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  1. Article ; Online: Enhanced Deep Convolutional Neural Network for SARS-CoV-2 Variants Classification

    Mwanga, Mike J. / Obura, Hesborn O. / Evans, Mudibo / Awe, Olaitan I.

    bioRxiv

    Abstract: High-throughput sequencing techniques and sequence analysis have enabled the taxonomic classification of pathogens present in clinical samples. Sequencing provides an unbiased identification and systematic classification of pathogens and this is ... ...

    Abstract High-throughput sequencing techniques and sequence analysis have enabled the taxonomic classification of pathogens present in clinical samples. Sequencing provides an unbiased identification and systematic classification of pathogens and this is generally achieved by comparing novel sequences to pre-existing annotated reference databases. However, this approach is limited by large-scale reference databases which require considerable computational resources and skills to compare against. Alternative robust methods such as machine learning are currently employed in genome sequence analysis and classification, and it can be applied in classifying SARS-CoV-2 variants, whose continued evolution has resulted in the emergence of multiple variants. We developed a deep learning Convolutional Neural Networks-Long Short Term Memory (CNN-LSTM) model to classify dominant SARS-CoV-2 variants (omicron, delta, beta, gamma and alpha) based on gene sequences from the surface glycoprotein (spike gene). We trained and validated the model using > 26,000 SARS-CoV-2 sequences from the GISAID database. The model was evaluated using unseen 3,057 SARS-CoV-2 sequences. The model was compared to existing molecular epidemiology tool, nextclade. Our model achieved an accuracy of 98.55% on training, 99.19% on the validation and 98.41% on the test dataset. Comparing the proposed model to nextclade, the model achieved significant accuracy in classifying SARS-CoV-2 variants from unseen data. Nextclade identified the presence of recombinant strains in the evaluation data, a mechanism that the proposed model did not detect. This study provides an alternative approach to pre-existing methods employed in the classification of SARS-CoV-2 variants. Timely classification will enable effective monitoring and tracking of SARS-CoV-2 variants and inform public health policies in the control and management of the COVID-19 pandemic.
    Keywords covid19
    Language English
    Publishing date 2023-08-10
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2023.08.09.552643
    Database COVID19

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  2. Article: Genomic epidemiology of the rotavirus G2P[4] strains in coastal Kenya pre- and post-rotavirus vaccine introduction, 2012-8.

    Makori, Timothy O / Bargul, Joel L / Lambisia, Arnold W / Mwanga, Mike J / Murunga, Nickson / de Laurent, Zaydah R / Lewa, Clement S / Mutunga, Martin / Kellam, Paul / Cotten, Matthew / Nokes, D James / Phan, My / Agoti, Charles N

    Virus evolution

    2023  Volume 9, Issue 1, Page(s) vead025

    Abstract: The introduction of rotavirus vaccines into the national immunization programme in many countries has led to a decline in childhood diarrhoea disease burden. Coincidentally, the incidence of some rotavirus group A (RVA) genotypes has increased, which may ...

    Abstract The introduction of rotavirus vaccines into the national immunization programme in many countries has led to a decline in childhood diarrhoea disease burden. Coincidentally, the incidence of some rotavirus group A (RVA) genotypes has increased, which may result from non-vaccine-type replacement. Here, we investigate the evolutionary genomics of rotavirus G2P[4] which has shown an increase in countries that introduced the monovalent Rotarix® vaccine. We examined sixty-three RVA G2P[4] strains sampled from children (aged below 13 years) admitted to Kilifi County Hospital, coastal Kenya, pre- (2012 to June 2014) and post-(July 2014 to 2018) rotavirus vaccine introduction. All the sixty-three genome sequences showed a typical DS-1-like genome constellation (G2-P[4]-I2-R2-C2-M2-A2-N2-T2-E2-H2). Pre-vaccine G2 sequences predominantly classified as sub-lineage IVa-3 and co-circulated with low numbers of sub-lineage IVa-1 strains, whereas post-vaccine G2 sequences mainly classified into sub-lineage IVa-3. In addition, in the pre-vaccine period, P[4] sub-lineage IVa strains co-circulated with low numbers of P[4] lineage II strains, but P[4] sub-lineage IVa strains predominated in the post-vaccine period. On the global phylogeny, the Kenyan pre- and post-vaccine G2P[4] strains clustered separately, suggesting that different virus populations circulated in the two periods. However, the strains from both periods exhibited conserved amino acid changes in the known antigenic epitopes, suggesting that replacement of the predominant G2P[4] cluster was unlikely a result of immune escape. Our findings demonstrate that the pre- and post-vaccine G2P[4] strains circulating in Kilifi, coastal Kenya, differed genetically but likely were antigenically similar. This information informs the discussion on the consequences of rotavirus vaccination on rotavirus diversity.
    Language English
    Publishing date 2023-04-15
    Publishing country England
    Document type Journal Article
    ZDB-ID 2818949-8
    ISSN 2057-1577
    ISSN 2057-1577
    DOI 10.1093/ve/vead025
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: New SARS-CoV-2 Omicron Variant with Spike Protein Mutation Y451H, Kilifi, Kenya, March-May 2023.

    Mwanga, Mike J / Lambisia, Arnold W / Morobe, John Mwita / Murunga, Nickson / Moraa, Edidah / Ndwiga, Leonard / Cheruiyot, Robinson / Musyoki, Jennifer / Mutunga, Martin / Guzman-Rincon, Laura M / Sande, Charles / Mwangangi, Joseph / Bejon, Philip / Ochola-Oyier, Lynette Isabella / Nokes, D James / Agoti, Charles N / Nyiro, Joyce / Githinji, George

    Emerging infectious diseases

    2023  Volume 29, Issue 11, Page(s) 2376–2379

    Abstract: We report a newly emerged SARS-CoV-2 Omicron subvariant FY.4 that has mutations Y451H in spike and P42L in open reading frame 3a proteins. FY.4 emergence coincided with increased SARS-CoV-2 cases in coastal Kenya during April-May 2023. Continued SARS-CoV- ...

    Abstract We report a newly emerged SARS-CoV-2 Omicron subvariant FY.4 that has mutations Y451H in spike and P42L in open reading frame 3a proteins. FY.4 emergence coincided with increased SARS-CoV-2 cases in coastal Kenya during April-May 2023. Continued SARS-CoV-2 genomic surveillance is needed to identify new lineages to inform COVID-19 outbreak prevention.
    MeSH term(s) Humans ; COVID-19/epidemiology ; Kenya/epidemiology ; SARS-CoV-2/genetics ; Spike Glycoprotein, Coronavirus/genetics ; Mutation
    Chemical Substances spike protein, SARS-CoV-2 ; Spike Glycoprotein, Coronavirus
    Language English
    Publishing date 2023-09-14
    Publishing country United States
    Document type Research Support, Non-U.S. Gov't ; Letter
    ZDB-ID 1380686-5
    ISSN 1080-6059 ; 1080-6040
    ISSN (online) 1080-6059
    ISSN 1080-6040
    DOI 10.3201/eid2911.230894
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: Molecular characterization of rotavirus group A strains circulating prior to vaccine introduction in rural coastal Kenya, 2002-2013.

    Owor, Betty E / Mwanga, Mike J / Njeru, Regina / Mugo, Robert / Ngama, Mwanajuma / Otieno, Grieven P / Nokes, D J / Agoti, C N

    Wellcome open research

    2019  Volume 3, Page(s) 150

    Abstract: Background: ...

    Abstract Background:
    Language English
    Publishing date 2019-05-15
    Publishing country England
    Document type Journal Article
    ISSN 2398-502X
    ISSN 2398-502X
    DOI 10.12688/wellcomeopenres.14908.2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: A new Omicron lineage with Spike Y451H mutation that dominated a new COVID-19 wave in Kilifi, Coastal Kenya: March-May 2023

    Mwanga, Mike J / Lambisia, Arnold W / Morobe, John Mwita / Murunga, Nickson / Moraa, Edidah / Ndwiga, Leonard / Cheruiyot, Robinson / Mutunga, Martin / Guzman-Rincon, Laura M / Sande, Charles / Mwangangi, Joseph / Bejon, Philip / Ochola-Oyier, Lynette Isabella / Nokes, D James / Agoti, Charles N / Nyiro, Joyce / Githinji, George

    medRxiv

    Abstract: We report a newly emerged SARS-CoV-2 Omicron lineage, named FY.4, that has two unique mutations; spike:Y451H and ORF3a:P42L. FY.4 emergence has coincided with increased SARS-CoV-2 cases in coastal Kenya, April-May 2023. We demonstrate the value of ... ...

    Abstract We report a newly emerged SARS-CoV-2 Omicron lineage, named FY.4, that has two unique mutations; spike:Y451H and ORF3a:P42L. FY.4 emergence has coincided with increased SARS-CoV-2 cases in coastal Kenya, April-May 2023. We demonstrate the value of continued SARS-CoV-2 genomic surveillance in the post-acute pandemic era in understanding new COVID-19 outbreaks.
    Keywords covid19
    Language English
    Publishing date 2023-07-03
    Publisher Cold Spring Harbor Laboratory Press
    Document type Article ; Online
    DOI 10.1101/2023.07.03.23292158
    Database COVID19

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  6. Article: Multiple Introductions and Predominance of Rotavirus Group A Genotype G3P[8] in Kilifi, Coastal Kenya, 4 Years after Nationwide Vaccine Introduction

    Mwanga, Mike J / Verani, Jennifer R / Omore, Richard / Tate, Jacqueline E / Parashar, Umesh D / Murunga, Nickson / Gicheru, Elijah / Breiman, Robert F / Nokes, D. James / Agoti, Charles N

    Pathogens. 2020 Nov. 24, v. 9, no. 12

    2020  

    Abstract: Globally, rotavirus group A (RVA) remains a major cause of severe childhood diarrhea, despite the use of vaccines in more than 100 countries. RVA sequencing for local outbreaks facilitates investigation into strain composition, origins, spread, and ... ...

    Abstract Globally, rotavirus group A (RVA) remains a major cause of severe childhood diarrhea, despite the use of vaccines in more than 100 countries. RVA sequencing for local outbreaks facilitates investigation into strain composition, origins, spread, and vaccine failure. In 2018, we collected 248 stool samples from children aged less than 13 years admitted with diarrheal illness to Kilifi County Hospital, coastal Kenya. Antigen screening detected RVA in 55 samples (22.2%). Of these, VP7 (G) and VP4 (P) segments were successfully sequenced in 48 (87.3%) and phylogenetic analysis based on the VP7 sequences identified seven genetic clusters with six different GP combinations: G3P[8], G1P[8], G2P[4], G2P[8], G9P[8] and G12P[8]. The G3P[8] strains predominated the season (n = 37, 67.2%) and comprised three distinct G3 genetic clusters that fell within Lineage I and IX (the latter also known as equine-like G3 Lineage). Both the two G3 lineages have been recently detected in several countries. Our study is the first to document African children infected with G3 Lineage IX. These data highlight the global nature of RVA transmission and the importance of increasing global rotavirus vaccine coverage.
    Keywords Rotavirus A ; antigens ; childhood ; children ; diarrhea ; feces ; genotype ; hospitals ; pathogens ; phylogeny ; sampling ; screening ; strains ; vaccines ; Kenya
    Language English
    Dates of publication 2020-1124
    Publishing place Multidisciplinary Digital Publishing Institute
    Document type Article
    Note NAL-light
    ZDB-ID 2695572-6
    ISSN 2076-0817
    ISSN 2076-0817
    DOI 10.3390/pathogens9120981
    Database NAL-Catalogue (AGRICOLA)

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  7. Article: Multiple Introductions and Predominance of Rotavirus Group A Genotype G3P[8] in Kilifi, Coastal Kenya, 4 Years after Nationwide Vaccine Introduction.

    Mwanga, Mike J / Verani, Jennifer R / Omore, Richard / Tate, Jacqueline E / Parashar, Umesh D / Murunga, Nickson / Gicheru, Elijah / Breiman, Robert F / Nokes, D James / Agoti, Charles N

    Pathogens (Basel, Switzerland)

    2020  Volume 9, Issue 12

    Abstract: Globally, rotavirus group A (RVA) remains a major cause of severe childhood diarrhea, despite the use of vaccines in more than 100 countries. RVA sequencing for local outbreaks facilitates investigation into strain composition, origins, spread, and ... ...

    Abstract Globally, rotavirus group A (RVA) remains a major cause of severe childhood diarrhea, despite the use of vaccines in more than 100 countries. RVA sequencing for local outbreaks facilitates investigation into strain composition, origins, spread, and vaccine failure. In 2018, we collected 248 stool samples from children aged less than 13 years admitted with diarrheal illness to Kilifi County Hospital, coastal Kenya. Antigen screening detected RVA in 55 samples (22.2%). Of these, VP7 (G) and VP4 (P) segments were successfully sequenced in 48 (87.3%) and phylogenetic analysis based on the VP7 sequences identified seven genetic clusters with six different GP combinations: G3P[8], G1P[8], G2P[4], G2P[8], G9P[8] and G12P[8]. The G3P[8] strains predominated the season (
    Language English
    Publishing date 2020-11-24
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2695572-6
    ISSN 2076-0817
    ISSN 2076-0817
    DOI 10.3390/pathogens9120981
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Rotavirus group A genotype circulation patterns across Kenya before and after nationwide vaccine introduction, 2010-2018.

    Mwanga, Mike J / Owor, Betty E / Ochieng, John B / Ngama, Mwanajuma H / Ogwel, Billy / Onyango, Clayton / Juma, Jane / Njeru, Regina / Gicheru, Elijah / Otieno, Grieven P / Khagayi, Sammy / Agoti, Charles N / Bigogo, Godfrey M / Omore, Richard / Addo, O Yaw / Mapaseka, Seheri / Tate, Jacqueline E / Parashar, Umesh D / Hunsperger, Elizabeth /
    Verani, Jennifer R / Breiman, Robert F / Nokes, D James

    BMC infectious diseases

    2020  Volume 20, Issue 1, Page(s) 504

    Abstract: Background: Kenya introduced the monovalent G1P [8] Rotarix® vaccine into the infant immunization schedule in July 2014. We examined trends in rotavirus group A (RVA) genotype distribution pre- (January 2010-June 2014) and post- (July 2014-December 2018) ...

    Abstract Background: Kenya introduced the monovalent G1P [8] Rotarix® vaccine into the infant immunization schedule in July 2014. We examined trends in rotavirus group A (RVA) genotype distribution pre- (January 2010-June 2014) and post- (July 2014-December 2018) RVA vaccine introduction.
    Methods: Stool samples were collected from children aged < 13 years from four surveillance sites across Kenya: Kilifi County Hospital, Tabitha Clinic Nairobi, Lwak Mission Hospital, and Siaya County Referral Hospital (children aged < 5 years only). Samples were screened for RVA using enzyme linked immunosorbent assay (ELISA) and VP7 and VP4 genes sequenced to infer genotypes.
    Results: We genotyped 614 samples in pre-vaccine and 261 in post-vaccine introduction periods. During the pre-vaccine introduction period, the most frequent RVA genotypes were G1P [8] (45.8%), G8P [4] (15.8%), G9P [8] (13.2%), G2P [4] (7.0%) and G3P [6] (3.1%). In the post-vaccine introduction period, the most frequent genotypes were G1P [8] (52.1%), G2P [4] (20.7%) and G3P [8] (16.1%). Predominant genotypes varied by year and site in both pre and post-vaccine periods. Temporal genotype patterns showed an increase in prevalence of vaccine heterotypic genotypes, such as the commonly DS-1-like G2P [4] (7.0 to 20.7%, P < .001) and G3P [8] (1.3 to 16.1%, P < .001) genotypes in the post-vaccine introduction period. Additionally, we observed a decline in prevalence of genotypes G8P [4] (15.8 to 0.4%, P < .001) and G9P [8] (13.2 to 5.4%, P < .001) in the post-vaccine introduction period. Phylogenetic analysis of genotype G1P [8], revealed circulation of strains of lineages G1-I, G1-II and P [8]-1, P [8]-III and P [8]-IV. Considerable genetic diversity was observed between the pre and post-vaccine strains, evidenced by distinct clusters.
    Conclusion: Genotype prevalence varied from before to after vaccine introduction. Such observations emphasize the need for long-term surveillance to monitor vaccine impact. These changes may represent natural secular variation or possible immuno-epidemiological changes arising from the introduction of the vaccine. Full genome sequencing could provide insights into post-vaccine evolutionary pressures and antigenic diversity.
    MeSH term(s) Child ; Child, Preschool ; Enzyme-Linked Immunosorbent Assay ; Feces/virology ; Female ; Gastroenteritis/etiology ; Genotype ; Humans ; Immunization Schedule ; Infant ; Kenya/epidemiology ; Male ; Phylogeny ; Prevalence ; Rotavirus/genetics ; Rotavirus/immunology ; Rotavirus Infections/epidemiology ; Rotavirus Infections/prevention & control ; Rotavirus Infections/virology ; Rotavirus Vaccines/adverse effects ; Rotavirus Vaccines/immunology ; Rotavirus Vaccines/therapeutic use ; Vaccination ; Vaccines, Attenuated/adverse effects ; Vaccines, Attenuated/immunology ; Vaccines, Attenuated/therapeutic use
    Chemical Substances RIX4414 vaccine ; Rotavirus Vaccines ; Vaccines, Attenuated
    Keywords covid19
    Language English
    Publishing date 2020-07-13
    Publishing country England
    Document type Journal Article
    ZDB-ID 2041550-3
    ISSN 1471-2334 ; 1471-2334
    ISSN (online) 1471-2334
    ISSN 1471-2334
    DOI 10.1186/s12879-020-05230-0
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Effectiveness of Monovalent Rotavirus Vaccine Against Hospitalization With Acute Rotavirus Gastroenteritis in Kenyan Children.

    Khagayi, Sammy / Omore, Richard / Otieno, Grieven P / Ogwel, Billy / Ochieng, John B / Juma, Jane / Apondi, Evans / Bigogo, Godfrey / Onyango, Clayton / Ngama, Mwanajuma / Njeru, Regina / Owor, Betty E / Mwanga, Mike J / Addo, Yaw / Tabu, Collins / Amwayi, Anyangu / Mwenda, Jason M / Tate, Jacqueline E / Parashar, Umesh D /
    Breiman, Robert F / Nokes, D James / Verani, Jennifer R

    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

    2019  Volume 70, Issue 11, Page(s) 2298–2305

    Abstract: Background: Rotavirus remains a leading cause of pediatric diarrheal illness and death worldwide. Data on rotavirus vaccine effectiveness in sub-Saharan Africa are limited. Kenya introduced monovalent rotavirus vaccine (RV1) in July 2014. We assessed ... ...

    Abstract Background: Rotavirus remains a leading cause of pediatric diarrheal illness and death worldwide. Data on rotavirus vaccine effectiveness in sub-Saharan Africa are limited. Kenya introduced monovalent rotavirus vaccine (RV1) in July 2014. We assessed RV1 effectiveness against rotavirus-associated hospitalization in Kenyan children.
    Methods: Between July 2014 and December 2017, we conducted surveillance for acute gastroenteritis (AGE) in 3 Kenyan hospitals. From children age-eligible for ≥1 RV1 dose, with stool tested for rotavirus and confirmed vaccination history we compared RV1 coverage among rotavirus positive (cases) vs rotavirus negative (controls) using multivariable logistic regression and calculated effectiveness based on adjusted odds ratio.
    Results: Among 677 eligible children, 110 (16%) were rotavirus positive. Vaccination data were available for 91 (83%) cases; 51 (56%) had 2 RV1 doses and 33 (36%) 0 doses. Among 567 controls, 418 (74%) had vaccination data; 308 (74%) had 2 doses and 69 (16%) 0 doses. Overall 2-dose effectiveness was 64% (95% confidence interval [CI], 35%-80%); effectiveness was 67% (95% CI, 30%-84%) for children aged <12 months and 72% (95% CI, 10%-91%) for children aged ≥12 months. Significant effectiveness was seen in children with normal weight for age, length/height for age and weight for length/height; however, no protection was found among underweight, stunted, or wasted children.
    Conclusions: RV1 in the Kenyan immunization program provides significant protection against rotavirus-associated hospitalization which persisted beyond infancy. Malnutrition appears to diminish vaccine effectiveness. Efforts to improve rotavirus uptake and nutritional status are important to maximize vaccine benefit.
    MeSH term(s) Child ; Gastroenteritis/epidemiology ; Gastroenteritis/prevention & control ; Hospitalization ; Humans ; Infant ; Kenya/epidemiology ; Rotavirus ; Rotavirus Infections/epidemiology ; Rotavirus Infections/prevention & control ; Rotavirus Vaccines ; Vaccination ; Vaccines, Attenuated
    Chemical Substances Rotavirus Vaccines ; Vaccines, Attenuated
    Language English
    Publishing date 2019-07-18
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 1099781-7
    ISSN 1537-6591 ; 1058-4838
    ISSN (online) 1537-6591
    ISSN 1058-4838
    DOI 10.1093/cid/ciz664
    Database MEDical Literature Analysis and Retrieval System OnLINE

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