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Article ; Online: Estimating household contact matrices structure from easily collectable metadata.

Dall'Amico, Lorenzo / Kleynhans, Jackie / Gauvin, Laetitia / Tizzoni, Michele / Ozella, Laura / Makhasi, Mvuyo / Wolter, Nicole / Language, Brigitte / Wagner, Ryan G / Cohen, Cheryl / Tempia, Stefano / Cattuto, Ciro

PloS one

2024 Volume 19, Issue 3, Page(s) e0296810

Abstract: Contact matrices are a commonly adopted data representation, used to develop compartmental models for epidemic spreading, accounting for the contact heterogeneities across age groups. Their estimation, however, is generally time and effort consuming and ... ...

Abstract	Contact matrices are a commonly adopted data representation, used to develop compartmental models for epidemic spreading, accounting for the contact heterogeneities across age groups. Their estimation, however, is generally time and effort consuming and model-driven strategies to quantify the contacts are often needed. In this article we focus on household contact matrices, describing the contacts among the members of a family and develop a parametric model to describe them. This model combines demographic and easily quantifiable survey-based data and is tested on high resolution proximity data collected in two sites in South Africa. Given its simplicity and interpretability, we expect our method to be easily applied to other contexts as well and we identify relevant questions that need to be addressed during the data collection procedure.
MeSH term(s)	Metadata ; Surveys and Questionnaires ; Epidemics ; Epidemiological Models ; South Africa ; Contact Tracing/methods
Language	English
Publishing date	2024-03-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0296810
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Correction: Transient increased risk of influenza infection following RSV infection in South Africa: findings from the PHIRST study, South Africa, 2016-2018.

Waterlow, Naomi R / Kleynhans, Jackie / Wolter, Nicole / Tempia, Stefano / Eggo, Rosalind M / Hellferscee, Orienka / Lebina, Limakatso / Martinson, Neil / Wagner, Ryan G / Moyes, Jocelyn / von Gottberg, Anne / Cohen, Cheryl / Flasche, Stefan

BMC medicine

2024 Volume 22, Issue 1, Page(s) 128

Language	English
Publishing date	2024-03-21
Publishing country	England
Document type	Published Erratum
ZDB-ID	2131669-7
ISSN	1741-7015 ; 1741-7015
ISSN (online)	1741-7015
ISSN	1741-7015
DOI	10.1186/s12916-024-03355-6
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Article ; Online: Comparison of multiple viral population characterization methods on a candidate cross-protection Citrus tristeza virus (CTV) source.

Kleynhans, Jackie / Pietersen, Gerhard

Journal of virological methods

2016 Volume 237, Page(s) 92–100

Abstract: Citrus tristeza virus (CTV) is the most economically important virus found on citrus and influences production worldwide. The 3' half of the RNA genome is generally conserved amongst sources, whereas the 5' portion is more divergent, allowing for the ... ...

Abstract	Citrus tristeza virus (CTV) is the most economically important virus found on citrus and influences production worldwide. The 3' half of the RNA genome is generally conserved amongst sources, whereas the 5' portion is more divergent, allowing for the classification of the virus into a number of genotypes based on sequence diversity. The acknowledged genotypes of CTV are continually being expanded, and thus far include T36, T30, T3, VT, B165, HA16-5, T68 and RB. The genotype composition of the CTV populations of a potential cross protection source in Mexican lime was studied whilst comparing different techniques of viral population characterization. Cloning and sequencing of an ORF 1a fragment, genotype specific RT-PCRs and Illumina sequencing of the p33 gene as well as RNA template enrichment through immuno-capture was done. Primers used in the cloning and sequencing proved to be biased towards detection of the VT genotype. RT-PCR and Illumina sequencing using the two different templates provided relatively comparable results, even though the immuno-captured enriched template provided less than expected CTV specific data, while the RT-PCRs and p33 sequencing cannot be used to make inferences about the rest of the genome; which may vary due to recombination. The source was found to contain multiple genotypes, including RB and VT. When choosing a characterization method, the features of the virus under study should be considered. It was found that Illumina sequencing offers an opportunity to gain a large amount of information regarding the entire viral genome, but challenges encountered are discussed.
MeSH term(s)	Citrus/virology ; Closterovirus/genetics ; Closterovirus/immunology ; Cross Protection ; DNA Primers ; Genetic Variation ; Genome, Viral ; Genotype ; Open Reading Frames ; Phylogeny ; Plant Diseases/immunology ; Plant Diseases/virology ; RNA, Viral/genetics ; Reverse Transcriptase Polymerase Chain Reaction/methods ; Sequence Analysis, DNA/instrumentation ; Sequence Analysis, DNA/methods
Chemical Substances	DNA Primers ; RNA, Viral
Keywords	covid19
Language	English
Publishing date	2016-11
Publishing country	Netherlands
Document type	Comparative Study ; Journal Article
ZDB-ID	8013-5
ISSN	1879-0984 ; 0166-0934
ISSN (online)	1879-0984
ISSN	0166-0934
DOI	10.1016/j.jviromet.2016.09.003
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Article ; Online: Estimated impact of the pneumococcal conjugate vaccine on pneumonia mortality in South Africa, 1999 through 2016: An ecological modelling study.

Kleynhans, Jackie / Tempia, Stefano / Shioda, Kayoko / von Gottberg, Anne / Weinberger, Daniel M / Cohen, Cheryl

PLoS medicine

2021 Volume 18, Issue 2, Page(s) e1003537

Abstract: Background: Data on the national-level impact of pneumococcal conjugate vaccine (PCV) introduction on mortality are lacking from Africa. PCV was introduced in South Africa in 2009. We estimated the impact of PCV introduction on all-cause pneumonia ... ...

Abstract	Background: Data on the national-level impact of pneumococcal conjugate vaccine (PCV) introduction on mortality are lacking from Africa. PCV was introduced in South Africa in 2009. We estimated the impact of PCV introduction on all-cause pneumonia mortality in South Africa, while controlling for changes in mortality due to other interventions. Methods and findings: We used national death registration data in South Africa from 1999 to 2016 to assess the impact of PCV introduction on all-cause pneumonia mortality in all ages, with the exclusion of infants aged <1 month. We created a composite (synthetic) control using Bayesian variable selection of nondiarrheal, nonpneumonia, and nonpneumococcal deaths to estimate the number of expected all-cause pneumonia deaths in the absence of PCV introduction post 2009. We compared all-cause pneumonia deaths from the death registry to the expected deaths in 2012 to 2016. We also estimated the number of prevented deaths during 2009 to 2016. Of the 9,324,638 deaths reported in South Africa from 1999 to 2016, 12·6% were pneumonia-related. Compared to number of deaths expected, we estimated a 33% (95% credible interval (CrI) 26% to 43%), 23% (95%CrI 17% to 29%), 25% (95%CrI 19% to 32%), and 23% (95%CrI 11% to 32%) reduction in pneumonia mortality in children aged 1 to 11 months, 1 to 4 years, 5 to 7 years, and 8 to 18 years in 2012 to 2016, respectively. In total, an estimated 18,422 (95%CrI 12,388 to 26,978) pneumonia-related deaths were prevented from 2009 to 2016 in children aged <19 years. No declines were estimated observed among adults following PCV introduction. This study was mainly limited by coding errors in original data that could have led to a lower impact estimate, and unmeasured factors could also have confounded estimates. Conclusions: This study found that the introduction of PCV was associated with substantial reduction in all-cause pneumonia deaths in children aged 1 month to <19 years. The model predicted an effect of PCV in age groups who were eligible for vaccination (1 months to 4 years), and an indirect effect in those too old (8 to 18 years) to be vaccinated. These findings support sustaining pneumococcal vaccination to reduce pneumonia-related mortality in children.
MeSH term(s)	Adolescent ; Adult ; Bayes Theorem ; Child ; Child, Preschool ; Humans ; Infant ; Male ; Pneumococcal Infections/mortality ; Pneumococcal Infections/prevention & control ; Pneumococcal Vaccines/immunology ; Pneumococcal Vaccines/pharmacology ; Pneumonia/mortality ; Pneumonia/prevention & control ; South Africa ; Streptococcus pneumoniae/pathogenicity ; Vaccination/statistics & numerical data ; Vaccines, Conjugate/pharmacology ; Young Adult
Chemical Substances	Pneumococcal Vaccines ; Vaccines, Conjugate
Language	English
Publishing date	2021-02-16
Publishing country	United States
Document type	Journal Article
ZDB-ID	2185925-5
ISSN	1549-1676 ; 1549-1277
ISSN (online)	1549-1676
ISSN	1549-1277
DOI	10.1371/journal.pmed.1003537
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Article: Comparison of multiple viral population characterization methods on a candidate cross-protection Citrus tristeza virus (CTV) source

Kleynhans, Jackie / Gerhard Pietersen

Journal of virological methods. 2016 Nov., v. 237

2016

Abstract: Citrus tristeza virus (CTV) is the most economically important virus found on citrus and influences production worldwide. The 3â² half of the RNA genome is generally conserved amongst sources, whereas the 5â² portion is more divergent, allowing for the ...

Abstract	Citrus tristeza virus (CTV) is the most economically important virus found on citrus and influences production worldwide. The 3â² half of the RNA genome is generally conserved amongst sources, whereas the 5â² portion is more divergent, allowing for the classification of the virus into a number of genotypes based on sequence diversity. The acknowledged genotypes of CTV are continually being expanded, and thus far include T36, T30, T3, VT, B165, HA16-5, T68 and RB. The genotype composition of the CTV populations of a potential cross protection source in Mexican lime was studied whilst comparing different techniques of viral population characterization. Cloning and sequencing of an ORF 1a fragment, genotype specific RT-PCRs and Illumina sequencing of the p33 gene as well as RNA template enrichment through immuno-capture was done. Primers used in the cloning and sequencing proved to be biased towards detection of the VT genotype. RT-PCR and Illumina sequencing using the two different templates provided relatively comparable results, even though the immuno-captured enriched template provided less than expected CTV specific data, while the RT-PCRs and p33 sequencing cannot be used to make inferences about the rest of the genome; which may vary due to recombination. The source was found to contain multiple genotypes, including RB and VT. When choosing a characterization method, the features of the virus under study should be considered. It was found that Illumina sequencing offers an opportunity to gain a large amount of information regarding the entire viral genome, but challenges encountered are discussed.
Keywords	Citrus ; Citrus tristeza virus ; cross immunity ; genes ; genotype ; molecular cloning ; open reading frames ; reverse transcriptase polymerase chain reaction ; RNA ; sequence diversity ; viruses ; covid19
Language	English
Dates of publication	2016-11
Size	p. 92-100.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	8013-5
ISSN	1879-0984 ; 0166-0934
ISSN (online)	1879-0984
ISSN	0166-0934
DOI	10.1016/j.jviromet.2016.09.003
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Association of close-range contact patterns with SARS-CoV-2: a household transmission study.

Kleynhans, Jackie / Dall'Amico, Lorenzo / Gauvin, Laetitia / Tizzoni, Michele / Maloma, Lucia / Walaza, Sibongile / Martinson, Neil A / von Gottberg, Anne / Wolter, Nicole / Makhasi, Mvuyo / Cohen, Cheryl / Cattuto, Ciro / Tempia, Stefano

eLife

2023 Volume 12

Abstract: Background: Households are an important location for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, especially during periods when travel and work was restricted to essential services. We aimed to assess the association of ... ...

Abstract	Background: Households are an important location for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, especially during periods when travel and work was restricted to essential services. We aimed to assess the association of close-range contact patterns with SARS-CoV-2 transmission. Methods: We deployed proximity sensors for two weeks to measure face-to-face interactions between household members after SARS-CoV-2 was identified in the household, in South Africa, 2020-2021. We calculated the duration, frequency, and average duration of close-range proximity events with SARS-CoV-2 index cases. We assessed the association of contact parameters with SARS-CoV-2 transmission using mixed effects logistic regression accounting for index and household member characteristics. Results: We included 340 individuals (88 SARS-CoV-2 index cases and 252 household members). On multivariable analysis, factors associated with SARS-CoV-2 acquisition were index cases with minimum C Conclusions: We did not find an association between close-range proximity events and SARS-CoV-2 household transmission. Our findings may be due to study limitations, that droplet-mediated transmission during close-proximity contacts plays a smaller role than airborne transmission of SARS-CoV-2 in the household, or due to high contact rates in households. Funding: Wellcome Trust (Grant number 221003/Z/20/Z) in collaboration with the Foreign, Commonwealth, and Development Office, United Kingdom.
MeSH term(s)	Humans ; Female ; SARS-CoV-2 ; COVID-19/epidemiology ; Family Characteristics ; Travel ; South Africa/epidemiology
Language	English
Publishing date	2023-07-18
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.84753
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Article ; Online: Transient increased risk of influenza infection following RSV infection in South Africa: findings from the PHIRST study, South Africa, 2016-2018.

BMC medicine

2023 Volume 21, Issue 1, Page(s) 441

Abstract: Background: Large-scale prevention of respiratory syncytial virus (RSV) infection may have ecological consequences for co-circulating pathogens, including influenza. We assessed if and for how long RSV infection alters the risk for subsequent influenza ... ...

Abstract	Background: Large-scale prevention of respiratory syncytial virus (RSV) infection may have ecological consequences for co-circulating pathogens, including influenza. We assessed if and for how long RSV infection alters the risk for subsequent influenza infection. Methods: We analysed a prospective longitudinal cohort study conducted in South Africa between 2016 and 2018. For participating households, nasopharyngeal samples were taken twice weekly, irrespective of symptoms, across three respiratory virus seasons, and real-time polymerase chain reaction (PCR) was used to identify infection with RSV and/or influenza. We fitted an individual-level hidden Markov transmission model in order to estimate RSV and influenza infection rates and their interdependence. Results: Of a total of 122,113 samples collected, 1265 (1.0%) were positive for influenza and 1002 (0.8%) positive for RSV, with 15 (0.01%) samples from 12 individuals positive for both influenza and RSV. We observed a 2.25-fold higher incidence of co-infection than expected if assuming infections were unrelated. We estimated that infection with influenza is 2.13 (95% CI 0.97-4.69) times more likely when already infected with, and for a week following, RSV infection, adjusted for age. This equates to 1.4% of influenza infections that may be attributable to RSV in this population. Due to the local seasonality (RSV season precedes the influenza season), we were unable to estimate changes in RSV infection risk following influenza infection. Conclusions: We find no evidence to suggest that RSV was associated with a subsequent reduced risk of influenza infection. Instead, we observed an increased risk for influenza infection for a short period after infection. However, the impact on population-level transmission dynamics of this individual-level synergistic effect was not measurable in this setting.
MeSH term(s)	Humans ; Influenza, Human/epidemiology ; Influenza, Human/complications ; Longitudinal Studies ; South Africa/epidemiology ; Prospective Studies ; Respiratory Syncytial Virus Infections/epidemiology ; Seasons
Language	English
Publishing date	2023-11-15
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	2131669-7
ISSN	1741-7015 ; 1741-7015
ISSN (online)	1741-7015
ISSN	1741-7015
DOI	10.1186/s12916-023-03100-5
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Article ; Online: Cytokine response in cerebrospinal fluid of meningitis patients and outcome associated with pneumococcal serotype.

Müller, Annelies / Schramm, Diana B / Kleynhans, Jackie / de Gouveia, Linda / Meiring, Susan / Ramette, Alban / von Gottberg, Anne / Hathaway, Lucy Jane

Scientific reports

2021 Volume 11, Issue 1, Page(s) 19920

Abstract: Streptococcus pneumoniae causes life-threatening meningitis. Its capsular polysaccharide determines the serotype and influences disease severity but the mechanism is largely unknown. Due to evidence of elevated cytokines levels in the meningeal ... ...

Abstract	Streptococcus pneumoniae causes life-threatening meningitis. Its capsular polysaccharide determines the serotype and influences disease severity but the mechanism is largely unknown. Due to evidence of elevated cytokines levels in the meningeal inflammatory response, we measured 41 cytokines/chemokines and growth factors in cerebrospinal fluid (CSF) samples from 57 South African meningitis patients (collected in the period 2018-2019), with confirmed S. pneumoniae serotypes, using a multiplexed bead-based immunoassay. Based on multivariable Bayesian regression, using serotype 10A as a reference and after adjusting for HIV and age, we found IL-6 concentrations significantly lower in patients infected with serotypes 6D (undetectable) and 23A (1601 pg/ml), IL-8 concentrations significantly higher in those infected with 22A (40,459 pg/ml), 7F (32,400 pg/ml) and 15B/C (6845 pg/ml), and TNFα concentration significantly higher in those infected with serotype 18A (33,097 pg/ml). Although a relatively small number of clinical samples were available for this study and 28% of samples could not be assigned to a definitive serotype, our data suggests 15B/C worthy of monitoring during surveillance as it is associated with in-hospital case fatality and not included in the 13-valent polysaccharide conjugate vaccine, PCV13. Our data provides average CSF concentrations of a range of cytokines and growth factors for 18 different serotypes (14, 19F, 3, 6A, 7F, 19A, 8, 9N, 10A, 12F, 15B/C, 22F, 16F, 23A, 31, 18A, 6D, 22A) to serve as a basis for future studies investigating host-pathogen interaction during pneumococcal meningitis. We note that differences in induction of IL-8 between serotypes may be particularly worthy of future study.
MeSH term(s)	Adolescent ; Adult ; Aged ; Biomarkers ; Child ; Child, Preschool ; Cytokines/cerebrospinal fluid ; Female ; Humans ; Infant ; Infant, Newborn ; Inflammation Mediators/cerebrospinal fluid ; Male ; Meningitis, Pneumococcal/cerebrospinal fluid ; Meningitis, Pneumococcal/epidemiology ; Meningitis, Pneumococcal/microbiology ; Meningitis, Pneumococcal/mortality ; Middle Aged ; Mortality ; Prognosis ; Public Health Surveillance ; Serogroup ; South Africa/epidemiology ; Streptococcus pneumoniae/classification ; Young Adult
Chemical Substances	Biomarkers ; Cytokines ; Inflammation Mediators
Language	English
Publishing date	2021-10-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-021-99190-3
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Article ; Online: Streptococcus pneumoniae Serotypes Associated with Death, South Africa, 2012-2018.

Müller, Annelies / Kleynhans, Jackie / de Gouveia, Linda / Meiring, Susan / Cohen, Cheryl / Hathaway, Lucy Jane / von Gottberg, Anne

Emerging infectious diseases

2021 Volume 28, Issue 1, Page(s) 166–179

Abstract: The Streptococcus pneumoniae polysaccharide capsule plays a role in disease severity. We assessed the association of serotype with case-fatality ratio (CFR) in invasive pneumococcal disease (IPD) and meningitis in South Africa, 2012-2018 (vaccine era), ... ...

Abstract	The Streptococcus pneumoniae polysaccharide capsule plays a role in disease severity. We assessed the association of serotype with case-fatality ratio (CFR) in invasive pneumococcal disease (IPD) and meningitis in South Africa, 2012-2018 (vaccine era), using multivariable logistic regression by manual backward elimination. The most common serotypes causing IPD were 8 and 19A. In patients <15 years of age, serotypes associated with increased CFR in IPD, compared with serotype 8 and controlling for confounding factors, were 11A, 13, 19F, 15A, and 6A. None of these serotypes were associated with increased CFR in meningitis. Among IPD patients >15 years of age, serotype 15B/C was associated with increased CFR. Among meningitis patients of all ages, serotype 1 was associated with increased CFR. PCV13 serotypes 1, 3, 6A, 19A, and 19F should be monitored, and serotypes 8, 12F, 15A, and 15B/C should be considered for inclusion in vaccines to reduce deaths caused by S. pneumoniae.
MeSH term(s)	Humans ; Infant ; Pneumococcal Infections/epidemiology ; Pneumococcal Vaccines ; Serogroup ; South Africa/epidemiology ; Streptococcus pneumoniae
Chemical Substances	Pneumococcal Vaccines
Language	English
Publishing date	2021-12-06
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	1380686-5
ISSN	1080-6059 ; 1080-6040
ISSN (online)	1080-6059
ISSN	1080-6040
DOI	10.3201/eid2801.210956
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Article ; Online: Incidence and transmission of respiratory syncytial virus in urban and rural South Africa, 2017-2018.

Nature communications

2024 Volume 15, Issue 1, Page(s) 116

Abstract: Data on respiratory syncytial virus (RSV) incidence and household transmission are limited. To describe RSV incidence and transmission, we conducted a prospective cohort study in rural and urban communities in South Africa over two seasons during 2017- ... ...

Abstract	Data on respiratory syncytial virus (RSV) incidence and household transmission are limited. To describe RSV incidence and transmission, we conducted a prospective cohort study in rural and urban communities in South Africa over two seasons during 2017-2018. Nasopharyngeal swabs were collected twice-weekly for 10 months annually and tested for RSV using PCR. We tested 81,430 samples from 1,116 participants in 225 households (follow-up 90%). 32% (359/1116) of individuals had ≥1 RSV infection; 10% (37/359) had repeat infection during the same season, 33% (132/396) of infections were symptomatic, and 2% (9/396) sought medical care. Incidence was 47.2 infections/100 person-years and highest in children <5 years (78.3). Symptoms were commonest in individuals aged <12 and ≥65 years. Individuals 1-12 years accounted for 55% (134/242) of index cases. Household cumulative infection risk was 11%. On multivariable analysis, index cases with ≥2 symptoms and shedding duration >10 days were more likely to transmit; household contacts aged 1-4 years vs. ≥65 years were more likely to acquire infection. Within two South African communities, RSV attack rate was high, and most infections asymptomatic. Young children were more likely to introduce RSV into the home, and to be infected. Future studies should examine whether vaccines targeting children aged <12 years could reduce community transmission.
MeSH term(s)	Child ; Humans ; Infant ; Child, Preschool ; Incidence ; South Africa/epidemiology ; Prospective Studies ; Respiratory Syncytial Virus, Human/genetics ; Respiratory Syncytial Virus Infections
Language	English
Publishing date	2024-01-02
Publishing country	England
Document type	Journal Article
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-023-44275-y
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