Background: The Ebola virus disease outbreak of 2014 was the largest, longest and most devastatin... more Background: The Ebola virus disease outbreak of 2014 was the largest, longest and most devastating in the history of the disease. It demonstrated the social and economic impact an emerging infectious disease can have in a globalized world. Health systems in affected countries were stretched to the point of near collapse, while social relations and traditional practices were negatively impacted. Heads of African research institutions, African government representatives, leaders of global pharmaceutical companies, global infectious disease experts and close to 100 young African researchers from 25 countries; Assembled in Geneva on 19 and 20th October 2015, for the inaugural UNESCO-Merck Africa Summit sponsored by the United Nations Educational, Science and Culture Organization and Merck KGA Goal of Summit: The primary goal of the summit was to develop strategies to increase health research capacity in Africa, with special focus on Ebola and enhancing pandemic preparation for emerging infectious diseases. The summit was also provide a forum to showcase the research taking place in Africa, and provided platform for African researchers to network. Some of the key issues discussed included; strategies for enhancing policy frameworks to promote knowledge translation, strengthening of health systems, enhancing knowledge and data sharing, and increasing innovation in Africa. Conclusions: Summit attendees recognized that Africa still bore the heaviest burden of infectious disease, and increased commitment by African governments to fund health research, offered the best hope for developing health solutions and interventions to improve the health of Africans. Improved health in turn would enhance the productivity of Africans, further supporting the socioeconomic transformation currently taking place on the continent. Research is a catalyst for Social, Economic and Sustainable development in Africa. The health of a population, is critical for social and economic productivity(WHO 2015). In recent years, majority of African countries have experienced positive growth and development. In order to expand and sustain the positive trends, African countries need to prioritize investments in health research as a means of reducing the heavy burden of disease on the continent. The hope is that, increased health research will translate into innovation, discovery of novel compounds or expanded knowledge, which would greatly assist the continent to address its most pressing health needs. Africa is also faced with novel health challenges, in the form of increasing prevalence of non-communicable diseases (NCDs), rising antimicrobial resistance and emerging infectious diseases (WHO-AFRO 2014). Some of the recent gains made at improving the health of Africans, can be built upon by further strengthening individual country health systems, an effort requiring partnerships between public and private sectors, non-governmental organizations (NGOs) and academia. UNESCO-MARS summit brought health researchers from Africa, together with to executives of global pharmaceutical companies, UNESCO officials and representatives of African government, to dialogue on ways to improve global cooperation on combating emerging infectious diseases and other challenges facing the life sciences and health research in Africa. It also provided a platform for discussing ways of improving knowledge translation of research already taking place on the continent as a means of bridging the 'know-do-gap'. The North (developed) to South (developing world) 'loans and aid' model initially used to bring development to postcolonial Africa, has since transitioned to the more 'collaborative' approach which seeks to enhance development through mutually beneficial North to South and South to South relationships. This collaborative approach in the words, Prof Imbuga Godia-Kenya's representative at UNESCO, enabled the World to make significant strides through initiatives such
Background Neisseria gonorrhoeae (Ng) is a common sexually transmitted infection (STI). Emerging ... more Background Neisseria gonorrhoeae (Ng) is a common sexually transmitted infection (STI). Emerging strains resistant to first-line ceftriaxone threaten Ng management. Hence, alternative treatments are needed. We evaluated the efficacy of ertapenem, gentamicin and fosfomycin as alternatives for Ng. Approach We included adults 18 years or older, with anorectal or urogenital gonorrhea in a randomized controlled, doubleblind, non-inferiority trial (three experimental-and one control-arm). Participants were randomized (1:1:1:1) to receive: intramuscular (IM) 500mg ceftriaxone, IM 1000mg ertapenem, IM 5mg/kg gentamicin (maximum 400mg), or 6g fosfomycin orally. The primary outcome was the proportion of participants with a negative nucleic acid amplification test of the primary infected site, 7-14 days after treatment. Non-inferiority was established if the lower Hochberg-corrected 95% confidence interval for difference between experimental and control arms was greater than-10%. Outcomes Between 18 September 2017 and 5 June 2020, we assigned 346 participants to ceftriaxone (n=103), ertapenem (n=103), gentamicin (n=102), and fosfomycin (n=38). The fosfomycin arm was terminated early after interim analysis revealed <60% efficacy. In the primary modified intent-totreat (mITT) analysis, all patients (93/93) in the ceftriaxone, 99% (86/87) in the ertapenem, 93% (79/85) in the gentamicin, and 12% (4/33) in the fosfomycin arm cleared Ng [risk difference, ertapenem versus ceftriaxone,-0.01(95 CI:-0.06,0.03); gentamicin versus ceftriaxone-0.07(95%CI:-0.16,-0.005)]. Both the secondary mITT analysis (clearance within 7-28 days), and the per-protocol analyses were consistent with the primary mITT analysis. Significance Single-dose 1000mg ertapenem is non-inferior to single-dose 500mg ceftriaxone in gonorrhea treatment. Given that ertapenem, an already registered antibiotic, is non-inferior to the standard of care, it may currently provide an alternative treatment option for gonorrhea if resistance against ceftriaxone becomes more widespread.
<p>RXH patient admission, Flu positivity and assumed source of viral acquisition (HAI/CAI) ... more <p>RXH patient admission, Flu positivity and assumed source of viral acquisition (HAI/CAI) cases/viral isolate data grouped according to viral sequence phylogeny.</p
<p>The branch supports that are indicated are posterior probabilities (pp). Four significan... more <p>The branch supports that are indicated are posterior probabilities (pp). Four significant putative transmission clusters containing sequences isolated from the study site (Red Cross Children’s Hospital and surrounding facilities) with pp support > 0.9 are highlighted in red.</p
Recent identification and structural modeling of Treponema pallidum ’s ( Tp ) repertoire of outer... more Recent identification and structural modeling of Treponema pallidum ’s ( Tp ) repertoire of outer membrane proteins (OMPs) represent a critical breakthrough in the decades long quest for a syphilis vaccine. However, little is known about the antigenic nature of these β-barrel-forming OMPs and, more specifically, their surface exposed regions, the extracellular loops (ECLs).
<p>Timeline displaying patient admission, movement and Influenza A (H1N1pdm) positivity wit... more <p>Timeline displaying patient admission, movement and Influenza A (H1N1pdm) positivity within hospital (patient/isolate identity according to ML Cluster identity).</p
<p>Four highly supported (by bootstrap score) probable transmission clusters involving sequ... more <p>Four highly supported (by bootstrap score) probable transmission clusters involving sequences isolated from the study site (RXH and surrounding facilities) are highlighted in red.</p
Background: Human papillomaviruses (HPVs) are genetically diverse, belonging to five distinct gen... more Background: Human papillomaviruses (HPVs) are genetically diverse, belonging to five distinct genera: Alpha, Beta, Gamma, Mu and Nu. All papillomaviruses have double stranded DNA genomes that are thought to evolve slowly because they co-opt high-fidelity host cellular DNA polymerases for their replication. Despite extensive efforts to catalogue all the HPV species that infect humans, it is likely that many still remain undiscovered. Here we use the sequences of ten novel Gammapapillomaviruses (Gamma-PVs) characterized in previous studies and related HPVs to analyse the evolutionary dynamics of these viruses at the whole genome and individual gene scales. Results: We found statistically significant incongruences between the phylogenetic trees of different genes which imply gene-to-gene variation in the evolutionary processes underlying the diversification of Gamma-PVs. We were, however, only able to detect convincing evidence of a single recombination event which, on its own, cannot explain the observed incongruences between gene phylogenies. The divergence times of the last common ancestor (LCA) of the Alpha, Beta, Mu, Nu and Gamma genera was predicted to have existed between 49.7-58.5 million years ago, before splitting into the five main lineages. The LCA of the Gamma-PVs at this time was predicted to have existed between 45.3 and 67.5 million years ago: approximately at the time when the simian and tarsier lineages of the primates diverged. Conclusion: Consequently, we report here phylogenetic tree incongruence without strong evidence of recombination.
HIV-1 subtype G has played an early and central role in the emergent complexity of the HIV-1 grou... more HIV-1 subtype G has played an early and central role in the emergent complexity of the HIV-1 group M (HIV-1M) epidemic in central/west Africa. Here, we analysed new subtype G env sequences sampled from 8 individuals in Yaoundé, Cameroon during 2007-2010, together with all publically available subtype G-attributed full-length env sequences with known sampling dates and locations. We inferred that the most recent common ancestor (MRCA) of the analysed subtype G env sequences most likely occurred in ∼1953 (95% Highest Posterior Density interval (HPD) 1939-1963): about 15years earlier than previous estimates. We found that the subtype G env phylogeny has a complex structure including seven distinct lineages, each likely dating back to the late 1960s or early 1970s. Sequences from Angola, Gabon and the Democratic Republic of Congo failed to group consistently in these lineages, possibly because they are related to more ancient sequences that are poorly sampled. The circulating recombinant form (CRF), CRF06_cpx env sequences but not CRF25_cpx env sequences are phylogenetically nested within the subtype G clade. This confirms that the CRF06_cpx env plausibly was derived through recombination from a subtype G parent, and suggests that the CRF25_cpx env was likely derived from an HIV-1M lineage related to the MRCA of subtype G that has remained undiscovered and may be extinct. Overall, this fills important gaps in our knowledge of the early events in the spread of HIV-1M.
International Journal of Infectious Diseases, 2014
to overcome varied ailments including worm disease condition, stomach-ache, jaundice and malaria ... more to overcome varied ailments including worm disease condition, stomach-ache, jaundice and malaria like fevers. This study is an attempt to assess AC as antimicrobial and antimalarial plant. Therefore, crude extract and fractions from AC nuts were tested against Plasmodium falciparum 3D7 and 11 strains of bacteria. Methods & Materials: Extract from AC nuts was obtained by Sohlet extraction using methanol as solvent. Fractions viz. hexane, chloroform, ethyacetate, butanol and water were obtained by partitioning methanol extract in water and different solvents in order of increased polarity. Antimalarial activity of extract and fractions from AC was performed through SYBR green method whilst antimicrobial activity was assessed through Disc Diffusion Assay (DDA). The antimicrobial potential was further confirmed quantitatively by determination of the Minimum Inhibitory Concentration (MIC) of extract and fractions from AC. Results: Extract and fractions from AC showed remarkable antimalarial activity against P. falciparum, the most potent being butanol fraction with an IC 50 of 18 g/ml. Significant antimicrobial activity of methanol extract, ethylacetate, butanol and water fraction towards four bacterial strains viz. Staphylococcus Aureus 96 (SA96), Staphylococcus Aureus 2940 (SA2940), Streptococcus mutans (SM) and Mycobacterium smegmatis (MS) was recorded. The most potent being butanol fraction with DDA of 14 mm. The MIC values were 125, 250, 62.5 and 250 g/ml for methanol extract, ethylacetate, butanol and water fractions towards SA96. Conclusion: AC demonstrated to possess antimalarial and broad antimicrobial activities which might be prospected as potential source for the development of new therapeutic agents.
Background: West Nile virus (WNV) has a wide geographical distribution and has been associated to... more Background: West Nile virus (WNV) has a wide geographical distribution and has been associated to cause neurological disease in humans and horses. Mosquitoes are the traditional vectors for WNV; however, the virus has also been isolated from tick species in North Africa and Europe which could be a means of introduction and spread of the virus over long distances through migratory birds. Although WNV has been isolated in mosquitoes in Kenya, paucity of genetic and pathogenicity data exists. We previously reported the isolation of WNV from ticks collected from livestock and wildlife in Ijara District of Kenya, a hotspot for arbovirus activity. Here we report the full genome sequence and phylogenetic investigation of their origin and relation to strains from other regions. Methods: A total of 10,488 ticks were sampled from animal hosts, classified to species and processed in pools of up to eight ticks per pool. Virus screening was performed by cell culture, RT-PCR and sequencing. Phylogenetic analysis was carried out to determine the evolutionary relationships of our isolate. Results: Among other viruses, WNV was isolated from a pool of Rhipicephalus pulchellus sampled from cattle, sequenced and submitted to GenBank (Accession number: KC243146). Comparative analysis with 27 different strains revealed that our isolate belongs to lineage 1 and clustered relatively closely to isolates from North Africa and Europe, Russia and the United States. Overall, Bayesian analysis based on nucleotide sequences showed that lineage 1 strains including the Kenyan strain had diverged 200 years ago from lineage 2 strains of southern Africa. Ijara strain collected from a tick sampled on livestock was closest to another Kenyan strain and had diverged 20 years ago from strains detected in Morocco and Europe and 30 years ago from strains identified in the USA. Conclusion: To our knowledge, this is the first characterized WNV strain isolated from R. pulchellus. The epidemiological role of this tick in WNV transmission and dissemination remains equivocal but presents tick verses mosquito virus transmission has been neglected. Genetic data of this strain suggest that lineage 1 strains from Africa could be dispersed through tick vectors by wild migratory birds to Europe and beyond.
RNA viruses are among the most virulent microorganisms that threaten the health of humans and liv... more RNA viruses are among the most virulent microorganisms that threaten the health of humans and livestock. Among the most socioeconomically important of the known RNA viruses are those found in the family Orthomyxovirus. In this era of rapid low cost genome sequencing and advancements in computational biology techniques, many previously difficult research questions relating to the molecular epidemiology and evolutionary dynamics of these viruses can now be answered with ease. Using sequence data together with associated meta-data, in chapter two of this dissertation I tested the hypothesis that the Influenza A/H1N1 2009 pandemic virus was introduced multiple times into Africa, and subsequently dispersed heterogeneously across the continent. I further tested to what degree factors such as road distances and air travel distances impacted the observed pattern of spread of this virus in Africa using a generalised linear model based approach.
Sindbis virus (SINV) is a mosquito borne virus maintained in nature in a mosquito-bird cycle, wit... more Sindbis virus (SINV) is a mosquito borne virus maintained in nature in a mosquito-bird cycle, with human outbreaks known to occur in Northern Europe and parts of Africa. We analyzed five SINV strains isolated in Kenya from five different mosquito species and geographic locations between 2007 and 2013. Phylogenetic relationships and evolutionary inferences were performed using maximum likelihood and Bayesian phylogenetic inference approaches. Selection analyses were carried out based on the virus envelope glycoproteins (E1, E2) and non-structural protein (nsP4) genes. Phylogenetic analysis revealed that all the Kenyan SINV isolates belonged to genotype 1 with selection analyses suggesting that SINV E1, E2 and nsP4 protein encoding genes were predominantly evolving under negative selection.
RNA viruses are among the most virulent microorganisms that threaten the health of humans and liv... more RNA viruses are among the most virulent microorganisms that threaten the health of humans and livestock. Among the most socio-economically important of the known RNA viruses are those found in the family Orthomyxovirus. In this era of rapid low-cost genome sequencing and advancements in computational biology techniques, many previously difficult research questions relating to the molecular epidemiology and evolutionary dynamics of these viruses can now be answered with ease. Using sequence data together with associated meta-data, in chapter two of this dissertation I tested the hypothesis that the Influenza A/H1N1 2009 pandemic virus was introduced multiple times into Africa, and subsequently dispersed heterogeneously across the continent. I further tested to what degree factors such as road distances and air travel distances impacted the observed pattern of spread of this virus in Africa using a generalised linear modelbased approach. The results suggested that their were multiple ...
An Escherichia coli strain (sequence type 636) was isolated from an adult residing in an urban in... more An Escherichia coli strain (sequence type 636) was isolated from an adult residing in an urban informal settlement in Nairobi, Kenya, and was sequenced using the Illumina MiSeq platform. The draft genome was 5,075,726 bp, with a Col(BS512) plasmid plus aph(6)-Id , bla TEM-1B , and dfrA7 genes, which encode kanamycin, ampicillin, and trimethoprim resistance proteins, respectively.
Background: It is imperative in the midst of a global epidemic to investigate the origins of the ... more Background: It is imperative in the midst of a global epidemic to investigate the origins of the infectious agent especially when it has reached parts of the world with either ailing economies or pre-existing political turmoil consistent with non-functional health systems. Methods: To explore the possibility of cross species infection, genomic recombination and the emergence of novel coronaviruses in the near future we carried out recombination and phylogenetic analysis to determine the spatio-temporal evolution and origins of the current SARS-CoV-2 virus. Results: Our findings prove using two robust recombination tools, RDPv4.100 and SimPlot3.5.1 analysis that SARS-CoV-2 is a recombinant of pangolin and bat RaTG13 sequences as been previously shown elsewhere. We also report one novel recombinantion event between two SARS-CoV-2 sequences ( SARS-CoV-2 sequence, MT188341 , SARS-CoV-2 sequence, MT293183). Bearing in mind that the prerequisite for recombination is the occurrence two vir...
Traditional modes of investigating influenza nosocomial transmission have entailed a combination ... more Traditional modes of investigating influenza nosocomial transmission have entailed a combination of confirmatory molecular diagnostic testing and epidemiological investigation. Common hospital-acquired infections like influenza require a discerning ability to distinguish between viral isolates to accurately identify patient transmission chains. We assessed whether influenza hemagglutinin sequence phylogenies can be used to enrich epidemiological data when investigating the extent of nosocomial transmission over a four-month period within a paediatric Hospital in Cape Town South Africa. Possible transmission chains/channels were initially determined through basic patient admission data combined with Maximum likelihood and time-scaled Bayesian phylogenetic analyses. These analyses suggested that most instances of potential hospital-acquired infections resulted from multiple introductions of Influenza A into the hospital, which included instances where virus hemagglutinin sequences were identical between different patients. Furthermore, a general inability to establish epidemiological transmission linkage of patients/viral isolates implied that identified isolates could have originated from asymptomatic hospital patients, visitors or hospital staff. In contrast, a traditional epidemiological investigation that used no viral phylogenetic analyses, based on patient co-admission into specific wards during a particular time-frame, suggested that multiple hospital acquired infection instances may have stemmed from a limited number of identifiable index viral isolates/patients. This traditional epidemiological analysis by itself could incorrectly suggest linkage between unrelated cases, underestimate the number of unique infections and may overlook the possible diffuse nature of hospital transmission, which was suggested by sequencing data to be caused by multiple unique introductions of influenza A isolates into individual hospital wards. We have demonstrated a functional role for viral sequence data in nosocomial transmission investigation through its ability to enrich traditional, non-molecular observational epidemiological investigation by teasing out possible transmission pathways and working toward more accurately enumerating the number of possible transmission events.
International Journal of Infectious Diseases, 2014
Background: West Nile virus (WNV) has a wide geographical distribution and has been associated to... more Background: West Nile virus (WNV) has a wide geographical distribution and has been associated to cause neurological disease in humans and horses. Mosquitoes are the traditional vectors for WNV; however, the virus has also been isolated from tick species in North Africa and Europe which could be a means of introduction and spread of the virus over long distances through migratory birds. Although WNV has been isolated in mosquitoes in Kenya, paucity of genetic and pathogenicity data exists. We previously reported the isolation of WNV from ticks collected from livestock and wildlife in Ijara District of Kenya, a hotspot for arbovirus activity. Here we report the full genome sequence and phylogenetic investigation of their origin and relation to strains from other regions.
HIV-1 subtype G has played an early and central role in the emergent complexity of the HIV-1 grou... more HIV-1 subtype G has played an early and central role in the emergent complexity of the HIV-1 group M (HIV-1M) epidemic in central/west Africa. Here, we analysed new subtype G env sequences sampled from 8 individuals in Yaoundé, Cameroon during 2007-2010, together with all publically available subtype G-attributed full-length env sequences with known sampling dates and locations. We inferred that the most recent common ancestor (MRCA) of the analysed subtype G env sequences most likely occurred in ∼1953 (95% Highest Posterior Density interval (HPD) 1939-1963): about 15years earlier than previous estimates. We found that the subtype G env phylogeny has a complex structure including seven distinct lineages, each likely dating back to the late 1960s or early 1970s. Sequences from Angola, Gabon and the Democratic Republic of Congo failed to group consistently in these lineages, possibly because they are related to more ancient sequences that are poorly sampled. The circulating recombinant form (CRF), CRF06_cpx env sequences but not CRF25_cpx env sequences are phylogenetically nested within the subtype G clade. This confirms that the CRF06_cpx env plausibly was derived through recombination from a subtype G parent, and suggests that the CRF25_cpx env was likely derived from an HIV-1M lineage related to the MRCA of subtype G that has remained undiscovered and may be extinct. Overall, this fills important gaps in our knowledge of the early events in the spread of HIV-1M.
West Nile virus (WNV) has a wide geographical distribution and has been associated to cause neuro... more West Nile virus (WNV) has a wide geographical distribution and has been associated to cause neurological disease in humans and horses. Mosquitoes are the traditional vectors for WNV; however, the virus has also been isolated from some tick species in North Africa and Europe which could be a means of introduction and spread of the virus over long distances through migratory birds. Although WNV has been isolated in mosquitoes in Kenya, paucity of genetic and pathogenicity data exists. We previously reported the isolation of WNV from ticks collected from livestock and wildlife in Ijara District of Kenya, a hotspot for arbovirus activity. Here we report the full genome sequence and phylogenetic investigation of their origin and relation to strains from other regions in Africa and beyond.
Background: The Ebola virus disease outbreak of 2014 was the largest, longest and most devastatin... more Background: The Ebola virus disease outbreak of 2014 was the largest, longest and most devastating in the history of the disease. It demonstrated the social and economic impact an emerging infectious disease can have in a globalized world. Health systems in affected countries were stretched to the point of near collapse, while social relations and traditional practices were negatively impacted. Heads of African research institutions, African government representatives, leaders of global pharmaceutical companies, global infectious disease experts and close to 100 young African researchers from 25 countries; Assembled in Geneva on 19 and 20th October 2015, for the inaugural UNESCO-Merck Africa Summit sponsored by the United Nations Educational, Science and Culture Organization and Merck KGA Goal of Summit: The primary goal of the summit was to develop strategies to increase health research capacity in Africa, with special focus on Ebola and enhancing pandemic preparation for emerging infectious diseases. The summit was also provide a forum to showcase the research taking place in Africa, and provided platform for African researchers to network. Some of the key issues discussed included; strategies for enhancing policy frameworks to promote knowledge translation, strengthening of health systems, enhancing knowledge and data sharing, and increasing innovation in Africa. Conclusions: Summit attendees recognized that Africa still bore the heaviest burden of infectious disease, and increased commitment by African governments to fund health research, offered the best hope for developing health solutions and interventions to improve the health of Africans. Improved health in turn would enhance the productivity of Africans, further supporting the socioeconomic transformation currently taking place on the continent. Research is a catalyst for Social, Economic and Sustainable development in Africa. The health of a population, is critical for social and economic productivity(WHO 2015). In recent years, majority of African countries have experienced positive growth and development. In order to expand and sustain the positive trends, African countries need to prioritize investments in health research as a means of reducing the heavy burden of disease on the continent. The hope is that, increased health research will translate into innovation, discovery of novel compounds or expanded knowledge, which would greatly assist the continent to address its most pressing health needs. Africa is also faced with novel health challenges, in the form of increasing prevalence of non-communicable diseases (NCDs), rising antimicrobial resistance and emerging infectious diseases (WHO-AFRO 2014). Some of the recent gains made at improving the health of Africans, can be built upon by further strengthening individual country health systems, an effort requiring partnerships between public and private sectors, non-governmental organizations (NGOs) and academia. UNESCO-MARS summit brought health researchers from Africa, together with to executives of global pharmaceutical companies, UNESCO officials and representatives of African government, to dialogue on ways to improve global cooperation on combating emerging infectious diseases and other challenges facing the life sciences and health research in Africa. It also provided a platform for discussing ways of improving knowledge translation of research already taking place on the continent as a means of bridging the 'know-do-gap'. The North (developed) to South (developing world) 'loans and aid' model initially used to bring development to postcolonial Africa, has since transitioned to the more 'collaborative' approach which seeks to enhance development through mutually beneficial North to South and South to South relationships. This collaborative approach in the words, Prof Imbuga Godia-Kenya's representative at UNESCO, enabled the World to make significant strides through initiatives such
Background Neisseria gonorrhoeae (Ng) is a common sexually transmitted infection (STI). Emerging ... more Background Neisseria gonorrhoeae (Ng) is a common sexually transmitted infection (STI). Emerging strains resistant to first-line ceftriaxone threaten Ng management. Hence, alternative treatments are needed. We evaluated the efficacy of ertapenem, gentamicin and fosfomycin as alternatives for Ng. Approach We included adults 18 years or older, with anorectal or urogenital gonorrhea in a randomized controlled, doubleblind, non-inferiority trial (three experimental-and one control-arm). Participants were randomized (1:1:1:1) to receive: intramuscular (IM) 500mg ceftriaxone, IM 1000mg ertapenem, IM 5mg/kg gentamicin (maximum 400mg), or 6g fosfomycin orally. The primary outcome was the proportion of participants with a negative nucleic acid amplification test of the primary infected site, 7-14 days after treatment. Non-inferiority was established if the lower Hochberg-corrected 95% confidence interval for difference between experimental and control arms was greater than-10%. Outcomes Between 18 September 2017 and 5 June 2020, we assigned 346 participants to ceftriaxone (n=103), ertapenem (n=103), gentamicin (n=102), and fosfomycin (n=38). The fosfomycin arm was terminated early after interim analysis revealed <60% efficacy. In the primary modified intent-totreat (mITT) analysis, all patients (93/93) in the ceftriaxone, 99% (86/87) in the ertapenem, 93% (79/85) in the gentamicin, and 12% (4/33) in the fosfomycin arm cleared Ng [risk difference, ertapenem versus ceftriaxone,-0.01(95 CI:-0.06,0.03); gentamicin versus ceftriaxone-0.07(95%CI:-0.16,-0.005)]. Both the secondary mITT analysis (clearance within 7-28 days), and the per-protocol analyses were consistent with the primary mITT analysis. Significance Single-dose 1000mg ertapenem is non-inferior to single-dose 500mg ceftriaxone in gonorrhea treatment. Given that ertapenem, an already registered antibiotic, is non-inferior to the standard of care, it may currently provide an alternative treatment option for gonorrhea if resistance against ceftriaxone becomes more widespread.
<p>RXH patient admission, Flu positivity and assumed source of viral acquisition (HAI/CAI) ... more <p>RXH patient admission, Flu positivity and assumed source of viral acquisition (HAI/CAI) cases/viral isolate data grouped according to viral sequence phylogeny.</p
<p>The branch supports that are indicated are posterior probabilities (pp). Four significan... more <p>The branch supports that are indicated are posterior probabilities (pp). Four significant putative transmission clusters containing sequences isolated from the study site (Red Cross Children’s Hospital and surrounding facilities) with pp support > 0.9 are highlighted in red.</p
Recent identification and structural modeling of Treponema pallidum ’s ( Tp ) repertoire of outer... more Recent identification and structural modeling of Treponema pallidum ’s ( Tp ) repertoire of outer membrane proteins (OMPs) represent a critical breakthrough in the decades long quest for a syphilis vaccine. However, little is known about the antigenic nature of these β-barrel-forming OMPs and, more specifically, their surface exposed regions, the extracellular loops (ECLs).
<p>Timeline displaying patient admission, movement and Influenza A (H1N1pdm) positivity wit... more <p>Timeline displaying patient admission, movement and Influenza A (H1N1pdm) positivity within hospital (patient/isolate identity according to ML Cluster identity).</p
<p>Four highly supported (by bootstrap score) probable transmission clusters involving sequ... more <p>Four highly supported (by bootstrap score) probable transmission clusters involving sequences isolated from the study site (RXH and surrounding facilities) are highlighted in red.</p
Background: Human papillomaviruses (HPVs) are genetically diverse, belonging to five distinct gen... more Background: Human papillomaviruses (HPVs) are genetically diverse, belonging to five distinct genera: Alpha, Beta, Gamma, Mu and Nu. All papillomaviruses have double stranded DNA genomes that are thought to evolve slowly because they co-opt high-fidelity host cellular DNA polymerases for their replication. Despite extensive efforts to catalogue all the HPV species that infect humans, it is likely that many still remain undiscovered. Here we use the sequences of ten novel Gammapapillomaviruses (Gamma-PVs) characterized in previous studies and related HPVs to analyse the evolutionary dynamics of these viruses at the whole genome and individual gene scales. Results: We found statistically significant incongruences between the phylogenetic trees of different genes which imply gene-to-gene variation in the evolutionary processes underlying the diversification of Gamma-PVs. We were, however, only able to detect convincing evidence of a single recombination event which, on its own, cannot explain the observed incongruences between gene phylogenies. The divergence times of the last common ancestor (LCA) of the Alpha, Beta, Mu, Nu and Gamma genera was predicted to have existed between 49.7-58.5 million years ago, before splitting into the five main lineages. The LCA of the Gamma-PVs at this time was predicted to have existed between 45.3 and 67.5 million years ago: approximately at the time when the simian and tarsier lineages of the primates diverged. Conclusion: Consequently, we report here phylogenetic tree incongruence without strong evidence of recombination.
HIV-1 subtype G has played an early and central role in the emergent complexity of the HIV-1 grou... more HIV-1 subtype G has played an early and central role in the emergent complexity of the HIV-1 group M (HIV-1M) epidemic in central/west Africa. Here, we analysed new subtype G env sequences sampled from 8 individuals in Yaoundé, Cameroon during 2007-2010, together with all publically available subtype G-attributed full-length env sequences with known sampling dates and locations. We inferred that the most recent common ancestor (MRCA) of the analysed subtype G env sequences most likely occurred in ∼1953 (95% Highest Posterior Density interval (HPD) 1939-1963): about 15years earlier than previous estimates. We found that the subtype G env phylogeny has a complex structure including seven distinct lineages, each likely dating back to the late 1960s or early 1970s. Sequences from Angola, Gabon and the Democratic Republic of Congo failed to group consistently in these lineages, possibly because they are related to more ancient sequences that are poorly sampled. The circulating recombinant form (CRF), CRF06_cpx env sequences but not CRF25_cpx env sequences are phylogenetically nested within the subtype G clade. This confirms that the CRF06_cpx env plausibly was derived through recombination from a subtype G parent, and suggests that the CRF25_cpx env was likely derived from an HIV-1M lineage related to the MRCA of subtype G that has remained undiscovered and may be extinct. Overall, this fills important gaps in our knowledge of the early events in the spread of HIV-1M.
International Journal of Infectious Diseases, 2014
to overcome varied ailments including worm disease condition, stomach-ache, jaundice and malaria ... more to overcome varied ailments including worm disease condition, stomach-ache, jaundice and malaria like fevers. This study is an attempt to assess AC as antimicrobial and antimalarial plant. Therefore, crude extract and fractions from AC nuts were tested against Plasmodium falciparum 3D7 and 11 strains of bacteria. Methods & Materials: Extract from AC nuts was obtained by Sohlet extraction using methanol as solvent. Fractions viz. hexane, chloroform, ethyacetate, butanol and water were obtained by partitioning methanol extract in water and different solvents in order of increased polarity. Antimalarial activity of extract and fractions from AC was performed through SYBR green method whilst antimicrobial activity was assessed through Disc Diffusion Assay (DDA). The antimicrobial potential was further confirmed quantitatively by determination of the Minimum Inhibitory Concentration (MIC) of extract and fractions from AC. Results: Extract and fractions from AC showed remarkable antimalarial activity against P. falciparum, the most potent being butanol fraction with an IC 50 of 18 g/ml. Significant antimicrobial activity of methanol extract, ethylacetate, butanol and water fraction towards four bacterial strains viz. Staphylococcus Aureus 96 (SA96), Staphylococcus Aureus 2940 (SA2940), Streptococcus mutans (SM) and Mycobacterium smegmatis (MS) was recorded. The most potent being butanol fraction with DDA of 14 mm. The MIC values were 125, 250, 62.5 and 250 g/ml for methanol extract, ethylacetate, butanol and water fractions towards SA96. Conclusion: AC demonstrated to possess antimalarial and broad antimicrobial activities which might be prospected as potential source for the development of new therapeutic agents.
Background: West Nile virus (WNV) has a wide geographical distribution and has been associated to... more Background: West Nile virus (WNV) has a wide geographical distribution and has been associated to cause neurological disease in humans and horses. Mosquitoes are the traditional vectors for WNV; however, the virus has also been isolated from tick species in North Africa and Europe which could be a means of introduction and spread of the virus over long distances through migratory birds. Although WNV has been isolated in mosquitoes in Kenya, paucity of genetic and pathogenicity data exists. We previously reported the isolation of WNV from ticks collected from livestock and wildlife in Ijara District of Kenya, a hotspot for arbovirus activity. Here we report the full genome sequence and phylogenetic investigation of their origin and relation to strains from other regions. Methods: A total of 10,488 ticks were sampled from animal hosts, classified to species and processed in pools of up to eight ticks per pool. Virus screening was performed by cell culture, RT-PCR and sequencing. Phylogenetic analysis was carried out to determine the evolutionary relationships of our isolate. Results: Among other viruses, WNV was isolated from a pool of Rhipicephalus pulchellus sampled from cattle, sequenced and submitted to GenBank (Accession number: KC243146). Comparative analysis with 27 different strains revealed that our isolate belongs to lineage 1 and clustered relatively closely to isolates from North Africa and Europe, Russia and the United States. Overall, Bayesian analysis based on nucleotide sequences showed that lineage 1 strains including the Kenyan strain had diverged 200 years ago from lineage 2 strains of southern Africa. Ijara strain collected from a tick sampled on livestock was closest to another Kenyan strain and had diverged 20 years ago from strains detected in Morocco and Europe and 30 years ago from strains identified in the USA. Conclusion: To our knowledge, this is the first characterized WNV strain isolated from R. pulchellus. The epidemiological role of this tick in WNV transmission and dissemination remains equivocal but presents tick verses mosquito virus transmission has been neglected. Genetic data of this strain suggest that lineage 1 strains from Africa could be dispersed through tick vectors by wild migratory birds to Europe and beyond.
RNA viruses are among the most virulent microorganisms that threaten the health of humans and liv... more RNA viruses are among the most virulent microorganisms that threaten the health of humans and livestock. Among the most socioeconomically important of the known RNA viruses are those found in the family Orthomyxovirus. In this era of rapid low cost genome sequencing and advancements in computational biology techniques, many previously difficult research questions relating to the molecular epidemiology and evolutionary dynamics of these viruses can now be answered with ease. Using sequence data together with associated meta-data, in chapter two of this dissertation I tested the hypothesis that the Influenza A/H1N1 2009 pandemic virus was introduced multiple times into Africa, and subsequently dispersed heterogeneously across the continent. I further tested to what degree factors such as road distances and air travel distances impacted the observed pattern of spread of this virus in Africa using a generalised linear model based approach.
Sindbis virus (SINV) is a mosquito borne virus maintained in nature in a mosquito-bird cycle, wit... more Sindbis virus (SINV) is a mosquito borne virus maintained in nature in a mosquito-bird cycle, with human outbreaks known to occur in Northern Europe and parts of Africa. We analyzed five SINV strains isolated in Kenya from five different mosquito species and geographic locations between 2007 and 2013. Phylogenetic relationships and evolutionary inferences were performed using maximum likelihood and Bayesian phylogenetic inference approaches. Selection analyses were carried out based on the virus envelope glycoproteins (E1, E2) and non-structural protein (nsP4) genes. Phylogenetic analysis revealed that all the Kenyan SINV isolates belonged to genotype 1 with selection analyses suggesting that SINV E1, E2 and nsP4 protein encoding genes were predominantly evolving under negative selection.
RNA viruses are among the most virulent microorganisms that threaten the health of humans and liv... more RNA viruses are among the most virulent microorganisms that threaten the health of humans and livestock. Among the most socio-economically important of the known RNA viruses are those found in the family Orthomyxovirus. In this era of rapid low-cost genome sequencing and advancements in computational biology techniques, many previously difficult research questions relating to the molecular epidemiology and evolutionary dynamics of these viruses can now be answered with ease. Using sequence data together with associated meta-data, in chapter two of this dissertation I tested the hypothesis that the Influenza A/H1N1 2009 pandemic virus was introduced multiple times into Africa, and subsequently dispersed heterogeneously across the continent. I further tested to what degree factors such as road distances and air travel distances impacted the observed pattern of spread of this virus in Africa using a generalised linear modelbased approach. The results suggested that their were multiple ...
An Escherichia coli strain (sequence type 636) was isolated from an adult residing in an urban in... more An Escherichia coli strain (sequence type 636) was isolated from an adult residing in an urban informal settlement in Nairobi, Kenya, and was sequenced using the Illumina MiSeq platform. The draft genome was 5,075,726 bp, with a Col(BS512) plasmid plus aph(6)-Id , bla TEM-1B , and dfrA7 genes, which encode kanamycin, ampicillin, and trimethoprim resistance proteins, respectively.
Background: It is imperative in the midst of a global epidemic to investigate the origins of the ... more Background: It is imperative in the midst of a global epidemic to investigate the origins of the infectious agent especially when it has reached parts of the world with either ailing economies or pre-existing political turmoil consistent with non-functional health systems. Methods: To explore the possibility of cross species infection, genomic recombination and the emergence of novel coronaviruses in the near future we carried out recombination and phylogenetic analysis to determine the spatio-temporal evolution and origins of the current SARS-CoV-2 virus. Results: Our findings prove using two robust recombination tools, RDPv4.100 and SimPlot3.5.1 analysis that SARS-CoV-2 is a recombinant of pangolin and bat RaTG13 sequences as been previously shown elsewhere. We also report one novel recombinantion event between two SARS-CoV-2 sequences ( SARS-CoV-2 sequence, MT188341 , SARS-CoV-2 sequence, MT293183). Bearing in mind that the prerequisite for recombination is the occurrence two vir...
Traditional modes of investigating influenza nosocomial transmission have entailed a combination ... more Traditional modes of investigating influenza nosocomial transmission have entailed a combination of confirmatory molecular diagnostic testing and epidemiological investigation. Common hospital-acquired infections like influenza require a discerning ability to distinguish between viral isolates to accurately identify patient transmission chains. We assessed whether influenza hemagglutinin sequence phylogenies can be used to enrich epidemiological data when investigating the extent of nosocomial transmission over a four-month period within a paediatric Hospital in Cape Town South Africa. Possible transmission chains/channels were initially determined through basic patient admission data combined with Maximum likelihood and time-scaled Bayesian phylogenetic analyses. These analyses suggested that most instances of potential hospital-acquired infections resulted from multiple introductions of Influenza A into the hospital, which included instances where virus hemagglutinin sequences were identical between different patients. Furthermore, a general inability to establish epidemiological transmission linkage of patients/viral isolates implied that identified isolates could have originated from asymptomatic hospital patients, visitors or hospital staff. In contrast, a traditional epidemiological investigation that used no viral phylogenetic analyses, based on patient co-admission into specific wards during a particular time-frame, suggested that multiple hospital acquired infection instances may have stemmed from a limited number of identifiable index viral isolates/patients. This traditional epidemiological analysis by itself could incorrectly suggest linkage between unrelated cases, underestimate the number of unique infections and may overlook the possible diffuse nature of hospital transmission, which was suggested by sequencing data to be caused by multiple unique introductions of influenza A isolates into individual hospital wards. We have demonstrated a functional role for viral sequence data in nosocomial transmission investigation through its ability to enrich traditional, non-molecular observational epidemiological investigation by teasing out possible transmission pathways and working toward more accurately enumerating the number of possible transmission events.
International Journal of Infectious Diseases, 2014
Background: West Nile virus (WNV) has a wide geographical distribution and has been associated to... more Background: West Nile virus (WNV) has a wide geographical distribution and has been associated to cause neurological disease in humans and horses. Mosquitoes are the traditional vectors for WNV; however, the virus has also been isolated from tick species in North Africa and Europe which could be a means of introduction and spread of the virus over long distances through migratory birds. Although WNV has been isolated in mosquitoes in Kenya, paucity of genetic and pathogenicity data exists. We previously reported the isolation of WNV from ticks collected from livestock and wildlife in Ijara District of Kenya, a hotspot for arbovirus activity. Here we report the full genome sequence and phylogenetic investigation of their origin and relation to strains from other regions.
HIV-1 subtype G has played an early and central role in the emergent complexity of the HIV-1 grou... more HIV-1 subtype G has played an early and central role in the emergent complexity of the HIV-1 group M (HIV-1M) epidemic in central/west Africa. Here, we analysed new subtype G env sequences sampled from 8 individuals in Yaoundé, Cameroon during 2007-2010, together with all publically available subtype G-attributed full-length env sequences with known sampling dates and locations. We inferred that the most recent common ancestor (MRCA) of the analysed subtype G env sequences most likely occurred in ∼1953 (95% Highest Posterior Density interval (HPD) 1939-1963): about 15years earlier than previous estimates. We found that the subtype G env phylogeny has a complex structure including seven distinct lineages, each likely dating back to the late 1960s or early 1970s. Sequences from Angola, Gabon and the Democratic Republic of Congo failed to group consistently in these lineages, possibly because they are related to more ancient sequences that are poorly sampled. The circulating recombinant form (CRF), CRF06_cpx env sequences but not CRF25_cpx env sequences are phylogenetically nested within the subtype G clade. This confirms that the CRF06_cpx env plausibly was derived through recombination from a subtype G parent, and suggests that the CRF25_cpx env was likely derived from an HIV-1M lineage related to the MRCA of subtype G that has remained undiscovered and may be extinct. Overall, this fills important gaps in our knowledge of the early events in the spread of HIV-1M.
West Nile virus (WNV) has a wide geographical distribution and has been associated to cause neuro... more West Nile virus (WNV) has a wide geographical distribution and has been associated to cause neurological disease in humans and horses. Mosquitoes are the traditional vectors for WNV; however, the virus has also been isolated from some tick species in North Africa and Europe which could be a means of introduction and spread of the virus over long distances through migratory birds. Although WNV has been isolated in mosquitoes in Kenya, paucity of genetic and pathogenicity data exists. We previously reported the isolation of WNV from ticks collected from livestock and wildlife in Ijara District of Kenya, a hotspot for arbovirus activity. Here we report the full genome sequence and phylogenetic investigation of their origin and relation to strains from other regions in Africa and beyond.
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Papers by Fredrick Nindo