Browsing by Author "Nicol, Mark P."
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- ItemCurrent knowledge and future research directions on fecal bacterial patterns and their association with asthma(Frontiers Media, 2016) Claassen-Weitz, Shantelle; Wiysonge, Charles S.; Machingaidze, Shingai; Thabane, Lehana; Horsnell, William G. C.; Zar, Heather J.; Nicol, Mark P.; Kaba, MamadouENGLISH SUMMARY : Asthma is a complex respiratory condition that involves interplay between genetic predisposition, environmental, and immunological factors (Edwards et al., 2012). It is considered to be one of the most common chronic diseases, affecting ~300 million people (Masoli et al., 2004), and causing an estimated 250,000 deaths annually (Bateman et al., 2008). Furthermore, because of an increased Westernized lifestyle and urbanization in developing countries, it is estimated that by 2025 the global burden of asthma will increase by 100 million people (Masoli et al., 2004).
- ItemEffect of Xpert MTB/RIF on clinical outcomes in routine care settings : individual patient data meta-analysis(Elsevier, 2019-02) Di Tanna, Gian Luca; Khaki, Ali Raza; Theron, Grant; McCarthy, Kerrigan; Cox, Helen; Mupfumi, Lucy; Trajman, Anete; Mason, Peter; Bandason, Tsitsi; Durovni, Betina; Bara, Wilbert; Hoelscher, Michael; Clowes, Petra; Mangu, Chacha; Chanda, Duncan; Pym, Alexander; Mwaba, Peter; Cobelens, Frank; Nicol, Mark P.; Dheda, Keertan; Churchyard, Gavin; Fielding, Katherine; Metcalfe, John Z.Background: Xpert MTB/RIF, the most widely used automated nucleic acid amplification test for tuberculosis, is available in more than 130 countries. Although diagnostic accuracy is well documented, anticipated improvements in patient outcomes have not been clearly identified. We performed an individual patient data meta-analysis to examine improvements in patient outcomes associated with Xpert MTB/RIF. Methods: We searched PubMed, Embase, ClinicalTrials.gov, and the Pan African Clinical Trials Registry from inception to Feb 1, 2018, for randomised controlled trials (RCTs) comparing the use of Xpert MTB/RIF with sputum smear microscopy as tests for tuberculosis diagnosis in adults (aged 18 years or older). We excluded studies of patients with extrapulmonary tuberculosis, and studies in which mortality was not assessed. We used a two-stage approach for our primary analysis and a one-stage approach for the sensitivity analysis. To assess the primary outcome of cumulative 6-month all-cause mortality, we first performed logistic regression models (random effects for cluster randomised trials, with robust SEs for multicentre studies) for each trial, and then pooled the odds ratio (OR) estimates by a fixed-effects (inverse variance) or random-effects (Der Simonian Laird) meta-analysis. We adjusted for age and gender, and stratified by HIV status and previous tuberculosis-treatment history. The study protocol has been registered with PROSPERO, number CRD42014013394. Findings Our search identified 387 studies, of which five RCTs were eligible for analysis. 8567 adult clinic attendees (4490 [63·5%] of 7074 participants for whom data were available were HIV-positive) were tested for tuberculosis with Xpert MTB/RIF (Xpert group) versus sputum smear microscopy (sputum smear group), across five low-income and middle-income countries (South Africa, Brazil, Zimbabwe, Zambia, and Tanzania). The primary outcome (reported in three studies) occurred in 182 (4·5%) of 4050 patients in the Xpert group and 217 (5·3%) of 4093 patients in the smear group (pooled adjusted OR 0·88, 95% CI 0·68–1·14 [p=0·34]; for HIV-positive individuals OR 0·83, 0·65–1·05 [p=0·12]). Kaplan-Meier estimates showed a lower rate of death (12·73 per 100 person-years in the Xpert group vs 16·38 per 100 person-years in the sputum smear group) for HIV-positive patients (hazard ratio 0·76, 95% CI 0·60–0·97; p=0·03). The risk of bias was assessed as reasonable and the statistical heterogeneity across studies was low (I²<20% for the primary outcome). Interpretation Despite individual patient data analysis from five RCTs, we were unable to confidently rule in nor rule out an Xpert MTB/RIF-associated reduction in mortality among outpatients tested for tuberculosis. Reduction in mortality among HIV-positive patients in a secondary analysis suggests the possibility of population-level impact.
- ItemHIV-exposure, early life feeding practices and delivery mode impacts on faecal bacterial profiles in a South African birth cohort(Nature Research, 2018) Claassen-Weitz, Shantelle; Gardner-Lubbe, Sugnet; Nicol, Paul; Botha, Gerrit; Mounaud, Stephanie; Shankar, Jyoti; Nierman, William C.; Mulder, Nicola; Budree, Shrish; Zar, Heather J.; Nicol, Mark P.; Kaba, MamadouThere are limited data on meconium and faecal bacterial profiles from African infants and their mothers. We characterized faecal bacterial communities of infants and mothers participating in a South African birth cohort. Stool and meconium specimens were collected from 90 mothers and 107 infants at birth, and from a subset of 72 and 36 infants at 4–12 and 20–28 weeks of age, respectively. HIV-unexposed infants were primarily exclusively breastfed at 4–12 (49%, 26/53) and 20–28 weeks (62%, 16/26). In contrast, HIV-exposed infants were primarily exclusively formula fed at 4–12 (53%; 10/19) and 20–28 weeks (70%, 7/10). Analysis (of the bacterial 16S rRNA gene sequences of the V4 hypervariable region) of the 90 mother-infant pairs showed that meconium bacterial profiles [dominated by Proteobacteria (89%)] were distinct from those of maternal faeces [dominated by Firmicutes (66%) and Actinobacteria (15%)]. Actinobacteria predominated at 4–12 (65%) and 20–28 (50%) weeks. HIV-exposed infants had significantly higher faecal bacterial diversities at both 4–12 (p = 0.026) and 20–28 weeks (p = 0.002). HIV-exposed infants had lower proportions of Bifidobacterium (p = 0.010) at 4–12 weeks. Maternal faecal bacterial profiles were influenced by HIV status, feeding practices and mode of delivery. Further longitudinal studies are required to better understand how these variables influence infant and maternal faecal bacterial composition.
- ItemIndoor air pollution and tobacco smoke exposure : impact on nasopharyngeal bacterial carriage in mothers and infants in an African birth cohort study(European Respiratory Society, 2019) Vanker, Aneesa; Nduru, Polite M.; Barnett, Whitney; Dube, Felix S.; Sly, Peter D.; Gie, Robert P.; Nicol, Mark P.; Zar, Heather J.ENGLISH ABSTRACT: Indoor air pollution (IAP) or environmental tobacco smoke (ETS) exposure may influence nasopharyngeal carriage of bacterial species and development of lower respiratory tract infection (LRTI). The aim of this study was to longitudinally investigate the impact of antenatal or postnatal IAP/ETS exposure on nasopharyngeal bacteria in mothers and infants. A South African cohort study followed mother–infant pairs from birth through the first year. Nasopharyngeal swabs were taken at birth, 6 and 12 months for bacterial culture. Multivariable and multivariate Poisson regression investigated associations between nasopharyngeal bacterial species and IAP/ETS. IAP exposures (particulate matter, carbon monoxide, nitrogen dioxide, volatile organic compounds) were measured at home visits. ETS exposure was measured through maternal and infant urine cotinine. Infants received the 13-valent pneumococcal and Haemophilus influenzae B conjugate vaccines. There were 881 maternal and 2605 infant nasopharyngeal swabs. Antenatal ETS exposure was associated with Streptococcus pneumoniae carriage in mothers (adjusted risk ratio (aRR) 1.73 (95% CI 1.03–2.92)) while postnatal ETS exposure was associated with carriage in infants (aRR 1.14 (95% CI 1.00–1.30)) Postnatal particulate matter exposure was associated with the nasopharyngeal carriage of H. influenzae (aRR 1.68 (95% CI 1.10– 2.57)) or Moraxella catarrhalis (aRR 1.42 (95% CI 1.03–1.97)) in infants. Early-life environmental exposures are associated with an increased prevalence of specific nasopharyngeal bacteria during infancy, which may predispose to LRTI.
- ItemInfluence of socio-economic and psychosocial profiles on the human breast milk bacteriome of South African women(MDPI, 2019-06-20) Ojo-Okunola, Anna; Claassen-Weitz, Shantelle; Mwaikono, Kilaza S.; Lubbe, Sugnet, 1973-; Stein, Dan J.; Zar, Heather J.; Nicol, Mark P.; Du Toit, ElloiseThe human breast milk (HBM) bacteriome is an important, continuous source of microbes to the neonate in early life, playing an important role in shaping the infant’s intestinal bacteriome. Study of the composition of the HBM bacteriome is an emerging area of research, with little information available, particularly from low- and middle-income countries. The aim of this study was to characterize the diversity of bacterial communities in HBM samples collected between 6–10 weeks postpartum from lactating South African women and to study potential influencing factors of the bacteriome. Using 16S rRNA gene sequencing of samples from 554 women, we demonstrated that the HBM bacteriome was largely dominated by the phyla Firmicutes (mean relative abundance: 71.1%) and Actinobacteria (mean relative abundance: 16.4%). The most abundant genera identified from the HBM bacteriome were Streptococcus (mean relative abundance: 48.6%), Staphylococcus (mean relative abundance: 17.8%), Rothia (mean relative abundance: 5.8%), and Corynebacterium (mean relative abundance: 4.3%). “Core” bacterial genera including Corynebacterium, Streptococcus, Staphylococcus, Rothia, Veillonella, Gemella, Acinetobacter, Micrococcus and a genus belonging to the Enterobacteriaceae family were present in 80% of samples. HBM samples were classified, according to their bacteriome, into three major clusters, dominated by the genera Staphylococcus (cluster 1), a combination of Staphylococcus and Streptococcus (cluster 2), and Streptococcus (cluster 3). The cluster groups differed significantly for Shannon and chao1 richness indices. Bacterial interactions were studied using co-occurrence networks with positive associations observed between the abundances of Staphylococcus and Corynebacteria (members of the skin microflora) and between Streptococcus, Rothia, Veillonella, and Gemella (members of the oral microflora). HBM from older mothers had a higher Shannon diversity index. The study site was associated with differences in HBM bacteriome composition (permutational multivariate analysis of variance using distance matrices (PERMANOVA), p < 0.05). No other tested socio-demographic or psychosocial factors were associated with HBM bacterial composition.
- ItemLongitudinal population dynamics of staphylococcus aureus in the nasopharynx during the first year of life(Frontiers Media, 2019) Abdulgader, Shima M.; Robberts, Lourens; Ramjith, Jordache; Nduru, Polite M.; Dube, Felix; Lubbe, Sugnet, 1973-; Zar, Heather J.; Nicol, Mark P.Background: Staphylococcus aureus colonization is a risk factor for invasive disease. Few studies have used strain genotype data to study S. aureus acquisition and carriage patterns. We investigated S. aureus nasopharyngeal carriage in infants in an intensively sampled South African birth cohort. Methods: Nasopharyngeal swabs were collected at birth and fortnightly from 137 infants through their first year of life. S. aureus was characterized by spa-typing. The incidence of S. aureus acquisition, and median carriage duration for each genotype was determined. S. aureus carriage patterns were defined by combining the carrier index (proportion of samples testing positive for S. aureus) with genotype diversity measures. Persistent or prolonged carriage were defined by a carrier index ≥0.8 or ≥0.5, respectively. Risk factors for time to acquisition of S. aureus were determined. Results: Eighty eight percent (121/137) of infants acquired S. aureus at least once. The incidence of acquisition at the species and genotype level was 1.83 and 2.8 episodes per child-year, respectively. No children had persistent carriage (defined as carrier index of >0.8). At the species level 6% had prolonged carriage, while only 2% had prolonged carriage with the same genotype. Carrier index correlated with the absolute number of spa-CCs carried by each infant (r = 0.5; 95% CI 0.35–0.62). Time to first acquisition of S. aureus was shorter in children from households with ≥5 individuals (HR 1.06, 95% CI 1.07–1.43), with S. aureus carrier mothers (HR; 1.5, 95% CI 1.2–2.47), or with a positive tuberculin skin test during the first year of life (HR; 1.81, 95% CI 0.97–3.3). Conclusion: Using measures of genotype diversity, we showed that S. aureus NP carriage is highly dynamic in infants. Prolonged carriage with a single strain occurred rarely; persistent carriage was not observed. A correlation was observed between carrier index and genotype diversity.
- ItemMolecular epidemiology of Staphylococcus aureus in African children from rural and urban communities with atopic dermatitis(BMC (part of Springer Nature), 2021-04-13) Ndhlovu, Gillian O. N.; Abotsi, Regina E.; Shittu, Adebayo O.; Abdulgader, Shima M.; Jamrozy, Dorota; Dupont, Christopher L.; Mankahla, Avumile; Nicol, Mark P.; Hlela, Carol; Levin, Michael E.; Lunjani, Nonhlanhla; Dube, Felix S.Background: Staphylococcus aureus has been associated with the exacerbation and severity of atopic dermatitis (AD). Studies have not investigated the colonisation dynamics of S. aureus lineages in African toddlers with AD. We determined the prevalence and population structure of S. aureus in toddlers with and without AD from rural and urban South African settings. Methods: We conducted a study of AD-affected and non-atopic AmaXhosa toddlers from rural Umtata and urban Cape Town, South Africa. S. aureus was screened from skin and nasal specimens using established microbiological methods and clonal lineages were determined by spa typing. Logistic regression analyses were employed to assess risk factors associated with S. aureus colonisation. Results: S. aureus colonisation was higher in cases compared to controls independent of geographic location (54% vs. 13%, p < 0.001 and 70% vs. 35%, p = 0.005 in Umtata [rural] and Cape Town [urban], respectively). Severe AD was associated with higher colonisation compared with moderate AD (86% vs. 52%, p = 0.015) among urban cases. Having AD was associated with colonisation in both rural (odds ratio [OR] 7.54, 95% CI 2.92–19.47) and urban (OR 4.2, 95% CI 1.57–11.2) toddlers. In rural toddlers, living in an electrified house that uses gas (OR 4.08, 95% CI 1.59– 10.44) or utilises kerosene and paraffin (OR 2.88, 95% CI 1.22–6.77) for heating and cooking were associated with increased S. aureus colonisation. However, exposure to farm animals (OR 0.3, 95% CI 0.11–0.83) as well as living in a house that uses wood and coal (OR 0.14, 95% CI 0.04–0.49) or outdoor fire (OR 0.31, 95% CI 0.13–0.73) were protective. Spa types t174 and t1476, and t272 and t1476 were dominant among urban and rural cases, respectively, but no main spa type was observed among controls, independent of geographic location. In urban cases, spa type t002 and t442 isolates were only identified in severe AD, t174 was more frequent in moderate AD, and t1476 in severe AD. Conclusion: The strain genotype of S. aureus differed by AD phenotypes and rural-urban settings. Continued surveillance of colonising S. aureus lineages is key in understanding alterations in skin microbial composition associated with AD pathogenesis and exacerbation.
- ItemOptimizing 16S rRNA gene profile analysis from low biomass nasopharyngeal and induced sputum specimens(BMC (part of Springer Nature), 2020-05-12) Claassen-Weitz, Shantelle; Gardner-Lubbe, Sugnet; Mwaikono, Kilaza S.; Du Toit, Elloise; Zar, Heather J.; Nicol, Mark P.Background: Careful consideration of experimental artefacts is required in order to successfully apply highthroughput 16S ribosomal ribonucleic acid (rRNA) gene sequencing technology. Here we introduce experimental design, quality control and “denoising” approaches for sequencing low biomass specimens. Results: We found that bacterial biomass is a key driver of 16S rRNA gene sequencing profiles generated from bacterial mock communities and that the use of different deoxyribonucleic acid (DNA) extraction methods [DSP Virus/Pathogen Mini Kit® (Kit-QS) and ZymoBIOMICS DNA Miniprep Kit (Kit-ZB)] and storage buffers [PrimeStore® Molecular Transport medium (Primestore) and Skim-milk, Tryptone, Glucose and Glycerol (STGG)] further influence these profiles. Kit-QS better represented hard-to-lyse bacteria from bacterial mock communities compared to Kit-ZB. Primestore storage buffer yielded lower levels of background operational taxonomic units (OTUs) from low biomass bacterial mock community controls compared to STGG. In addition to bacterial mock community controls, we used technical repeats (nasopharyngeal and induced sputum processed in duplicate, triplicate or quadruplicate) to further evaluate the effect of specimen biomass and participant age at specimen collection on resultant sequencing profiles. We observed a positive correlation (r = 0.16) between specimen biomass and participant age at specimen collection: low biomass technical repeats (represented by < 500 16S rRNA gene copies/μl) were primarily collected at < 14 days of age. We found that low biomass technical repeats also produced higher alpha diversities (r = − 0.28); 16S rRNA gene profiles similar to no template controls (Primestore); and reduced sequencing reproducibility. Finally, we show that the use of statistical tools for in silico contaminant identification, as implemented through the decontam package in R, provides better representations of indigenous bacteria following decontamination. Conclusions: We provide insight into experimental design, quality control steps and “denoising” approaches for 16S rRNA gene high-throughput sequencing of low biomass specimens. We highlight the need for careful assessment of DNA extraction methods and storage buffers; sequence quality and reproducibility; and in silico identification of contaminant profiles in order to avoid spurious results.
- ItemScreening for HIV-associated tuberculosis and rifampicin resistance before antiretroviral therapy using the Xpert MTB/RIF assay : a prospective study(Public Library of Science, 2011-07-26) Lawn, Stephen D.; Brooks, Sophie V.; Kranzer, Katharina; Nicol, Mark P.; Whitelaw, Andrew; Vogt, Monica; Bekker, Linda-Gail; Wood, RobinBackground: The World Health Organization has endorsed the Xpert MTB/RIF assay for investigation of patients suspected of having tuberculosis (TB). However, its utility for routine TB screening and detection of rifampicin resistance among HIV-infected patients with advanced immunodeficiency enrolling in antiretroviral therapy (ART) services is unknown. Methods and Findings: Consecutive adult HIV-infected patients with no current TB diagnosis enrolling in an ART clinic in a South African township were recruited regardless of symptoms. They were clinically characterised and invited to provide two sputum samples at a single visit. The accuracy of the Xpert MTB/RIF assay for diagnosing TB and drug resistance was assessed in comparison with other tests, including fluorescence smear microscopy and automated liquid culture (gold standard) and drug susceptibility testing. Of 515 patients enrolled, 468 patients (median CD4 cell count, 171 cells/μl; interquartile range, 102-236) produced at least one sputum sample, yielding complete sets of results from 839 samples. Mycobacterium tuberculosis was cultured from 81 patients (TB prevalence, 17.3%). The overall sensitivity of the Xpert MTB/RIF assay for culture-positive TB was 73.3% (specificity, 99.2%) compared to 28.0% (specificity, 100%) using smear microscopy. All smear-positive, culture-positive disease was detected by Xpert MTB/RIF from a single sample (sensitivity, 100%), whereas the sensitivity for smear-negative, culture-positive TB was 43.4% from one sputum sample and 62.3% from two samples. Xpert correctly identified rifampicin resistance in all four cases of multidrug-resistant TB but incorrectly identified resistance in three other patients whose disease was confirmed to be drug sensitive by gene sequencing (specificity, 94.1%; positive predictive value, 57%). Conclusions: In this population of individuals at high risk of TB, intensive screening using the Xpert MTB/RIF assay increased case detection by 45% compared with smear microscopy, strongly supporting replacement of microscopy for this indication. However, despite the ability of the assay to rapidly detect rifampicin-resistant disease, the specificity for drug-resistant TB was sub-optimal. © 2011 Lawn et al.