scholarly journals Kelch 13-propeller polymorphisms in Plasmodium falciparum from Jazan region, southwest Saudi Arabia

2020 ◽  
Vol 19 (1) ◽  
Author(s):  
Ommer Mohammed Dafalla ◽  
Mohammed Alzahrani ◽  
Ahmed Sahli ◽  
Mohammed Abdulla Al Helal ◽  
Mohammad Mohammad Alhazmi ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Saudi Arabia ◽  
Parasite Clearance ◽  
Sub Saharan Africa ◽  
Local Alignment ◽  
Nucleotide Polymorphisms ◽  
Gene Encoding ◽  
Synonymous Mutations ◽  
Search Tool ◽  
Sub Saharan

Abstract Background Artemisinin-based combination therapy (ACT) is recommended at the initial phase for treatment of Plasmodium falciparum, to reduce morbidity and mortality in all countries where malaria is endemic. Polymorphism in portions of P. falciparum gene encoding kelch (K13)-propeller domains is associated with delayed parasite clearance after ACT. Of about 124 different non-synonymous mutations, 46 have been identified in Southeast Asia (SEA), 62 in sub-Saharan Africa (SSA) and 16 in both the regions. This is the first study designed to analyse the prevalence of polymorphism in the P. falciparum k13-propeller domain in the Jazan region of southwest Saudi Arabia, where malaria is endemic. Methods One-hundred and forty P. falciparum samples were collected from Jazan region of southwest Saudi Arabia at three different times: 20 samples in 2011, 40 samples in 2016 and 80 samples in 2020 after the implementation of ACT. Plasmodium falciparum kelch13 (k13) gene DNA was extracted, amplified, sequenced, and analysed using a basic local alignment search tool (BLAST). Results This study obtained 51 non-synonymous (NS) mutations in three time groups, divided as follows: 6 single nucleotide polymorphisms (SNPs) ‘11.8%’ in samples collected in 2011 only, 3 (5.9%) in 2011and 2016, 5 (9.8%) in 2011 and 2020, 5 (9.8%) in 2016 only, 8 (15.7%) in 2016 and 2020, 14 (27.5%) in 2020 and 10 (19.6%) in all the groups. The BLAST revealed that the 2011 isolates were genetically closer to African isolates (53.3%) than Asian ones (46.7%). Interestingly, this proportion changed completely in 2020, to become closer to Asian isolates (81.6%) than to African ones (18.4%). Conclusions Despite the diversity of the identified mutations in the k13-propeller gene, these data did not report widespread artemisinin-resistant polymorphisms in the Jazan region where these samples were collected. Such a process would be expected to increase frequencies of mutations associated with the resistance of ACT.

scholarly journals The Diversity of the Plasmodium falciparum K13 Propeller Domain Did Not Increase after Implementation of Artemisinin-Based Combination Therapy in Uganda

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Melissa D. Conrad ◽  
Sam L. Nsobya ◽  
Philip J. Rosenthal
Keyword(s):  
Plasmodium Falciparum ◽  
Southeast Asia ◽  
Artemisinin Resistance ◽  
Standard Of Care ◽  
Parasite Clearance ◽  
Sub Saharan Africa ◽  
Clinical Isolates ◽  
Nucleotide Polymorphisms ◽  
Content Type ◽  
Sub Saharan

ABSTRACT Artemisinin-based combination therapies (ACTs) are the standard of care to treat uncomplicated falciparum malaria. However, resistance to artemisinins, defined as delayed parasite clearance after therapy, has emerged in Southeast Asia, and the spread of resistance to sub-Saharan Africa could have devastating consequences. Artemisinin resistance has been associated in Southeast Asia with multiple nonsynonymous single nucleotide polymorphisms (NS-SNPs) in the propeller domain of the gene encoding the Plasmodium falciparum K13 protein (K13PD). Some K13PD NS-SNPs have been seen in Africa, but the relevance of these mutations is unclear. To assess whether ACT use has selected for specific K13PD mutations, we compared the K13PD genetic diversity in clinical isolates collected before and after the implementation of ACT use from seven sites across Uganda. We detected K13PD NS-SNPs in 16 of 683 (2.3%) clinical isolates collected between 1999 and 2004 and in 26 of 716 (3.6%) isolates collected between 2012 and 2016 (P = 0.16), representing a total of 29 different polymorphisms at 27 codons. Individual NS-SNPs were usually detected only once, and none were found in more than 0.7% of the isolates. Three SNPs (C469F, P574L, and A675V) associated with delayed clearance in Southeast Asia were seen in samples collected between 2012 and 2016, each in a single isolate. No differences in diversity following implementation of ACT use were found at any of the seven sites, nor was there evidence of selective pressures acting on the locus. Our results suggest that selection by ACTs is not impacting on K13PD diversity in Uganda.

scholarly journals Prevalence and predictors of vitamin D deficiency in young African children

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Reagan M. Mogire ◽  
Alireza Morovat ◽  
John Muthii Muriuki ◽  
Alexander J. Mentzer ◽  
Emily L. Webb ◽  
...  
Keyword(s):  
South Africa ◽  
Vitamin D ◽  
Vitamin D Deficiency ◽  
Sub Saharan Africa ◽  
Nucleotide Polymorphisms ◽  
Vitamin D Status ◽  
Older Children ◽  
Gene Encoding ◽  
African Children ◽  
Sub Saharan

Abstract Background Children living in sub-Saharan Africa have a high burden of rickets and infectious diseases, conditions that are linked to vitamin D deficiency. However, data on the vitamin D status of young African children and its environmental and genetic predictors are limited. We aimed to examine the prevalence and predictors of vitamin D deficiency in young African children. Methods We measured 25-hydroxyvitamin D (25(OH)D) and typed the single nucleotide polymorphisms, rs4588 and rs7041, in the GC gene encoding the vitamin D binding protein (DBP) in 4509 children aged 0–8 years living in Kenya, Uganda, Burkina Faso, The Gambia and South Africa. We evaluated associations between vitamin D status and country, age, sex, season, anthropometric indices, inflammation, malaria and DBP haplotypes in regression analyses. Results Median age was 23.9 months (interquartile range [IQR] 12.3, 35.9). Prevalence of vitamin D deficiency using 25(OH)D cut-offs of < 30 nmol/L and < 50 nmol/L was 0.6% (95% CI 0.4, 0.9) and 7.8% (95% CI 7.0, 8.5), respectively. Overall median 25(OH)D level was 77.6 nmol/L (IQR 63.6, 94.2). 25(OH)D levels were lower in South Africa, in older children, during winter or the long rains, and in those with afebrile malaria, and higher in children with inflammation. 25(OH)D levels did not vary by stunting, wasting or underweight in adjusted regression models. The distribution of Gc variants was Gc1f 83.3%, Gc1s 8.5% and Gc2 8.2% overall and varied by country. Individuals carrying the Gc2 variant had lower median 25(OH)D levels (72.4 nmol/L (IQR 59.4, 86.5) than those carrying the Gc1f (77.3 nmol/L (IQR 63.5, 92.8)) or Gc1s (78.9 nmol/L (IQR 63.8, 95.5)) variants. Conclusions Approximately 0.6% and 7.8% of young African children were vitamin D deficient as defined by 25(OH)D levels < 30 nmol/L and < 50 nmol/L, respectively. Latitude, age, season, and prevalence of inflammation and malaria should be considered in strategies to assess and manage vitamin D deficiency in young children living in Africa.

scholarly journals Mutation in Plasmodium falciparum BTB/POZ domain of K13 protein confers artemisinin resistance

2021 ◽  
Author(s):  
Lucie Paloque ◽  
Romain Coppée ◽  
Barbara H. Stokes ◽  
Nina F. Gnädig ◽  
Karamoko Niaré ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Artemisinin Resistance ◽  
Parasite Clearance ◽  
West African ◽  
Whole Genome Sequence ◽  
Drug Pressure ◽  
Synonymous Mutations ◽  
Survival Assay ◽  
One Year

Partial artemisinin resistance, defined in patients as a delayed parasite clearance following artemisinin-based treatment, is conferred by non-synonymous mutations in the Kelch beta-propeller domain of the Plasmodium falciparum k13 ( pfk13 ) gene. Here, we carried out in vitro selection over a one-year period on a West African P. falciparum strain isolated from Kolle (Mali) under a dose-escalating artemisinin regimen. After 18 cycles of sequential drug pressure, the selected parasites exhibited enhanced survival to dihydroartemisinin in the ring-stage survival assay (RSA 0-3h = 9.2%). Sanger and whole-genome sequence analyses identified the PfK13 P413A mutation, localized in the BTB/POZ domain, upstream of the propeller domain. This mutation was sufficient to confer in vitro artemisinin resistance when introduced into the PfK13 coding sequence of the parasite strain Dd2 by CRISPR/Cas9 gene editing. These results together with structural studies of the protein demonstrate that the propeller domain is not the sole in vitro mediator of PfK13-mediated artemisinin resistance, and highlight the importance of monitoring for mutations throughout PfK13.

scholarly journals Study of the genetic heterogeneity of SAT-2 foot-and-mouth disease virus in sub-Saharan Africa with specific focus on East Africa

2007 ◽  
Vol 74 (4) ◽  
Author(s):  
M. Sahle ◽  
R.M. Dwarka ◽  
E.H. Venter ◽  
W. Vosloo
Keyword(s):  
East Africa ◽  
Foot And Mouth Disease ◽  
Mouth Disease ◽  
Sub Saharan Africa ◽  
Gene Encoding ◽  
Western Africa ◽  
Mouth Disease Virus ◽  
Foot And Mouth ◽  
Sub Saharan ◽  
Unrelated Strain

The epidemiology of serotype SAT-2 foot-and-mouth disease was investigated in sub-Saharan Africa by phylogenetic analysis using the 1D gene encoding the major antigenic determinant. Fourteen genotypes were identified of which three are novel and belong to East Africa, bringing the total number of genotypes for that region to eight. The genotypes clustered into three lineages that demonstrated surprising links between East, southern and south-western Africa. One lineage was unique to West Africa. These results established numerous incursions across country borders in East Africa and long term conservation of sequences for periods up to 41 years. Ethiopia, Kenya and Uganda have all experienced outbreaks from more than one unrelated strain, demonstrating the potential for new introductions. The amount of variation observed within this serotype nearly equalled that which was found between serotypes; this has severe implications for disease control using vaccination.

scholarly journals Acquired Immunity to Malaria

2009 ◽  
Vol 22 (1) ◽  
pp. 13-36 ◽  
Author(s):  
Denise L. Doolan ◽  
Carlota Dobaño ◽  
J. Kevin Baird
Keyword(s):  
Plasmodium Falciparum ◽  
High Risk ◽  
Immune Status ◽  
Severe Disease ◽  
Sub Saharan Africa ◽  
Acquired Immunity ◽  
Sub Saharan ◽  
High Risk Infants ◽  
Induced Immunity ◽  
Infants And Young Children

SUMMARY Naturally acquired immunity to falciparum malaria protects millions of people routinely exposed to Plasmodium falciparum infection from severe disease and death. There is no clear concept about how this protection works. There is no general agreement about the rate of onset of acquired immunity or what constitutes the key determinants of protection; much less is there a consensus regarding the mechanism(s) of protection. This review summarizes what is understood about naturally acquired and experimentally induced immunity against malaria with the help of evolving insights provided by biotechnology and places these insights in the context of historical, clinical, and epidemiological observations. We advocate that naturally acquired immunity should be appreciated as being virtually 100% effective against severe disease and death among heavily exposed adults. Even the immunity that occurs in exposed infants may exceed 90% effectiveness. The induction of an adult-like immune status among high-risk infants in sub-Saharan Africa would greatly diminish disease and death caused by P. falciparum. The mechanism of naturally acquired immunity that occurs among adults living in areas of hyper- to holoendemicity should be understood with a view toward duplicating such protection in infants and young children in areas of endemicity.

scholarly journals Plasmodium falciparum resistance to artemisinin-based combination therapies: A sword of Damocles in the path toward malaria elimination

Parasite ◽  
2018 ◽  
Vol 25 ◽  
pp. 24 ◽  
Author(s):  
Manel Ouji ◽  
Jean-Michel Augereau ◽  
Lucie Paloque ◽  
Françoise Benoit-Vical
Keyword(s):  
Plasmodium Falciparum ◽  
Multidrug Resistant ◽  
Sub Saharan Africa ◽  
High Rate ◽  
Combination Therapies ◽  
Parasite Resistance ◽  
The Past ◽  
Sub Saharan ◽  
Treatment Policies ◽  
Related Mortality

The use of artemisinin-based combination therapies (ACTs), which combine an artemisinin derivative with a partner drug, in the treatment of uncomplicated malaria has largely been responsible for the significant reduction in malaria-related mortality in tropical and subtropical regions. ACTs have also played a significant role in the 18% decline in the incidence of malaria cases from 2010 to 2016. However, this progress is seriously threatened by the reduced clinical efficacy of artemisinins, which is characterised by delayed parasitic clearance and a high rate of recrudescence, as reported in 2008 in Western Cambodia. Resistance to artemisinins has already spread to several countries in Southeast Asia. Furthermore, resistance to partner drugs has been shown in some instances to be facilitated by pre-existing decreased susceptibility to the artemisinin component of the ACT. A major concern is not only the spread of these multidrug-resistant parasites to the rest of Asia but also their possible appearance in Sub-Saharan Africa, the continent most affected by malaria, as has been the case in the past with parasite resistance to other antimalarial treatments. It is therefore essential to understand the acquisition of resistance to artemisinins by Plasmodium falciparum to adapt malaria treatment policies and to propose new therapeutic solutions.

scholarly journals Asexual and sexual stages of Plasmodium falciparum in Nigerian pregnant women attending antenatal booking clinic

2010 ◽  
Vol 3 (3) ◽  
pp. 106-109 ◽  
Author(s):  
S T Balogun ◽  
F A Fehintola ◽  
O A Adeyanju ◽  
A A Adedeji
Keyword(s):  
Plasmodium Falciparum ◽  
Preterm Birth ◽  
Infant Mortality ◽  
Pregnant Women ◽  
Blood Meal ◽  
Sub Saharan Africa ◽  
Female Mosquito ◽  
Susceptibility To Infection ◽  
Sexual Stages ◽  
Sub Saharan

Susceptibility to infection by Plasmodium falciparum is increased in pregnant women. In sub-Saharan Africa, the consequences of maternal malaria include preterm birth, fetal growth restriction and increased infant mortality. Malaria transmission requires the circulation of viable gametocytes that can be ingested by the female mosquito taking a blood meal. This study was conducted to evaluate the presence of asexual and sexual stages of P. falciparum in pregnant women attending antenatal booking clinics in south-western Nigeria, an area hyper-endemic for malaria. Gametocyte carriage was about 13%, similar to that documented for children symptomatic for malaria in our area of study.

scholarly journals Plasmodium falciparum msp1, msp2 and glurp allele frequency and diversity in sub-Saharan Africa

2011 ◽  
Vol 10 (1) ◽  
pp. 79 ◽  
Author(s):  
Felista Mwingira ◽  
Gamba Nkwengulila ◽  
Sonja Schoepflin ◽  
Deborah Sumari ◽  
Hans-Peter Beck ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Allele Frequency ◽  
Sub Saharan Africa ◽  
Sub Saharan
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