Journal Article > ReviewFull Text
Lancet Infect Dis. 12 December 2024; Volume S1473-3099 (Issue 24); 00727-8.; DOI:10.1016/S1473-3099(24)00727-8
Rojek A, Fieggen J, Paterson A, Byakika-Kibwika P, Camara M, et al.
Lancet Infect Dis. 12 December 2024; Volume S1473-3099 (Issue 24); 00727-8.; DOI:10.1016/S1473-3099(24)00727-8
Journal Article > ResearchFull Text
Lancet Infect Dis. 1 September 2024; Volume 24 (Issue 9); 1037-1044.; DOI:10.1016/S1473-3099(24)00184-1
Elsinga J, Sunyoto T, di Stefano L, Giorgetti PF, Kyi HA, et al.
Lancet Infect Dis. 1 September 2024; Volume 24 (Issue 9); 1037-1044.; DOI:10.1016/S1473-3099(24)00184-1
BACKGROUND
Lassa fever is a viral haemorrhagic fever with few options for diagnosis and treatment; it is also under-researched with knowledge gaps on its epidemiology. A point-of-care bedside test diagnosing Lassa fever, adhering to REASSURED criteria, is not currently available but is urgently needed in west African regions with high Lassa fever burden. We aimed to assess the validity and feasibility of a rapid diagnostic test (RDT) to confirm Lassa fever in people in Nigeria.
METHODS
We estimated the diagnostic performance of the ReLASV Pan-Lassa RDT (Zalgen Labs, Frederick, MD, USA) as a research-use-only test, compared to RT-PCR as a reference standard, in 217 participants at a federal tertiary hospital in Abakaliki, Nigeria. We recruited participants between Feb 17, 2022, and April 17, 2023. The RDT was performed using capillary blood at the patient bedside and using plasma at the laboratory. The performance of the test, based on REASSURED criteria, was assessed for user friendliness, rapidity and robustness, sensitivity, and specificity.
FINDINGS
Participants were aged between 0 and 85 years, with a median age of 33·0 years (IQR 22·0-44·3), and 24 participants were younger than 18 years. 107 (50%) participants were women and 109 (50%) were men; one participant had missing sex data. Although the specificity of the Pan-Lassa RDT was high (>90%), sensitivity at bedside using capillary blood was estimated as 4% (95% CI 1-14) at 15 min and 10% (3-22) at 25 min, far below the target of 90%. The laboratory-based RDT using plasma showed better sensitivity (46% [32-61] at 15 min and 50% [36-64] at 25 min) but did not reach the target sensitivity. Among the 52 PCR-positive participants with Lassa fever, positive RDT results were associated with lower cycle threshold values (glycoprotein precursor [GPC] gene mean 30·3 [SD 4·3], Large [L] gene mean 32·3 [3·7] vs GPC gene mean 24·5 [3·9], L gene mean 28·0 [3·6]). Personnel conducting the bedside test procedure reported being hindered by the inconvenient use of full personal protective equipment and long waiting procedures before a result could be read.
INTERPRETATION
The Pan-Lassa RDT is not currently recommended as a diagnostic or screening tool for suspected Lassa fever cases. Marked improvement in sensitivity and user friendliness is needed for the RDT to be adopted clinically. There remains an urgent need for better Lassa fever diagnostics to promote safety of in-hospital care and better disease outcomes in low-resource settings.
Lassa fever is a viral haemorrhagic fever with few options for diagnosis and treatment; it is also under-researched with knowledge gaps on its epidemiology. A point-of-care bedside test diagnosing Lassa fever, adhering to REASSURED criteria, is not currently available but is urgently needed in west African regions with high Lassa fever burden. We aimed to assess the validity and feasibility of a rapid diagnostic test (RDT) to confirm Lassa fever in people in Nigeria.
METHODS
We estimated the diagnostic performance of the ReLASV Pan-Lassa RDT (Zalgen Labs, Frederick, MD, USA) as a research-use-only test, compared to RT-PCR as a reference standard, in 217 participants at a federal tertiary hospital in Abakaliki, Nigeria. We recruited participants between Feb 17, 2022, and April 17, 2023. The RDT was performed using capillary blood at the patient bedside and using plasma at the laboratory. The performance of the test, based on REASSURED criteria, was assessed for user friendliness, rapidity and robustness, sensitivity, and specificity.
FINDINGS
Participants were aged between 0 and 85 years, with a median age of 33·0 years (IQR 22·0-44·3), and 24 participants were younger than 18 years. 107 (50%) participants were women and 109 (50%) were men; one participant had missing sex data. Although the specificity of the Pan-Lassa RDT was high (>90%), sensitivity at bedside using capillary blood was estimated as 4% (95% CI 1-14) at 15 min and 10% (3-22) at 25 min, far below the target of 90%. The laboratory-based RDT using plasma showed better sensitivity (46% [32-61] at 15 min and 50% [36-64] at 25 min) but did not reach the target sensitivity. Among the 52 PCR-positive participants with Lassa fever, positive RDT results were associated with lower cycle threshold values (glycoprotein precursor [GPC] gene mean 30·3 [SD 4·3], Large [L] gene mean 32·3 [3·7] vs GPC gene mean 24·5 [3·9], L gene mean 28·0 [3·6]). Personnel conducting the bedside test procedure reported being hindered by the inconvenient use of full personal protective equipment and long waiting procedures before a result could be read.
INTERPRETATION
The Pan-Lassa RDT is not currently recommended as a diagnostic or screening tool for suspected Lassa fever cases. Marked improvement in sensitivity and user friendliness is needed for the RDT to be adopted clinically. There remains an urgent need for better Lassa fever diagnostics to promote safety of in-hospital care and better disease outcomes in low-resource settings.
Conference Material > Poster
Elsinga J, Sunyoto T, Di Stefano L, Giorgetti PF, Kyi HA, et al.
MSF Scientific Day International 2024. 16 May 2024; DOI:10.57740/63l6oZ
Journal Article > Short ReportFull Text
Euro Surveill. 11 December 2014
Baggi FM, Taybi A, Kurth A, Van Herp M, Di Caro A, et al.
Euro Surveill. 11 December 2014
Journal Article > ResearchFull Text
Lancet Infect Dis. 13 February 2018; Volume 18 (Issue 5); 536-544.; DOI:10.1016/S1473-3099(18)30100-2
Ferlazzo G, Mohr E, Laxmeshwar C, Hewison CCH, Hughes J, et al.
Lancet Infect Dis. 13 February 2018; Volume 18 (Issue 5); 536-544.; DOI:10.1016/S1473-3099(18)30100-2
BACKGROUND
Bedaquiline and delamanid have been approved for treatment of multidrug-resistant (MDR) tuberculosis in the past 5 years. Because of theoretical safety concerns, patients have been unable to access the two drugs in combination. Médecins Sans Frontières has supported the use of combination bedaquiline and delamanid for people with few treatment options since 2016. We describe early safety and efficacy of regimens containing the bedaquiline and delamanid combination in patients with drug-resistant tuberculosis in Yerevan, Armenia; Mumbai, India; and Khayelitsha, South Africa.
METHODS
We retrospectively analysed a cohort of all patients who received 6-12 months of oral bedaquiline and delamanid in combination (400 mg bedaquiline once per day for 2 weeks, then 200 mg bedaquiline three times per week and 100 mg delamanid twice per day) in MSF-supported projects. We report serious adverse events, QTc corrected using the Fridericia formula (QTcF) interval data, and culture conversion data during the first 6 months of treatment.
FINDINGS
Between Jan 1, 2016, and Aug 31, 2016, 28 patients (median age 32·5 years [IQR 28·5-40·5], 17 men) were included in the analysis. 11 (39%) of 28 patients were HIV-positive. 24 patients (86%) had isolates resistant to fluoroquinolones; 14 patients (50%) had extensively drug-resistant tuberculosis. No patient had an increase of more than 500 ms in their QTcF interval. Four patients (14%) had six instances of QTcF increase of more than 60 ms from baseline but none permanently discontinued the drugs. 16 serious adverse events were reported in seven patients. Of 23 individuals with positive baseline cultures, 17 (74%) converted to negative by month 6 of treatment.
INTERPRETATION
Use of the bedaquiline and delamanid combination appears to reveal no additive or synergistic QTcF-prolonging effects. Access to bedaquiline and delamanid in combination should be expanded for people with few treatment options while awaiting the results of formal clinical trials.
Bedaquiline and delamanid have been approved for treatment of multidrug-resistant (MDR) tuberculosis in the past 5 years. Because of theoretical safety concerns, patients have been unable to access the two drugs in combination. Médecins Sans Frontières has supported the use of combination bedaquiline and delamanid for people with few treatment options since 2016. We describe early safety and efficacy of regimens containing the bedaquiline and delamanid combination in patients with drug-resistant tuberculosis in Yerevan, Armenia; Mumbai, India; and Khayelitsha, South Africa.
METHODS
We retrospectively analysed a cohort of all patients who received 6-12 months of oral bedaquiline and delamanid in combination (400 mg bedaquiline once per day for 2 weeks, then 200 mg bedaquiline three times per week and 100 mg delamanid twice per day) in MSF-supported projects. We report serious adverse events, QTc corrected using the Fridericia formula (QTcF) interval data, and culture conversion data during the first 6 months of treatment.
FINDINGS
Between Jan 1, 2016, and Aug 31, 2016, 28 patients (median age 32·5 years [IQR 28·5-40·5], 17 men) were included in the analysis. 11 (39%) of 28 patients were HIV-positive. 24 patients (86%) had isolates resistant to fluoroquinolones; 14 patients (50%) had extensively drug-resistant tuberculosis. No patient had an increase of more than 500 ms in their QTcF interval. Four patients (14%) had six instances of QTcF increase of more than 60 ms from baseline but none permanently discontinued the drugs. 16 serious adverse events were reported in seven patients. Of 23 individuals with positive baseline cultures, 17 (74%) converted to negative by month 6 of treatment.
INTERPRETATION
Use of the bedaquiline and delamanid combination appears to reveal no additive or synergistic QTcF-prolonging effects. Access to bedaquiline and delamanid in combination should be expanded for people with few treatment options while awaiting the results of formal clinical trials.
Journal Article > ResearchFull Text
Emerg Infect Dis. 1 February 2016; Volume 22 (Issue 2); DOI:10.3201/eid2202.151238
Van der Bergh R, Chaillet P, Sow MS, Amand M, van Vyve C, et al.
Emerg Infect Dis. 1 February 2016; Volume 22 (Issue 2); DOI:10.3201/eid2202.151238
Rapid diagnostic methods are essential in control of Ebola outbreaks and lead to timely isolation of cases and improved epidemiologic surveillance. Diagnosis during Ebola outbreaks in West Africa has relied on PCR performed in laboratories outside this region. Because time between sampling and PCR results can be considerable, we assessed the feasibility and added value of using the Xpert Ebola Assay in an Ebola control program in Guinea. A total of 218 samples were collected during diagnosis, treatment, and convalescence of patients. Median time for obtaining results was reduced from 334 min to 165 min. Twenty-six samples were positive for Ebola virus. Xpert cycle thresholds were consistently lower, and 8 (31%) samples were negative by routine PCR. Several logistic and safety issues were identified. We suggest that implementation of the Xpert Ebola Assay under programmatic conditions is feasible and represents a major advance in diagnosis of Ebola virus disease without apparent loss of assay sensitivity.
Journal Article > ResearchFull Text
HIV/AIDS Res Treat Open J. 11 May 2015; Volume 2 (Issue 2); 44-50.; DOI:10.17140/HARTOJ-2-107
Vandendyck M, Motsamai M, Mubanga M, Makhakhe S, Tunggal S, et al.
HIV/AIDS Res Treat Open J. 11 May 2015; Volume 2 (Issue 2); 44-50.; DOI:10.17140/HARTOJ-2-107
OBJECTIVES
We conducted a mixed method study to evaluate the pilot of community ART groups (CAG’s) in Lesotho.
METHODS
At the end of 2012 CAGs were piloted in Nazareth clinic, a facility in rural Lesotho. In CAG’s stable patients take turns to collect antiretroviral therapy (ART) for fellow group members. Kaplan-Meier techniques were used to estimate retention among stable patients in CAG and not in CAG. Eight focus group discussions with 40 purposively selected CAG members, nine village health workers, six community leaders and nine clinicians provided insights in how CAGs are perceived by different stakeholders. The thematic analysis approach was employed for data analysis.
RESULTS
Among 596 stable patients 199 (33%) had joined a CAG. One year retention among CAG members and patients not in CAG was 98.7% (95% CI, 94.9-99.7) and 90.2% (95% CI, 86.6-92.9) respectively. CAG members commented that membership in CAG: 1) reduced time, effort, and money spent to get a monthly ART refill; 2) induced peer support, which enhanced adherence, socio-economic support and empowered members to deal with stigma; and 3) resulted in a feeling of relief and comfort. Village health workers confirmed increased openness about HIV in their community. Community leaders added that CAG members promoted health seeking behaviour to community members. Clinicians reported a workload reduction.
CONCLUSION
Participation in CAG impacted positively on the lives of members, not only on their access to ART, but also on their life within the community.
We conducted a mixed method study to evaluate the pilot of community ART groups (CAG’s) in Lesotho.
METHODS
At the end of 2012 CAGs were piloted in Nazareth clinic, a facility in rural Lesotho. In CAG’s stable patients take turns to collect antiretroviral therapy (ART) for fellow group members. Kaplan-Meier techniques were used to estimate retention among stable patients in CAG and not in CAG. Eight focus group discussions with 40 purposively selected CAG members, nine village health workers, six community leaders and nine clinicians provided insights in how CAGs are perceived by different stakeholders. The thematic analysis approach was employed for data analysis.
RESULTS
Among 596 stable patients 199 (33%) had joined a CAG. One year retention among CAG members and patients not in CAG was 98.7% (95% CI, 94.9-99.7) and 90.2% (95% CI, 86.6-92.9) respectively. CAG members commented that membership in CAG: 1) reduced time, effort, and money spent to get a monthly ART refill; 2) induced peer support, which enhanced adherence, socio-economic support and empowered members to deal with stigma; and 3) resulted in a feeling of relief and comfort. Village health workers confirmed increased openness about HIV in their community. Community leaders added that CAG members promoted health seeking behaviour to community members. Clinicians reported a workload reduction.
CONCLUSION
Participation in CAG impacted positively on the lives of members, not only on their access to ART, but also on their life within the community.
Journal Article > ResearchFull Text
Nature. 4 May 2016; Volume 533 (Issue 7601); 100-104.; DOI:10.1038/nature17949
Ruibal P, Oestereich L, Ludtke A, Becker-Ziaja B, Wozniak DM, et al.
Nature. 4 May 2016; Volume 533 (Issue 7601); 100-104.; DOI:10.1038/nature17949
Despite the magnitude of the Ebola virus disease (EVD) outbreak in West Africa, there is still a fundamental lack of knowledge about the pathophysiology of EVD. In particular, very little is known about human immune responses to Ebola virus. Here we evaluate the physiology of the human T cell immune response in EVD patients at the time of admission to the Ebola Treatment Center in Guinea, and longitudinally until discharge or death. Through the use of multiparametric flow cytometry established by the European Mobile Laboratory in the field, we identify an immune signature that is unique in EVD fatalities. Fatal EVD was characterized by a high percentage of CD4(+) and CD8(+) T cells expressing the inhibitory molecules CTLA-4 and PD-1, which correlated with elevated inflammatory markers and high virus load. Conversely, surviving individuals showed significantly lower expression of CTLA-4 and PD-1 as well as lower inflammation, despite comparable overall T cell activation. Concomitant with virus clearance, survivors mounted a robust Ebola-virus-specific T cell response. Our findings suggest that dysregulation of the T cell response is a key component of EVD pathophysiology.
Journal Article > ReviewFull Text
Am J Respir Crit Care Med. 17 November 2016; Volume 195 (Issue 101); 1300-1310.; DOI:10.1164/rccm.201606-1227CI
Harausz EP, Garcia-Prats AJ, Seddon JA, Schaaf HS, Hesseling AC, et al.
Am J Respir Crit Care Med. 17 November 2016; Volume 195 (Issue 101); 1300-1310.; DOI:10.1164/rccm.201606-1227CI
It is estimated that 33,000 children develop multidrug-resistant tuberculosis (MDR-TB) each year. In spite of these numbers, children and adolescents have limited access to the new and repurposed MDR-TB drugs. There is also little clinical guidance for the use of these drugs and for the shorter MDR-TB regimen in the pediatric population. This is despite the fact that these drugs and regimens are associated with improved interim outcomes and acceptable safety profiles in adults. This review fills a gap in the pediatric MDR-TB literature by providing practice-based recommendations for the use of the new (delamanid and bedaquiline) and repurposed (linezolid and clofazimine) MDR-TB drugs and the new shorter MDR-TB regimen in children and adolescents.
Journal Article > ResearchFull Text
PLOS One. 9 September 2016; Volume 11 (Issue 9); DOI:10.1371/journal.pone.0162138
Mehta S, Das M, Laxmeshwar C, Jonckheere S, Thi SS, et al.
PLOS One. 9 September 2016; Volume 11 (Issue 9); DOI:10.1371/journal.pone.0162138
Patients on linezolid-containing drug-resistant TB (DR-TB) regimen often develop adverse-events, particularly peripheral and optic neuropathy. Programmatic data and experiences of linezolid-associated optic neuropathy from high DR-TB burden settings are lacking. The study aimed to determine the frequency of and risk-factors associated with linezolid-associated optic neuropathy and document the experiences related to treatment/care of DR-TB patients on linezolid-containing regimens.