Zika: Zika virus surveillance in human and mosquito populations in Cape Verde
Lead Research Organisation:
London School of Hygiene and Tropical Medicine
Department Name: UNLISTED
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
Technical Summary
The Zika virus, originally identified in Uganda, has spread rapidly across regions occupied by Aedes mosquitos in Africa, Asia, and recently to the Americas. Although originally only causing mild illness, the recent outbreak in Brazil has been linked to a sudden spike of
neurological disorders and congenital microcephaly cases. Since the current outbreak in the Americas, Cape Verde has become the first African country declaring an epidemic of Zika, reporting ~7000 cases since October 2015. The strong historical and economic links with
Brazil suggest that the Cape Verde epidemic is caused by the same viral strain. Due to Cape Verde’s international travel links there is a fear of the potentially severe viral strain spreading to mainland Africa and Europe.
To determine the origin and spread of infection, and support the implementation of a rapid public health response, we will perform a surveillance study of the Zika virus in Cape Verde.
We propose to provide accurate clinical and epidemiological data on Zika infection, by
(1) Identifying transmission hotspots, and survey Aedes mosquito populations therein;
(2) Using serological techniques to estimate Zika virus community exposure;
(3) Sequence viral samples sourced from the collected mosquitos and confirmed patient cases;
(4) Compare the genetic diversity of viral samples to sequenced strains from elsewhere
(Brazil, other African), thereby determining the origin of Zika infection in Cape Verde.
This project has a multidisciplinary approach- viro-entomo-epidemio-genomics working together to support the investigation of the Zika virus infection epidemic. The surveillance and research components of this proposal will support the development of timely effective actions to help contain Zika infections, and insights could assist other global control efforts,
especially in the Americas.
neurological disorders and congenital microcephaly cases. Since the current outbreak in the Americas, Cape Verde has become the first African country declaring an epidemic of Zika, reporting ~7000 cases since October 2015. The strong historical and economic links with
Brazil suggest that the Cape Verde epidemic is caused by the same viral strain. Due to Cape Verde’s international travel links there is a fear of the potentially severe viral strain spreading to mainland Africa and Europe.
To determine the origin and spread of infection, and support the implementation of a rapid public health response, we will perform a surveillance study of the Zika virus in Cape Verde.
We propose to provide accurate clinical and epidemiological data on Zika infection, by
(1) Identifying transmission hotspots, and survey Aedes mosquito populations therein;
(2) Using serological techniques to estimate Zika virus community exposure;
(3) Sequence viral samples sourced from the collected mosquitos and confirmed patient cases;
(4) Compare the genetic diversity of viral samples to sequenced strains from elsewhere
(Brazil, other African), thereby determining the origin of Zika infection in Cape Verde.
This project has a multidisciplinary approach- viro-entomo-epidemio-genomics working together to support the investigation of the Zika virus infection epidemic. The surveillance and research components of this proposal will support the development of timely effective actions to help contain Zika infections, and insights could assist other global control efforts,
especially in the Americas.
Organisations
- London School of Hygiene and Tropical Medicine (Lead Research Organisation)
- Ministry of Health and Social Security, Cape Verde (Collaboration)
- Pasteur Institute Dakar (Collaboration)
- Jean Piaget University of Cape Verde (Collaboration)
- New University of Lisbon (Collaboration)
- Agency for Science, Technology and Research (A*STAR) (Collaboration)
Publications
Andreu N
(2017)
Primary macrophages and J774 cells respond differently to infection with Mycobacterium tuberculosis.
in Scientific reports
Auburn S
(2018)
Genomic analysis of a pre-elimination Malaysian Plasmodium vivax population reveals selective pressures and changing transmission dynamics.
in Nature communications
Benjamin Sobkowiak
(2018)
Identifying mixed Mycobacterium tuberculosis infections from whole genome sequence data
Benjamin Sobkowiak
(2018)
Identifying mixed Mycobacterium tuberculosis infections from whole genome sequence data
Broad JB
(2019)
Diverticulosis and nine connective tissue disorders: epidemiological support for an association.
in Connective tissue research
Campos M
(2020)
Surveillance of Aedes aegypti populations in the city of Praia, Cape Verde: Zika virus infection, insecticide resistance and genetic diversity.
in Parasites & vectors
Campos MC
(2017)
Genome-wide mutagenesis and multi-drug resistance in American trypanosomes induced by the front-line drug benznidazole.
in Scientific reports
Coll F
(2018)
Genome-wide analysis of multi- and extensively drug-resistant Mycobacterium tuberculosis.
in Nature genetics
Da Veiga Leal S
(2021)
Drug resistance profile and clonality of Plasmodium falciparum parasites in Cape Verde: the 2017 malaria outbreak.
in Malaria journal
| Title | Additional file 10: of Genome-wide analysis of Mycobacterium tuberculosis polymorphisms reveals lineage-specific associations with drug resistance |
| Description | Sublineage frequency table, Numbers and percentage by lineage assigned to each sublineage. (PPTX 36 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2019 |
| URL | https://springernature.figshare.com/articles/Additional_file_10_of_Genome-wide_analysis_of_Mycobacte... |
| Title | Additional file 10: of Genome-wide analysis of Mycobacterium tuberculosis polymorphisms reveals lineage-specific associations with drug resistance |
| Description | Sublineage frequency table, Numbers and percentage by lineage assigned to each sublineage. (PPTX 36 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2019 |
| URL | https://springernature.figshare.com/articles/Additional_file_10_of_Genome-wide_analysis_of_Mycobacte... |
| Title | Additional file 1: of Genome-wide analysis of Mycobacterium tuberculosis polymorphisms reveals lineage-specific associations with drug resistance |
| Description | Variant Summary Tables, Summary tables of variants called in comparison to the H37rv reference, with monomorphic variants removed for each dataset. a Total numbers of variants by lineage; b Number of variants per sample; c Non-reference variant frequency summary; variants called in comparison to the H37rv reference. (PPTX 39 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2019 |
| URL | https://springernature.figshare.com/articles/Additional_file_1_of_Genome-wide_analysis_of_Mycobacter... |
| Title | Additional file 1: of Genome-wide analysis of Mycobacterium tuberculosis polymorphisms reveals lineage-specific associations with drug resistance |
| Description | Variant Summary Tables, Summary tables of variants called in comparison to the H37rv reference, with monomorphic variants removed for each dataset. a Total numbers of variants by lineage; b Number of variants per sample; c Non-reference variant frequency summary; variants called in comparison to the H37rv reference. (PPTX 39 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2019 |
| URL | https://springernature.figshare.com/articles/Additional_file_1_of_Genome-wide_analysis_of_Mycobacter... |
| Title | Additional file 2: of Genome-wide analysis of Mycobacterium tuberculosis polymorphisms reveals lineage-specific associations with drug resistance |
| Description | Non-reference variant frequency histogram, A histogram showing log10(frequency + 1) of non-reference alleles compared to the H37rv reference for a lineage 2 and b lineage4. (PPTX 69 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2019 |
| URL | https://springernature.figshare.com/articles/Additional_file_2_of_Genome-wide_analysis_of_Mycobacter... |
| Title | Additional file 2: of Genome-wide analysis of Mycobacterium tuberculosis polymorphisms reveals lineage-specific associations with drug resistance |
| Description | Non-reference variant frequency histogram, A histogram showing log10(frequency + 1) of non-reference alleles compared to the H37rv reference for a lineage 2 and b lineage4. (PPTX 69 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2019 |
| URL | https://springernature.figshare.com/articles/Additional_file_2_of_Genome-wide_analysis_of_Mycobacter... |
| Title | Additional file 3: of Genome-wide analysis of Mycobacterium tuberculosis polymorphisms reveals lineage-specific associations with drug resistance |
| Description | Population diversity within investigated strains, a Principal component 1 (PC1) by principal component 2 (PC2) for lineage 2, The first 10 principal components account for 71.9% of the variation in lineage 2; b Distance plot for lineage 2 showing pairwise number of variant differences between samples; c Principal component 1 (PC1) by principal component 2 (PC2) for lineage 4, the first 10 principal components account for 88.9% of the variation in lineage 4. d Distance plot for lineage 2 showing pairwise number of variant differences between samples. (PPTX 5650 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2019 |
| URL | https://springernature.figshare.com/articles/Additional_file_3_of_Genome-wide_analysis_of_Mycobacter... |
| Title | Additional file 3: of Genome-wide analysis of Mycobacterium tuberculosis polymorphisms reveals lineage-specific associations with drug resistance |
| Description | Population diversity within investigated strains, a Principal component 1 (PC1) by principal component 2 (PC2) for lineage 2, The first 10 principal components account for 71.9% of the variation in lineage 2; b Distance plot for lineage 2 showing pairwise number of variant differences between samples; c Principal component 1 (PC1) by principal component 2 (PC2) for lineage 4, the first 10 principal components account for 88.9% of the variation in lineage 4. d Distance plot for lineage 2 showing pairwise number of variant differences between samples. (PPTX 5650 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2019 |
| URL | https://springernature.figshare.com/articles/Additional_file_3_of_Genome-wide_analysis_of_Mycobacter... |
| Title | Additional file 4: of Genome-wide analysis of Mycobacterium tuberculosis polymorphisms reveals lineage-specific associations with drug resistance |
| Description | Scree plots for the principal component analyses, Scree plots showing the proportion of variation accounted for by the first ten principal components, calculated for the pairwise distances within a lineage 4 and b lineage 2. (PPTX 142 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2019 |
| URL | https://springernature.figshare.com/articles/Additional_file_4_of_Genome-wide_analysis_of_Mycobacter... |
| Title | Additional file 4: of Genome-wide analysis of Mycobacterium tuberculosis polymorphisms reveals lineage-specific associations with drug resistance |
| Description | Scree plots for the principal component analyses, Scree plots showing the proportion of variation accounted for by the first ten principal components, calculated for the pairwise distances within a lineage 4 and b lineage 2. (PPTX 142 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2019 |
| URL | https://springernature.figshare.com/articles/Additional_file_4_of_Genome-wide_analysis_of_Mycobacter... |
| Title | Additional file 5: of Genome-wide analysis of Mycobacterium tuberculosis polymorphisms reveals lineage-specific associations with drug resistance |
| Description | Drug-resistance phenotype frequency table, Drug-resistance phenotype frequency table by lineage. 'Totals' shows the number and percentage of each lineage with a known drug-resistance phenotype. (PPTX 45 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2019 |
| URL | https://springernature.figshare.com/articles/Additional_file_5_of_Genome-wide_analysis_of_Mycobacter... |
| Title | Additional file 5: of Genome-wide analysis of Mycobacterium tuberculosis polymorphisms reveals lineage-specific associations with drug resistance |
| Description | Drug-resistance phenotype frequency table, Drug-resistance phenotype frequency table by lineage. 'Totals' shows the number and percentage of each lineage with a known drug-resistance phenotype. (PPTX 45 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2019 |
| URL | https://springernature.figshare.com/articles/Additional_file_5_of_Genome-wide_analysis_of_Mycobacter... |
| Title | Additional file 6: of Genome-wide analysis of Mycobacterium tuberculosis polymorphisms reveals lineage-specific associations with drug resistance |
| Description | Cross-resistance phenotype table, Cross-Resistance Table upper diagonal shows proportion of samples phenotyped for both vertical and horizontal phenotype, that test positive for vertical phenotype. Diagonal shows number of samples with each phenotype. Lower diagonal shows number of samples with phenotype for both horizontal and vertical phenotype. (PPTX 45 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2019 |
| URL | https://springernature.figshare.com/articles/Additional_file_6_of_Genome-wide_analysis_of_Mycobacter... |
| Title | Additional file 6: of Genome-wide analysis of Mycobacterium tuberculosis polymorphisms reveals lineage-specific associations with drug resistance |
| Description | Cross-resistance phenotype table, Cross-Resistance Table upper diagonal shows proportion of samples phenotyped for both vertical and horizontal phenotype, that test positive for vertical phenotype. Diagonal shows number of samples with each phenotype. Lower diagonal shows number of samples with phenotype for both horizontal and vertical phenotype. (PPTX 45 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2019 |
| URL | https://springernature.figshare.com/articles/Additional_file_6_of_Genome-wide_analysis_of_Mycobacter... |
| Title | Additional file 7: of Genome-wide analysis of Mycobacterium tuberculosis polymorphisms reveals lineage-specific associations with drug resistance |
| Description | Variant Position Table, Table detailing variants at all positions with at least one non-synonymous variant found to be significantly associated with a phenotype in any of the variant-based analyses. (PPTX 52 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2019 |
| URL | https://springernature.figshare.com/articles/Additional_file_7_of_Genome-wide_analysis_of_Mycobacter... |
| Title | Additional file 7: of Genome-wide analysis of Mycobacterium tuberculosis polymorphisms reveals lineage-specific associations with drug resistance |
| Description | Variant Position Table, Table detailing variants at all positions with at least one non-synonymous variant found to be significantly associated with a phenotype in any of the variant-based analyses. (PPTX 52 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2019 |
| URL | https://springernature.figshare.com/articles/Additional_file_7_of_Genome-wide_analysis_of_Mycobacter... |
| Title | Additional file 8: of Genome-wide analysis of Mycobacterium tuberculosis polymorphisms reveals lineage-specific associations with drug resistance |
| Description | Locus Comparison Table, Locus comparison table showing which analyses and in which lineage each loci was identified. An 'x' indicates a locus which was not identified by the method of analysis in question. Loci without a known association with the phenotype are highlighted in bold. (PPTX 44 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2019 |
| URL | https://springernature.figshare.com/articles/Additional_file_8_of_Genome-wide_analysis_of_Mycobacter... |
| Title | Additional file 8: of Genome-wide analysis of Mycobacterium tuberculosis polymorphisms reveals lineage-specific associations with drug resistance |
| Description | Locus Comparison Table, Locus comparison table showing which analyses and in which lineage each loci was identified. An 'x' indicates a locus which was not identified by the method of analysis in question. Loci without a known association with the phenotype are highlighted in bold. (PPTX 44 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2019 |
| URL | https://springernature.figshare.com/articles/Additional_file_8_of_Genome-wide_analysis_of_Mycobacter... |
| Title | Additional file 9: of Genome-wide analysis of Mycobacterium tuberculosis polymorphisms reveals lineage-specific associations with drug resistance |
| Description | Study frequency table, Study frequency table, showing numbers and percentage of strains from each study by lineage. (PPTX 40 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2019 |
| URL | https://springernature.figshare.com/articles/Additional_file_9_of_Genome-wide_analysis_of_Mycobacter... |
| Title | Additional file 9: of Genome-wide analysis of Mycobacterium tuberculosis polymorphisms reveals lineage-specific associations with drug resistance |
| Description | Study frequency table, Study frequency table, showing numbers and percentage of strains from each study by lineage. (PPTX 40 kb) |
| Type Of Art | Film/Video/Animation |
| Year Produced | 2019 |
| URL | https://springernature.figshare.com/articles/Additional_file_9_of_Genome-wide_analysis_of_Mycobacter... |
| Description | The award led to the development of serological and molecular diagnostics for the Zika outbreak in Cape Verde. The work profiled the Aedes aegypti mosquito population (n=1000) on Cabo Verde, the primary vector of Zika virus transmission. The work investigated their susceptibility to insecticides, through the targeted sequencing of a cross-section of entomological samples collected in Praia, the capital city. The analysis revealed a predominance of the 296S rdl mutation (98%), consistent with the past use of an organochlorine compound (e.g., DDT). Two Aedes aegypti mosquitoes had detectable levels of Zika virus. Building on these findings, molecular techniques were developed to profile the vectors' virome and proceeded to enrich and sequence whole-genome data for Zika virus. The resulting sequence data, combined with global Zika sequences, were placed phylogenetically into the broader epidemiological context of the 2015-2016 Zika epidemic, revealing two discrete introductions of Zika that occurred from the Americas to Cabo Verde in this period. In parallel, a sero-epidemiological analysis was performed based on a cross-sectional cohort of human participants (n=500), sampled shortly after the cessation of Zika transmission. By comparing a panel of arbovirus serological assays and using a multivariate logistic modelling approach, key risk-factors for Zika seropositivity were determined, including gender, age, self-reported Zika infection, and dengue seropositivity. This work was followed up by an investigation on how virus serological diagnostics may be improved. Overall, the work describes the application of molecular and serological techniques to understand the dynamics of the Zika outbreak in Cabo Verde, with some novel methodologies developed to improve on current serological tools, translating them to address current challenges in the surveillance of emerging infectious diseases. |
| Exploitation Route | The methods developed have been applied during the COVID-19 pandemic. |
| Sectors | Healthcare |
| Description | BBSRC UK-Philippines Swine & Poultry Research Initiative |
| Amount | £600,000 (GBP) |
| Funding ID | BB/R013063/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 04/2018 |
| End | 03/2021 |
| Description | Newton Institutional Links Grant |
| Amount | £279,000 (GBP) |
| Funding ID | 261868591 |
| Organisation | British Council |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 03/2017 |
| End | 04/2019 |
| Description | Newton Researcher Links Workshop Grants (Infectious Disease 'Omics (Philippines) ) |
| Amount | £60,000 (GBP) |
| Funding ID | Ref. 2017-RLWK9-110970 |
| Organisation | Newton Fund |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2018 |
| End | 12/2018 |
| Description | Newton Researcher Links Workshop Grants (Infectious Disease 'Omics (Philippines) ) |
| Amount | £60,000 (GBP) |
| Funding ID | 2017-RLWK8-10671 |
| Organisation | Newton Fund |
| Sector | Public |
| Country | United Kingdom |
| Start | 01/2018 |
| End | 12/2018 |
| Title | Zika antibody approach |
| Description | As part of our work, we developed an antibody-based approach to detect Zika, which does not cross-react with Dengue. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2017 |
| Provided To Others? | No |
| Impact | It will have impact, as some commercial kits have difficulty with dengue cross-reaction, and our approach is cheaper. A manuscript is being drafted, and we have already shared the method with others working on Zika at the LSHTM and elsewhere. |
| Title | Additional file 1: of Identifying mixed Mycobacterium tuberculosis infections from whole genome sequence data |
| Description | Strain information and full results table for clinically-derived Malawi samples, in silico replicate samples and Portuguese replicate samples. Lineage, total number of SNPs, number of heterozygous sites and the mixture analysis result for both Bayesian clustering and heterozygous sites approaches is included for each sample. (XLSX 162 kb) |
| Type Of Material | Database/Collection of data |
| Year Produced | 2018 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/Additional_file_1_of_Identifying_mixed_Mycobacterium_tu... |
| Title | Additional file 1: of Identifying mixed Mycobacterium tuberculosis infections from whole genome sequence data |
| Description | Strain information and full results table for clinically-derived Malawi samples, in silico replicate samples and Portuguese replicate samples. Lineage, total number of SNPs, number of heterozygous sites and the mixture analysis result for both Bayesian clustering and heterozygous sites approaches is included for each sample. (XLSX 162 kb) |
| Type Of Material | Database/Collection of data |
| Year Produced | 2018 |
| Provided To Others? | Yes |
| URL | https://springernature.figshare.com/articles/Additional_file_1_of_Identifying_mixed_Mycobacterium_tu... |
| Title | Replication Data for: Human Coronavirus NL63 Molecular Epidemiology and Evolutionary Patterns in Rural Coastal Kenya |
| Description | This dataset contains demographic and laboratory results of human corona virus for samples collected in a household survey study in rural coastal Kenya. Data was collected in December 2009 to June 2010. |
| Type Of Material | Database/Collection of data |
| Year Produced | 2018 |
| Provided To Others? | Yes |
| URL | https://dataverse.harvard.edu/citation?persistentId=doi:10.7910/DVN/62MTQC |
| Description | Collaboration with Pasteur Institute, Senegal |
| Organisation | Pasteur Institute Dakar |
| Country | Senegal |
| Sector | Charity/Non Profit |
| PI Contribution | Sequencing of Zika samples. |
| Collaborator Contribution | Contributing Zika samples from Senegal. |
| Impact | Transfer of samples. |
| Start Year | 2017 |
| Description | Malaria outbreak in Cape Verde |
| Organisation | New University of Lisbon |
| Department | Portuguese Institute of Hygiene and Tropical Medicine |
| Country | Portugal |
| Sector | Academic/University |
| PI Contribution | Genotyping of the mosquito and parasite samples from the 2017 malaria outbreak. |
| Collaborator Contribution | Contributed samples and epidemiological data, and local knowledge in Cape Verde. |
| Impact | A submitted manuscript, and training to Cape Verde scientists in genomic analysis. |
| Start Year | 2018 |
| Description | Outbreak support for the Ministry of Health, Cabo Verde |
| Organisation | Ministry of Health and Social Security, Cape Verde |
| Country | Cape Verde |
| Sector | Public |
| PI Contribution | We have provided genomics support to outbreak investigations in Cabo Verde. |
| Collaborator Contribution | They have provided clinical samples for sequence-based investigations and contributed to insights into infection control practice and policies. |
| Impact | The identification of pathogens circulating in Cabo Verde that are causing morbidity and infection outbreaks. |
| Start Year | 2021 |
| Description | Sequencing - GIS |
| Organisation | Agency for Science, Technology and Research (A*STAR) |
| Department | Genome Institute of Singapore |
| Country | Singapore |
| Sector | Academic/University |
| PI Contribution | Samples for pacino sequencing |
| Collaborator Contribution | Sequencing data. |
| Impact | Sequence data, and scientific publications. |
| Start Year | 2016 |
| Description | Zika virus diversity from mosquito and human samples - Lara Gomez |
| Organisation | Jean Piaget University of Cape Verde |
| Country | Cape Verde |
| Sector | Academic/University |
| PI Contribution | We have provided financial and technical resources to the collection of samples from Cape Verde. We will be providing whole genome sequencing training to a Cape Verde Phd student. |
| Collaborator Contribution | Providing samples and meta data. |
| Impact | To date, 1000 Aedes mosquitos and 800 sera and urine samples from volunteers. |
| Start Year | 2016 |
| Description | Cape Verde stakeholder meetings |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Local |
| Primary Audience | Study participants or study members |
| Results and Impact | An open meeting to discuss the objectives of the study (included Ministry of Health, WHO and Public Health representation). Also, there was a community walk-about with tee shirt and pamphlet promotion, as well as a radio interview to describe the study. |
| Year(s) Of Engagement Activity | 2016 |
| Description | Workshop on genomic data analysis in London |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | This was a 3 day infectious disease 'omics workshop in September 2019, which was attended by collaborators and students. |
| Year(s) Of Engagement Activity | 2019 |