Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Plasmodium species are the causative agents of coronavirus disease 2019 (COVID-19) and malaria respectively with similar clinical presentations. The obj...Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Plasmodium species are the causative agents of coronavirus disease 2019 (COVID-19) and malaria respectively with similar clinical presentations. The objective of this study is to determine the burden of co-infection of SARS-CoV-2 and malaria in the general population. Five (5 mLs) of blood samples were collected for SARS-CoV-2 and malaria parasite test. The malaria test was performed using a commercially available one-step malaria antigen Plasmodium falciparum histidine-rich protein 2 (Pf HRP-II) rapid test kit. The results of the study showed that the participants that were coinfected with SARS-CoV-2 IgG and malaria were 13 (2.5%) in Lagos, 1114 (39.1%) in Delta and 49 (2.3%) in Sokoto States. The prevalence of coinfection of SARS-CoV-2 and malaria in urban areas in Lagos, Delta and Sokoto States were 7 (2.2%), 1373 (48.1%), and 5 (0.2%) respectively. In rural areas, the prevalence of coinfection of SARS-CoV-2 and malaria in Lagos, Delta and Sokoto States were 6 (0.3%), 365 (12.8%), and 44 (2.1%) respectively in this study. This suggests that participants in the urban areas were more prone to co-infections than the rural areas in Lagos and Delta states, while it was otherwise in Sokoto State. In conclusion, the co-infection of SARS-CoV-2 and malaria was very high in Delta State compared to the other States. It is important for clinics to screen for both diseases when patients present with symptoms of malaria. This is because the infections have similar symptoms and the public is quick to assume malaria infection without diagnosing for COVID-19 and vice versa.展开更多
AIM To assess the burden of norovirus(No V) and to determine the diversity of circulating strains among hospitalized children in Lebanon. METHODS Stool samples were collected from children presenting with acute gastro...AIM To assess the burden of norovirus(No V) and to determine the diversity of circulating strains among hospitalized children in Lebanon. METHODS Stool samples were collected from children presenting with acute gastroenteritis to six major hospitals in Lebanon. A total of 739 eligible stool samples, testing negative for diarrhea caused by rotavirus as a possible viral pathogen, were collected between January 2011 and June 2013. A standardized questionnaire including demographic, epidemiological and clinical observations was used at the time of hospitalization of children presenting with diarrhea. Viral RNA was extracted from stool samples followed by reverse transcription polymerase chain reaction and nucleotide sequencing of a fragment of the viral protein 1 capsid gene. Multiple sequence alignments were carried out and phylogenetic trees were constructed using the MEGA 6 software.RESULTS Overall, 11.2% of stool samples collected from children aged < 5 years tested positive for No V genogroups Ⅰ(GⅠ) and Ⅱ(GⅡ). GⅡ accounted for 10.6% of the gastroenteritis cases with only five samples being positive for GⅠ(0.7%). The majority of hospitalized children showed symptoms of diarrhea, dehydration, vomiting and fever. Upon sequencing of positive samples and based on their clustering in the phylogenetic tree, 4/5 of GⅠ gastroenteritis cases were designated GⅠ.3 and one case as GⅠ.4. GⅡ.4 was predominantly detected in stool of our study participants(68%). We report a JB-15/KOR/2008 GⅡ.4 Apeldoorn 2008-like variant strain circulating in 2011; this strain was replaced between 2012 and 2013 by a variant sharing homology with the Sydney/NSW0514/2012/AUS GⅡ.4 Sydney 2012 and Sydney 2012/FRA GⅡ.4 strains. We also report the co-circulation of non-GⅡ.4 genotypes among hospitalized children. Our data show that No V gastroenteritis can occur throughout the year with the highest number of cases detected during the hot months.CONCLUSION The majority of No V-associated viral gastroenteritis cases among our participants are attributable to GⅡ.4, which is compatible with results reported worldwide.展开更多
<strong>Background:</strong> Listeriosis affects immunosuppressed individual’s especially pregnant women. Maternal infections are usually mild for the woman, but may have devastating effects on the unborn...<strong>Background:</strong> Listeriosis affects immunosuppressed individual’s especially pregnant women. Maternal infections are usually mild for the woman, but may have devastating effects on the unborn child, including miscarriage, stillbirth, preterm labour and serious neonatal illness. WHO recommends that pregnant women should be educated to avoid foods with high risk of contamination. This study seeks to evaluate knowledge and practices predisposing to listeria infections during pregnancy. <strong>Methodology:</strong> This is a cross-sectional study on pregnant women, attending the antenatal clinic of Lagos University Teaching Hospital (LUTH) using semi structured questionnaires. The knowledge score of participants was collated and analyzed using SPSS version 26. <strong>Results:</strong> The mean age of the participants was 32.07 ± 5.6 years. Forty-three (30.7%) women have had previous miscarriages with the mean no of miscarriage of 1.54. Out of 147 participants, only 20 (13.6%) admitted having heard of listeriosis while 127 (86.4%) had never heard of listeriosis and none of the participants has ever been tested for listeriosis. The Overall knowledge score was poor, and this was irrespective of age and duration of pregnancy. However, women with graduate and/or postgraduate degrees were more likely to have heard of Listeriosis (X2 = 10.88, P = 0.028). <strong>Conclusion:</strong> Our study shows a low level of knowledge about this food-borne illness, which can lead to severe illnesses in pregnant women and their unborn child. It is necessarily to educate pregnant women on the risk of listeriosis. This would be a key factor in creating and implementing accurate measures of prevention and control.展开更多
Objective: To evaluate the expression of DNA plasmid-harboring modified antibody gene that produces neutralizing human monoclonal antibodies against four serotypes of dengue virus(DENV) without enhancing activity in B...Objective: To evaluate the expression of DNA plasmid-harboring modified antibody gene that produces neutralizing human monoclonal antibodies against four serotypes of dengue virus(DENV) without enhancing activity in BALB/c mice. Methods: We constructed pFUSE-based vectors(pFUSE1 G7 C2hVH and pFUSE1 G7 C2hVL) containing genes encoding the variable domains of the heavy or light chain of the anti-dengue virus antibody 1 G7 C2, a human IgG1 that has been characterized for its neutralizing activity to DENV-1-4. Leucine(L) at positions 234 and 235 on the Fc CH2 domain in pFUSE1 G7 C2hVH was mutated to alanine(A)(LALA mutation) by site direct mutagenesis, and the new plasmid was termed pFUSE1 G7 C2hVHLALA. An equal amount of pFUSE1 G7 C2hVL and 1 G7 C2hG1-LALA plasmids were co-transfected into Chinese hamster ovary cells(CHO-K1) and a single dose of 100 μg 1 G7 C2hG1-LALA plasmid was intramuscularly injected, followed by electroporation in BALB/c mice. The secreted 1 G7 C2hG1-LALA antibodies in cell culture supernatant and mouse serum were examined for their biological functions, neutralization and enhancing activity. Results: The co-transfection of heavy-and light-chain 1 G7 C2hG1-LALA plasmids in CHO-K1 cells produced approximately 3 900 ng/mL human IgG and neutralized 90%-100% all four DENV, with no enhancing activity. Furthermore, the modified human IgG was produced more than 1 000 ng/mL in mouse serum on day 7 post plasmid injection and showed cross-neutralization to four DENV serotypes. Subsequently, antibody production and neutralization decreased rapidly. Nevertheless, the secreted neutralizing 1 G7 C2hG1-LALA in mouse serum demonstrated complete absence of enhancing activities to all DENV serotypes. Conclusions: These findings reveal that a new modified 1 G7 C2h G1-LALA expressing plasmid based on gene transfer is a possible therapeutic antibody candidate against DENV infection.展开更多
<strong>Background:</strong> Listeriosis is a common zoonotic disease caused by a foodborne pathogen, <em>Listeria monocytogenes</em>. Poultry meat and products have been established as vehicle...<strong>Background:</strong> Listeriosis is a common zoonotic disease caused by a foodborne pathogen, <em>Listeria monocytogenes</em>. Poultry meat and products have been established as vehicles of transmission of pathogenic <em>Listeria</em> strains to humans. This study evaluates the occurrence of <em>Listeria species</em> in faeces of poultry chicken in Lagos. <strong>Methods:</strong> One hundred and fourteen pooled fresh faecal samples from cage-reared broiler chickens were collected from 12 farms in three rural areas in Lagos State from May to August 2019. All samples were analysed for <em>Listeria</em> species detection according to ISO11290-1 standard and confirmed using PCR assay. Susceptibility testing was performed using the Kirby-Bauer disc diffusion technique. <strong>Results:</strong> Twenty-eight (24.6%) <em>Listeria </em>species were detected from 114 faecal samples. The isolated <em>Listeria</em> species were<em> L. monocytogenes</em> 8 (7.0%), <em>L. ivanovii</em> 9 (7.9%),<em> L. grayi </em>7 (6.1%) and<em> L. innocua</em> 4 (3.5%). There was no significant difference in the frequency of occurrence of <em>Listeria</em> species across the different locations (X<sup>2</sup> = 4.98, p = 0.08). The listeria species were susceptible to Augmentin (96.4%), vancomycin (85.7%) and co-trimoxazole (82.1%), but resistant to ceftazidime (100%), tetracycline (75.0%) and ciprofloxacin (71.4%). <strong>Conclusion:</strong> This study reveals high occurrence of multi-drug resistant <em>Listeria</em> species in faecal samples of poultry chickens in Lagos state which may be an important vector in the contamination of the environment and transmission of antibiotic resistant <em>Listeria</em> species to consumers.展开更多
Since the outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019, the virus has rapidly spread worldwide. This has led to an unprecedented ...Since the outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019, the virus has rapidly spread worldwide. This has led to an unprecedented global pandemic, marked by millions of COVID-19 cases and a significant number of fatalities. Over a relatively short period, several different vaccine platforms are developed and deployed for use globally to curb the pandemic. However, the genome of SARS-CoV-2 continuously undergoes mutation and/or recombination, resulting in the emergence of several variants of concern (VOC). These VOCs can elevate viral transmission and evade the neutralizing antibodies induced by vaccines, leading to reinfections. Understanding the impact of the SARS-CoV-2 genomic mutation on viral pathogenesis and immune escape is crucial for assessing the threat of new variants to public health. This review focuses on the emergence and pathogenesis of VOC, with particular emphasis on their evasion of neutralizing antibodies. Furthermore, the memory B cell, CD4+, and CD8+ T cell memory induced by different COVID-19 vaccines or infections are discussed, along with how these cells recognize VOC. This review summarizes the current knowledge on adaptive immunology regarding SARS-CoV-2 infection and vaccines. Such knowledge may also be applied to vaccine design for other pathogens.展开更多
Over the past few years,the human virome and its complex interactions with microbial communities and the immune system have gained recognition as a crucial factor in human health.Individuals with compromised immune fu...Over the past few years,the human virome and its complex interactions with microbial communities and the immune system have gained recognition as a crucial factor in human health.Individuals with compromised immune function encounter distinctive challenges due to their heightened vulnerability to a diverse range of infectious diseases.This review aims to comprehensively explore and analyze the growing evidence regarding the role of the virome in immunocompromised disease status.By surveying the latest literature,we present a detailed overview of virome alterations observed in various immunodeficiency conditions.We then delve into the influence and mechanisms of these virome changes on the pathogenesis of specific diseases in immunocompromised individuals.Furthermore,this review explores the clinical relevance of virome studies in the context of immunodeficiency,highlighting the potential diagnostic and therapeutic gains from a better understanding of virome contributions to disease manifestations.展开更多
Influenza A virus(IAV),responsible for seasonal epidemics and recurring pandemics,represents a global threat to public health.Given the risk of a potential IAV pandemic,it is increasingly important to better understan...Influenza A virus(IAV),responsible for seasonal epidemics and recurring pandemics,represents a global threat to public health.Given the risk of a potential IAV pandemic,it is increasingly important to better understand virushost interactions and develop new anti-viral strategies.Here,we reported nonmuscle myosin IIA(MYH9)-mediated regulation of IAV infection.MYH9 depletion caused a profound inhibition of IAV infection by reducing viral attachment and internalization in human lung epithelial cells.Surprisingly,overexpression of MYH9 also led to a significant reduction in viral productive infection.Interestingly,overexpression of MYH9 retained viral attachment,internalization,or uncoating,but suppressed the viral ribonucleoprotein(vRNP)activity in a minigenome system.Further analyses found that excess MYH9 might interrupt the formation of vRNP by interacting with the viral nucleoprotein(NP)and result in the reduction of the completed vRNP in the nucleus,thereby inhibiting subsequent viral RNA transcription and replication.Together,we discovered that MYH9 can interact with IAV NP protein and engage in the regulation of vRNP complexes,thereby involving viral replication.These findings enlighten new mechanistic insights into the complicated interface of host-IAV interactions,ultimately making it an attractive target for the generation of antiviral drugs.展开更多
Although the development of covID-19 vaccines has been a remarkable success,the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict.In this study,blood samples were...Although the development of covID-19 vaccines has been a remarkable success,the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict.In this study,blood samples were collected from 163 participants who next received two doses of an inactivated COvVID-19 vaccine(CoronaVac)at a 28-day interval.Using TMT-based proteomics,we identified 1,715 serum and 7,342 peripheral blood mononuclear cells(PBMCs)proteins.We proposed two sets of potential biomarkers(seven from serum,five from PBMCs)at baseline using machine learning,and predicted the individual seropositivity 57 days after vaccination(AUC=0.87).Based on the four PBMC's potential biomarkers,we predicted the antibody persistence until 180 days after vaccination(AUC=0.79).Our data highlighted characteristic hematological host responses,including altered lymphocyte migration regulation,neutrophil degranulation,and humoral immune response.This study proposed potential blood-derived protein biomarkers before vaccination for predicting heterogeneous antibody generation and decline after coVID-19 vaccination,shedding light on immunization mechanisms and individual booster shot planning.展开更多
Dear Editor,Identifying the host factors that are utilized for virus infection and mapping their cell-type expression profile can help to understand the viral tissue/organ tropism and pathogenesis.Much effort has been...Dear Editor,Identifying the host factors that are utilized for virus infection and mapping their cell-type expression profile can help to understand the viral tissue/organ tropism and pathogenesis.Much effort has been devoted to the identification of SARS-CoV-2 infection-dependent host factors.CRISPR-based activation(Konermann et al.,2015).展开更多
Clostridioides difficile is a leading cause of healthcare-associated infections,causing billions of economic losses every year.Its symptoms range from mild diarrhea to life-threatening damage to the colon.Transmission...Clostridioides difficile is a leading cause of healthcare-associated infections,causing billions of economic losses every year.Its symptoms range from mild diarrhea to life-threatening damage to the colon.Transmission and recurrence of c.difficile infection(CDl)are mediated by the metabolically dormant spores,while the virulence of C.difficile is mainly due to the two large clostridial toxins,TcdA and TcdB.Producing toxins or forming spores are two different strategies for C.difficile to cope with harsh environmental conditions.It is of great significance to understand the molecular mechanisms for C.difficile to skew to either of the cellular processes.Here,we summarize the current understanding of the regulation and connections between toxin production and sporulation in C.difficile and further discuss the potential solutions for yet-to-be-answered questions.展开更多
SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic.As part of the innate immune response to viral infe...SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic.As part of the innate immune response to viral infection, type Ⅰ interferons(IFN-Ⅰ) trigger a signaling cascade that culminates in the activation of hundreds of genes, known as interferon stimulated genes(ISGs), that collectively foster an antiviral state.We report here the identification of a group of type Ⅰ interferon suppressed genes,including fatty acid synthase(FASN), which are involved in lipid metabolism.Overexpression of FASN or the addition of its downstream product, palmitate, increased viral infection while knockout or knockdown of FASN reduced infection.More importantly, pharmacological inhibitors of FASN effectively blocked infections with a broad range of viruses, including SARS-CoV-2 and its variants of concern.Thus, our studies not only suggest that downregulation of metabolic genes may present an antiviral strategy by type Ⅰ interferon, but they also introduce the potential for FASN inhibitors to have a therapeutic application in combating emerging infectious diseases such as COVID-19.展开更多
Gut microbial dysbiosis has been linked to many noncommunicable diseases.However,little is known about specific gut microbiota composition and its correlated metabolites associated with molecular signatures underlying...Gut microbial dysbiosis has been linked to many noncommunicable diseases.However,little is known about specific gut microbiota composition and its correlated metabolites associated with molecular signatures underlying host response to infection.Here,we describe the construction of a proteomic risk score based on 20 blood proteomic biomarkers,which have recently been identified as molecular signatures predicting the progression of the COVID-19.We demonstrate that in our cohort of 990 healthy individuals without infection,this proteomic risk score is positively associated with proinflammatory cytokines mainly among older,but not younger,individuals.We further discover that a core set of gut microbiota can accurately predict the above proteomic biomarkers among 301 individuals using a machine learning model and that these gut microbiota features are highly correlated with proinflammatory cytokines in another independent set of 366 individuals.Fecal metabolomics analysis suggests potential amino acid-related pathways linking gut microbiota to host metabolism and inflammation.Overall,our multi-omics analyses suggest that gut microbiota composition and function are closely related to inflammation and molecular signatures of host response to infection among healthy individuals.These results may provide novel insights into the cross-talk between gut microbiota and host immune system.展开更多
Noncoding RNAs(ncRNAs) play important roles in many biological processes and provide materials for evolutionary adaptations beyond protein-coding genes, such as in the arms race between the host and pathogen. However,...Noncoding RNAs(ncRNAs) play important roles in many biological processes and provide materials for evolutionary adaptations beyond protein-coding genes, such as in the arms race between the host and pathogen. However, currently, a comprehensive high-resolution analysis of primate genomes that includes the latest annotated ncRNAs is not available. Here, we developed a computational pipeline to estimate the selections that act on noncoding regions based on comparisons with a large number of reference sequences in introns adjacent to the interested regions. Our method yields result comparable with those of the established codon-based method and phyloP method for coding genes;thus, it provides a holistic framework for estimating the selection on the entire genome. We further showed that fastevolving protein-coding genes and their corresponding 50 UTRs have a significantly lower frequency of the CpG dinucleotides than those evolving at an average pace, and these fast-evolving genes are enriched in the process of immunity and host defense. We also identified fast-evolving miRNAs with antiviral functions in cells. Our results provide a resource for high-resolution evolution analysis of the primate genomes.展开更多
The evolution of coronaviruses,such as SARS-CoV-2,makes broad-spectrum coronavirus preventional or therapeutical strategies highly sought after.Here we report a human angiotensin-converting enzyme 2(ACE2)-targeting mo...The evolution of coronaviruses,such as SARS-CoV-2,makes broad-spectrum coronavirus preventional or therapeutical strategies highly sought after.Here we report a human angiotensin-converting enzyme 2(ACE2)-targeting monoclonal antibody,3E8,blocked the S1-subunits and pseudo-typed virus constructs from multiple coronaviruses including SARS-CoV-2,SARS-CoV-2 mutant variants(SARS-CoV-2-D614G,B.1.1.7,B.1.351,B.1.617.1,and P.1).展开更多
Despite the success of antiretroviral therapy(ART),efforts to develop new classes of antiviral agents have been hampered by the emergence of drug resistance.Dibenzo-indole-bearing aristolactams are compounds that have...Despite the success of antiretroviral therapy(ART),efforts to develop new classes of antiviral agents have been hampered by the emergence of drug resistance.Dibenzo-indole-bearing aristolactams are compounds that have been isolated from various plants species and which show several clinically relevant effects,including anti-inflammatory,antiplatelet,and antimycobacterial actions.However,the effect of these compounds on human immunodeficiency virus type 1(HIV-1)infection has not yet been studied.In this study,we discovered an aristolactam derivative bearing dibenzo[cd,f]indol-4(5 H)-one that had a potent anti-HIV-1 effect.A structure-activity relationship(SAR)study using nine synthetic derivatives of aristolactam identified the differing effects of residue substitutions on the inhibition of HIV-1 infection and cell viability.Among the compounds tested,1,2,8,9-tetramethoxy-5-(2-(piperidin-1-yl)ethyl)-dibenzo[cd,f]indol-4(5 H)-one(Compound 2)exhibited the most potent activity by inhibiting HIV-1 infection with a half-maximal inhibitory concentration(IC50)of 1.03 lmol/L and a half-maximal cytotoxic concentration(CC50)of 16.91 lmol/L(selectivity index,16.45).The inhibitory effect of the compounds on HIV-1 infection was linked to inhibition of the viral replication cycle.Mode-of-action studies showed that the aristolactam derivatives did not affect reverse transcription or integration;instead,they specifically inhibited Tat-mediated viral transcription.Taken together,these findings show that several aristolactam derivatives impaired HIV-1 infection by inhibiting the activity of Tat-mediated viral transcription,and suggest that these derivatives could be antiviral drug candidates.展开更多
The SARS-CoV-2 Omicron variant shows substantial resistance to neutralization by infection-and vaccination-induced antibodies,highlighting the demands for research on the continuing discovery of broadly neutralizing a...The SARS-CoV-2 Omicron variant shows substantial resistance to neutralization by infection-and vaccination-induced antibodies,highlighting the demands for research on the continuing discovery of broadly neutralizing antibodies(bnAbs).Here,we developed a panel of bnAbs against Omicron and other variants of concern(VOCs)elicited by vaccination of adenovirus-vectored COVID-19 vaccine(Ad5-nCoV).展开更多
Background Plasmodium falciparum-resistance to sulphadoxine-pyrimethamine(SP)has been largely reported among pregnant women.However,the profile of resistance markers to SP dihydrofolate reductase(dhfr)and dihydroptero...Background Plasmodium falciparum-resistance to sulphadoxine-pyrimethamine(SP)has been largely reported among pregnant women.However,the profile of resistance markers to SP dihydrofolate reductase(dhfr)and dihydropteroate synthase(dhps)in the general population are varied and not frequently monitored.Currently,SP is used as partner drug for artemisinin combination therapy(SP-artesunate)in some sub-Saharan African countries or as a prophylactic drug in intermittent preventive treatment of malaria during pregnancy and infants and in seasonal malaria chemoprevention(SMC).Profiling of P.falciparum-resistant genotypes to SP is dynamic and critical in providing data that would be useful for malaria control programmes.This study assessed the profile of dhfr and dhps genes genotypes among individuals with malaria in Lagos,Nigeria.Methods Molecular markers of SP resistance were identified by nested PCR and sequenced among malaria positive dried blood spots(DBS)that were collected from individuals attending health facilities from January 2013 to February 2014 and during community surveys from October 2010 to September 2011 across different Local Government Areas of Lagos State,Nigeria.Results A total of 242 and 167 samples were sequenced for dhfr and dhps,respectively.Sequence analysis of dhfr showed that 95.5%(231/242),96.3%(233/242)and 96.7%(234/242)of the samples had N51I,C59R and S108N mutant alleles,respectively.The prevalence of dhps mutation at codons A437G,A613S,S436A,A581G,I431V and K540E were 95.8%(160/167),41.9%(70/167),41.3%(69/167),31.1%(52/167),25.1%(42/167),and 1.2%(2/167)respectively.The prevalence of triple mutations(CIRNI)in dhfr was 93.8%and 44.3%for the single dhps haplotype mutation(SGKAA).Partial SP-resistance due to quadruple dhfr-dhps haplotype mutations(CIRNI-SGKAA)and octuple haplotype mutations(CIRNI-VAGKGS)with rate of 42.6%and 22.0%,respectively has been reported.Conclusions There was increased prevalence in dhfr triple haplotype mutations when compared with previous reports in the same environment but aligned with high prevalence in other locations in Nigeria and other countries in Africa.Also,high prevalence of dhfr and dhps mutant alleles occurred in the study areas in Lagos,Nigeria five to eight years after the introduction of artemisinin combination therapy underscores the need for continuous monitoring.展开更多
文摘Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and Plasmodium species are the causative agents of coronavirus disease 2019 (COVID-19) and malaria respectively with similar clinical presentations. The objective of this study is to determine the burden of co-infection of SARS-CoV-2 and malaria in the general population. Five (5 mLs) of blood samples were collected for SARS-CoV-2 and malaria parasite test. The malaria test was performed using a commercially available one-step malaria antigen Plasmodium falciparum histidine-rich protein 2 (Pf HRP-II) rapid test kit. The results of the study showed that the participants that were coinfected with SARS-CoV-2 IgG and malaria were 13 (2.5%) in Lagos, 1114 (39.1%) in Delta and 49 (2.3%) in Sokoto States. The prevalence of coinfection of SARS-CoV-2 and malaria in urban areas in Lagos, Delta and Sokoto States were 7 (2.2%), 1373 (48.1%), and 5 (0.2%) respectively. In rural areas, the prevalence of coinfection of SARS-CoV-2 and malaria in Lagos, Delta and Sokoto States were 6 (0.3%), 365 (12.8%), and 44 (2.1%) respectively in this study. This suggests that participants in the urban areas were more prone to co-infections than the rural areas in Lagos and Delta states, while it was otherwise in Sokoto State. In conclusion, the co-infection of SARS-CoV-2 and malaria was very high in Delta State compared to the other States. It is important for clinics to screen for both diseases when patients present with symptoms of malaria. This is because the infections have similar symptoms and the public is quick to assume malaria infection without diagnosing for COVID-19 and vice versa.
基金Supported by an investigator-initiated research grant from Merck Sharpe and Dohme(MSD)University Review Board Grant,American University of Beirut
文摘AIM To assess the burden of norovirus(No V) and to determine the diversity of circulating strains among hospitalized children in Lebanon. METHODS Stool samples were collected from children presenting with acute gastroenteritis to six major hospitals in Lebanon. A total of 739 eligible stool samples, testing negative for diarrhea caused by rotavirus as a possible viral pathogen, were collected between January 2011 and June 2013. A standardized questionnaire including demographic, epidemiological and clinical observations was used at the time of hospitalization of children presenting with diarrhea. Viral RNA was extracted from stool samples followed by reverse transcription polymerase chain reaction and nucleotide sequencing of a fragment of the viral protein 1 capsid gene. Multiple sequence alignments were carried out and phylogenetic trees were constructed using the MEGA 6 software.RESULTS Overall, 11.2% of stool samples collected from children aged < 5 years tested positive for No V genogroups Ⅰ(GⅠ) and Ⅱ(GⅡ). GⅡ accounted for 10.6% of the gastroenteritis cases with only five samples being positive for GⅠ(0.7%). The majority of hospitalized children showed symptoms of diarrhea, dehydration, vomiting and fever. Upon sequencing of positive samples and based on their clustering in the phylogenetic tree, 4/5 of GⅠ gastroenteritis cases were designated GⅠ.3 and one case as GⅠ.4. GⅡ.4 was predominantly detected in stool of our study participants(68%). We report a JB-15/KOR/2008 GⅡ.4 Apeldoorn 2008-like variant strain circulating in 2011; this strain was replaced between 2012 and 2013 by a variant sharing homology with the Sydney/NSW0514/2012/AUS GⅡ.4 Sydney 2012 and Sydney 2012/FRA GⅡ.4 strains. We also report the co-circulation of non-GⅡ.4 genotypes among hospitalized children. Our data show that No V gastroenteritis can occur throughout the year with the highest number of cases detected during the hot months.CONCLUSION The majority of No V-associated viral gastroenteritis cases among our participants are attributable to GⅡ.4, which is compatible with results reported worldwide.
文摘<strong>Background:</strong> Listeriosis affects immunosuppressed individual’s especially pregnant women. Maternal infections are usually mild for the woman, but may have devastating effects on the unborn child, including miscarriage, stillbirth, preterm labour and serious neonatal illness. WHO recommends that pregnant women should be educated to avoid foods with high risk of contamination. This study seeks to evaluate knowledge and practices predisposing to listeria infections during pregnancy. <strong>Methodology:</strong> This is a cross-sectional study on pregnant women, attending the antenatal clinic of Lagos University Teaching Hospital (LUTH) using semi structured questionnaires. The knowledge score of participants was collated and analyzed using SPSS version 26. <strong>Results:</strong> The mean age of the participants was 32.07 ± 5.6 years. Forty-three (30.7%) women have had previous miscarriages with the mean no of miscarriage of 1.54. Out of 147 participants, only 20 (13.6%) admitted having heard of listeriosis while 127 (86.4%) had never heard of listeriosis and none of the participants has ever been tested for listeriosis. The Overall knowledge score was poor, and this was irrespective of age and duration of pregnancy. However, women with graduate and/or postgraduate degrees were more likely to have heard of Listeriosis (X2 = 10.88, P = 0.028). <strong>Conclusion:</strong> Our study shows a low level of knowledge about this food-borne illness, which can lead to severe illnesses in pregnant women and their unborn child. It is necessarily to educate pregnant women on the risk of listeriosis. This would be a key factor in creating and implementing accurate measures of prevention and control.
基金supported by the Faculty of Tropical Medicine,Mahidol University,Thailand,Research Fund through a Research and Researcher for Industry(RRi,Grant Number PHD59I0063 for SB)TRF Grant for New Researcher(TRG,Grant Number TRG5980015 for CP)the Office of the National Research Council of Thailand-Japan Society for the Promotion of Science(JSPS)or NRCT-JSPS
文摘Objective: To evaluate the expression of DNA plasmid-harboring modified antibody gene that produces neutralizing human monoclonal antibodies against four serotypes of dengue virus(DENV) without enhancing activity in BALB/c mice. Methods: We constructed pFUSE-based vectors(pFUSE1 G7 C2hVH and pFUSE1 G7 C2hVL) containing genes encoding the variable domains of the heavy or light chain of the anti-dengue virus antibody 1 G7 C2, a human IgG1 that has been characterized for its neutralizing activity to DENV-1-4. Leucine(L) at positions 234 and 235 on the Fc CH2 domain in pFUSE1 G7 C2hVH was mutated to alanine(A)(LALA mutation) by site direct mutagenesis, and the new plasmid was termed pFUSE1 G7 C2hVHLALA. An equal amount of pFUSE1 G7 C2hVL and 1 G7 C2hG1-LALA plasmids were co-transfected into Chinese hamster ovary cells(CHO-K1) and a single dose of 100 μg 1 G7 C2hG1-LALA plasmid was intramuscularly injected, followed by electroporation in BALB/c mice. The secreted 1 G7 C2hG1-LALA antibodies in cell culture supernatant and mouse serum were examined for their biological functions, neutralization and enhancing activity. Results: The co-transfection of heavy-and light-chain 1 G7 C2hG1-LALA plasmids in CHO-K1 cells produced approximately 3 900 ng/mL human IgG and neutralized 90%-100% all four DENV, with no enhancing activity. Furthermore, the modified human IgG was produced more than 1 000 ng/mL in mouse serum on day 7 post plasmid injection and showed cross-neutralization to four DENV serotypes. Subsequently, antibody production and neutralization decreased rapidly. Nevertheless, the secreted neutralizing 1 G7 C2hG1-LALA in mouse serum demonstrated complete absence of enhancing activities to all DENV serotypes. Conclusions: These findings reveal that a new modified 1 G7 C2h G1-LALA expressing plasmid based on gene transfer is a possible therapeutic antibody candidate against DENV infection.
文摘<strong>Background:</strong> Listeriosis is a common zoonotic disease caused by a foodborne pathogen, <em>Listeria monocytogenes</em>. Poultry meat and products have been established as vehicles of transmission of pathogenic <em>Listeria</em> strains to humans. This study evaluates the occurrence of <em>Listeria species</em> in faeces of poultry chicken in Lagos. <strong>Methods:</strong> One hundred and fourteen pooled fresh faecal samples from cage-reared broiler chickens were collected from 12 farms in three rural areas in Lagos State from May to August 2019. All samples were analysed for <em>Listeria</em> species detection according to ISO11290-1 standard and confirmed using PCR assay. Susceptibility testing was performed using the Kirby-Bauer disc diffusion technique. <strong>Results:</strong> Twenty-eight (24.6%) <em>Listeria </em>species were detected from 114 faecal samples. The isolated <em>Listeria</em> species were<em> L. monocytogenes</em> 8 (7.0%), <em>L. ivanovii</em> 9 (7.9%),<em> L. grayi </em>7 (6.1%) and<em> L. innocua</em> 4 (3.5%). There was no significant difference in the frequency of occurrence of <em>Listeria</em> species across the different locations (X<sup>2</sup> = 4.98, p = 0.08). The listeria species were susceptible to Augmentin (96.4%), vancomycin (85.7%) and co-trimoxazole (82.1%), but resistant to ceftazidime (100%), tetracycline (75.0%) and ciprofloxacin (71.4%). <strong>Conclusion:</strong> This study reveals high occurrence of multi-drug resistant <em>Listeria</em> species in faecal samples of poultry chickens in Lagos state which may be an important vector in the contamination of the environment and transmission of antibiotic resistant <em>Listeria</em> species to consumers.
文摘Since the outbreak of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in late 2019, the virus has rapidly spread worldwide. This has led to an unprecedented global pandemic, marked by millions of COVID-19 cases and a significant number of fatalities. Over a relatively short period, several different vaccine platforms are developed and deployed for use globally to curb the pandemic. However, the genome of SARS-CoV-2 continuously undergoes mutation and/or recombination, resulting in the emergence of several variants of concern (VOC). These VOCs can elevate viral transmission and evade the neutralizing antibodies induced by vaccines, leading to reinfections. Understanding the impact of the SARS-CoV-2 genomic mutation on viral pathogenesis and immune escape is crucial for assessing the threat of new variants to public health. This review focuses on the emergence and pathogenesis of VOC, with particular emphasis on their evasion of neutralizing antibodies. Furthermore, the memory B cell, CD4+, and CD8+ T cell memory induced by different COVID-19 vaccines or infections are discussed, along with how these cells recognize VOC. This review summarizes the current knowledge on adaptive immunology regarding SARS-CoV-2 infection and vaccines. Such knowledge may also be applied to vaccine design for other pathogens.
基金supported by grants from the Start-up Foundation of Tsinghua University(No.400-53332101822)the Tsinghua-Peking Center for Life Sciences(No.045-61000100122)+4 种基金the National Key R&D Program of China(Nos.2021YFC2301900 and 2021YFC2301905)the National Natural Science Foundation of China(Nos.32200036 and 81974303)the Beijing Natural Science Foundation(Nos.L222068 and Z220018)the High-Level Public Health Specialized Talents Project of Beijing Municipal Health Commission(No.2022-2-018)the Beijing Key Laboratory for HIV/AIDS Research(No.BZ0089)
文摘Over the past few years,the human virome and its complex interactions with microbial communities and the immune system have gained recognition as a crucial factor in human health.Individuals with compromised immune function encounter distinctive challenges due to their heightened vulnerability to a diverse range of infectious diseases.This review aims to comprehensively explore and analyze the growing evidence regarding the role of the virome in immunocompromised disease status.By surveying the latest literature,we present a detailed overview of virome alterations observed in various immunodeficiency conditions.We then delve into the influence and mechanisms of these virome changes on the pathogenesis of specific diseases in immunocompromised individuals.Furthermore,this review explores the clinical relevance of virome studies in the context of immunodeficiency,highlighting the potential diagnostic and therapeutic gains from a better understanding of virome contributions to disease manifestations.
基金supported by the National Natural Science Foundation of China(82071788,81901598,81771704,and 82041015)National Key R&D Program of China(2022YFC2604100).
文摘Influenza A virus(IAV),responsible for seasonal epidemics and recurring pandemics,represents a global threat to public health.Given the risk of a potential IAV pandemic,it is increasingly important to better understand virushost interactions and develop new anti-viral strategies.Here,we reported nonmuscle myosin IIA(MYH9)-mediated regulation of IAV infection.MYH9 depletion caused a profound inhibition of IAV infection by reducing viral attachment and internalization in human lung epithelial cells.Surprisingly,overexpression of MYH9 also led to a significant reduction in viral productive infection.Interestingly,overexpression of MYH9 retained viral attachment,internalization,or uncoating,but suppressed the viral ribonucleoprotein(vRNP)activity in a minigenome system.Further analyses found that excess MYH9 might interrupt the formation of vRNP by interacting with the viral nucleoprotein(NP)and result in the reduction of the completed vRNP in the nucleus,thereby inhibiting subsequent viral RNA transcription and replication.Together,we discovered that MYH9 can interact with IAV NP protein and engage in the regulation of vRNP complexes,thereby involving viral replication.These findings enlighten new mechanistic insights into the complicated interface of host-IAV interactions,ultimately making it an attractive target for the generation of antiviral drugs.
基金supported by the National Natural Science Foundation of China(32200763)Key medical disciplines of Hangzhou,the Medical Health Science and Technology Project of Hangzhou municipal Health Commission(A20210205)+1 种基金the National Key R&D Program of China(2020YFE0202200)Funding for Clinical Trials from the Affiliated Drum Tower Hospital,Medical School of Nanjing University(2022-LCYJ-MS-08).
文摘Although the development of covID-19 vaccines has been a remarkable success,the heterogeneous individual antibody generation and decline over time are unknown and still hard to predict.In this study,blood samples were collected from 163 participants who next received two doses of an inactivated COvVID-19 vaccine(CoronaVac)at a 28-day interval.Using TMT-based proteomics,we identified 1,715 serum and 7,342 peripheral blood mononuclear cells(PBMCs)proteins.We proposed two sets of potential biomarkers(seven from serum,five from PBMCs)at baseline using machine learning,and predicted the individual seropositivity 57 days after vaccination(AUC=0.87).Based on the four PBMC's potential biomarkers,we predicted the antibody persistence until 180 days after vaccination(AUC=0.79).Our data highlighted characteristic hematological host responses,including altered lymphocyte migration regulation,neutrophil degranulation,and humoral immune response.This study proposed potential blood-derived protein biomarkers before vaccination for predicting heterogeneous antibody generation and decline after coVID-19 vaccination,shedding light on immunization mechanisms and individual booster shot planning.
文摘Dear Editor,Identifying the host factors that are utilized for virus infection and mapping their cell-type expression profile can help to understand the viral tissue/organ tropism and pathogenesis.Much effort has been devoted to the identification of SARS-CoV-2 infection-dependent host factors.CRISPR-based activation(Konermann et al.,2015).
文摘Clostridioides difficile is a leading cause of healthcare-associated infections,causing billions of economic losses every year.Its symptoms range from mild diarrhea to life-threatening damage to the colon.Transmission and recurrence of c.difficile infection(CDl)are mediated by the metabolically dormant spores,while the virulence of C.difficile is mainly due to the two large clostridial toxins,TcdA and TcdB.Producing toxins or forming spores are two different strategies for C.difficile to cope with harsh environmental conditions.It is of great significance to understand the molecular mechanisms for C.difficile to skew to either of the cellular processes.Here,we summarize the current understanding of the regulation and connections between toxin production and sporulation in C.difficile and further discuss the potential solutions for yet-to-be-answered questions.
基金supported by the Research Funds from US National Institute of Health funds (AI069120, AI158154, and AI149718)the UCLA AIDS Institute and UCLA David Geffen School of Medicine-Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research Award ProgramTumor Immunology Training Grant (T32CA912036A1, USA)
文摘SARS-CoV-2 is an emerging viral pathogen and a major global public health challenge since December of 2019, with limited effective treatments throughout the pandemic.As part of the innate immune response to viral infection, type Ⅰ interferons(IFN-Ⅰ) trigger a signaling cascade that culminates in the activation of hundreds of genes, known as interferon stimulated genes(ISGs), that collectively foster an antiviral state.We report here the identification of a group of type Ⅰ interferon suppressed genes,including fatty acid synthase(FASN), which are involved in lipid metabolism.Overexpression of FASN or the addition of its downstream product, palmitate, increased viral infection while knockout or knockdown of FASN reduced infection.More importantly, pharmacological inhibitors of FASN effectively blocked infections with a broad range of viruses, including SARS-CoV-2 and its variants of concern.Thus, our studies not only suggest that downregulation of metabolic genes may present an antiviral strategy by type Ⅰ interferon, but they also introduce the potential for FASN inhibitors to have a therapeutic application in combating emerging infectious diseases such as COVID-19.
基金supported by the National Natural Science Foundation of China(82073529,81903316,81773416,81972492,21904107,81672086)Zhejiang Ten-thousand Talents Program(2019R52039)+3 种基金Zhejiang Provincial Natural Science Foundation for Distinguished Young Scholars(LR19C050001)the 5010 Program for Clinical Researches(2007032)the Sun Yat-sen University,Hangzhou Agriculture and Society Advancement Program(20190101A04)Tencent foundation(2020)。
文摘Gut microbial dysbiosis has been linked to many noncommunicable diseases.However,little is known about specific gut microbiota composition and its correlated metabolites associated with molecular signatures underlying host response to infection.Here,we describe the construction of a proteomic risk score based on 20 blood proteomic biomarkers,which have recently been identified as molecular signatures predicting the progression of the COVID-19.We demonstrate that in our cohort of 990 healthy individuals without infection,this proteomic risk score is positively associated with proinflammatory cytokines mainly among older,but not younger,individuals.We further discover that a core set of gut microbiota can accurately predict the above proteomic biomarkers among 301 individuals using a machine learning model and that these gut microbiota features are highly correlated with proinflammatory cytokines in another independent set of 366 individuals.Fecal metabolomics analysis suggests potential amino acid-related pathways linking gut microbiota to host metabolism and inflammation.Overall,our multi-omics analyses suggest that gut microbiota composition and function are closely related to inflammation and molecular signatures of host response to infection among healthy individuals.These results may provide novel insights into the cross-talk between gut microbiota and host immune system.
基金supported by the National Natural Science Foundation of China (Grant No. 31670777)the China National Funds for Distinguished Young Scientists (Grant No. 31722030)+2 种基金the Beijing Advanced Innovation Center for Structural Biology to X.T.the Tsinghua-Peking Joint Center for Life Sciences (Grant No. 61020100119)the National Thousand Young Talents Program of China (Grant No. 042021011) to X.L.
文摘Noncoding RNAs(ncRNAs) play important roles in many biological processes and provide materials for evolutionary adaptations beyond protein-coding genes, such as in the arms race between the host and pathogen. However, currently, a comprehensive high-resolution analysis of primate genomes that includes the latest annotated ncRNAs is not available. Here, we developed a computational pipeline to estimate the selections that act on noncoding regions based on comparisons with a large number of reference sequences in introns adjacent to the interested regions. Our method yields result comparable with those of the established codon-based method and phyloP method for coding genes;thus, it provides a holistic framework for estimating the selection on the entire genome. We further showed that fastevolving protein-coding genes and their corresponding 50 UTRs have a significantly lower frequency of the CpG dinucleotides than those evolving at an average pace, and these fast-evolving genes are enriched in the process of immunity and host defense. We also identified fast-evolving miRNAs with antiviral functions in cells. Our results provide a resource for high-resolution evolution analysis of the primate genomes.
基金This work was supported by the China National Major Scientific and Technological Special Project for"Significant New Drugs Innovation and Development"(2019ZX09732002-006)the Strategic Priority Research Program of the Chinese Academy of Sciences(CAS)(XDA12020223 and XDA12020330)+7 种基金the National Natural Science Foundation of China(81872785,81673347,31971123,32022037,81920108015,and 31930059)Shanghai Municipal Commission of Science and Technology of China(17431904400 and 19YF1457400)Institutes for Drug Discovery and Development,Chinese Academy of Sciences(CASIMM0120202008 and CASIMM0120202007)the National Key R&D Program(2020YFA0509303)Major Scientific and Technological Special Project of Zhongshan City(191022172638719 and 210205143867019)the Key R&D Program of Zhejiang Province(2020C04001)the SARS-CoV-2 emergency project of the Science and Technology Department of Zhejiang Province(2020C03129)the Leading Innovative and Entrepreneur Team Introduction Program of Hangzhou,Westlake Education Foundation and Tencent Foundation.
文摘The evolution of coronaviruses,such as SARS-CoV-2,makes broad-spectrum coronavirus preventional or therapeutical strategies highly sought after.Here we report a human angiotensin-converting enzyme 2(ACE2)-targeting monoclonal antibody,3E8,blocked the S1-subunits and pseudo-typed virus constructs from multiple coronaviruses including SARS-CoV-2,SARS-CoV-2 mutant variants(SARS-CoV-2-D614G,B.1.1.7,B.1.351,B.1.617.1,and P.1).
基金supported by grants from the Korea National Institute of Health (Grant Number:2019-NI-066-00 and 2020-ER5106-00)。
文摘Despite the success of antiretroviral therapy(ART),efforts to develop new classes of antiviral agents have been hampered by the emergence of drug resistance.Dibenzo-indole-bearing aristolactams are compounds that have been isolated from various plants species and which show several clinically relevant effects,including anti-inflammatory,antiplatelet,and antimycobacterial actions.However,the effect of these compounds on human immunodeficiency virus type 1(HIV-1)infection has not yet been studied.In this study,we discovered an aristolactam derivative bearing dibenzo[cd,f]indol-4(5 H)-one that had a potent anti-HIV-1 effect.A structure-activity relationship(SAR)study using nine synthetic derivatives of aristolactam identified the differing effects of residue substitutions on the inhibition of HIV-1 infection and cell viability.Among the compounds tested,1,2,8,9-tetramethoxy-5-(2-(piperidin-1-yl)ethyl)-dibenzo[cd,f]indol-4(5 H)-one(Compound 2)exhibited the most potent activity by inhibiting HIV-1 infection with a half-maximal inhibitory concentration(IC50)of 1.03 lmol/L and a half-maximal cytotoxic concentration(CC50)of 16.91 lmol/L(selectivity index,16.45).The inhibitory effect of the compounds on HIV-1 infection was linked to inhibition of the viral replication cycle.Mode-of-action studies showed that the aristolactam derivatives did not affect reverse transcription or integration;instead,they specifically inhibited Tat-mediated viral transcription.Taken together,these findings show that several aristolactam derivatives impaired HIV-1 infection by inhibiting the activity of Tat-mediated viral transcription,and suggest that these derivatives could be antiviral drug candidates.
基金We thank the cryo-EM facility and the High-Performance Computing Center of Westlake University for providing technical support.We thank the Institute of Microbiology and Epidemiology,Academy of Military Medical Sciences,China,for providing the SARS-CoV-2.This research was supported by grants from the National Natural Science Foundation of China(projects 32022037,81803429)the Young Elite Scientists Sponsorship Program by CAST,the Leading Innovative and Entrepreneur Team Introduction Program of Hangzhou,the Special Research Program of Novel Coronavirus Pneumonia of Westlake University and Tencent Foundation.
文摘The SARS-CoV-2 Omicron variant shows substantial resistance to neutralization by infection-and vaccination-induced antibodies,highlighting the demands for research on the continuing discovery of broadly neutralizing antibodies(bnAbs).Here,we developed a panel of bnAbs against Omicron and other variants of concern(VOCs)elicited by vaccination of adenovirus-vectored COVID-19 vaccine(Ad5-nCoV).
文摘Background Plasmodium falciparum-resistance to sulphadoxine-pyrimethamine(SP)has been largely reported among pregnant women.However,the profile of resistance markers to SP dihydrofolate reductase(dhfr)and dihydropteroate synthase(dhps)in the general population are varied and not frequently monitored.Currently,SP is used as partner drug for artemisinin combination therapy(SP-artesunate)in some sub-Saharan African countries or as a prophylactic drug in intermittent preventive treatment of malaria during pregnancy and infants and in seasonal malaria chemoprevention(SMC).Profiling of P.falciparum-resistant genotypes to SP is dynamic and critical in providing data that would be useful for malaria control programmes.This study assessed the profile of dhfr and dhps genes genotypes among individuals with malaria in Lagos,Nigeria.Methods Molecular markers of SP resistance were identified by nested PCR and sequenced among malaria positive dried blood spots(DBS)that were collected from individuals attending health facilities from January 2013 to February 2014 and during community surveys from October 2010 to September 2011 across different Local Government Areas of Lagos State,Nigeria.Results A total of 242 and 167 samples were sequenced for dhfr and dhps,respectively.Sequence analysis of dhfr showed that 95.5%(231/242),96.3%(233/242)and 96.7%(234/242)of the samples had N51I,C59R and S108N mutant alleles,respectively.The prevalence of dhps mutation at codons A437G,A613S,S436A,A581G,I431V and K540E were 95.8%(160/167),41.9%(70/167),41.3%(69/167),31.1%(52/167),25.1%(42/167),and 1.2%(2/167)respectively.The prevalence of triple mutations(CIRNI)in dhfr was 93.8%and 44.3%for the single dhps haplotype mutation(SGKAA).Partial SP-resistance due to quadruple dhfr-dhps haplotype mutations(CIRNI-SGKAA)and octuple haplotype mutations(CIRNI-VAGKGS)with rate of 42.6%and 22.0%,respectively has been reported.Conclusions There was increased prevalence in dhfr triple haplotype mutations when compared with previous reports in the same environment but aligned with high prevalence in other locations in Nigeria and other countries in Africa.Also,high prevalence of dhfr and dhps mutant alleles occurred in the study areas in Lagos,Nigeria five to eight years after the introduction of artemisinin combination therapy underscores the need for continuous monitoring.