Is there an association between trimethoprim-sulfamethoxazole use as prophylaxis and multi-drug resistant non-typhoidal salmonella? A secondary data analysis of antibiotic co-resistance surveillance data in South Africa - 2003-2005

MSc (Med), Epidemiology and Biostatistics, Faculty of Health Sciences, University of the WitwatersrandIntroduction Given the increasing prevalence of non-typhoidal salmonella in humans, especially as an opportunistic illness associated with HIV, enhanced surveillance for non-typhoidal salmonella (NTS), including screening for antibiotic resistance, is conducted annually in South Africa. We aimed to determine whether there is an association between trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis and multi-drug resistant NTS infection, to establish whether various factors modify the relationship between TMP-SMX resistance and invasive NTS infection, to examine whether these associations vary by province, and to quantify the resistance rates of NTS to a range of antibiotics. Methods This study was a secondary analysis of enhanced surveillance data on NTS collected between 2003 and 2005. We used descriptive methods to assess the prevalence of NTS by year, province and serotype, and to determine the prevalence of four MDR patterns. Univariate and multivariate regression models were used to investigate the relationships between TMP-SMX prophylaxis and MDR NTS. Univariate logistic regression was used to assess the relationship between invasive NTS and TMP-SMX resistance. Results TMP-SMX prophylaxis is associated with the ACKSSuT pattern (OR 1.91, 95% CI 1.14 – 3.19, p=0.0080) and the AKSSuT MDR pattern (OR 2.00, 95% CI 1.26 – 3.15, p=0.0015). Being on TMP-SMX prophylaxis is associated with an increased odds of having at least one of the four MDR patterns investigated (OR 1.43, 95% CI 1.00 – 2.04, p=0.0388). We also found high rates of resistance to all antibiotics tested except for ciprofloxacin and imipenem. The highest resistance rate was observed for sulfamethoxazole (>75.85%). S. enterica Isangi isolates showed the highest levels of resistance, with 94.43% having at least one MDR pattern. Other factors significantly associated with MDR NTS were ESBL production, prior treatment with antibiotics, HIV status and resistance to TMP-SMX. Discussion and conclusions Isolates from patients on TMP-SMX prophylaxis were associated with an increased odds of having the ACKSSuT and AKSSuT MDR patterns, not taking into account other explanatory factors. These associations did not remain significant when possible confounders were taken into account. Despite the threat of increased multi-drug resistance, TMP-SMX prophylaxis remains important in certain clinical settings

Assessing healthcare quality using routine data: evaluating the performance of the national tuberculosis programme in South Africa

ObjectiveTo assess the performance of healthcare facilities by means of indicators based on guidelines for clinical care of TB, which is likely a good measure of overall facility quality.MethodsWe assessed quality of care in all public health facilities in South Africa using graphical, correlation and locally weighted kernel regression analysis of routine TB test data.ResultsFacility performance falls short of national standards of care. Only 74% of patients with TB provided a second specimen for testing, 18% received follow‐up testing and 14% received drug resistance testing. Only resistance testing rates improved over time, tripling between 2004 and 2011. National awareness campaigns and changes in clinical guidelines had only a transient impact on testing rates. The poorest performing facilities remained at the bottom of the rankings over the period of study.ConclusionThe optimal policy strategy requires both broad‐based policies and targeted resources to poor performers. This approach to assessing facility quality of care can be adapted to other contexts and also provides a low‐cost method for evaluating the effectiveness of proposed interventions. Devising targeted policies based on routine data is a cost‐effective way to improve the quality of public health care provided.ObjectifEvaluer la performance des établissements de santé au moyen d’indicateurs basés sur des directives pour les soins cliniques de la tuberculose (TB), qui sont probablement une bonne mesure de la qualité globale des établissements.MéthodesNous avons évalué la qualité des soins dans tous les établissements de santé publique en Afrique du Sud à l’aide d’une analyse de régression graphique, de corrélation et localement pondérée des données de dépistage de routine de la TB.RésultatsLa performance des établissements ne respecte pas les normes nationales de soins. Seuls 74% des patients TB ont fourni un deuxième échantillon pour les tests, 18% ont reçu des tests de suivi et 14% ont reçu des tests de résistance aux médicaments. Seuls les taux de dépistage de la résistance se sont améliorés au cours du temps, en triplant entre 2004 et 2011. Les campagnes de sensibilisation nationales et les changements apportés aux directives cliniques n’ont eu qu’un impact transitoire sur les taux de dépistage. Les établissements avec la plus mauvaise performance sont restés au bas du classement au cours de la période étudiée.ConclusionLa stratégie politique optimale requiert à la fois des politiques générales et des ressources ciblées pour la mauvaise performance. Cette méthode d’évaluation de la qualité des soins peut être adaptée à d’autres contextes et procure également une méthode peu coûteuse pour évaluer l’efficacité des interventions proposées. L’élaboration de politiques ciblées basées sur des données de routine est un moyen rentable pour améliorer la qualité des soins de santé publique fournis.Mots‐clésqualité des soins, mesure de la qualité, prestation des soins de santé, politique de santé, tuberculose, résistance aux antibiotiques, Afrique du SudObjetivoEvaluar el desempeño de los centros sanitarios por medio de indicadores basados en guías para la atención clínica de la TB, lo cual podría ser una buena medida de la calidad general de las instalaciones.MétodosHemos evaluado la calidad de la atención en centros sanitarios públicos de Sudáfrica mediante análisis gráficos, correlaciones y regresiones ponderadas de Kernel utilizando datos rutinarios de TB.ResultadosEl desempeño de los centros está por debajo de los estándares nacionales de cuidado. Solo un 74% de los pacientes con TB proveyeron un segundo espécimen para pruebas, un 18% recibió pruebas de seguimiento, y un 14% pruebas de resistencia a medicamentos. Solo mejoraron a lo largo del tiempo las tasas de las pruebas de resistencia, triplicándose entre el 2004‐2011. Las campañas de concienciación nacionales y los cambios en las guías clínicas solo tenían un impacto transitorio sobre las tasas de las pruebas. Los centros con los peores resultados continuaron en lo más bajo de la clasificación a lo largo del periodo de estudio.ConclusiónLa estrategia óptima requiere tanto el uso de políticas de base amplia como de recursos dirigidos a quienes tienen un peor desempeño. Esta aproximación para evaluar la calidad de la atención de los centros puede adaptarse a otros contextos, y también provee un método de bajo coste para evaluar la efectividad de las intervenciones propuestas. La elaboración de políticas orientadas, basadas en datos rutinarios, es una forma coste‐efectiva de mejorar la calidad de la atención sanitaria pública.Palabras clavecalidad de la atención, calidad de medidas, entrega de atención sanitaria, política sanitaria, tuberculosis, resistencia a antibióticos, SudáfricaPeer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/135966/1/tmi12819.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/135966/2/tmi12819_am.pd

Nationwide and regional incidence of microbiologically confirmed pulmonary tuberculosis in South Africa, 2004-12 : a time series analysis

BACKGROUND : South Africa has the highest incidence of tuberculosis in the world, largely resulting from a high population prevalence of HIV infection. We investigated the incidence of microbiologically confirmed pulmonary tuberculosis, and new cases of pulmonary tuberculosis registered for treatment, nationally and provincially in South Africa from 2004 to 2012, during which time there were changes in antiretroviral therapy (ART) coverage among individuals with HIV infection. METHODS : We identifi ed cases of microbiologically confi rmed pulmonary tuberculosis from 2004 to 2012 from the National Health Laboratory Service Corporate Data Warehouse. New cases registered for treatment were identifi ed from National Department of Health electronic registries. A time series analysis, using autoregressive models, was undertaken on incidence of microbiologically confi rmed pulmonary disease nationally and provincially; this trend was also examined relative to ART coverage of adults with HIV infection. FINDINGS : During the 9-year period, 3 523 371 cases of microbiologically confirmed pulmonary tuberculosis were recorded nationally. Annual incidence (per 100 000 population) increased from 650 (95% CI 648–652) in 2004 to 848 (845–850) in 2008, declining to 774 (771–776) by 2012 (9% decrease from 2008 to 2012). Incidence varied by age group, sex, and province. There was an inverse association between incidence of microbiologically confirmed disease and ART coverage among HIV-infected individuals nationally and provincially. Trends in incidence of tuberculosis cases registered for treatment mirrored those of microbiologically confirmed cases nationally and provincially; however, incidence of microbiologically confirmed cases was consistently higher than cases registered for treatment nationally and in seven of nine provinces. INTERPRETATION : Since its peak in 2008, the incidence of microbiologically confirmed pulmonary tuberculosis in South Africa had declined by 2012; this decline is associated with an increase in ART coverage. Future integration of registries for microbiologically confirmed cases and new cases registered for treatment would improve the assessment of the burden of pulmonary tuberculosis in South Africa. FUNDING : National Institute for Communicable Diseases: Division of the National Health Laboratory Service, South Africa.SAM has received grants and personal fees from GlaxoSmithKline, Pfizer, and Sanofi Pasteur, and grants from Novartis.http://www.thelancet.com/infectionhb2017Medical Microbiolog

Prevalence of drug-resistant tuberculosis and imputed burden in South Africa : a national and sub-national cross-sectional survey

BACKGROUND : Globally, per-capita, South Africa reports a disproportionately high number of cases of multidrug-resistant (MDR) tuberculosis and extensively drug-resistant (XDR) tuberculosis. We sought to estimate the prevalence of resistance to tuberculosis drugs in newly diagnosed and retreated patients with tuberculosis provincially and nationally, and compared these with the 2001–02 estimates. METHODS : A cross-sectional survey was done between June 15, 2012–June 14, 2014, using population proportionate randomised cluster sampling in the nine provinces in South Africa. 343 clusters were included, ranging between 31 and 48 per province. A patient was eligible for inclusion in the survey if he or she presented as a presumptive case during the intake period at a drug resistance survey enrolling facility. Consenting participants (≥18 years old) completed a questionnaire and had a sputum sample tested for resistance to first-line and second-line drugs. Analysis was by logistic regression with robust SEs, inverse probability weighted against routine data, and estimates were derived using a random effects model. FINDINGS : 101 422 participants were tested in 2012–14. Nationally, the prevalence of MDR tuberculosis was 2·1% (95% CI 1·5–2·7) among new tuberculosis cases and 4·6% (3·2–6·0) among retreatment cases. The provincial point prevalence of MDR tuberculosis ranged between 1·6% (95% CI 0·9–2·9) and 5·1% (3·7–7·0). Overall, the prevalence of rifampicin-resistant tuberculosis (4·6%, 95% CI 3·5–5·7) was higher than the prevalence of MDR tuberculosis (2·8%, 2·0–3·6; p=0·01). Comparing the current survey with the previous (2001–02) survey, the overall MDR tuberculosis prevalence was 2·8% versus 2·9% and prevalance of rifampicin-resistant tuberculosis was 3·4% versus 1·8%, respectively. The prevalence of isoniazid mono-resistant tuberculosis was above 5% in all provinces. The prevalence of ethionamide and pyrazinamide resistance among MDR tuberculosis cases was 44·7% (95% CI 25·9–63·6) and 59·1% (49·0–69·1), respectively. The prevalence of XDR tuberculosis was 4·9% (95% CI 1·0–8·8). Nationally, the estimated numbers of cases of rifampicin-resistant tuberculosis, MDR tuberculosis, and isoniazid mono-resistant tuberculosis for 2014 were 13 551, 8249, and 17 970, respectively. INTERPRETATION : The overall prevalence of MDR tuberculosis in South Africa in 2012–14 was similar to that in 2001–02; however, prevalence of rifampicin-resistant tuberculosis almost doubled among new cases. Furthermore, the high prevalence of isoniazid mono-resistant tuberculosis, not routinely screened for, and resistance to second-line drugs has implications for empirical management.President's Emergency Plan for AIDS Relief through the Centers for Disease Control and Prevention under the terms of 1U19GH000571.http://www.thelancet.com/infection2019-07-01hj2018Medical Microbiolog

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Long-term consistent use of a vaginal microbicide gel among HIV-1 sero-discordant couples in a phase III clinical trial (MDP 301) in rural south-west Uganda.

BACKGROUND: A safe and effective vaginal microbicide could substantially reduce HIV acquisition for women. Consistent gel use is, however, of great importance to ensure continued protection against HIV infection, even with a safe and effective microbicide. We assessed the long-term correlates of consistent gel use in the MDP 301 clinical trial among HIV-negative women in sero-discordant couples in south-west Uganda. METHODS: HIV-negative women living with an HIV-infected partner were enrolled between 2005 and 2008, in a three-arm phase III microbicide trial and randomized to 2% PRO2000, 0.5% PRO2000 or placebo gel arms. Follow-up visits continued up to September 2009. The 2% arm was stopped early due to futility and the 229 women enrolled in this arm were excluded from this analysis. Data were analyzed on 544 women on the 0.5% and placebo arms who completed at least 52 weeks of follow-up, sero-converted or became pregnant before 52 weeks. Consistent gel use was defined as satisfying all of the following three conditions: (i) reported gel use at the last sex act for at least 92% of the 26 scheduled visits or at least 92% of the visits attended if fewer than 26; (ii) at least one used applicator returned for each visit for which gel use was reported at the last sex act; (iii) attended at least 13 visits (unless the woman sero-converted or became pregnant during follow-up). Logistic regression models were fitted to investigate factors associated with consistent gel use. RESULTS: Of the 544 women, 473 (86.9%) were followed for at least 52 weeks, 29 (5.3%) sero-converted and 42 (7.7%) became pregnant before their week 52 visit. Consistent gel use was reported by 67.8%. Women aged 25 to 34 years and those aged 35 years or older were both more than twice as likely to have reported consistently using gel compared to women aged 17 to 24 years. Living in a household with three or more rooms used for sleeping compared to one room was associated with a twofold increase in consistent gel use. CONCLUSION: In rural Uganda younger women and women in houses with less space are likely to require additional support to achieve consistent microbicide gel use. TRIAL REGISTRATION: Protocol Number ISRCTN64716212

Excess Mortality Associated with Influenza among Tuberculosis Deaths in South Africa, 1999-2009.

Published data on the interaction between influenza and pulmonary tuberculosis (PTB) are limited. We aimed to estimate the influenza-associated mortality among individuals with PTB in South Africa from 1999-2009.We modelled the excess influenza-associated mortality by applying Poisson regression models to monthly PTB and non-tuberculosis respiratory deaths, using laboratory-confirmed influenza as a covariate.PTB deaths increased each winter, coinciding with influenza virus circulation. Among individuals of any age, mean annual influenza-associated PTB mortality rate was 164/100,000 person-years (n = 439). The rate of non-tuberculosis respiratory deaths was 27/100,000 (n = 1125) for HIV-infected and 5/100,000 (n = 2367) for HIV-uninfected individuals of all ages. Among individuals aged <65 years, influenza-associated PTB mortality risk was elevated compared to influenza-associated non-tuberculosis respiratory deaths in HIV-infected (relative risk (RR): 5.2; 95% CI: 4.6-5.9) and HIV-uninfected individuals (RR: 61.0; CI: 41.4-91.0). Among individuals aged ≥65 years, influenza-associated PTB mortality risk was elevated compared to influenza-associated non-tuberculosis respiratory deaths in HIV-uninfected individuals (RR: 13.0; 95% CI: 12.0-14.0).We observed an increased risk of influenza-associated mortality in persons with PTB compared to non-tuberculosis respiratory deaths. If confirmed in other settings, our findings may support recommendations for active inclusion of patients with TB for influenza vaccination and empiric influenza anti-viral treatment of patients with TB during influenza epidemics

Preferred method of response to the survey among study participants, July—September 2016, South Africa (N = 459).

<p>Preferred method of response to the survey among study participants, July—September 2016, South Africa (N = 459).</p

Prevalence of TB among the study participants, July—September 2016, South Africa.

<p>Prevalence of TB among the study participants, July—September 2016, South Africa.</p

Characteristics of the study participants, July—September 2016, South Africa.

<p>Characteristics of the study participants, July—September 2016, South Africa.</p