Drug Resistance of <i>Mycobacterium tuberculosis</i> Complex in a Rural Setting, Angola

Rando-Segura, Ariadna; Aznar, María Luisa; Moreno, María Milagros; Espasa, Mateu; Sulleiro, Elena; Bocanegra, Cristina; Gil, Eva; Eugénio, Arlete N.E.; Escartin, Carlos; Zacarias, Adriano; Vegue, Josep; Katimba, Domingos; Vivas, María Carmen; Étienne, Gabriel; Marina, María Concepción; Peña, Jacobo Mendioroz; López, María Teresa Rugeles; Pumarola, Tomás; Molina, Israel; Tórtola, María Teresa

doi:10.3201/eid2403.171562

Cited by 8 publications

(8 citation statements)

References 8 publications

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“…LAM1 is dominant in Angola and Namibia [37]. While there is limited information regarding M. tuberculosis drug resistance in Namibia, MDR-Mtb among retreatment cases was reported to be as high as 71% in Angola [38]. It is likely that an MDR-Mtb LAM1 clone susceptible to STR had been introduced in Zambia from Angola by displacement of people due to war.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Mutations Associated with Streptomycin Resistance in Multidrug-Resistant Mycobacterium tuberculosis in Zambia

et al. 2021

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Streptomycin (STR) is recommended for the management of multidrug-resistant tuberculosis (MDR-TB). Streptomycin resistance-conferring mutation types and frequency are shown to be influenced by genotypes of circulating strains in a population. This study aimed to characterize the mutations in MDR-TB isolates and examine their relationship with the genotypes in Zambia. A total of 138 MDR-TB isolates stored at the University Teaching Hospital Tuberculosis Reference Laboratory in Zambia were analyzed using spoligotyping and sequencing of STR resistance-associated genes. Streptomycin resistance was observed in 65.9% (91/138) of MDR-TB isolates. Mutations in rpsL, rrs, and gidB accounted for 33%, 12.1%, and 49.5%, respectively. Amino acid substitution K43R in rpsL was strongly associated with the CAS1_Kili genotype (p < 0.0001). The combination of three genes could predict 91.2% of STR resistance. Clustering of isolates based on resistance-conferring mutations and spoligotyping was observed. The clustering of isolates suggests that the increase in STR-resistant MDR-TB in Zambia is largely due to the spread of resistant strains from inadequate treatment. Therefore, rapid detection of STR resistance genetically is recommended before its use in MDR-TB treatment in Zambia.

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Section: Discussionmentioning

confidence: 99%

Characterization of Mutations Associated with Streptomycin Resistance in Multidrug-Resistant Mycobacterium tuberculosis in Zambia

et al. 2021

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“…Samples were collected from patients with TB attended in Hospital Nossa Senhora da Paz (Cubal, Angola) and sent to the Mycobacteriology Unit (WHO Supranational TB Reference Laboratory in Spain) of Vall d'Hebron University Hospital for culture and DST. Details of the inclusion and exclusion criteria and sample shipping have been previously described by our research team [14]. DNA sequencing of the rpoB gene and MIC determination by the macrodilution method were performed on isolates that showed RIF resistance by culture-based DST, but were identified as susceptible by GenoType MTBDRplus Hain Lifescience or did not give hybridization results with the mutation-specific probes, and on those that showed RIF susceptibility by culturebased DST but were identified as resistant by molecular methods.…”

Section: Study Design and Data Collectionmentioning

confidence: 99%

“…Of the latter, 69 gave positive hybridization results with the mutation-specific probes S450L (49), D435V (15), H445D (3) and H445Y (2). The remaining 8 isolates were identified as resistant by the absence of the wild-type probes [14]. Mutations detected by sequencing were rpoB L430P plus S493L (1), Q432ins (1), N437del (1), H445L (1), L449M plus S450F (1), S450F (1), S450W (1), and S450Y (1), and the distribution of MICs among these isolates ranged from 1.0 to > 4.0 μg/ml.…”

Section: Phenotypic Rif Resistant Casesmentioning

confidence: 99%

Molecular characterization of rpoB gene mutations in isolates from tuberculosis patients in Cubal, Republic of Angola

Rando‐Segura

Aznar

Moreno³

et al. 2021

BMC Infect Dis

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Background The importance of Mycobacterium tuberculosis strains with disputed rpoB mutations remains to be defined. This study aimed to assess the frequency and types of rpoB mutations in M. tuberculosis isolates from Cubal, Angola, a country with a high incidence of tuberculosis. Methods All isolates included (n = 308) were analyzed using phenotypic drug susceptibility testing and GenoType MTBDRplus assay. DNA sequencing of the rpoB gene and determination of rifampicin MIC by macrodilution method were additionally performed on isolates yielding discordant results (n = 12) and those in which the mutation detected was not characterized (n = 8). Results In total, 85.1% (74/87) of rifampicin-resistant strains had undisputed rpoB mutations -S450L (49), D435V (15), H445D (3), H445Y (2), Q432ins (1), L449M plus S450F (1), S450F (1), S450W (1) and S450Y (1)-; 10.3% (9/87) had disputed rpoB mutations—L430P plus S493L (1), N437del (1), H445L (3), D435Y (2), L452P (2)-, 2.3% (2.3%) showed no rpoB mutations and 2.3% (2/87) showed heteroresistance—D435Y plus L452P and L430P plus S493L-. Conclusion Disputed rpoB mutations were common, occurring in 10.3% of rifampicin resistant isolates. Current phenotyping techniques may be unable to detect this resistance pattern. To increase their sensitivity, a lower concentration of RIF could be used in these tests or alternatively, rpoB mutations could be screened and characterized in all M. tuberculosis strains.

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“…Future studies could investigate whether retreatment patients may seek treatment far from their homes which could also reduce stigma. Retreatment cases also have a higher likelihood of developing multi-drug resistant (MDR) TB due to prior exposure to TB drugs 50 . These findings could be attributed to the strong focus on retreatment cases within TB programmes to improve treatment outcomes and control MDR TB.…”

Section: Discussionmentioning

confidence: 99%

Stigma among tuberculosis patients and associated factors in urban slum populations in Uganda

Ashaba¹,

Musoke²,

Wafula³

et al. 2021

Afr H. Sci.

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Background: Stigma continues to be a major barrier to tuberculosis (TB) control particularly in urban populations. Stigma can influence health seeking behaviour and affect adherence to TB treatment, yet few studies have examined TB related stigma and associated factors in Uganda. This study was therefore conducted to determine the level of stigma and associated factors among TB patients in an urban setting in Kampala, Uganda. Methods: A cross-sectional study was conducted in Makindye division, Kampala among 204 patients with TB aged 18 years and above. Data were collected on socio-demographic, individual patient and HIV/AIDS related factors using an intervieweradministered questionnaire. The outcome variable (stigma) was assessed on a four-point Likert scale from the participants’ perspective. Stigma scores ranged from 0 to 36 which were summed up and a median stigma score calculated. Individuals with a stigma score equal or greater than the median were categorized as having high stigma. A multivariable logistic regression analysis was performed to determine factors associated with TB stigma. Results: Over half (52%) of the participants were found to have high TB stigma. Knowing someone who had died of TBAOR = 4.42, 95% CI (1.69 - 11.50) and believing that TB and HIV symptoms were similarAOR = 3.05, 95% CI (1.29 - 7.22) were positively associated with high TB stigma. The odds of having high stigma were 79% lower among individuals who had been previously treated for TBAOR = 0.21, 95% CI (0.09 - 0.52). Conclusions: Stigma towards TB was high in this urban population and mainly associated with knowing a person who had died of TB, perception that symptoms of TB are similar to those of HIV/AIDS, and previous TB treatment. Interventions to mitigate TB stigma are needed in urban populations and should also address HIV/AIDS related stigma. Key terms: Stigma; tuberculosis; health facility; urban population; Uganda.

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Drug Resistance of Mycobacterium tuberculosis Complex in a Rural Setting, Angola

Cited by 8 publications

References 8 publications

Characterization of Mutations Associated with Streptomycin Resistance in Multidrug-Resistant Mycobacterium tuberculosis in Zambia

Characterization of Mutations Associated with Streptomycin Resistance in Multidrug-Resistant Mycobacterium tuberculosis in Zambia

Molecular characterization of rpoB gene mutations in isolates from tuberculosis patients in Cubal, Republic of Angola

Stigma among tuberculosis patients and associated factors in urban slum populations in Uganda

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