Secondary bacterial infections of buruli ulcer lesions before and after chemotherapy with streptomycin and rifampicin

Buruli ulcer (BU), caused by Mycobacterium ulcerans is a chronic necrotizing skin disease. It usually starts with a subcutaneous nodule or plaque containing large clusters of extracellular acid-fast bacilli. Surrounding tissue is destroyed by the cytotoxic macrolide toxin mycolactone produced by microcolonies of M. ulcerans. Skin covering the destroyed subcutaneous fat and soft tissue may eventually break down leading to the formation of large ulcers that progress, if untreated, over months and years. Here we have analyzed the bacterial flora of BU lesions of three different groups of patients before, during and after daily treatment with streptomycin and rifampicin for eight weeks (SR8) and determined drug resistance of the bacteria isolated from the lesions. Before SR8 treatment, more than 60% of the examined BU lesions were infected with other bacteria, with Staphylococcus aureus and Pseudomonas aeruginosa being the most prominent ones. During treatment, 65% of all lesions were still infected, mainly with P. aeruginosa. After completion of SR8 treatment, still more than 75% of lesions clinically suspected to be infected were microbiologically confirmed as infected, mainly with P. aeruginosa or Proteus miriabilis. Drug susceptibility tests revealed especially for S. aureus a high frequency of resistance to the first line drugs used in Ghana. Our results show that secondary infection of BU lesions is common. This could lead to delayed healing and should therefore be further investigated

Evaluation of a peer support group programme for vulnerable host population and refugees living with diabetes and/or hypertension in Lebanon: a before-after study.

Background: Non-communicable diseases (NCDs) are the leading cause of death globally, and many humanitarian crises occur in countries with high NCD burdens. Peer support is a promising approach to improve NCD care in these settings. However, evidence on peer support for people living with NCDs in humanitarian settings is limited. We evaluated the implementation of peer support groups (PSGs) for people with diabetes and/or hypertension as part of an integrated NCD care model in four primary care centers in Lebanon. Methods: Our objectives were to: (1) evaluate the reach of the PSGs; (2) evaluate the association of PSGs with patient-reported outcomes; and (3) evaluate the association of PSGs with clinical outcomes (blood pressure, HbA1c, and BMI). We used a before-after study design and included a control group for clinical outcomes. The PSG intervention began in December 2022 and was carried out in two waves. The first wave was implemented from December 2022 to July 2023, and the second wave from July 2023 to January 2024. For the control group on clinical outcomes, we used data collected from January 2023 to January 2024. We used routinely collected programmatic and administrative data. The patient reported outcomes (PROMs) were collected at baseline and at six months by trained volunteers for all PSG participants. We performed a before-after analysis of PROMs for all patients who completed the PSG sessions. T-tests were used to analyze the differences in PROMs from baseline. Change in PROMs, together with 95% confidence intervals (CIs), and p-values for the changes were reported. To assess the association between the implementation of the PSG strategy and changes in clinical outcomes, including systolic blood pressure (SBP), glycated hemoglobin A1c (HbA1c), and body mass index (BMI), analysis of covariance (ANCOVA) models were used, adjusting for age, sex, and the baseline values of the outcome being analyzed (baseline SBP and baseline HbA1c, respectively). Results: A total of 445 patients were approached for enrolment in wave 1, 259 (58%) consented, of whom 81 were enrolled. In wave 2, 169 patients were approached, 92 (54%) consented of whom 91 were enrolled. We found some statistical evidence that PSG improved certain PROMs, including potentially clinical meaningful improvements in overall quality of life (wave 1), physical quality of life (wave 1), social quality of life (wave 2), environmental quality of life (wave 1), adherence (wave 2), patient centeredness (wave 1), and exercise (wave 1). However, we did not find strong statistical evidence of an improvement in clinical outcomes (SBP, HbA1c, or BMI) in participants of the PSGs compared to the control group. We found differences in the association of PSGs and outcomes between the two waves. Conclusion: Our study showed mixed results. In terms of reach, over 50% of those approached consented to participate. Regarding the impact on PROMs, we observed improvements in most outcomes; however we found some statistical evidence only for some. We did not find strong statistical evidence of improvement in clinical outcomes compared to the control group. Differences between the two waves may be due to differences in the populations, the way the intervention was delivered, or the individuals implementing it. Additionally, as multiple outcomes were measured, some observed differences may be due to chance. We demonstrated that it is feasible to implement PSGs in humanitarian settings and found some statistical evidence of improvement in quality of life. Further studies should assess the implementation and impact of PSGs in ways that are well accepted by local stakeholders (including humanitarian actors and people living with NCDs) and are potentially amenable to scale-up

Implementing (and evaluating) peer support with people living with noncommunicable diseases in humanitarian settings.

In line with the peer reviewers comments, the authors have added highlights in stead of an abstract. It was felt that it was better able to capture the findings and is more in line with the paper's target audience

Microbiological analysis of recycled bandages.

<p><i>AMP = Ampicillin, CXM = Cefixime, CXC = Cloxacillin, COT = Cotrimoxazole, ERY = Erythromycin, GEN = Gentamicin, TET = Tetracycline, PEN = Penicillin, CRX = Cefuroxime, CHL = Chloramphenicol, CTR = Ceftriaxone, CTX = Cefotaxime</i>.</p

Spectrum of bacterial species isolated from BU lesions before, during or after SR8 treatment.

<p>Spectrum of bacterial species isolated from BU lesions before, during or after SR8 treatment.</p

Histopathological analysis of tissue from two patients excised weeks after SR8 treatment respectively.

<p>Histological sections were stained with Ziehl-Neelsen (acid fast bacteria) and methylene blue (DNA, secondary infection). A: clinical presentation of patient 9 presenting with a large lesion on the right foot. B: overview over excised tissue specimen (open ulcer surface) revealing the presence of an infection (blue band, box). C/D: higher magnification confirming the presence of densely packed rods. E: clinical presentation of patient 16 presenting with a large lesion covering the left leg. F: overview over excised tissue specimen revealing an epidermal hyperplasia as well as a strong edema. G/H: secondary infection with rods of the dermal and subcutaneous tissue.</p

Antibiotic susceptibility pattern of different bacterial species isolated from BU wounds.

<p>Antibiotic susceptibility pattern of different bacterial species isolated from BU wounds.</p

Histopathological analysis of tissue excised before start of SR8 treatment.

<p>Histological sections were stained with Ziehl-Neelsen (acid fast bacteria) and methylene blue (DNA, secondary infection). A: Overview over excised tissue specimen revealing infection at the lower end of the specimen (box), as well as BU characteristic histopathological features, including fat cell ghosts, necrosis and epidermal hyperplasia. B/C: higher magnification revealing the presence of cocci. D: clinical presentation of the lesion on the belly.</p

Presentation of wounds that were clinically infected after SR8 compared to microbiology and histology findings.

<p>We compared the clinical presentation to microbiological categorization based on quantification and histological findings. Lesions with a bacterial load less than 10⁶ CFU/ml (or CFU/g) were categorized as contaminated, while lesions with bacterial loads above were considered as infected.</p>1<p>WHD = Wound healing delay.</p>2<p>SGF = Skin grafting failure.</p><p>n/d = not done.</p