Journal Article > CommentaryFull Text
PLoS Negl Trop Dis. 2015 November 12; Volume 9 (Issue 11); e0004075.; DOI:10.1371/journal.pntd.0004075
O'Brien DP, Ford NP, Vitoria M, Asiedu K, Calmy A, et al.
PLoS Negl Trop Dis. 2015 November 12; Volume 9 (Issue 11); e0004075.; DOI:10.1371/journal.pntd.0004075
Conference Material > Video (talk)
Ntone R
Epicentre Scientific Day Paris 2021. 2021 June 10
Journal Article > ResearchFull Text
Afr J Biotechnol. 2009 February 28; Volume 8 (Issue 4); 536-546.; DOI:10.5897/AJB2009.000-9091
Ahoua L, Guetta AN, Ekaza E, Bouzid S, N’Guessan R, et al.
Afr J Biotechnol. 2009 February 28; Volume 8 (Issue 4); 536-546.; DOI:10.5897/AJB2009.000-9091
A case-control study was carried out in 3 highly endemic regions of Côte d’Ivoire to study risk factors for Buruli ulcer. A case was defined as a Buruli ulcer occurring less than one year before the date of survey, resident in one of the regions investigated and there was no history of Buruli ulcer illness. Controls were selected from the general population by a two stage cluster sampling method. A total of 116 cases and 116 controls were included. For the cases, the male/female sex ratio was 0.84, the median age was 19.5 years and 40.5% were children 15 years. Biological results were obtained for 86 (74%) cases using skin exudate samples. Positive rates were 22.0, 22.1 and 27.9% respectively for smear examination, culture and PCR IS2404, respectively. After adjusting for possible confounders, no history of BCG vaccination (ORa = 5.0, CI 1.7 - 14.3), presence of a case 15 years (ORa = 8.3, CI 2.8 -24.1), having a river/lake/dam near the housing (ORa = 4.4, CI 1.6 - 12.2) and the type of place for fishing (p = 0.001) were associated with illness. Young children and women having daily water related activities were most at risk. Swab samples were not sensitive enough for Buruli ulcer diagnosis. There is an urgent need for a rapid field test to diagnosis Buruli Ulcer as PCR IS2404 remains expensive for most of the endemic countries.
Conference Material > Abstract
Ahortor E, Mahazu S, Manful T, Erber A, Ablordey A
MSF Scientific Day International 2024. 2024 May 16; DOI:10.57740/MAt4h7
INTRODUCTION
Buruli ulcer caused by Mycobacterium ulcerans is a devastating necrotic skin disease. PCR, recommended for confirmation of Buruli ulcer by WHO, requires an adequately equipped laboratory, often delaying diagnosis and treatment of patients in remote or humanitarian settings. We aimed to assess loop- mediated isothermal amplification (LAMP), which is a molecular assay for isothermal amplification of DNA suggested for timely diagnosis of Buruli ulcer in low-resource settings.
METHODS
This study combines quantitative and qualitative methods. First, we evaluated a simple rapid syringe DNA extraction method (SM) in comparison with a conventional extraction method (CM), followed by a LAMP assay targeting IS2404 for the detection of M ulcerans, either using a pocket warmer (pw) or a heat block (hb) for incubation of the reaction. 83 clinical specimens (swabs and fine-needle aspirates from different centres in Ghana) were tested. We assessed sensitivity, specificity, and positive and negative predictive value (PPV and NPV). Second, we explored the diagnostic workflow for Buruli ulcer at a community-based health centre in rural Ghana, a potential target setting. We used observations and interviews with researchers and healthcare workers (HCWs) and community-based surveillance volunteers. We discuss evaluation results in relation to the target setting and requirements of a target product profile for Buruli ulcer diagnosis.
RESULTS
DNA extraction using SM followed by IS2404 PCR (IS2404 PCRSM) identified M ulcerans DNA in 73 of 83 clinical specimens. The sensitivity, specificity, PPV, and NPV of IS2404 PCRSM were 90.12%, 100%, 100%, and 65.21%, respectively, compared
with the reference standard IS2404 PCR with the CM protocol. Evaluation of the LAMP assay on 64 SM DNA extracts showed a sensitivity, specificity, PPV, and NPV of 83.6%, 100%, 100%, and 50%, respectively, using either pw (pwLAMPSM) or hb (hbLAMPSM) for incubation, compared with the same reference standard. The limit of detection of both pwLAMPSM and hbLAMPSM was 30 target copies. Interviews confirmed that, despite great engagement from HCWs and volunteers, patients met challenges regarding transport and costs for initial diagnosis and follow- up and often sought alternative treatments first. Diagnostic confirmation via PCR in a reference laboratory led to a delay in the initiation of treatment. A diagnosis at the point of care, following clinical screening, was considered advantageous to prevent delays and loss to follow-up, therefore ensuring timely patient treatment.
CONCLUSION
Our findings support the potential use of pwLAMP for rapid diagnosis of Buruli Ulcer in patients with a suspected infection at the community or primary health-care level, with limited equipment and without reliable electricity supply such as found in humanitarian settings.
Buruli ulcer caused by Mycobacterium ulcerans is a devastating necrotic skin disease. PCR, recommended for confirmation of Buruli ulcer by WHO, requires an adequately equipped laboratory, often delaying diagnosis and treatment of patients in remote or humanitarian settings. We aimed to assess loop- mediated isothermal amplification (LAMP), which is a molecular assay for isothermal amplification of DNA suggested for timely diagnosis of Buruli ulcer in low-resource settings.
METHODS
This study combines quantitative and qualitative methods. First, we evaluated a simple rapid syringe DNA extraction method (SM) in comparison with a conventional extraction method (CM), followed by a LAMP assay targeting IS2404 for the detection of M ulcerans, either using a pocket warmer (pw) or a heat block (hb) for incubation of the reaction. 83 clinical specimens (swabs and fine-needle aspirates from different centres in Ghana) were tested. We assessed sensitivity, specificity, and positive and negative predictive value (PPV and NPV). Second, we explored the diagnostic workflow for Buruli ulcer at a community-based health centre in rural Ghana, a potential target setting. We used observations and interviews with researchers and healthcare workers (HCWs) and community-based surveillance volunteers. We discuss evaluation results in relation to the target setting and requirements of a target product profile for Buruli ulcer diagnosis.
RESULTS
DNA extraction using SM followed by IS2404 PCR (IS2404 PCRSM) identified M ulcerans DNA in 73 of 83 clinical specimens. The sensitivity, specificity, PPV, and NPV of IS2404 PCRSM were 90.12%, 100%, 100%, and 65.21%, respectively, compared
with the reference standard IS2404 PCR with the CM protocol. Evaluation of the LAMP assay on 64 SM DNA extracts showed a sensitivity, specificity, PPV, and NPV of 83.6%, 100%, 100%, and 50%, respectively, using either pw (pwLAMPSM) or hb (hbLAMPSM) for incubation, compared with the same reference standard. The limit of detection of both pwLAMPSM and hbLAMPSM was 30 target copies. Interviews confirmed that, despite great engagement from HCWs and volunteers, patients met challenges regarding transport and costs for initial diagnosis and follow- up and often sought alternative treatments first. Diagnostic confirmation via PCR in a reference laboratory led to a delay in the initiation of treatment. A diagnosis at the point of care, following clinical screening, was considered advantageous to prevent delays and loss to follow-up, therefore ensuring timely patient treatment.
CONCLUSION
Our findings support the potential use of pwLAMP for rapid diagnosis of Buruli Ulcer in patients with a suspected infection at the community or primary health-care level, with limited equipment and without reliable electricity supply such as found in humanitarian settings.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2007 December 19; Volume 1 (Issue 3); DOI:10.1371/journal.pntd.0000101
Pouillot R, Matias G, Wondje CM, Portaels F, Valin N, et al.
PLoS Negl Trop Dis. 2007 December 19; Volume 1 (Issue 3); DOI:10.1371/journal.pntd.0000101
BACKGROUND: Buruli ulcer is an infectious disease involving the skin, caused by Mycobacterium ulcerans. This disease is associated with areas where the water is slow-flowing or stagnant. However, the exact mechanism of transmission of the bacillus and the development of the disease through human activities is unknown. METHODOLOGY/PRINCIPAL FINDINGS: A case-control study to identify Buruli ulcer risk factors in Cameroon compared case-patients with community-matched controls on one hand and family-matched controls on the other hand. Risk factors identified by the community-matched study (including 163 pairs) were: having a low level of education, swamp wading, wearing short, lower-body clothing while farming, living near a cocoa plantation or woods, using adhesive bandages when hurt, and using mosquito coils. Protective factors were: using bed nets, washing clothes, and using leaves as traditional treatment or rubbing alcohol when hurt. The family-matched study (including 118 pairs) corroborated the significance of education level, use of bed nets, and treatment with leaves. CONCLUSIONS/SIGNIFICANCE: Covering limbs during farming activities is confirmed as a protective factor guarding against Buruli ulcer disease, but newly identified factors including wound treatment and use of bed nets may provide new insight into the unknown mode of transmission of M. ulcerans or the development of the disease.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2009 June 23; Volume 3 (Issue 6); DOI:10.1371/journal.pntd.0000466
Porten K, Sailor K, Comte E, Njikap A, Sobry A, et al.
PLoS Negl Trop Dis. 2009 June 23; Volume 3 (Issue 6); DOI:10.1371/journal.pntd.0000466
BACKGROUND: Buruli ulcer (BU) is a chronic, indolent necrotizing disease of the skin and underlying tissues caused by Mycobacterium ulcerans, which may result in functional incapacity. In 2002, Médecins Sans Frontières (MSF) opened a BU programme in Akonolinga Hospital, Cameroon, offering antibiotic treatment, surgery and general medical care. Six hundred patients have been treated in the project to date. However, due to the nature of the disease and its stigmatization, determining the exact prevalence and burden of disease is difficult and current estimates may not reflect the magnitude of the problem. The objectives of this survey were to estimate the prevalence of BU in the health district of Akonolinga, describe the geographic extension of the highly endemic area within the health district, and determine the programme coverage and its geographical distribution. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a cross-sectional population survey using centric systematic area sampling (CSAS). A 15x15 km grid (quadrats of 225 km(2)) was overlaid on a map of Akonolinga district with its position chosen to maximize the area covered by the survey. Quadrats were selected if more than 50% of the quadrat was inside of the health district. The chiefdom located closest to the centre of each quadrat was selected and Buruli cases were identified using an active case finding strategy (the sensitivity of the strategy was estimated by capture-recapture). WHO-case definitions were used for nodules, plaque, ulcer, oedema and sequelae. Out of a total population of 103,000 inhabitants, 26,679 were surveyed within the twenty quadrats. Sensitivity of the case finding strategy was estimated to be 84% (95%CI 54-97%). The overall prevalence was 0.47% (n = 105) for all cases including sequelae and 0.25% (n = 56) for active stages of the disease. Five quadrats had a high prevalence of >0.6% to 0.9%, 5 a prevalence >0.3% to 0.6% and 10 quadrats <0.3%. The quadrats with the high prevalence were situated along the rivers Nyong and Mfoumou. Overall coverage of the project was 18% (12-27%) for all cases and 16% (9-18%) for active cases, but was limited to the quadrats neighbouring Akonolinga Hospital. CONCLUSIONS/SIGNIFICANCE: Prevalence was highest in the area neighbouring the Nyong River. Coverage was limited to the area close to the hospital and efforts have to be made to increase access to care in the high prevalence areas. Use of the CSAS method was particularly useful for project planning and to identify priority areas of intervention. An added benefit of the method is that the survey procedure incorporated an awareness campaign, providing information about the disease and treatment to the population.
Journal Article > ResearchFull Text
Open Forum Infect Dis. 2014 April 26; Volume 1 (Issue 1); DOI:10.1093/ofid/ofu021
Christinet V, Rossel L, Serafini M, Delhumeau C, Odermatt P, et al.
Open Forum Infect Dis. 2014 April 26; Volume 1 (Issue 1); DOI:10.1093/ofid/ofu021
Journal Article > ResearchAbstract
Journal Pediatric Child Health. 2019 December 10; Volume 56 (Issue 4); DOI:10.1111/jpc.14704
Walker G, Friedman ND, O'Brien DP
Journal Pediatric Child Health. 2019 December 10; Volume 56 (Issue 4); DOI:10.1111/jpc.14704
AIM:
This study describes an Australian cohort of paediatric Buruli ulcer (BU) patients and compares them with adult BU patients.
METHODS:
Analysis of a prospective cohort of all BU cases managed at Barwon Health, Victoria, from 1 January 1998 to 31 May 2018 was performed. Children were defined as ≤15 years of age.
RESULTS:
A total of 565 patients were included: 52 (9.2%) children, 289 (51.2%) adults aged 16-64 years and 224 (39.6%) adults aged ≥65 years. Among children, half were female and the median age was 8.0 years (interquartile range 4.8-12.3 years). Six (11.5%) cases were diagnosed from 2001 to 2006, 14 (26.9%) from 2007 to 2012 and 32 (61.5%) from 2013 to 2018. Compared to adults, children had a significantly higher proportion of non-ulcerative lesions (32.7%, P < 0.001) and a higher proportion of severe lesions (26.9%, P < 0.01). The median duration of symptoms prior to diagnosis was shorter for children compared with adults aged 16-64 years (42 vs. 56 days, P = 0.04). Children were significantly less likely to experience antibiotic complications (6.1%) compared with adults (20.6%, P < 0.001), but had a significantly higher rate of paradoxical reactions (38.8%) compared with adults aged 16-64 (19.2%) (P < 0.001). Paradoxical reactions in children occurred significantly earlier than in adults (median 17 vs. 56 days, P < 0.01). Cure rates were similarly high for children compared to adults treated with antibiotics alone or with antibiotics and surgery.
CONCLUSIONS:
Paediatric BU cases in Australia are increasing and represent an important but stable proportion of Australian BU cohorts. Compared with adults, there are significant differences in clinical presentation and treatment outcomes.
This study describes an Australian cohort of paediatric Buruli ulcer (BU) patients and compares them with adult BU patients.
METHODS:
Analysis of a prospective cohort of all BU cases managed at Barwon Health, Victoria, from 1 January 1998 to 31 May 2018 was performed. Children were defined as ≤15 years of age.
RESULTS:
A total of 565 patients were included: 52 (9.2%) children, 289 (51.2%) adults aged 16-64 years and 224 (39.6%) adults aged ≥65 years. Among children, half were female and the median age was 8.0 years (interquartile range 4.8-12.3 years). Six (11.5%) cases were diagnosed from 2001 to 2006, 14 (26.9%) from 2007 to 2012 and 32 (61.5%) from 2013 to 2018. Compared to adults, children had a significantly higher proportion of non-ulcerative lesions (32.7%, P < 0.001) and a higher proportion of severe lesions (26.9%, P < 0.01). The median duration of symptoms prior to diagnosis was shorter for children compared with adults aged 16-64 years (42 vs. 56 days, P = 0.04). Children were significantly less likely to experience antibiotic complications (6.1%) compared with adults (20.6%, P < 0.001), but had a significantly higher rate of paradoxical reactions (38.8%) compared with adults aged 16-64 (19.2%) (P < 0.001). Paradoxical reactions in children occurred significantly earlier than in adults (median 17 vs. 56 days, P < 0.01). Cure rates were similarly high for children compared to adults treated with antibiotics alone or with antibiotics and surgery.
CONCLUSIONS:
Paediatric BU cases in Australia are increasing and represent an important but stable proportion of Australian BU cohorts. Compared with adults, there are significant differences in clinical presentation and treatment outcomes.
Journal Article > CommentaryFull Text
Trop Med Int Health. 2014 June 20; Volume 19 (Issue 9); DOI:10.1111/tmi.12342
O'Brien DP, Ford NP, Vitoria M, Christinet V, Comte E, et al.
Trop Med Int Health. 2014 June 20; Volume 19 (Issue 9); DOI:10.1111/tmi.12342
Journal Article > ResearchFull Text
Open Forum Infect Dis. 2014 May 21; Volume 1 (Issue 1); DOI:10.1093/ofid/ofu021
Christinet V, Comte E, Ciaffi L, Odermatt P, Serafini M, et al.
Open Forum Infect Dis. 2014 May 21; Volume 1 (Issue 1); DOI:10.1093/ofid/ofu021
Background: Buruli ulcer (BU) is the third most common mycobacterial disease after tuberculosis and leprosy and is particularly frequent in rural West and Central Africa. However, the impact of HIV infection on BU severity and prevalence remains unclear. Methods: This was a retrospective study of data collected at the Akonolinga district hospital, Cameroon, from 1 January 2002 to 27 March 2013. HIV prevalence among BU patients was compared to regional HIV prevalence. Baseline characteristics of BU patients were compared between HIV-negative and HIV-positive patients, and according to CD4 cell count strata in the latter group. BU time-to-healing was assessed in different CD4 count strata and factors associated with BU main lesion size at baseline were identified. Results: HIV prevalence among BU patients was significantly higher than the regional estimated prevalence in each group (children, 4.00% vs 0.68% [P < .001]; men, 17.0% vs 4.7% [P < .001]; women, 36.0% vs 8.0% [P < .001]). HIV-positive individuals had a more severe form of BU with an increased severity in those with a higher level of immunosuppression. Low CD4 cell count was significantly associated with a larger main lesion size (beta-coefficient, -0.50; P = .015; 95% confidence interval [CI], -0.91 – 0.10). BU time-to-healing was more than double in patients with a CD4 cell count below 500 cell/mm3 (hazard ratio, 2.39; P = .001, 95% CI, 1.44 - 3.98). Conclusion: HIV-positive patients are at higher risk for BU. HIV-induced immunosuppression appears to have an impact on BU clinical presentation and disease evolution.