  
Elifaged Hailemeskel ◽  
Surafel K Tebeje ◽  
Sinknesh Behaksra ◽  
Girma Shumie ◽  
Getasew Shitaye ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Age Groups ◽  
Diagnostic Tools ◽  
Asymptomatic Malaria ◽  
Rapid Diagnostics ◽  
Cross Sectional ◽  
Low Transmission ◽  
High Transmission ◽  
School Based ◽  
Study Sites

Abstract Background: As countries move to malaria elimination, detecting and targeting asymptomatic malaria infections might be needed. Here, we investigated the epidemiology and detectability of asymptomatic Plasmodium falciparum and P. vivax infections in different transmission settings in Ethiopia.Method: A total of 1093 dried blood spot (DBS) samples were collected from afebrile and apparently healthy individuals across ten study sites in Ethiopia from 2016 to 2020. Of these, 862 were from community and 231 from school based cross-sectional surveys. Malaria infection status was determined by microscopy or rapid diagnostics tests (RDT) and 18S rRNA based nested PCR (nPCR). The annual parasite index (API) was used to classify endemicity as low (API>0 and<5), moderate (API ≥5 and <100) and high transmission (API≥100) and detectability of infections was assessed in these settings. Results: In community surveys, the overall prevalence of asymptomatic Plasmodium infections by microscopy/RDT, nPCR and all methods combined was 12.2% (105/860), 21.6% (183/846) and 24.1% (208/862), respectively. The proportion of nPCR positive infections that was detectable by microscopy/RDT was 48.7% (73/150) for P. falciparum and 4.6% (2/44) for P. vivax. Compared to low transmission settings, the likelihood of detecting infections by microscopy/RDT was increased in moderate (Adjusted odds ratio [AOR]: 3.4; 95% confidence interval [95%CI]:1.6-7.2, P=0.002) and high endemic settings (AOR=5.1; 95%CI=2.6-9.9, P<0.001). After adjustment for site and correlation between observations from the same survey, the likelihood of detecting asymptomatic infections by microscopy/RDT (AOR per year increase = 0.95, 95%CI=0.9-1.0, P=0.013) declined with age.Conclusion: Conventional diagnostics missed nearly half of the asymptomatic Plasmodium reservoir detected by nPCR. The detectability of infections was particularly low in older age groups and low transmission settings. These findings highlight the need for sensitive diagnostic tools to detect the entire parasite reservoir and potential infection transmitters.

scholarly journals Increased Frequency of Pfdhps A581G Mutation in Plasmodium falciparum Isolates from Gabonese HIV-Infected Individuals

2019 ◽  
Vol 2019 ◽  
pp. 1-8
Author(s):  
Jeanne Vanessa Koumba Lengongo ◽  
Yaye Dié Ndiaye ◽  
Marie Louise Tshibola Mbuyi ◽  
Jacques Mari Ndong Ngomo ◽  
Daouda Ndiaye ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Plasmodium Falciparum ◽  
Cross Sectional Study ◽  
Capital City ◽  
Hiv Care ◽  
New Combination ◽  
Cross Resistance ◽  
Single Mutation ◽  
Cross Sectional ◽  
First Time

Background. Studying malaria parasites cross resistance to sulfadoxine-pyrimethamine (SP) and trimethoprim-sulfamethoxazole (cotrimoxazole, CTX) is necessary in areas coendemic for malaria and HIV. Polymorphism and frequency of drug resistance molecular markers, Pfdhfr and Pfdhps genes have been assessed in Plasmodium falciparum isolates from HIV-infected adults, in Gabon. Materiel and Methods. A cross-sectional study was conducted in three HIV care and treatment centers, at Libreville, the capital city of Gabon and at Oyem and Koulamoutou, two rural cities between March 2015 and June 2016. P. falciparum-infected HIV adults were selected. Analysis of Pfdhfr and Pfdhps genes was performed using high resolution melting (HRM) technique. Results. Pfdhps A581G mutation was found in 23.5% (8/34) of the isolates. Triple Pfdhfr mutation (51I-59R-108N) was predominant (29.4%; n=10) while 17.6% (n=6) of the isolates carried a quadruple mutation (Pfdhfr 51I-59R-108N + Pfdhps 437G; Pfdhfr 51I-108N + Pfdhps 437G-Pfdhps581G; Pfdhfr 51I-59R-108N + Pfdhps 581G). Highly resistant genotype was detected in around 10% (n=3) of the isolates. The quintuple mutation (triple Pfdhfr 51I-59R-108N and double Pfdhps437-581) was only found in isolates from two patients who did not use CTX. The most frequent haplotypes were those with a single mutation (NCNIAKA) (36%) and a quadruple mutation (NCIIGKG, NRIIGKA, and NRIIAKG). Mixed unknown genotypes were found at codon 164 in three isolates. Mixed genotypes were more frequent at codons 51 (23.5%; n=8) and 59 (20.5%; n=7) (p<0.01). Conclusion. Pfdhps A581G mutation as well as new combination of quintuple mutations is found for the first time in isolates from HIV-infected patients in Gabon in comparison to a previous study. The detection of these genotypes at a nonnegligible frequency underlines the need of a regular surveillance of antifolates drug resistance.

scholarly journals Epidemiological trends of malaria in the Western regions of Saudi Arabia: a cross sectional study

2020 ◽  
Vol 14 (11) ◽  
pp. 1332-1337
Author(s):  
Omar SO Amer ◽  
Mohamed I Waly ◽  
Izhar W Burhan ◽  
Esam S Al-Malki ◽  
Amor Smida ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Saudi Arabia ◽  
Malaria Infection ◽  
Plasmodium Malariae ◽  
Cross Sectional Study ◽  
Age Group ◽  
Cross Sectional ◽  
The Mean ◽  
Almost All ◽  
Epidemiological Trends

Introduction: Saudi Arabia has successfully reduced malaria cases to be constrained largely in the western regions. This study aimed to determine the epidemiological trends of malaria infection in five western regions of Saudi Arabia. Methodology: A retrospective analysis was conducted to investigate the epidemiological trends of malaria infection in the western regions, based on the published registry of the Saudi Ministry of Health, during the period from 2014 to 2017 using the appropriate statistical tools. Results: A total of 8925 confirmed cases of malaria were reported in the western regions during the period from 2014 to 2017 with the mean of 2231 malaria cases per year. The minimum (n = 1097) and maximum (n = 4075) number of cases were reported in 2014 and 2016 respectively. The highest (n = 5919, 66.3%) number of cases were reported from Jazan region, while lowest (n = 86, 1.0%) number of cases were reported from Al-Bahah region. Plasmodium falciparum was the most frequently reported species with 7485 (83.9%) cases, while Plasmodium vivax accounted 1386 (15.5%) cases. Plasmodium malariae and mixed infections were insignificant and accounted 0.5% (n = 48) and 0.1% (n = 6) cases respectively. In relation to malaria infection and age group, malaria was predominant in > 15 age group. The highest number of malaria cases in almost all years was observed from January until March and the lowest number was reported from May until July. Conclusions: Plasmodium falciparum was the most dominant species in this survey and Jazan was the most affected region.

scholarly journals Genetic diversity and population structure of the human malaria parasite Plasmodium falciparum surface protein Pfs47 in isolates from the lowlands in Western Kenya

PLoS ONE ◽  
2021 ◽  
Vol 16 (11) ◽  
pp. e0260434
Author(s):  
Shirley A. Onyango ◽  
Kevin O. Ochwedo ◽  
Maxwell G. Machani ◽  
Collince J. Omondi ◽  
Isaiah Debrah ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Plasmodium Falciparum ◽  
Population Structure ◽  
Haplotype Diversity ◽  
Population Expansion ◽  
Surface Protein ◽  
Dried Blood Spots ◽  
Cross Sectional ◽  
Western Kenya ◽  
Study Sites

Plasmodium falciparum parasites have evolved genetic adaptations to overcome immune responses mounted by diverse Anopheles vectors hindering malaria control efforts. Plasmodium falciparum surface protein Pfs47 is critical in the parasite’s survival by manipulating the vector’s immune system hence a promising target for blocking transmission in the mosquito. This study aimed to examine the genetic diversity, haplotype distribution, and population structure of Pfs47 and its implications on malaria infections in endemic lowlands in Western Kenya. Cross-sectional mass blood screening was conducted in malaria endemic regions in the lowlands of Western Kenya: Homa Bay, Kombewa, and Chulaimbo. Dried blood spots and slide smears were simultaneously collected in 2018 and 2019. DNA was extracted using Chelex method from microscopic Plasmodium falciparum positive samples and used to genotype Pfs47 using polymerase chain reaction (PCR) and DNA sequencing. Thirteen observed haplotypes of the Pfs47 gene were circulating in Western Kenya. Population-wise, haplotype diversity ranged from 0.69 to 0.77 and the nucleotide diversity 0.10 to 0.12 across all sites. All the study sites displayed negative Tajima’s D values although not significant. However, the negative and significant Fu’s Fs statistical values were observed across all the study sites, suggesting population expansion or positive selection. Overall genetic differentiation index was not significant (FST = -0.00891, P > 0.05) among parasite populations. All Nm values revealed a considerable gene flow in these populations. These results could have important implications for the persistence of high levels of malaria transmission and should be considered when designing potential targeted control interventions.

Asymptomatic falciparum and Non-falciparum Malarial Parasitemia in Adult Volunteers with and without HIV-1 Coinfection in a Cohort Study in Western Kenya

2021 ◽  
Author(s):  
Carolyne Kifude ◽  
Deborah Stiffler ◽  
David Rockabrand ◽  
Robin Miller ◽  
Emily Parsons ◽  
...  
Keyword(s):  
Quantitative Polymerase Chain Reaction ◽  
Plasmodium Malariae ◽  
Dried Blood Spots ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Western Kenya ◽  
Specific Pcr ◽  
Species Specific ◽  
The Impact ◽  
Hiv 1

Asymptomatic malarial parasitemia represents the largest reservoir of infection and transmission, and the impact of coinfection with HIV-1 on this reservoir remains incompletely described. Accordingly, we sought to determine the prevalence of asymptomatic malarial parasitemia in Kombewa, Western Kenya, a region that is endemic for both malaria and HIV-1. A total of 1,762 dried blood spots were collected from asymptomatic adults in a cross-sectional study. The presence of parasitemia was first determined by a sensitive Plasmodium genus–specific 18S assay, followed by less sensitive species-specific DNA-based quantitative polymerase chain reaction (PCR) assays. The prevalence of asymptomatic malarial parasitemia by 18S genus-specific PCR assay was 64.4% (1,134/1,762). Of the 1,134 malaria positive samples, Plasmodium falciparum was the most prevalent species (57.4%), followed by Plasmodium malariae (3.8%) and Plasmodium ovale (2.6%) as single or mixed infections. As expected, the majority of infections were below the detection limit of microscopy and rapid diagnostic tests. HIV-1 prevalence was 10.6%, and we observed a significant association with malarial parasitemia by χ2 analysis (P = 0.0475). Seventy-one percent of HIV-1 infected volunteers were positive for Plasmodium 18S (132/186), with only 29% negative (54/186). In HIV-1-negative volunteers, the proportion was lower; 64% were found to be positive for 18S (998/1,569) and 36% were negative (571/1,569). Overall, the prevalence of asymptomatic malarial parasitemia in Western Kenya is high, and knowledge of these associations with HIV-1 infection are critically important for malaria elimination and eradication efforts focused on this important reservoir population.

scholarly journals High prevalence of asymptomatic malaria infections in adults, Ashanti Region, Ghana, 2018

2020 ◽  
Author(s):  
Melina Heinemann ◽  
Richard O. Phillips ◽  
Christof D. Vinnemeier ◽  
Christina Rolling ◽  
Egbert Tannich ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Plasmodium Malariae ◽  
Asymptomatic Malaria ◽  
Plasmodium Ovale ◽  
Forest Zone ◽  
Ashanti Region ◽  
Plasmodium Ovale Curtisi ◽  
High Prevalence ◽  
Asymptomatic Adult ◽  
Species Specific

Abstract Background Ghana is among the high-burden countries for malaria infection and recently reported a notably increase in malaria cases. While asymptomatic parasitemia is increasingly recognized as a hurdle for malaria elimination, studies on asymptomatic malaria are scarce and usually focus on children and on non-falciparum species. The present study aims to assess the prevalence of asymptomatic Plasmodium falciparum and non-falciparum infections in Ghanaian adults in the Ashanti region during the high transmission season. Methods Asymptomatic adult residents from five villages in the Ashanti Region, Ghana, were screened for Plasmodium spp. by rapid diagnostic test (RDT) and polymerase chain reaction (PCR) during the rainy season. Samples tested positive were subtyped using species-specific real-time PCR. For all P. ovale infections additional sub-species identification was performed.Results Molecular prevalence of asymptomatic Plasmodium infection was 284/391 (73%); only 126 (32%) infections were detected by RDT. While 266 (68%) participants were infected with Plasmodium falciparum, 33 (8%) were infected with Plasmodium malariae and 34 (9%) with Plasmodium ovale. The sub-species Plasmodium ovale curtisi and P. ovale wallikeri were identified to similar proportions. Non-falciparum infections usually presented as mixed infections with Plasmodium falciparum.Conclusions Most adult residents in the Ghanaian forest zone are asymptomatic Plasmodium carriers. The high Plasmodium prevalence not detected by RDT in adults highlights that malaria eradication efforts must target all members of the population. Beneath Plasmodium falciparum, screening and treatment must also include infections with Plasmodium malariae, P. ovale curtisi and P. ovale wallikeri .

Sign in / Sign up

Export Citation Format

Share Document