Low prevalence of fluoroquinolone resistance among patients with tuberculosis in the Philippines: results of a national survey

Lim, Dodge R.; Dean, Anna S.; Taguinod-Santiago, Mary Rosary; Borbe-Reyes, Angeli; Cabibbe, Andrea Maurizio; Zignol, Matteo; Basilio, Ramon P.; Garfin, Anna Marie Celina; Ama, Maria Cecilia G.

doi:10.1183/13993003.02571-2017

Cited by 8 publications

(5 citation statements)

References 10 publications

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“…The DST results revealed 97 (54.5%) isolates as pan-susceptible, 34 (19.1%) MDR-TB (resistance to both rifampicin and isoniazid) and 47 (26.4%) non-MDR-TB drug-resistant (resistance to at least one drug but not to both rifampicin and isoniazid). No XDR-TB isolates were found, confirming earlier reports of low levels of fluoroquinolone resistance 10 . Mapping of the raw sequence data led to high average genome-wide coverage across the samples (median: 100.5-fold; range: 52- to 2,263-fold).…”

Section: Resultssupporting

confidence: 89%

Mycobacterium tuberculosis whole genome sequencing provides insights into the Manila strain and drug-resistance mutations in the Philippines

Phelan

Lim

Mitarai

et al. 2019

Sci Rep

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The Philippines has a high incidence of tuberculosis disease (TB), with an increasing prevalence of multidrug-resistant Mycobacterium tuberculosis (MDR-TB) strains making its control difficult. Although the M . tuberculosis “Manila” ancient lineage 1 strain-type is thought to be prevalent in the country, with evidence of export to others, little is known about the genetic diversity of circulating strains. By whole genome sequencing (WGS) 178 isolates from the Philippines National Drug Resistance Survey, we found the majority (143/178; 80.3%) belonged to the lineage 1 Manila clade, with the minority belonging to lineages 4 (European-American; n = 33) and 2 (East Asian; n = 2). A high proportion were found to be multidrug-resistant (34/178; 19.1%), established through highly concordant laboratory drug susceptibility testing and in silico prediction methods. Some MDR-TB isolates had near identical genomic variation, providing potential evidence of transmission. By placing the Philippine isolates within a phylogeny of global M . tuberculosis (n > 17,000), we established that they are genetically similar to those observed outside the country, including a clade of Manila-like strain-types in Thailand. An analysis of the phylogeny revealed a set of ~200 SNPs that are specific for the Manila strain-type, and a subset can be used within a molecular barcode. Sixty-eight mutations known to be associated with 10 anti-TB drug resistance were identified in the Philippine strains, and all have been observed in other populations. Whilst nine putative streptomycin resistance conferring markers in gid (8) and rrs (1) genes appear to be novel and with functional consequences. Overall, this study provides an important baseline characterisation of M . tuberculosis genetic diversity for the Philippines, and will fill a gap in global datasets and aid the development of a nation-wide database for epidemiological studies and clinical decision making. Further, by establishing a molecular barcode for detecting Manila strains it will assist with the design of diagnostic tools for disease control activities.

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Section: Resultssupporting

confidence: 89%

Mycobacterium tuberculosis whole genome sequencing provides insights into the Manila strain and drug-resistance mutations in the Philippines

Phelan

Lim

Mitarai

et al. 2019

Sci Rep

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“…Between November, 2009, and May, 2014, population-based surveys to measure anti-tuberculosis drug resistance of M tuberculosis isolates were done in hospitals and clinics in Azerbaijan, 9 Bangladesh, 10 Belarus (Minsk), 11 Pakistan, 12 Philippines, 13 South Africa (Gauteng and Kwazulu Natal provinces), 14 and Ukraine. 15 Details on the design of these surveys are provided elsewhere.…”

Section: Methodsmentioning

confidence: 99%

“…The results of each study are described in the individual country reports. 9 , 10 , 11 , 12 , 13 , 14 , 15 , 17 Each study obtained ethical approval and written informed consent from patients.…”

Section: Methodsmentioning

confidence: 99%

Genetic sequencing for surveillance of drug resistance in tuberculosis in highly endemic countries: a multi-country population-based surveillance study

Zignol

Cabibbe

Dean

et al. 2018

The Lancet Infectious Diseases

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SummaryBackgroundIn many countries, regular monitoring of the emergence of resistance to anti-tuberculosis drugs is hampered by the limitations of phenotypic testing for drug susceptibility. We therefore evaluated the use of genetic sequencing for surveillance of drug resistance in tuberculosis.MethodsPopulation-level surveys were done in hospitals and clinics in seven countries (Azerbaijan, Bangladesh, Belarus, Pakistan, Philippines, South Africa, and Ukraine) to evaluate the use of genetic sequencing to estimate the resistance of Mycobacterium tuberculosis isolates to rifampicin, isoniazid, ofloxacin, moxifloxacin, pyrazinamide, kanamycin, amikacin, and capreomycin. For each drug, we assessed the accuracy of genetic sequencing by a comparison of the adjusted prevalence of resistance, measured by genetic sequencing, with the true prevalence of resistance, determined by phenotypic testing.FindingsIsolates were taken from 7094 patients with tuberculosis who were enrolled in the study between November, 2009, and May, 2014. In all tuberculosis cases, the overall pooled sensitivity values for predicting resistance by genetic sequencing were 91% (95% CI 87–94) for rpoB (rifampicin resistance), 86% (74–93) for katG, inhA, and fabG promoter combined (isoniazid resistance), 54% (39–68) for pncA (pyrazinamide resistance), 85% (77–91) for gyrA and gyrB combined (ofloxacin resistance), and 88% (81–92) for gyrA and gyrB combined (moxifloxacin resistance). For nearly all drugs and in most settings, there was a large overlap in the estimated prevalence of drug resistance by genetic sequencing and the estimated prevalence by phenotypic testing.InterpretationGenetic sequencing can be a valuable tool for surveillance of drug resistance, providing new opportunities to monitor drug resistance in tuberculosis in resource-poor countries. Before its widespread adoption for surveillance purposes, there is a need to standardise DNA extraction methods, recording and reporting nomenclature, and data interpretation.FundingBill & Melinda Gates Foundation, United States Agency for International Development, Global Alliance for Tuberculosis Drug Development.

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“…Details of these surveys are provided elsewhere [11]. The 6 countries represented a range of programmatic and epidemiological settings and included Azerbaijan [12], Bangladesh [13], Belarus (city of Minsk) [14], Pakistan [15], the Philippines [16], and South Africa (Gauteng and Kwazulu Natal provinces) [17]. Data on molecular markers of isoniazid resistance were also available from these countries, as well as for Ukraine [18].…”

Section: Study Populationmentioning

confidence: 99%

Prevalence and genetic profiles of isoniazid resistance in tuberculosis patients: A multicountry analysis of cross-sectional data

et al. 2020

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BackgroundThe surveillance of drug resistance among tuberculosis (TB) patients is central to combatting the global TB epidemic and preventing the spread of antimicrobial resistance. Isoniazid and rifampicin are two of the most powerful first-line anti-TB medicines, and resistance to either of them increases the risk of treatment failure, relapse, or acquisition of resistance to other drugs. The global prevalence of rifampicin resistance is well documented, occurring in 3.4% (95% CI 2.5%-4.4%) of new TB patients and 18% (95% CI 7.6%-31%) of previously treated TB patients in 2018, whereas the prevalence of isoniazid resistance at global and regional levels is less understood. In 2018, the World Health Organization (WHO) recommended a modified 6-month treatment regimen for people with isoniazid-resistant, rifampicin-susceptible TB (Hr-TB), which includes rifampicin, pyrazinamide, ethambutol, and levofloxacin. We estimated the global prevalence of Hr-TB among TB patients and investigated associated phenotypic and genotypic drug resistance patterns. Methods and findingsAggregated drug resistance data reported to WHO from either routine continuous surveillance or nationally representative periodic surveys of TB patients for the period 2003-2017 were reviewed. Isoniazid data were available from 156 countries or territories for 211,753 patients. Among these, the global prevalence of Hr-TB was 7.4% (95% CI 6.5%-8.4%) among new TB patients and 11.4% (95% CI 9.4%-13.4%) among previously treated TB patients. Additional data on pyrazinamide and levofloxacin resistance were available from 6 PLOS Medicine | https://doi.

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Low prevalence of fluoroquinolone resistance among patients with tuberculosis in the Philippines: results of a national survey

Cited by 8 publications

References 10 publications

Mycobacterium tuberculosis whole genome sequencing provides insights into the Manila strain and drug-resistance mutations in the Philippines

Mycobacterium tuberculosis whole genome sequencing provides insights into the Manila strain and drug-resistance mutations in the Philippines

Genetic sequencing for surveillance of drug resistance in tuberculosis in highly endemic countries: a multi-country population-based surveillance study

Prevalence and genetic profiles of isoniazid resistance in tuberculosis patients: A multicountry analysis of cross-sectional data

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