scholarly journals Genomic Analysis of Plasmodium vivax in Southern Ethiopia Reveals Selective Pressures in Multiple Parasite Mechanisms

2019 ◽  
Vol 220 (11) ◽  
pp. 1738-1749 ◽  
Author(s):  
Sarah Auburn ◽  
Sisay Getachew ◽  
Richard D Pearson ◽  
Roberto Amato ◽  
Olivo Miotto ◽  
...  

Abstract The Horn of Africa harbors the largest reservoir of Plasmodium vivax in the continent. Most of sub-Saharan Africa has remained relatively vivax-free due to a high prevalence of the human Duffy-negative trait, but the emergence of strains able to invade Duffy-negative reticulocytes poses a major public health threat. We undertook the first population genomic investigation of P. vivax from the region, comparing the genomes of 24 Ethiopian isolates against data from Southeast Asia to identify important local adaptions. The prevalence of the Duffy binding protein amplification in Ethiopia was 79%, potentially reflecting adaptation to Duffy negativity. There was also evidence of selection in a region upstream of the chloroquine resistance transporter, a putative chloroquine-resistance determinant. Strong signals of selection were observed in genes involved in immune evasion and regulation of gene expression, highlighting the need for a multifaceted intervention approach to combat P. vivax in the region.

Author(s):  
Daniel Kepple ◽  
Alfred Hubbard ◽  
Musab M Ali ◽  
Beka R Abargero ◽  
Karen Lopez ◽  
...  

Abstract Plasmodium vivax malaria was thought to be rare in Africa, but an increasing number of P. vivax cases reported across Africa and in Duffy-negative individuals challenges this conventional dogma. The genetic characteristics of P. vivax in Duffy-negative infections, the transmission of P. vivax in East Africa, and the impact of environments on transmission remain largely unknown. This study examined genetic and transmission features of P. vivax from 107 Duffy-negative and 305 Duffy-positive individuals in Ethiopia and Sudan. No clear genetic differentiation was found in P. vivax between the two Duffy groups, indicating between-host transmission. P. vivax from Ethiopia and Sudan showed similar genetic clusters, except samples from Khartoum, possibly due to distance and road density that inhibited parasite gene flow. This study is the first to show that P. vivax can transmit to and from Duffy-negative individuals and provides critical insights into the spread of P. vivax in sub-Saharan Africa.


Author(s):  
Séni Nikiema ◽  
Samuel Sindié Sermé ◽  
Salif Sombié ◽  
Amidou Diarra ◽  
Noelie Bere Henry ◽  
...  

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.


Author(s):  
Isaac K. Quaye ◽  
Larysa Aleksenko

In recent times, several countries in sub-Saharan Africa have reported cases of Plasmodium vivax (Pv) with a considerable number being Duffy negative. Current efforts at malaria elimination are focused solely on Plasmodium falciparum (Pf) excluding non-falciparum malaria. Pv and Plasmodium ovale (Po) have hypnozoite forms that can serve as reservoirs of infection and sustain transmission. The burden of these parasites in Africa seems to be more than acknowledged, playing roles in migrant and autochthonous infections. Considering that elimination and eradication is a current aim for WHO and Roll Back Malaria (RBM), the inclusion of Pv and Po in the elimination agenda cannot be over-emphasized. The biology of Pv and Po are such that the same elimination strategies as are used for Pf cannot be applied so, going forward, new approaches will be required to attain elimination and eradication targets.


2019 ◽  
Vol 2019 ◽  
pp. 1-5 ◽  
Author(s):  
Alla Baranova ◽  
Vladimir Sergiev ◽  
Lola Morozova ◽  
Natalia Turbabina ◽  
Evgeny Morozov

Background. Imported cases of Plasmodium vivax malaria from western Africa are reported annually in the Russian Federation. Infected native African people moving from western Africa for different purposes (students, businessmen, specialists, etc.) or Russian citizens (tourists, diplomats, businessmen, etc.) incubate the pathogen until reaching their Russian destination. Methods. All imported and other confirmed malaria cases and the associated Plasmodium species recorded over the past twenty years throughout the Russian Federation were inventoried. These data were included in the national register. The data of imported malaria cases were analysed according to the species of Plasmodium, case origin, dates of importation, and patient nationality. Results. A total of 267 P. vivax-infected patients who contracted the disease in western Africa were diagnosed in the Russian Federation from 1984 to 2017. Among them, 3 cases had mixed infections (2 with P. vivax + P. falciparum and 1 P. vivax + P. ovale). Conclusion. Our data reveal an existing risk of contracting P. vivax infections in towns of West sub-Saharan Africa despite the absence of local P. vivax infection records.


2019 ◽  
Vol 116 (14) ◽  
pp. 7053-7061 ◽  
Author(s):  
Karthigayan Gunalan ◽  
Juliana M. Sá ◽  
Roberto R. Moraes Barros ◽  
Sarah L. Anzick ◽  
Ramoncito L. Caleon ◽  
...  

Unlike the case in Asia and Latin America,Plasmodium vivaxinfections are rare in sub-Saharan Africa due to the absence of the Duffy blood group antigen (Duffy antigen), the only known erythrocyte receptor for theP. vivaxmerozoite invasion ligand, Duffy binding protein 1 (DBP1). However,P. vivaxinfections have been documented in Duffy-negative individuals throughout Africa, suggesting thatP. vivaxmay use ligands other than DBP1 to invade Duffy-negative erythrocytes through other receptors. To identify potentialP. vivaxligands, we compared parasite gene expression inSaimiriandAotusmonkey erythrocytes infected withP. vivaxSalvador I (Sal I). DBP1 bindsAotusbut does not bind toSaimirierythrocytes; thus,P. vivaxSal I must invadeSaimirierythrocytes independent of DBP1. Comparing RNA sequencing (RNAseq) data for late-stage infections inSaimiriandAotuserythrocytes when invasion ligands are expressed, we identified genes that belong to tryptophan-rich antigen and merozoite surface protein 3 (MSP3) families that were more abundantly expressed inSaimiriinfections compared withAotusinfections. These genes may encode potential ligands responsible forP. vivaxinfections of Duffy-negative Africans.


2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Maowia M. Mukhtar ◽  
Omer A. Eisawi ◽  
Seth A. Amanfo ◽  
Elwaleed M. Elamin ◽  
Zeinab S. Imam ◽  
...  

Abstract Background Plasmodium vivax infection is rising in sub-Saharan Africa, where Plasmodium falciparum is responsible for more than 90% of malaria cases. While P. vivax is identified as a major cause of severe and cerebral malaria in South east Asia, the Pacific and South America, most of the severe and cerebral cases in Africa were attributed to P. falciparum. Cases of severe malaria due to P. vivax are emerging in Africa. A few severe P. vivax cases were reported in Eastern Sudan and they were underestimated due to the lack of accurate diagnosis, low parasitaemia and seldom use of rapid diagnostic tests (RDTs). Case presentation A 60-year-old Sudanese male presented to the Al Kuwaiti hospital in the Sudan capital Khartoum. On admission, the patient was complaining of fever (measured temperature was 38 °C), sweating, chills, vomiting and confusion in the past 2 days prior to his admission. He rapidly deteriorated into a coma state within 48 h of the admission, with significant neck stiffness. He was admitted to the intensive care unit and was suspected of meningitis. Lumbar puncture was not performed since the patient was suffering from spinal cord disc. Brain CT scan was unremarkable. Several biochemical, haematological tests, and blood film for malaria were performed. The results of the laboratory tests were within the normal range except of mild elevation of the total white blood cell count and a significant decrease in the platelets count. Malaria parasites were seen in the blood film with high parasitaemia (quantified as 3 +++). The patient was diagnosed as P. vivax cerebral malaria based on the positive blood film and the amplification of P. vivax specific 499 bp amplicon using Plasmodium multi-species multiplex Polymerase Chain Reaction (PCR). The patient was treated with quinine 10 mg/kg body weight for 10 days followed by primaquine 15 mg/days PO for 2 weeks. The symptoms subsided within 48 h and the patients was cured and released from the hospital. Conclusions Plasmodium vivax is an emerging cause of cerebral malaria in adults in Sudan and should be considered in the differential diagnosis of cerebral malaria for proper management of patients.


2020 ◽  
Author(s):  
MARY Aigbiremo OBOH ◽  
Upasana Shyamsunder Singh ◽  
Daouda Ndiaye ◽  
Aida Sadikh Badiane ◽  
Nazia Anwar Ali ◽  
...  

Abstract Background Malaria in sub-Saharan Africa (sSA) is thought to be hugely caused by Plasmodium falciparum . Recently, growing reports of cases due to P. ovale , P. malariae , and P. vivax have been significantly reported to play a role in malaria epidemiology in sSA. This in fact is due to the usage of very sensitive diagnostic tools (e.g. PCR) which have highlighted the underestimation of non-falciparum malaria in this sub-region. P. vivax was historically thought to be absent in sSA due to the high prevalence of the Duffy null antigen in individuals residing in this sub-continent. For example, recent studies reporting the detection of vivax malaria in Duffy-negative individuals from Mali, Mauritania, Cameroon to mention a few challenges this notion.Methods Following our earlier report of P. vivax in Duffy-negative individuals, we have collected and assessed RDT and/or microscope malaria positive samples following the conventional PCR method and DNA sequencing to confirm both single/mixed infections as well as the Duffy status of the individuals.Results Amplification of Plasmodium gDNA was possible in 59.9% (145/242) of the evaluated isolates and as expected P. falciparum was the most predominant (91.7%) species identified. Interestingly, four P. vivax isolates were identified either as single (3) or mixed (1 – P. falciparum / P. vivax ) infection. Sequencing results confirmed, all vivax isolates as truly vivax malaria and their Duffy status to be that of the Duffy-negative genotype.Conclusion Identification of more vivax isolates among these Duffy-negative individuals from Nigeria, substantiate the expanding body of evidence on the ability of P. vivax to infect RBCs that do not express the DARC gene. Hence, such genetic-epidemiological study should be conducted at the national level in order to evaluate the actual burden of P. vivax in the country.


2019 ◽  
Vol 74 (5) ◽  
pp. 1223-1232 ◽  
Author(s):  
Patrick Musicha ◽  
Chisomo L Msefula ◽  
Alison E Mather ◽  
Chrispin Chaguza ◽  
Amy K Cain ◽  
...  

Abstract Objectives ESBL-producing Klebsiella pneumoniae (KPN) pose a major threat to human health globally. We carried out a WGS study to understand the genetic background of ESBL-producing KPN in Malawi and place them in the context of other global isolates. Methods We sequenced genomes of 72 invasive and carriage KPN isolates collected from patients admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi. We performed phylogenetic and population structure analyses on these and previously published genomes from Kenya (n = 66) and from outside sub-Saharan Africa (n = 67). We screened for presence of antimicrobial resistance (AMR) genetic determinants and carried out association analyses by genomic sequence cluster, AMR phenotype and time. Results Malawian isolates fit within the global population structure of KPN, clustering into the major lineages of KpI, KpII and KpIII. KpI isolates from Malawi were more related to those from Kenya, with both collections exhibiting more clonality than isolates from the rest of the world. We identified multiple ESBL genes, including blaCTX-M-15, several blaSHV, blaTEM-63 and blaOXA-10, and other AMR genes, across diverse lineages of the KPN isolates from Malawi. No carbapenem resistance genes were detected; however, we detected IncFII and IncFIB plasmids that were similar to the carbapenem resistance-associated plasmid pNDM-mar. Conclusions There are multiple ESBL genes across diverse KPN lineages in Malawi and plasmids in circulation that are capable of carrying carbapenem resistance. Unless appropriate interventions are rapidly put in place, these may lead to a high burden of locally untreatable infection in vulnerable populations.


2020 ◽  
Vol 10 ◽  
pp. e00596
Author(s):  
Mary Aigbiremo Oboh ◽  
Kolapo Muyiwa Oyebola ◽  
Emmanuel Taiwo Idowu ◽  
Aida Sadikh Badiane ◽  
Olubunmi Adetoro Otubanjo ◽  
...  

2020 ◽  
Author(s):  
Nicholas F. Brazeau ◽  
Cedar L. Mitchell ◽  
Andrew P. Morgan ◽  
Molly Deutsch-Feldman ◽  
Oliver John Watson ◽  
...  

ABSTRACTBackgroundReports of P. vivax infections among Duffy-negative hosts have begun to accumulate throughout sub-Saharan Africa. Despite this growing body of evidence, no nationally representative epidemiological surveys of P. vivax in sub-Saharan Africa nor population genetic analyses to determine the source of these infections have been performed.MethodsTo overcome this critical gap in knowledge, we screened nearly 18,000 adults in the Democratic Republic of the Congo (DRC) for P. vivax using samples from the 2013-2014 Demographic Health Survey. Infections were identified by quantitative PCR and confirmed with nested-PCR. P. vivax mitochondrial genomes were constructed after short-read sequencing. Risk factors, spatial distributions and population genetic analyses were explored.FindingsOverall, we found a 2.96% (95% CI: 2.28%, 3.65%) prevalence of P. vivax infections across the DRC. Nearly all infections were among Duffy-negative adults (486/489). Infections were not associated with typical malaria risk-factors and demonstrated small-scale heterogeneity in prevalence across space. Mitochondrial genomes suggested that DRC P. vivax is an older clade that shares its most recent common ancestor with South American isolates.InterpretationP. vivax is more prevalent across the DRC than previously believed despite widespread Duffy-negativity. Comparison to global and historical P. vivax sequences suggests that historic DRC P. vivax may have been transported to the New World on the wave of European expansion. Our findings suggest congolese P. vivax is an innocuous threat given its relatively flat distribution across space, lack of malaria risk factors, and potentially ancestral lineage.FundingNational Institutes of Health and the Wellcome Trust.


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