Browsing by Author "McCarthy, Kerrigan"
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- 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.
- ItemEstablishment of outbreak thresholds for Hepatitis A in South Africa using laboratory surveillance, 2017–2020(MDPI, 2021) Prabdial-Sing, Nishi; Motaze, Nkengafac Villyen; Manamela, Jack; McCarthy, Kerrigan; Suchard, MelindaAs South Africa transitions from endemic to intermediate endemicity, hepatitis A surveillance needs strengthening to monitor trends in disease incidence and to identify outbreaks. We used passive laboratory-based surveillance data from the National Health Laboratory Services to calculate national hepatitis A incidence and to establish thresholds for outbreaks. Incidence was calculated by age and geographic location. The static threshold used two or three standard deviations (SDs) above the mean hepatitis A incidence in 2017–2019, and a cumulative summation (CuSum2) threshold used three SDs above the mean of the preceding seven months. These thresholds were applied to hepatitis A data for 2020. From 2017 to 2020, the mean incidence of hepatitis A IgM was 4.06/100,000 and ranged from 4.23 to 4.85/100,000 per year. Hepatitis A incidence was highest in the Western Cape province (WCP) (7.00–10.92/100,000 per year). The highest incidence was in the 1–9-year-olds. The incidence of hepatitis A in 2020 exceeded the static threshold in two districts of the WCP: Cape Winelands in January and Overberg district in August. The provincial incidence did not exceed the static and CuSum2 thresholds. District-level analysis using either threshold was sensitive enough to monitor trends and to alert district health authorities, allowing early outbreak responses.
- ItemHepatitis A virus seroprevalence in South Africa - Estimates using routine laboratory data, 2005–2015(Public Library of Science, 2019-06-26) Mazanderani, Ahmad Haeri; Motaze, Nkengafac Villyen; McCarthy, Kerrigan; Suchard, Melinda; Du Plessis, Nicolette MarieIntroduction: South Africa is considered highly endemic for hepatitis A virus (HAV) although few seroprevalence studies have been conducted over the past two decades. The World Health Organization recommends integrating HAV vaccination into national childhood immunization schedules where there is transition from high to intermediate endemicity. As a means of gauging age-specific rates of infection, we report HAV seroprevalence rates among specimens tested for HAV serology within South Africa’s public health sector from 2005–2015. Materials and methods: Hepatitis A serology results (Anti-HAV IgM, IgG and total antibody) from 2005–2015 were extracted from South Africa’s National Health Laboratory Service’s Corporate Data Warehouse (NHLS CDW), the central data repository of all laboratory test-sets within the public health sector. Results were extracted according to test-set, result, date of testing, health facility, name, surname, age, and sex. Anti-HAV IgG results were merged with total antibody results to reflect anti-HAV seroprevalence. Testing volume, positivity rates and age-specific anti-HAV seroprevalence rates by year and geographic distribution are described. Results and discussion: A total of 501 083 HAV IgM results were retrieved, of which 16 423 (3.3%) were positive, 484 259 (96.6%) negative and 401 (0.1%) equivocal; and 34 710 HAV total antibody/IgG tests of which 30 675 (88.4%) were positive, 4 020 (11.6%) negative and 15 equivocal. Whereas IgM positivity was highest among the 1–4 year age group (33.5%) and lowest among patients >45 years (<0.5%), total antibody positivity ranged from its lowest level of 52.7% in the 1–4 year age group increasing to levels of >90% only after 25 years of age. Conclusion: Anti-HAV total antibody testing within the South African public health sector demonstrates seroprevalence rates reach levels >90% only in adulthood, suggesting South Africa could be in transition from high to intermediate endemicity. Prospective studies with geographically representative sampling are required to confirm these findings and evaluate provincial and urban/rural heterogeneity.
- ItemMolecular characterisation and epidemiology of enterovirus-associated aseptic meningitis in the Western and Eastern Cape Provinces, South Africa 2018–2019(Elsevier B.V., 2021-04) Nkosi, Nokwazi; Preiser, Wolfgang; Van Zyl, Gert; Claassen, Mathilda; Cronje, Nadine; Maritz, Jean; Newman, Howard; McCarthy, Kerrigan; Ntshoe, Genevie; Essel, Vivien; Korsman, Stephen; Hardie, Diana; Smuts, HeidiBackground: Enteroviruses are amongst the most common causes of aseptic meningitis. Between November 2018 and May 2019, an outbreak of enterovirus-associated aseptic meningitis cases was noted in the Western and Eastern Cape Provinces, South Africa. Objectives: To describe the epidemiology and phylogeography of enterovirus infections during an aseptic meningitis outbreak in the Western and Eastern Cape Provinces of South Africa. Methods: Cerebrospinal fluid samples from suspected cases were screened using a polymerase chain reaction targeting the 5’UTR. Confirmed enterovirus-associated meningitis samples underwent molecular typing through species–specific VP1/VP2 primers and pan-species VP1 primers. Results: Between November 2018 and May 2019, 3497 suspected cases of aseptic meningitis were documented in the Western and Eastern Cape Provinces. Median age was 8 years (range 0–61), interquartile range (IQR=4–13 years), 405/735 (55%) male. 742/3497 (21%) cases were laboratory – confirmed enterovirus positive by routine diagnostic PCR targeting the 5’UTR. 128/742 (17%) underwent molecular typing by VP1 gene sequencing. Echovirus 4 (E4) was detected in 102/128 (80%) cases. Echovirus 9 was found in 7%, Coxsackievirus A13 in 3%. 10 genotypes contributed to the remaining 10% of cases. Synonymous mutations were found in most cases, with sporadic amino acid changes in 13 (12.7%) cases. Conclusion: The aseptic meningitis outbreak was associated with echovirus 4. Stool samples are valuable for molecular typing in CSF confirmed EV-associated aseptic meningitis.