Journal Article > ResearchFull Text
Open Forum Infect Dis. 27 September 2024; Volume 11 (Issue 10); DOI:10.1093/ofid/ofae579
Taher AQM, Aqel R, Alnajjar M, Walker C, Repetto E, et al.
Open Forum Infect Dis. 27 September 2024; Volume 11 (Issue 10); DOI:10.1093/ofid/ofae579
BACKGROUND
The history of conflicts in the Middle East has resulted in a high burden of complications from conflict-related wounds like posttraumatic osteomyelitis (PTO). This is particularly challenging to manage in settings like Mosul, Iraq and Gaza, Palestine, where healthcare systems are weakened. In nonconflict settings, PTO caused by Pseudomonas aeruginosa (PAPTO) can lead to >20% of treatment failures. We aim to describe the clinical characteristics, outcomes, and management, in PAPTO patients admitted to Médecins Sans Frontières (MSF) facilities in Mosul and Gaza between 1 April 2018 and 31 January 2022.
METHODS
We conducted a retrospective cohort study on patients with PAPTO diagnosed with culture of intraoperative bone biopsy, using routinely collected data.
RESULTS
Among 66 PAPTO episodes from 61 enrolled patients, 37.9% had a multidrug-resistant Pseudomonas aeruginosa, with higher antibiotic resistance in Gaza. Polymicrobial infections were prevalent (74.2%), mainly involving Staphylococcus aureus (74.1%), being predominantly methicillin-resistant (95.0%). Overall, 81.7% received appropriate antibiotic treatment, with monotherapy used in 60.6% of episodes and a median treatment duration of 45.5 days. Recurrence was observed in 24.6% of episodes within a median of 195 days (interquartile range, 64-440 days). No significant differences were found in recurrence rates based on the type of antibiotic treatment (mono- or dual therapy) or episode (mono- or polymicrobial).
CONCLUSIONS
Management of PAPTO in the conflict-affected, low-resource settings of Mosul and Gaza achieved a recurrence rate aligned with global reports through appropriate and targeted antibiotic use, primarily in monotherapy, provided over a mean treatment duration of 45.5 days.
Journal Article > ResearchFull Text
Open Forum Infect Dis. 8 July 2024; Volume 11 (Issue 8); ofae379.; DOI:10.1093/ofid/ofae379
Abdulrahman Ahmed H, Hasheem Mahmood H, Hosam Aldin Sami H, Natiq Taher A, Garcia-Vello P, et al.
Open Forum Infect Dis. 8 July 2024; Volume 11 (Issue 8); ofae379.; DOI:10.1093/ofid/ofae379
The Médecins Sans Frontières Tertiary Orthopaedic Care center in Mosul, Iraq, provides reconstructive surgery, microbiological analysis, integrated infection prevention and control, and antibiotic stewardship services. Between May 2018 and February 2020, we recorded soft tissue and/or bone infections caused by gram-negative extensively drug-resistant (XDR) bacteria in 4.9% (13/266) of the admitted patients. The XDR bacteria identified among 12 patients in this case series were extended-spectrum β-lactamase–producing Klebsiella pneumoniae (n = 5, 41.7%) with intermediate sensitivity or resistance to imipenem and/or meropenem, Acinetobacter spp (n = 3, 25.0%; 2 Acinetobacter baumannii strains) resistant to imipenem and/or meropenem, Pseudomonas aeruginosa (n = 2, 16.7%) resistant to imipenem and meropenem, and extended-spectrum β-lactamase–producing Proteus mirabilis (n = 2, 16.7%) resistant to meropenem. Most XDR isolates were sensitive only to colistin or polymyxin B, neither of which is available in Iraq. Therefore, the only treatment option was multiple rounds of surgical debridement and wound care. The infection was deemed cured before discharge in 7 patients (58.3%). Meanwhile, 4 patients (33.3%) were discharged with unhealed wounds, and outpatient follow-up was planned. One patient died in the intensive care unit of a referral hospital after developing septicemia postsurgery. XDR bacteria pose substantial health risks in Iraq. Thus, improving antimicrobial stewardship and accessibility to essential antibiotics is critical to address this issue.
Journal Article > ResearchFull Text
Open Forum Infect Dis. 2 May 2024; Volume 11 (Issue 5); ofae221.; DOI:10.1093/ofid/ofae221
Moretó-Planas L, Mahajan R, Fidelle Nyikayo L, Ajack YBP, Tut Chol B, et al.
Open Forum Infect Dis. 2 May 2024; Volume 11 (Issue 5); ofae221.; DOI:10.1093/ofid/ofae221
BACKGROUND
Over half of childhood tuberculosis (TB) remains undiagnosed yearly. WHO recommends Xpert-Ultra as a first paediatric diagnosis test, but microbiological confirmation remains low. We aimed to determine the diagnostic performance of Xpert-Ultra on stool and urine in presumptive paediatric TB cases in two high-TB burden settings.
METHODS
This Médecins sans Frontières cross-sectional multicentric study took place at Simão Mendes hospital, Guinea-Bissau (July 2019 to April 2020) and in Malakal hospital, South Sudan (April 2021 to June 2023). Children 6 months to 15 years with presumptive TB underwent clinical and laboratory assessment, with one respiratory and/or extrapulmonary sample (gold standard (GS)), one stool and one urine specimen analysed with Xpert-Ultra.
RESULTS
A total of 563 children were enrolled in the study, 133 from Bissau, 400 from Malakal; 30 were excluded. Confirmation of TB was achieved in 75 (14.1%) while 248 (46.5%) had unconfirmed TB. Of 553 with GS specimen, the overall diagnostic yield was 12.4% (66/533). A total of 493 and 524 samples were used to evaluate Xpert-Ultra on stool and on urine, respectively. Compared to GS, sensitivity and specificity of Xpert-Ultra on stool were 62.5%(95%CI:49.4-74) and 98.3%(95%CI:96.7-99.2), whereas on urine were 13.9%(95%CI:7.5-24.3) and 99.4%(95%CI:98.1-99.8), respectively. Nine patients were positive on stool and/or urine but negative on GS.
CONCLUSIONS
Xpert-Ultra on stool showed moderate to high sensitivity and high specificity when compared to GS and an added diagnostic yield when GS was negative. Xpert-Ultra on stool was useful in extrapulmonary cases. Xpert-Ultra in urine showed low test performance.
Over half of childhood tuberculosis (TB) remains undiagnosed yearly. WHO recommends Xpert-Ultra as a first paediatric diagnosis test, but microbiological confirmation remains low. We aimed to determine the diagnostic performance of Xpert-Ultra on stool and urine in presumptive paediatric TB cases in two high-TB burden settings.
METHODS
This Médecins sans Frontières cross-sectional multicentric study took place at Simão Mendes hospital, Guinea-Bissau (July 2019 to April 2020) and in Malakal hospital, South Sudan (April 2021 to June 2023). Children 6 months to 15 years with presumptive TB underwent clinical and laboratory assessment, with one respiratory and/or extrapulmonary sample (gold standard (GS)), one stool and one urine specimen analysed with Xpert-Ultra.
RESULTS
A total of 563 children were enrolled in the study, 133 from Bissau, 400 from Malakal; 30 were excluded. Confirmation of TB was achieved in 75 (14.1%) while 248 (46.5%) had unconfirmed TB. Of 553 with GS specimen, the overall diagnostic yield was 12.4% (66/533). A total of 493 and 524 samples were used to evaluate Xpert-Ultra on stool and on urine, respectively. Compared to GS, sensitivity and specificity of Xpert-Ultra on stool were 62.5%(95%CI:49.4-74) and 98.3%(95%CI:96.7-99.2), whereas on urine were 13.9%(95%CI:7.5-24.3) and 99.4%(95%CI:98.1-99.8), respectively. Nine patients were positive on stool and/or urine but negative on GS.
CONCLUSIONS
Xpert-Ultra on stool showed moderate to high sensitivity and high specificity when compared to GS and an added diagnostic yield when GS was negative. Xpert-Ultra on stool was useful in extrapulmonary cases. Xpert-Ultra in urine showed low test performance.
Journal Article > ResearchFull Text
Open Forum Infect Dis. 1 February 2024; Volume 11 (Issue 3); ofae058.; DOI:10.1093/ofid/ofae058
Bugeme PM, Xu H, Hutchins C, Dent J, Saidi JM, et al.
Open Forum Infect Dis. 1 February 2024; Volume 11 (Issue 3); ofae058.; DOI:10.1093/ofid/ofae058
Our understanding of the burden and drivers of cholera mortality is hampered by limited surveillance and confirmation capacity. Leveraging enhanced clinical and laboratory surveillance in the cholera-endemic community of Uvira, eastern Democratic Republic of Congo, we describe cholera deaths across 3 epidemics between September 2021 and September 2023 following mass vaccination.
Journal Article > ResearchFull Text
Open Forum Infect Dis. 21 February 2023; Volume 10 (Issue 3); ofad087.; DOI:10.1093/ofid/ofad087
Apolisi I, Cox HS, Tyeku N, Daniels J, Mathee S, et al.
Open Forum Infect Dis. 21 February 2023; Volume 10 (Issue 3); ofad087.; DOI:10.1093/ofid/ofad087
BACKGROUND
Children and adolescents with household exposure to multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB) are at high risk of developing TB disease. Tuberculosis preventive therapy (TPT) is recommended, but programmatic experience is limited, particularly for adolescents.
METHODS
We conducted a prospective cohort study to describe MDR/RR-TB diagnosis and TPT provision for individuals aged <18 years with MDR/RR-TB exposure. Participants were assessed for TB either in homes or health facilities, with referral for chest x-ray or specimen collection at clinician discretion. The TPT regimens included levofloxacin, isoniazid, or delamanid monotherapy for 6 months, based on source patient drug-resistance profile.
RESULTS
Between March 1, 2020 and July 31, 2021, 112 participants were enrolled; median age was 8.5 years, 57 (51%) were female, and 6 (5%) had human immunodeficiency virus. On screening, 11 (10%) were diagnosed with TB: 10 presumptive MDR/RR-TB and 1 drug-susceptible TB. Overall, 95 (94% of 101) participants started TPT: 79 with levofloxacin, 9 with isoniazid, and 7 with delamanid. Seventy-six (80%) completed TPT, 12 (13%) were lost to follow up, and 7 (7%) stopped TPT early due to adverse events. Potential adverse events were reported for 12 (13%) participants; none were serious. There were no further TB diagnoses (200 days median follow up).
CONCLUSIONS
Post-MDR/RR-TB exposure management for children and adolescents resulted in significant MDR/RR-TB detection and both high TPT initiation and completion. Tuberculosis preventive monotherapy was well tolerated and there were no further TB diagnoses after initial assessment. Key factors supporting these outcomes included use of pediatric formulations for young children, monotherapy, and community-based options for assessment and follow up.
Children and adolescents with household exposure to multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB) are at high risk of developing TB disease. Tuberculosis preventive therapy (TPT) is recommended, but programmatic experience is limited, particularly for adolescents.
METHODS
We conducted a prospective cohort study to describe MDR/RR-TB diagnosis and TPT provision for individuals aged <18 years with MDR/RR-TB exposure. Participants were assessed for TB either in homes or health facilities, with referral for chest x-ray or specimen collection at clinician discretion. The TPT regimens included levofloxacin, isoniazid, or delamanid monotherapy for 6 months, based on source patient drug-resistance profile.
RESULTS
Between March 1, 2020 and July 31, 2021, 112 participants were enrolled; median age was 8.5 years, 57 (51%) were female, and 6 (5%) had human immunodeficiency virus. On screening, 11 (10%) were diagnosed with TB: 10 presumptive MDR/RR-TB and 1 drug-susceptible TB. Overall, 95 (94% of 101) participants started TPT: 79 with levofloxacin, 9 with isoniazid, and 7 with delamanid. Seventy-six (80%) completed TPT, 12 (13%) were lost to follow up, and 7 (7%) stopped TPT early due to adverse events. Potential adverse events were reported for 12 (13%) participants; none were serious. There were no further TB diagnoses (200 days median follow up).
CONCLUSIONS
Post-MDR/RR-TB exposure management for children and adolescents resulted in significant MDR/RR-TB detection and both high TPT initiation and completion. Tuberculosis preventive monotherapy was well tolerated and there were no further TB diagnoses after initial assessment. Key factors supporting these outcomes included use of pediatric formulations for young children, monotherapy, and community-based options for assessment and follow up.
Journal Article > ResearchFull Text
Open Forum Infect Dis. 23 December 2020; Volume 8 (Issue 2); ofaa639.; DOI:10.1093/ofid/ofaa639
Huerga H, Rucker SCM, Bastard M, Mpunga J, Amoros Quiles I, et al.
Open Forum Infect Dis. 23 December 2020; Volume 8 (Issue 2); ofaa639.; DOI:10.1093/ofid/ofaa639
BACKGROUND
Diagnosing tuberculosis (TB), the leading cause of death in people with HIV, remains a challenge in resource-limited countries. We assessed TB diagnosis using a strategy that included systematic urine lipoarabinomannan (LAM) testing for all HIV patients hospitalized in the medical wards and 6-month mortality according to the LAM result.
METHODS
This prospective, observational study included adult HIV patients hospitalized in the medical wards of a public district hospital in Malawi regardless of their TB symptoms or CD4 count. Each patient had a clinical examination and Alere Determine TB-LAM, sputum microscopy, sputum GeneXpert MTB/RIF (Xpert), chest X-ray, and CD4 count were systematically requested.
RESULTS
Among 387 inpatients, 54% had a CD4<200 cells/µL, 64% had presumptive TB and 90% had ≥1 TB symptom recorded in the medical file. LAM results were available for 99.0% of the patients, microscopy for 62.8% and Xpert for 60.7%. In total, 26.1% (100/383) had LAM-positive results, 48% (48/100) of which were grades 2-4. Any TB laboratory test result was positive in 30.8% (119/387). Among patients with no Xpert result, 28.5% (43/151) were LAM-positive. Cumulative 6-months mortality was 40.1% (151/377): 50.5% (49/97) in LAM-positives and 36.2% (100/276) in LAM-negatives, p=0.013. In multivariable regression analyses, LAM-positive patients had higher risk of mortality than LAM-negatives (aOR: 2.5, 95%CI: 1.1-5.8, p=0.037).
CONCLUSIONS
In resource-limited hospital medical wards with high TB prevalence, a diagnostic strategy including systematic urine-LAM testing for all HIV patients is an easily implementable strategy that identifies a large proportion of patients with TB at risk of death.
Diagnosing tuberculosis (TB), the leading cause of death in people with HIV, remains a challenge in resource-limited countries. We assessed TB diagnosis using a strategy that included systematic urine lipoarabinomannan (LAM) testing for all HIV patients hospitalized in the medical wards and 6-month mortality according to the LAM result.
METHODS
This prospective, observational study included adult HIV patients hospitalized in the medical wards of a public district hospital in Malawi regardless of their TB symptoms or CD4 count. Each patient had a clinical examination and Alere Determine TB-LAM, sputum microscopy, sputum GeneXpert MTB/RIF (Xpert), chest X-ray, and CD4 count were systematically requested.
RESULTS
Among 387 inpatients, 54% had a CD4<200 cells/µL, 64% had presumptive TB and 90% had ≥1 TB symptom recorded in the medical file. LAM results were available for 99.0% of the patients, microscopy for 62.8% and Xpert for 60.7%. In total, 26.1% (100/383) had LAM-positive results, 48% (48/100) of which were grades 2-4. Any TB laboratory test result was positive in 30.8% (119/387). Among patients with no Xpert result, 28.5% (43/151) were LAM-positive. Cumulative 6-months mortality was 40.1% (151/377): 50.5% (49/97) in LAM-positives and 36.2% (100/276) in LAM-negatives, p=0.013. In multivariable regression analyses, LAM-positive patients had higher risk of mortality than LAM-negatives (aOR: 2.5, 95%CI: 1.1-5.8, p=0.037).
CONCLUSIONS
In resource-limited hospital medical wards with high TB prevalence, a diagnostic strategy including systematic urine-LAM testing for all HIV patients is an easily implementable strategy that identifies a large proportion of patients with TB at risk of death.
Journal Article > ResearchFull Text
Open Forum Infect Dis. 24 July 2015; Volume 2 (Issue 3); DOI:10.1093/ofid/ofv111
Mwanga-Amumpaire J, Carroll R, Baudin E, Kemigisha E, Nampijja D, et al.
Open Forum Infect Dis. 24 July 2015; Volume 2 (Issue 3); DOI:10.1093/ofid/ofv111
Journal Article > ResearchFull Text
Open Forum Infect Dis. 26 April 2014; 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. 26 April 2014; Volume 1 (Issue 1); DOI:10.1093/ofid/ofu021
Journal Article > ResearchFull Text
Open Forum Infect Dis. 21 May 2014; 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. 21 May 2014; 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.
Journal Article > ResearchFull Text
Open Forum Infect Dis. 1 October 2020; Volume 7 (Issue Supplement_1); S38-S38.; DOI:10.1093/ofid/ofaa439.073
Simon JK, Kennedy SB, Mahon BE, Dubey SA, Grant-Klein RJ, et al.
Open Forum Infect Dis. 1 October 2020; Volume 7 (Issue Supplement_1); S38-S38.; DOI:10.1093/ofid/ofaa439.073
BACKGROUND
The recent Ebola virus disease (EVD) outbreak in the Democratic Republic of the Congo highlights the sustained threat of EVD morbidity and mortality where healthcare and vaccine delivery are challenging. ERVEBO®, a live recombinant vesicular stomatitis virus (VSV) vaccine containing the Zaire ebolavirus glycoprotein (GP) in place of the VSV GP (rVSVΔG-ZEBOV-GP), was developed by Merck & Co., Inc., Kenilworth, NJ, USA in collaboration with multiple partners to prevent EVD and has been approved for human use in several countries.
METHODS
We pooled data from three Phase 2/3 clinical trials conducted in Guinea (FLW), Sierra Leone (STRIVE), and Liberia (PREVAIL) during the 2013–2016 West African outbreak to assess immune responses using a validated assay in each of the three studies and performed a post hoc analysis by sex, age (18–50 yrs & >50 yrs) and baseline (BL) GP-enzyme-linked immunosorbent assay (ELISA) titer (< 200 & ≥200 EU/ml). The full analysis set (FAS) population included the primary immunogenicity populations (all vaccinated participants with serology data collected within an acceptable day range) from all three trials. The endpoints were total IgG antibody response (EU/mL) measured by the GP-ELISA and neutralizing antibody response measured by the plaque reduction neutralization test (PRNT) to rVSVΔG-ZEBOV-GP at Days 14, 28, 180, and 365 postvaccination.
RESULTS
In the overall population and in all subgroups, GP-ELISA and PRNT geometric mean titers increased from BL, with most peaking at Day 28 and persisting through Day 365. There were differences between males and females and between participants with BL GP-ELISA < 200 & ≥200 EU/ml. There did not appear to be a difference between age groups.
CONCLUSION
These data demonstrate that rVSVΔG-ZEBOV-GP elicits a robust and durable immune response up to 12 months in participants regardless of age, sex, or BL GP-ELISA titer. The higher immune responses observed in females and participants with preexisting immunity are consistent with those described in published literature for other vaccines.
The recent Ebola virus disease (EVD) outbreak in the Democratic Republic of the Congo highlights the sustained threat of EVD morbidity and mortality where healthcare and vaccine delivery are challenging. ERVEBO®, a live recombinant vesicular stomatitis virus (VSV) vaccine containing the Zaire ebolavirus glycoprotein (GP) in place of the VSV GP (rVSVΔG-ZEBOV-GP), was developed by Merck & Co., Inc., Kenilworth, NJ, USA in collaboration with multiple partners to prevent EVD and has been approved for human use in several countries.
METHODS
We pooled data from three Phase 2/3 clinical trials conducted in Guinea (FLW), Sierra Leone (STRIVE), and Liberia (PREVAIL) during the 2013–2016 West African outbreak to assess immune responses using a validated assay in each of the three studies and performed a post hoc analysis by sex, age (18–50 yrs & >50 yrs) and baseline (BL) GP-enzyme-linked immunosorbent assay (ELISA) titer (< 200 & ≥200 EU/ml). The full analysis set (FAS) population included the primary immunogenicity populations (all vaccinated participants with serology data collected within an acceptable day range) from all three trials. The endpoints were total IgG antibody response (EU/mL) measured by the GP-ELISA and neutralizing antibody response measured by the plaque reduction neutralization test (PRNT) to rVSVΔG-ZEBOV-GP at Days 14, 28, 180, and 365 postvaccination.
RESULTS
In the overall population and in all subgroups, GP-ELISA and PRNT geometric mean titers increased from BL, with most peaking at Day 28 and persisting through Day 365. There were differences between males and females and between participants with BL GP-ELISA < 200 & ≥200 EU/ml. There did not appear to be a difference between age groups.
CONCLUSION
These data demonstrate that rVSVΔG-ZEBOV-GP elicits a robust and durable immune response up to 12 months in participants regardless of age, sex, or BL GP-ELISA titer. The higher immune responses observed in females and participants with preexisting immunity are consistent with those described in published literature for other vaccines.