Safety, efficacy and determinants of effectiveness of antimalarial drugs during pregnancy: implications for prevention programmes in Plasmodium falciparum-endemic sub-Saharan Africa

Introduction: In spite of considerable progress, malaria remains a public health problem in many areas, particularly in sub-Saharan Africa. One major complexity of malaria disease is caused by the development and the spread of vector and parasite resistance to insecticides and antimalarial drugs respectively. The Pfcrt76T gene mutation has been validated as a marker conferring resistance to chloroquine and other antimalarial drugs. The extension of Plasmodium falciparum resistance to commonly used antimalarial drugs (chloroquine, sulfadoxine-pyrimethamine) led to the adoption and the use of artemisinin-based combinations in Burkina Faso since 2005. Aims: The present study was initiated to assess the prevalence of the Pfcrt76T mutation in two different malaria epidemiological setting after a decade of introduction of artemisinin-based combination therapies (ACTs) in Burkina Faso. Methodology: The study population consisted of 181 uncomplicated malaria patients recruited in Banfora and Saponé health districts in 2012 and 2013. Blood samples were collected from finger prick on filter paper, dried and sent to the Molecular Biology Laboratory at Centre National de Recherche et de Formation sur le Paludisme (CNRFP) for molecular analyzes. DNA of Plasmodium falciparum was extracted with DNA extraction kit (Qiagen®) and the Pfcrt76T mutation was determined based on Polymerase Chain Reaction / Restriction Fragment Length Polymorphism technique (RFLP). Results: The results of this study showed that the frequency of the pfcrt76T mutant allele (33.7%) was statistically lower than the Pfcrt76K wild-type allele (57.4%) in the study area. Moreover, the prevalence of Pfcrt76T mutation was neither associated with the patient age nor with the parasite density while a significant difference was observed between the two epidemiological setting, Banfora and Saponé. Conclusion: The findings of this study has shown a drop in the prevalence of mutant parasites Pfcrt76T in both the study area eight years after the introduction of ACTs compared to previous studies.

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

Malaria Journal ◽

10.1186/s12936-020-03467-3 ◽

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.

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Cost-Effectiveness of the Introduction of a Pre-Erythrocytic Malaria Vaccine into the Expanded Program on Immunization in Sub-Saharan Africa: Analysis of Uncertainties Using a Stochastic Individual-Based Simulation Model of Plasmodium falciparum Malaria

Value in Health ◽

10.1016/j.jval.2011.06.004 ◽

2011 ◽

Vol 14 (8) ◽

pp. 1028-1038 ◽

Cited By ~ 20

Author(s):

Nicolas Maire ◽

Samuel D. Shillcutt ◽

Damian G. Walker ◽

Fabrizio Tediosi ◽

Thomas A. Smith

Keyword(s):

Plasmodium Falciparum ◽

Cost Effectiveness ◽

Simulation Model ◽

Falciparum Malaria ◽

Malaria Vaccine ◽

Plasmodium Falciparum Malaria ◽

Sub Saharan Africa ◽

Sub Saharan ◽

Individual Based Simulation ◽

Expanded Program On Immunization

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Plasmodium falciparum Infection Status among Children with Schistosoma in Sub-Saharan Africa: A Systematic Review and Meta-analysis

PLoS Neglected Tropical Diseases ◽

10.1371/journal.pntd.0005193 ◽

2016 ◽

Vol 10 (12) ◽

pp. e0005193 ◽

Cited By ~ 14

Author(s):

Abraham Degarege ◽

Dawit Degarege ◽

Emir Veledar ◽

Berhanu Erko ◽

Mathieu Nacher ◽

...

Keyword(s):

Systematic Review ◽

Plasmodium Falciparum ◽

Meta Analysis ◽

Falciparum Infection ◽

Sub Saharan Africa ◽

Infection Status ◽

Plasmodium Falciparum Infection ◽

Sub Saharan

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Acquired Immunity to Malaria

Clinical Microbiology Reviews ◽

10.1128/cmr.00025-08 ◽

2009 ◽

Vol 22 (1) ◽

pp. 13-36 ◽

Cited By ~ 627

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.

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

Parasite ◽

10.1051/parasite/2018021 ◽

2018 ◽

Vol 25 ◽

pp. 24 ◽

Cited By ~ 37

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.

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

Obstetric Medicine ◽

10.1258/om.2010.090060 ◽

2010 ◽

Vol 3 (3) ◽

pp. 106-109 ◽

Cited By ~ 2

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.

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