Abstract Introduction Fluoroquinolones (FQ) are an essential component of current and new regimens for the treatment of tuberculosis (TB). The 2014 Global TB report indicates a FQ resistance rate of ...17% amongst multidrug-resistant (MDR) strains of Mycobacterium tuberculosis (MTB) tested in 2013. There is, however, a paucity of FQ-resistance data from high burden countries. In this study the trend of FQ-resistance amongst MDR–MTB and non-MDR–MTB is analyzed over a four-and-a-half-year period (January 2010–July 2014). Methods This study was conducted at the Aga Khan University laboratory, a technical partner of the Pakistan National TB Program and part of the World Health Organization (WHO) Supra-national Laboratory Network for TB. The laboratory receives specimens from across the country through its peripheral collection units. MTB was isolated using standard methods. Susceptibility testing was performed using the agar proportion method with drug concentrations as recommended by Clinical Laboratory Institute Standards (CLSI). FQ susceptibilities were determined using ofloxacin (2 μg/ml). MTB H37Rv was used as a control with each batch of susceptibility testing. MDR was defined as resistance to both isoniazid (0.2 μg/ml) and rifampicin (1.0 μg/ml). Results During the study period 14,711 MTB strains were isolated. Of these, 6403 (43.5%) were MDR and 8308 were non-MDR. FQ resistance in MDR strains ranged between 54% and 58%. Amongst non-MDR MTB strains, FQ resistance increased from 214/2059 (10.3%) in 2010 to 180/1049 (17.1%) in 2014. The proportion of FQ mono-resistant TB strains averaged at 10.5% of the non-MDR isolates during this period. Conclusions FQ resistance in non-MDR–MTB strains with a considerable proportion of FQ mono-resistant strains in Pakistan is alarming. These data highlight the limited potential of empirical FQ usage for TB treatment in both MDR and non-MDR cases and the need to implement regular surveillance for FQ-resistance in MTB in the country. High FQ resistance amongst MTB isolates further emphasizes the importance of stewardship and the responsible use of FQs in particular, and antimicrobials in general in the country.
Limited capacity of laboratories for antimicrobial susceptibility testing (AST) presents a critical diagnostic bottleneck in resource limited countries. This paper aims to identify such gaps and to ...explore whether laboratory networks could contribute towards improving AST in low resource settings.
A self-assessment tool to assess antimicrobial susceptibility testing capacity was administered as a pre-workshop activity to participants from 30 microbiology laboratories in 3 cities in Pakistan. Data from public and private laboratories was analyzed and capacity of each scored in percentage terms. Laboratories from Karachi were invited to join a support network. A cohort of five laboratories that consented were provided additional training and updates sessions over a period of 15 months. Impact of training activities in these laboratories was evaluated using a point scoring (0-11) tool.
Results of self-assessment component identified a number of areas that required strengthening (scores of ≤60%). These included; readiness for AMR surveillance; 38 and 46%, quality assurance; 49 and 55%, and detection of specific organisms; 56 and 60% for public and private laboratories respectively. No significant difference was detected in AST capacity between public and private laboratories ANOVA;
> 0.05. Scoring tool used to assess impact of training within the longitudinal cohort showed an increase from a baseline of 1-5.5 (August 2015) to improved post training scores of 7-11 (October 2016) for the 5 laboratories included. Moreover, statistical analysis using paired t-Test Analysis, assuming unequal variance, indicated that the increase in scored noted represents a statistically significant improvement in the components evaluated
< 0.05.
Strengthening of laboratory capacity for AMR surveillance is important. Our data shows that close mentoring and support can help enhance capacity for antimicrobial sensitivity testing in resource limited settings. Our study further presents a model wherein laboratory networks can be successfully established and used towards improving diagnostic capacity in such settings.
Antimicrobial resistance is an emerging public health concern. Ten-valent pneumococcal vaccine (PCV10) was introduced in Pakistan's Expanded Program on Immunization (EPI) in 2012 as a 3 + 0 schedule ...without catchup. From 2014 to 2018, children <2 years were randomly selected in two rural union councils of Matiari, Pakistan. Nasopharyngeal swabs were collected using standard WHO guidelines by trained staff and processed at Infectious Disease Research Laboratory at The Aga Khan University, Karachi using culture on sheep blood agar and Multiplex PCR methods described by CDC, USA. Pneumococcal isolates were identified by optochin sensitivity and bile solubility tests. Isolates were then tested for antimicrobial susceptibility by standard Kirby-Bauer disk-diffusion method on Mueller-Hinton Agar (MHA) with 5% sheep blood agar as per Clinical & Laboratory Standards Institute (CLSI) recommendations. Of 3140 children enrolled, pneumococcal isolates were detected in 2370 (75%). Vaccine coverage improved from 41% to 68.4%. Out of the 2370 isolates, 88.4%, 37.6% and 25% were resistant to cotrimoxazole, tetracycline and erythromycin, respectively. There was no resistance to penicillin, ceftriaxone, and vancomycin. For erythromycin, resistance increased from 20% in 2014/15 to 30.8% in 2017/18 and for tetracycline it increased from 34.9% to 41.8% both of which were explained by an increase in prevalence of serotype 19A. Pneumococcal isolates were susceptible to penicillin, ceftriaxone, and vancomycin. They were largely resistant to cotrimoxazole and tetracycline. There was an increase in erythromycin and tetracycline resistance attributed to increasing prevalence of serotype 19A. Pneumococcal isolates from carriage and invasive disease should be closely monitored for antimicrobial susceptibility.
Antimicrobial resistance is an emerging public health concern particularly in low- and middle-income countries where there is poor regulation and easy availability of antibiotics. This is the first study from Pakistan to report antimicrobial resistance patterns of pneumococcus after vaccine introduction in the community. Pakistan was the first South-Asian country to introduce PCV10 in its Expanded Program on Immunization (EPI) in 2012 as a 3 + 0 schedule without catchup. In this study, we describe the PCV10 impact on antimicrobial resistance patterns of pneumococcal nasopharyngeal carriage in children younger than 2 years of age in a rural district in Pakistan after the introduction of the vaccine.
Abstract Aims and objectives Extrapulmonary disease accounts for a significant proportion of all cases of tuberculosis (TB) in endemic areas. With increasing prevalence of human immunodeficiency ...virus (HIV), the case numbers are rising; extrapulmonary involvement can be seen in >50% of patients with concurrent AIDS and TB. In both HIV-positive and HIV-negative cases, due to diagnostic difficulties, extrapulmonary disease is often recognized late and, hence, although completely curable in many cases, as far as bacterial eradication is concerned, is not without consequence. Methods Sequelae of extrapulmonary TB were explored through literature review. Additionally, case files of patients presenting to the TB clinics in a tertiary care hospital in Karachi, Pakistan were examined for sequelae during variable periods of follow up. Results The sequelae of TB can be divided into: those of ongoing inflammation, for example, vasculitis in central nervous system infection leading to neurologic deficit, or amyloidosis with renal failure in longstanding, inappropriately managed cases, or where the diagnosis is missed; healing with fibrosis, for example, intestinal obstruction, pericardial constriction, infertility; loss of function secondary to bone and joint deformity, for example, gibbus formation and paraplegia in spinal TB. Conclusion Early reliable diagnosis and anti-TB treatment, often with steroids, is essential for control of disease and prevention of complications. Patients need to be monitored clinically and supported psychologically, logistically, and socially to return to lead productive lives after extrapulmonary TB infections.
The applicability of cucumis sativus peel (CSP) waste as a low-cost adsorbent for the removal of hazardous methylene blue dye from wastewater was evaluated. The efficacy of dye removal of the ...adsorbent is determined by investigating the various parameters such as adsorbent dose, contact time, initial dye concentration, particle size, pH, and temperature. The adsorbent was characterized by Scanning Electron Microscopy (SEM) and Fourier Transform Infra-Red (FTIR) spectroscopy. The isotherm analysis reveals that the adsorption process can be better described by Freundlich adsorption isotherm indicating the heterogeneous nature of the adsorbent surface. The deviation from normal or ideal Langmuir adsorption has been explained in light of non-idealized cooperative adsorption. Adsorption kinetics was found to obey pseudo-second order kinetics. Thermodynamic data reveals that the adsorption process is spontaneous and exothermic in nature. The values of ∆H° and ∆S° have been found to be negative which indicate that the feasibility of process decreases with increasing temperature. The isotherm and kinetics results have been compared and discussed with those available in the literature. The adsorbent regeneration was found to be best obtained in hydrochloric acid. The results indicate that CSP is an efficient low-cost adsorbent for the removal of methylene blue dye from wastewater.
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•The CSP adsorbent was an efficient and specific adsorbent for the removal of MB.•The equilibrium adsorption data fitted the Freundlich isotherm model well.•The pseudo-second-order model could be better to describe the adsorption of MB by CSP.•The adsorption of MB onto the CSP adsorbent was exothermic and spontaneous.•The adsorbent surface was heterogeneous with multilayer cooperative adsorption.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Pneumonia is the leading cause of morbidity and mortality in children worldwide. The ten valent pneumococcal vaccine (PCV10) was introduced in Pakistan's Expanded Program on Immunization (EPI) in ...2012 as a 3 + 0 schedule without catchup immunization. Nasopharyngeal carriage is taken as a surrogate marker to measure the impact of pneumococcal vaccine on populations. Carriage surveys are necessary to monitor the persistence of Vaccine Type (VT) serotypes, the emergence of Non-Vaccine Type (NVT) serotypes, and their role in both transmission and disease. This article describes various troubleshooting measures which we undertook to adopt the protocol to our setting. We also used an innovative approach to describe various epidemiological parameters of vaccine effectiveness against carriage. It is important to publish these methods to allow for valid regional and temporal comparisons of results in different settings. Thus, in this article, we describe the following methods for isolating upper airway pneumococcal carriage:•Methods for the collection, transport, and storage of nasopharyngeal samples.•Methods for identification and serotyping of pneumococci.•Methods for estimation of the direct and indirect effects of pneumococcal vaccines on nasopharyngeal carriage.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: Invasive pneumococcal disease (IPD) has high mortality among children. Pneumococcal bacteremia is an important marker of IPD but has received limited attention in predicting the outcomes ...of illness. The aim of this study was to evaluate clinical features, focus of infection, and comorbid of pneumococcal bacteremia in a pediatric cohort at a tertiary care center in Karachi, Pakistan. Methods: Children aged 0–14 years admitted to the Aga Khan University Hospital with pneumococcal bacteremia were identified through a laboratory database. Demographic, clinical, and outcome data were obtained from patients' medical records. Data entry and analysis were carried out in MS Excel and SPSS version 19.0. Results: Forty (n = 40) episodes of pneumococcal bacteremia in 39 children were identified. The median age of the cohort was 2.5 (interquartile range 4.15–1.1) years; 30% (n = 12) of these were infants aged 0–12 months. The primary focus of infection was identified as pneumonia in 47.5% (n = 19) and meningitis in 7.5% (n = 3). The prevalence of occult bacteremia was 27.5% (n = 11). Outcomes of infection at hospital discharge were assessed in 31 patients as nine patients were either transferred out or left against advice. Of 31 patients, 6 (19.4%) died and 25 (80.6%) were discharged home. Associations with mortality included sepsis (P = 0.017) and absence of a focus (occult bacteremia) (P = 0.007). Conclusion: Sepsis and occult bacteremia (without an underlying focus) were associated with mortality. No association was found between choice of antibiotics administered, penicillin minimum inhibitory concentration, and poor outcome at discharge. Other factors such as comorbidities, immune status, and focus of infection play an important role in predicting the outcomes of pneumococcal bacteremia.
Abstract The use of bronchoscopes has increased in tuberculosis (TB) diagnostics to circumvent the diagnostic challenges that are associated with low sputum volume and smear-negative TB. In ...healthcare facilities situated in low income countries that have a high burden of TB, adequate decontamination of bronchoscopes is a challenge and often overlooked to save on time and costs. This amplifies the risk of outbreaks and pseudo-outbreaks due to Mycobacterium tuberculosis and nontuberculosis mycobacteria. In this minireview, we review published literature of contaminated bronchoscopes causing pseudo-outbreaks of M. tuberculosis and nontuberculosis mycobacteria in an effort to determine common sources, and possible mitigation strategies in low-resource settings.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The dataset described in this paper was collected for a time-series cross-sectional study exploring the impact of 10-valent Pneumococcal Conjugate Vaccine (PCV10) on nasopharyngeal (NP) carriage in ...children under 2 years of age from a rural population in Sindh, Pakistan. The study was carried out in two union councils of Matiari - Khyber and Shah Alam Shah Jee Wasi (Latitude 25.680298 / Longitude 68.502711). Data was collected on socio-demographics, clinical characteristics and vaccination status using android phone-based application. NP samples were collected using standard World Health Organisation (WHO) techniques, culture and serotyping was done using sequential Multiplex PCR described by Centre for Disease Control, USA. We looked at the carriage rate of vaccine type (VT) and non-vaccine type (NVT) serotypes over time in vaccinated and unvaccinated children. We additionally looked at the predictors for pneumococcal carriage. The uploaded dataset, available on Mendeley data repository (Nisar, Muhammad Imran (2021), “Impact of PCV10 on nasopharyngeal carriage in children in Pakistan”, Mendeley Data, V1, doi:10.17632/t79h6g97gr.1), has 3140 observations in CSV format. Additional files uploaded include a data dictionary and the set of questionnaires. The dataset and accompanying files can be used by other interested researchers to replicate our analysis, carry similar analysis under varying set of assumptions or perform additional exploratory or metanalysis
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract The percentage of extrapulmonary tuberculosis (EPTB) among new and relapse tuberculosis cases in South Asia (Afghanistan, Pakistan, India, and Bangladesh) ranged from 19% to 23% in 2014. ...While tuberculosis was reportedly more prevalent in males, a higher preponderance of EPTB was observed in females. National tuberculosis control programs are highly focused on pulmonary tuberculosis. This creates gaps in the surveillance, diagnosis, and study of EPTB among females, which is especially pronounced in the South Asian setting. We have reviewed recently published literatures from January 2010 to June 2016 reporting EPTB in females with a view to evaluate the current epidemiology, risk factors, diagnostic modalities, and treatment outcomes. We report significant gaps in the surveillance of EPTB among women in South Asia, emphasizing the need for greater focus on EPTB in females to overcome current surveillance and knowledge gaps.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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