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Article ; Online: Challenges and knowledge gaps in the management of non-tuberculous mycobacterial pulmonary disease in sub-Saharan African countries with a high tuberculosis burden

Leen Rigouts / Tom Decroo / Natalie Lorent / Anita Mesic / Lutgarde Lynen / Dorcas Obiri-Yeboah / Elizabeth Tabitha Abbew / Ablo Prudence Wachinou

BMJ Open, Vol 14, Iss

a scoping review

2024 Volume 1

Abstract: Introduction In sub-Saharan African (SSA) countries endemic for tuberculosis (TB), previous TB is a significant risk factor for non-tuberculous mycobacterial pulmonary disease (NTM-PD). The deployment of GeneXpert MTB/RIF in pulmonary TB diagnostic work- ... ...

Abstract	Introduction In sub-Saharan African (SSA) countries endemic for tuberculosis (TB), previous TB is a significant risk factor for non-tuberculous mycobacterial pulmonary disease (NTM-PD). The deployment of GeneXpert MTB/RIF in pulmonary TB diagnostic work-up regularly identifies symptomatic patients with a positive smear microscopy but negative GeneXpert, indicative of NTM presence. This scoping review outlines recent evidence for NTM-PD diagnosis and management in SSA.Objective The review’s objective was to outline the risk factors, available diagnostics, management options and outcomes of NTM-PD in high-burden TB settings in SSA using the population-concept-context framework.Design and data sources We searched existing literature from PubMed, Web of Science, African Journals Online, Google Scholar and grey literature. Studies published between January 2005 and December 2022 were retained. Data were extracted into Rayyan software and Mendeley and summarised using Excel.Results We identified 785 potential articles, of which 105 were included in the full-text review, with 7 papers retained. Included articles used international criteria for diagnosing NTM-PD. Multiple papers were excluded due to non-application of the criteria, suggesting challenging application in the SSA setting. Identified risk factors include previous TB, smoking and mining. Most commonly, chest radiography and not CT was used for the radiological diagnosis of PD, which may miss early changes related to NTM-PD. Molecular methods for NTM species identification were employed in research settings, usually at referral centres, but were unavailable for routine care. Most studies did not report a standardised approach to treatment and they were not offered treatment for the specific disease, marking a lack of guidance in treatment decision-making. When treatment was provided, the outcome was often not reported due to the lack of implementation of standardised outcome definitions.Conclusions These outlined challenges present a unique opportunity for ...
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2024-01-01T00:00:00Z
Publisher	BMJ Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: GeneXpert MTB/RIF Ultra performance to detect uncommon rpoB mutations in Mycobacterium tuberculosis

Leen Rigouts / Jelle Keysers / Reenaers Rabab / Kristina Fissette / Armand van Deun / Bouke Catherine de Jong

BMC Research Notes, Vol 16, Iss 1, Pp 1-

2023 Volume 5

Abstract: Abstract Objective To investigate the performance of GeneXpert MTB/RIF Ultra to accurately detect rifampicin resistance for less common rpoB mutations that potentially confer phenotypic resistance, we tested 28 such Mycobacterium tuberculosis cultures ... ...

Abstract	Abstract Objective To investigate the performance of GeneXpert MTB/RIF Ultra to accurately detect rifampicin resistance for less common rpoB mutations that potentially confer phenotypic resistance, we tested 28 such Mycobacterium tuberculosis cultures with Xpert Ultra. Results They represented 22 different (combinations of) rpoB mutations. Of 28 isolates tested, one was reported by Xpert Ultra as “No rifampicin resistance detected”, 8 yielded a “Rifampicin indeterminate” result, and 19 were identified as rifampicin resistant. Overall, our results corroborate previous observations on the “Indeterminate” results for mutations at codon 432, while we add Lys446Gln as additional “Indeterminate” result and Pro439Leu as a false rifampicin-susceptible result. Furthermore, we document other uncommon point mutations and indels across the rpoB gene that are mostly correctly identified as rifampicin resistant by Xpert ultra (V3). Taken together, “Indeterminate” results in Xpert Ultra may indicate underlying rpoB mutations within the rifampicin-resistance determining region and thus increase the post-test probability of rifampicin resistance, albeit to an unknown extent.
Keywords	GeneXpert MTB/RIF Ultra ; rpoB ; Rifampicin resistance ; Tuberculosis ; Medicine ; R ; Biology (General) ; QH301-705.5 ; Science (General) ; Q1-390
Subject code	616
Language	English
Publishing date	2023-07-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Broad diversity of Mycobacterium tuberculosis complex strains isolated from humans and cattle in Northern Algeria suggests a zoonotic transmission cycle.

Hanane Damene / Djamel Tahir / Maren Diels / Ali Berber / Naima Sahraoui / Leen Rigouts

PLoS Neglected Tropical Diseases, Vol 14, Iss 11, p e

2020 Volume 0008894

Abstract: Mycobacterium tuberculosis complex (MTBC) comprises closely related species responsible for human and animal tuberculosis (TB). Efficient species determination is useful for epidemiological purposes, especially for the elucidation of the zoonotic ... ...

Abstract	Mycobacterium tuberculosis complex (MTBC) comprises closely related species responsible for human and animal tuberculosis (TB). Efficient species determination is useful for epidemiological purposes, especially for the elucidation of the zoonotic contribution. In Algeria, data on MTBC genotypes are largely unknown. In this study, we aimed to investigate the occurrence and diversity of MTBC genotypes causing human and bovine TB in Northern Algeria. During a two-year sampling period (2017-2019) in two regions of Northern Algeria, we observed an overall prevalence of 6.5% of tuberculosis (TB) among slaughtered cattle, which is higher than previous Algerian data yet comparable to neighboring countries. A total of 296 Mycobacterium tuberculosis complex (MTBC) isolates were genotyped by spoligotyping: 181 from tissues with TB-like lesions collected from 181 cattle carcasses and 115 from TB patients. In human isolates, we identified 107 M. tuberculosis, seven M. bovis and one "M. pinnipedii-like", while for bovine samples, 174 isolates were identified as M. bovis, three as M. caprae, three as "M. pinnipedii-like" and one as "M. microti-like". The majority of isolates (89.2%) belonged to 72 different known Shared International Types (SIT) or M. bovis spoligotypes (SB), while we also identified seven new SB profiles (SB2695 to SB2701). Twenty-eight of the SB profiles were new to Algeria. Our data suggest zoonotic transmission in Sétif, where significantly more TB was observed among cattle (20%) compared to the slaughterhouses from the three other regions (5.4%-7.3%) (p < 0.0001), with the isolation of the same M. bovis genotypes from TB patients. The present study showed a high genetic diversity of MTBC isolated from human and cattle in Northern Algeria. Even though relatively small in terms of numbers, our data suggest the zoonotic transmission of TB from cattle to humans, suggesting the need for stronger eradication strategies for bovine TB.
Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Community-supported self-administered tuberculosis treatment combined with active tuberculosis screening

Souleymane Hassane-Harouna / Tinne Gils / Tom Decroo / Nimer Ortuño-Gutiérrez / Alexandre Delamou / Gba-Foromo Cherif / Lansana Mady Camara / Leen Rigouts / Bouke Catherine de Jong

Global Health Action, Vol 16, Iss

a pilot experience in Conakry, Guinea

2023 Volume 1

Abstract: Directly observed treatment (DOT) for tuberculosis (TB) is recommended by the World Health Organization. However, DOT does not always meet patients’ preferences, burdens health facilities, and is hard to implement in settings where access to healthcare ... ...

Abstract	Directly observed treatment (DOT) for tuberculosis (TB) is recommended by the World Health Organization. However, DOT does not always meet patients’ preferences, burdens health facilities, and is hard to implement in settings where access to healthcare services is regularly interrupted. A model addressing these limitations of DOT is community-supported self-administered treatment (CS-SAT), in which patients who self-administer TB treatment receive regular visits from community members. Guinea is a country with a high TB burden, recurrent epidemics, and periodic socio-political unrest. We piloted a CS-SAT model for drug-susceptible TB patients in Conakry, led by community volunteers, who also conducted active TB case finding among household contacts and referrals for isoniazid preventive treatment (IPT) in children below 5 years old. We aimed to assess TB treatment outcomes of patients on CS-SAT and describe the number of patients identified with TB case finding and IPT provision. Prospectively enrolled bacteriologically confirmed TB patients, presenting to two facilities, received monthly TB medication. Community volunteers performed bi-weekly (initiation phase) and later monthly (continuation phase) home visits to verify treatment adherence, screen household contacts for TB, and assess IPT uptake in children under five. Among 359 enrolled TB patients, 237 (66.0%) were male, and 37 (10.3%) were HIV-positive. Three hundred forty (94.7%) participants had treatment success, seven (1.9%) died, seven (1.9%) experienced treatment failure, and five (1.4%) were lost-to-follow-up. Among 1585 household contacts screened for TB, 26 (1.6%) had TB symptoms, of whom five (19.2%) were diagnosed with pulmonary TB. IPT referral was done for 376 children from 198 households. In a challenging setting, where DOT is often not feasible, CS-SAT led to successful TB treatment outcomes and created an opportunity for active TB case finding and IPT referral. We recommend the Guinean CS-SAT model for implementation in similar settings.
Keywords	sat ; decentralized treatment ; tb-case finding ; tpt ; differentiated tb care ; Public aspects of medicine ; RA1-1270
Subject code	150
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	Taylor & Francis Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Management of falsepositive rifampicin resistant Xpert MTB/RIF – Authors' reply

Jean Claude Semuto Ngabonziza / Tom Decroo / Gabriela Torrea / Patrick Migambi / Armand Van Deun / Leen Rigouts / Bouke Catherine de Jong

The Lancet Microbe, Vol 1, Iss 6, Pp e239- (2020)

2020

Keywords	Medicine (General) ; R5-920 ; Microbiology ; QR1-502
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
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Article ; Online: Resistance to second-line anti-tuberculosis drugs among peruvian multidrug resistant Mycobacterium tuberculosis strains

Francesca Barletta / Carlos Zamudio / Leen Rigouts / Carlos Seas

Revista Peruana de Medicina Experimental y Salud Pública, Vol 31, Iss

2014 Volume 4

Abstract: Objectives. To determine the drug resistance profiles for quinolones: ciprofloxacin (CFX), ofloxacin (OFX), moxifloxacin (MFX), and gatifloxacin (GFX); and for injectables: kanamycin (KAN), amikacin (AMK), and capreomycin (CAP) in multidrug resistant ( ... ...

Abstract	Objectives. To determine the drug resistance profiles for quinolones: ciprofloxacin (CFX), ofloxacin (OFX), moxifloxacin (MFX), and gatifloxacin (GFX); and for injectables: kanamycin (KAN), amikacin (AMK), and capreomycin (CAP) in multidrug resistant (MDR) strains. We also investigated the correlation between mutations in rrs, tlyA and gyrA/B genes, and the in vitro resistance to the second-line anti-tuberculosis drugs. Materials and methods. In this pilot study we selected MDR clinical isolates collected from June-December 2004 in the Tropical Medicine Institute “Alexander von Humboldt” (Lima, Perú). The Minimum Inhibitory Concentration (MIC) of CFX, OFX, MFX, GFX, KAN, AMK and CAP for 14 clinical isolates were determined and the sequences of rrs, tlyA and gyrA/B genes were analyzed by conventional PCR followed by sequencing. Results. We obtained valid results for 11 samples. Four isolates were resistant to injectable drugs, and in all the cases the MICs were; 120 μg/mL for KAN and 160 μg/mL for AMK and CAP. Only 2 isolates were resistant to OFX with MIC = 4 μg/mL. Sequencing results suggested that the mutation A1401T in rrs gene could be the molecular cause of the resistance to injectable drugs. In this study we did not find any mutation in tlyA and gyrA/B associated to resistance. Conclusions. Our study suggests a possible association between the mutation A1401T in rrs and resistance to injectable drugs. However further studies should be done to confirm this hypothesis in Perú.
Keywords	resistencia a múltiples drogas ; mycobacterium tuberculosis ; farmacorresistencia microbiana ; Medicine ; R ; Medicine (General) ; R5-920
Subject code	630
Language	Spanish
Publishing date	2014-12-01T00:00:00Z
Publisher	Instituto Nacional de Salud
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Genotypic characterization directly applied to sputum improves the detection of Mycobacterium africanum West African 1, under-represented in positive cultures.

C N'Dira Sanoussi / Dissou Affolabi / Leen Rigouts / Séverin Anagonou / Bouke de Jong

PLoS Neglected Tropical Diseases, Vol 11, Iss 9, p e

2017 Volume 0005900

Abstract: This study aimed to compare the prevalence of Mycobacterium tuberculosis complex (MTBc) lineages between direct genotyping (on sputum) and indirect genotyping (on culture), to characterize potential culture bias against difficult growers.Smear-positive ... ...

Abstract	This study aimed to compare the prevalence of Mycobacterium tuberculosis complex (MTBc) lineages between direct genotyping (on sputum) and indirect genotyping (on culture), to characterize potential culture bias against difficult growers.Smear-positive sputa from consecutive new tuberculosis patients diagnosed in Cotonou, (Benin) were included, before patients had started treatment. An aliquot of decontaminated sputum was used for direct spoligotyping, and another aliquot was cultured on Löwenstein Jensen (LJ) medium (90 days), for indirect spoligotyping. After DNA extraction, spoligotyping was done according to the standard method for all specimens, and patterns obtained from sputa were compared versus those from the derived culture isolates. From 199 patient's sputa, 146 (73.4%) yielded a positive culture. In total, direct spoligotyping yielded a pattern in 98.5% (196/199) of the specimens, versus 73.4% (146/199) for indirect spoligotyping on cultures. There was good agreement between sputum- and isolate derived patterns: 94.4% (135/143) at spoligotype level and 96.5% (138/143) at (sub)lineage level. Two of the 8 pairs with discrepant pattern were suggestive of mixed infection in sputum. Ancestral lineages (Lineage 1, and M. africanum Lineages 5 and 6) were less likely to grow in culture (OR = 0.30, 95%CI (0.14 to 0.64), p = 0.0016); especially Lineage 5 (OR = 0.37 95%CI (0.17 to 0.79), p = 0.010). Among modern lineages, Lineage 4 was over-represented in positive-culture specimens (OR = 3.01, 95%CI (1.4 to 6.51), p = 0.005).Ancestral lineages, especially M. africanum West African 1 (Lineage 5), are less likely to grow in culture relative to modern lineages, especially M. tuberculosis Euro-American (Lineage 4). Direct spoligotyping on smear positive sputum is effective and efficient compared to indirect spoligotyping of cultures. It allows for a more accurate unbiased determination of the population structure of the M. tuberculosis complex.ClinicalTrials.gov NCT02744469.
Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
Subject code	572 ; 590
Language	English
Publishing date	2017-09-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Targeted next-generation sequencing of sputum for diagnosis of drug-resistant TB

Michel Kaswa Kayomo / Vital Nkake Mbula / Muriel Aloni / Emmanuel André / Leen Rigouts / Fairouz Boutachkourt / Bouke C. de Jong / Nicolas M. Nkiere / Anna S. Dean

Scientific Reports, Vol 10, Iss 1, Pp 1-

results of a national survey in Democratic Republic of the Congo

2020 Volume 8

Abstract: Abstract The surveillance of drug resistance among tuberculosis (TB) patients is central to preventing the spread of antimicrobial resistance. The Democratic Republic of the Congo (DR Congo) is classified by the World Health Organization (WHO) as a ... ...

Abstract	Abstract The surveillance of drug resistance among tuberculosis (TB) patients is central to preventing the spread of antimicrobial resistance. The Democratic Republic of the Congo (DR Congo) is classified by the World Health Organization (WHO) as a country with a high burden of TB and multidrug-resistant TB (MDR-TB), but there are no nationally representative data on drug resistance. In 2016–2017, a national survey of TB patients was conducted in 108 microscopy centres across all 11 provinces of the country using innovative molecular approaches. Sputum samples were collected from 1,545 new and 163 previously treated patients. These were tested by the Xpert MTB/RIF assay, followed by targeted next-generation sequencing performed directly on sputum. The prevalence of rifampicin resistance was low, at 1.8% (95% CI: 1.0–3.2) among new and 17.3% (95% CI: 11.9–24.4) among previously treated patients. Resistance to pyrazinamide, fluoroquinolones and second-line injectables was also low. The prevalence of resistance to isoniazid among rifampicin-susceptible patients was higher, at 6.6% (95% CI: 4.4–9.8) among new and 8.7% (95% : 3.2–21.2) among previously treated patients. Diagnosing and treating isoniazid-resistant patients remains a challenge, given that many will be missed by the current national diagnostic algorithm that is driven by detecting rifampicin resistance by Xpert MTB/RIF. This is the first nationwide survey incorporating targeted sequencing directly on sputum. It serves as a proof-of-concept for other settings that do yet have rapid specimen transport networks or capacity to conduct culture.
Keywords	Medicine ; R ; Science ; Q
Subject code	610 ; 616
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Minimally invasive sampling to identify leprosy patients with a high bacterial burden in the Union of the Comoros

Sofie Marijke Braet / Anouk van Hooij / Epco Hasker / Erik Fransen / Abdou Wirdane / Abdallah Baco / Saverio Grillone / Nimer Ortuno-Gutierrez / Younoussa Assoumani / Aboubacar Mzembaba / Paul Corstjens / Leen Rigouts / Annemieke Geluk / Bouke Catherine de Jong

PLoS Neglected Tropical Diseases, Vol 15, Iss

2021 Volume 11

Abstract: The World Health Organization (WHO) endorsed diagnosis of leprosy (also known as Hansen’s disease) entirely based on clinical cardinal signs, without microbiological confirmation, which may lead to late or misdiagnosis. The use of slit skin smears is ... ...

Abstract	The World Health Organization (WHO) endorsed diagnosis of leprosy (also known as Hansen’s disease) entirely based on clinical cardinal signs, without microbiological confirmation, which may lead to late or misdiagnosis. The use of slit skin smears is variable, but lacks sensitivity. In 2017–2018 during the ComLep study, on the island of Anjouan (Union of the Comoros; High priority country according to WHO, 310 patients were diagnosed with leprosy (paucibacillary = 159; multibacillary = 151), of whom 263 were sampled for a skin biopsy and fingerstick blood, and 260 for a minimally-invasive nasal swab. In 74.5% of all skin biopsies and in 15.4% of all nasal swabs, M. leprae DNA was detected. In 63.1% of fingerstick blood samples, M. leprae specific antibodies were detected with the quantitative αPGL-I test. Results show a strong correlation of αPGL-I IgM levels in fingerstick blood and RLEP-qPCR positivity of nasal swabs, with the M. leprae bacterial load measured by RLEP-qPCR of skin biopsies. Patients with a high bacterial load (≥50,000 bacilli in a skin biopsy) can be identified with combination of counting lesions and the αPGL-I test. To our knowledge, this is the first study that compared αPGL-I IgM levels in fingerstick blood with the bacterial load determined by RLEP-qPCR in skin biopsies of leprosy patients. The demonstrated potential of minimally invasive sampling such as fingerstick blood samples to identify high bacterial load persons likely to be accountable for the ongoing transmission, merits further evaluation in follow-up studies. Author summary Leprosy is the oldest infectious disease known to humankind. We still do not succeed in curbing its transmission, with more than 200,000 new patients detected worldwide each year. Identifying persons with a high burden of bacteria is key to curb transmission. To identify these persons, bacteria are counted in invasive and painful samples like slit skin smears and skin biopsies. We evaluated whether we can use less invasive samples, like fingerstick blood or ...
Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
Subject code	610
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Minimally invasive sampling to identify leprosy patients with a high bacterial burden in the Union of the Comoros.

PLoS Neglected Tropical Diseases, Vol 15, Iss 11, p e

2021 Volume 0009924

Abstract: The World Health Organization (WHO) endorsed diagnosis of leprosy (also known as Hansen's disease) entirely based on clinical cardinal signs, without microbiological confirmation, which may lead to late or misdiagnosis. The use of slit skin smears is ... ...

Abstract	The World Health Organization (WHO) endorsed diagnosis of leprosy (also known as Hansen's disease) entirely based on clinical cardinal signs, without microbiological confirmation, which may lead to late or misdiagnosis. The use of slit skin smears is variable, but lacks sensitivity. In 2017-2018 during the ComLep study, on the island of Anjouan (Union of the Comoros; High priority country according to WHO, 310 patients were diagnosed with leprosy (paucibacillary = 159; multibacillary = 151), of whom 263 were sampled for a skin biopsy and fingerstick blood, and 260 for a minimally-invasive nasal swab. In 74.5% of all skin biopsies and in 15.4% of all nasal swabs, M. leprae DNA was detected. In 63.1% of fingerstick blood samples, M. leprae specific antibodies were detected with the quantitative αPGL-I test. Results show a strong correlation of αPGL-I IgM levels in fingerstick blood and RLEP-qPCR positivity of nasal swabs, with the M. leprae bacterial load measured by RLEP-qPCR of skin biopsies. Patients with a high bacterial load (≥50,000 bacilli in a skin biopsy) can be identified with combination of counting lesions and the αPGL-I test. To our knowledge, this is the first study that compared αPGL-I IgM levels in fingerstick blood with the bacterial load determined by RLEP-qPCR in skin biopsies of leprosy patients. The demonstrated potential of minimally invasive sampling such as fingerstick blood samples to identify high bacterial load persons likely to be accountable for the ongoing transmission, merits further evaluation in follow-up studies.
Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
Subject code	610
Language	English
Publishing date	2021-11-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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