TB therapeutic drug monitoring - analysis of opportunities in Romania and Ukraine.

INTRODUCTION: Therapeutic drug monitoring (TDM) could improve TB treatment outcomes by avoiding drug toxicity or underdosing. In this study, we describe the patient burden in three TB centres in Romania and Ukraine with a TDM indication, as per the current guidelines, in order to estimate the feasibility of implementing TDM.METHODS: A retrospective multi-centre study was conducted at the Iasi Lung Hospital (Iasi, Romania), Bucharest Marius Nasta Institute (Bucharest, Romania) and Chernivtsi TB Centre (Chernivtsi, Ukraine) in adult hospitalised TB patients.RESULTS: A total of 927 participants were admitted, of whom 37.8% had at least one indication for TDM, the most frequent being slow response to TB treatment (202/345, 58.6%); 55.5% had at least one cavity present on chest X-ray. Patients with a TDM indication stayed in the hospital for a median of 67 days and took on average 2 months more to reach a successful TB outcome.CONCLUSION: TDM could be a valuable tool to improve management of selected TB patients. The decision on whether to perform TDM is often delayed by 2 months due to waiting for culture results after treatment initiation. A randomised control trial should be performed in order to define TDM's precise role in TB therapy.

eHealth in TB clinical management.

BACKGROUND: The constant expansion of internet and mobile technologies has created new opportunities in the field of eHealth, or the digital delivery of healthcare services. This TB meta-analysis aims to examine eHealth and its impact on TB clinical management in order to formulate recommendations for further development.METHODS: A systematic search was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses framework in PubMed and Embase of articles published up to April 2021. Screening, extraction and quality assessment were performed by two independent researchers. Studies evaluating an internet and/or mobile-based eHealth intervention with an impact on TB clinical management were included. Outcomes were organised following the five domains described in the WHO "Recommendations on Digital Interventions for Health System Strengthening" guideline.RESULTS: Search strategy yielded 3,873 studies, and 89 full texts were finally included. eHealth tended to enhance screening, diagnosis and treatment indicators, while being cost-effective and acceptable to users. The main challenges concern hardware malfunction and software misuse.CONCLUSION: This study offers a broad overview of the innovative field of eHealth applications in TB. Different studies implementing eHealth solutions consistently reported on benefits, but also on specific challenges. eHealth is a promising field of research and could enhance clinical management of TB.

Clinical outcomes of Ghanaian Buruli ulcer patients who defaulted from antimicrobial therapy.

OBJECTIVES: Buruli ulcer (BU) is a tropical skin disease caused by infection with Mycobacterium ulcerans, which is currently treated with 8 weeks of streptomycin and rifampicin. The evidence to treat BU for a duration of 8 weeks is limited; a recent retrospective study from Australia suggested that a shorter course of antimicrobial therapy might be equally effective. We studied the outcomes of BU in a cohort of Ghanaian patients who defaulted from treatment and as such received less than 8 weeks of antimicrobial therapy. METHODS: A number of days of antimicrobial therapy and patient and lesion characteristics were recorded from charts from a cohort of BU patients treated at Nkawie-Toase hospital between 2008 and 2012. Patients who defaulted from treatment were retrieved, and lesion characteristics and functional limitations were recorded. RESULTS: About 54% of patients defaulted from therapy or wound care. Forty-seven defaulters with follow-up completed had received <56 days of antibiotics. 84% of these patients healed after 32 days or less of antibiotics. There appeared to be an increased rate of healing in smaller lesions; 94% of WHO category I lesions had healed after 32 days or less of antibiotics. CONCLUSION: Although numbers were small, and a potential for bias exists, our findings suggest that a reduction in the duration of antimicrobial therapy in BU in small, early lesions is feasible. These findings can serve as a basis for future well-designed studies.

A cluster of tularaemia after contact with a dead hare in the Netherlands.

Tularemia is thought to be rare in the Netherlands. Here we describe a cluster of two patients who contracted tularaemia after field dressing of a hare found dead. Additionally, infection from the same source is suggested in three animals.

Louse-borne relapsing fever (Borrelia recurrentis) in asylum seekers from Eritrea, the Netherlands, July 2015.

Two patients from Eritrea, recently arrived in the Netherlands, presented with fever and were investigated for malaria. Bloodfilms showed spirochetes but no blood parasites. Louse-borne relapsing fever caused by Borrelia recurrentis was diagnosed. Treatment was complicated by severe Jarisch-Herxheimer reactions in both patients. Physicians should be aware of the possibility of B. recurrentis infection in migrant populations who travel under crowded conditions, especially after passing through endemic areas such as Ethiopia and neighbouring countries.

Management of BU-HIV co-infection.

BACKGROUND: Buruli Ulcer (BU)-HIV co-infection is an important emerging management challenge for BU disease. Limited by paucity of scientific studies, guidance for management of this co-infection has been lacking. METHODS: Initiated by WHO, a panel of experts in BU and HIV management developed guidance principles for the management of BU-HIV co-infection based on review of available scientific evidence, current treatment experience, and global recommendations established for management of HIV infection and tuberculosis. RESULTS: The expert panel agreed that all BU patients should be offered quality provider-initiated HIV testing and counselling. In areas with high prevalence of malaria and/or bacterial infections, all patients with HIV co-infection should be started on cotrimoxazole preventative therapy. Combination antibiotic treatment for BU should be commenced before starting antiretroviral therapy (ART) and provided for 8 weeks duration. The suggested combination is rifampicin (10 mg/kg daily up to a maximum of 600 mg/day) plus streptomycin (15 mg/kg daily). An alternative regimen is rifampicin plus clarithromycin (7.5 mg/kg twice daily up to a maximum of 1000 mg daily) although due to drug interactions with antiretroviral drugs this regimen should be used with caution. ART should be initiated in all BU-HIV co-infected patients with symptomatic HIV disease (WHO clinical stage 3 or 4) regardless of CD4 cell count and in asymptomatic individuals with CD4 count ≤500 cells/mm(3) . If CD4 count is not available, BU-HIV co-infected individuals with category 2 or 3 BU disease should be offered ART. For eligible individuals, ART should be commenced as soon as possible within 8 weeks after commencing BU treatment, and as a priority in those with advanced HIV disease (CD4 ≤ 350 cells/mm(3) or WHO stage 3 or 4 disease). All co-infected patients should be actively screened for tuberculosis before commencing BU treatment and before starting ART. Programmes should implement a monitoring and reporting system to document the outcomes of BU-HIV interventions. CONCLUSIONS: Knowledge of the clinical and epidemiological interactions between BU and HIV disease is limited. While awaiting more urgently needed evidence, current management practice of both diseases has been useful to build simple 'common sense' preliminary guidance on how to manage BU-HIV co-infection.

[Distribution of Buruli ulcer in the Zè district of Benin]. / Distribution spatiale de l'ulcère de Buruli dans la commune de Zê (Bénin).

The goals of this cross-sectional study conducted in the Zè district of Benin were to determine the overall distribution and prevalence of Buruli ulcer (BU) and to identify environmental and behavioral risk factors. A total of 425 current or previous BU patients from the study district were included. Data was obtained by direct observation, semi-structured interviews, and document review. The main findings can be summarized as follows. The overall prevalence of BU in the Zè district in 2006 was 52 cases per 10000 inhabitants. The prevalence of current and previous cases was 28.1 and 23.9 per 10 000 inhabitants respectively. The distribution of BU within the district was highly variable from one subdistrict to another and from one village to another within the same subdistrict. The subdistricts showing the highest and lowest endemicity were Djigbé with 265 cases per 10 000 inhabitants and Koundokpoé with 3 cases per 10 000 inhabitants respectively. Proximity of the hamlets to water bodies was a risk factor for the disease.

Decreased capillary permeability and capillary density in patients with systemic sclerosis using large-window sodium fluorescein videodensitometry of the ankle.

OBJECTIVE: Local capillary permeability in patients with SSc has been reported increased when assessed by nail-fold capillaroscopy. We measured capillary permeability at a clinically less affected site by using large-window fluorescein videodensitometry of the ankle. We hypothesized that increased capillary permeability or leakage is a generalized phenomenon in SSc. METHODS: Large-window videodensitometry with sodium fluorescein was performed in 38 SSc patients and 20 healthy controls. Capillary permeability was expressed as the average relative light intensity over the first 7 min [I(av)(7)] after appearance of fluorescein in skin capillaries. RESULTS: Capillary permeability, expressed as I(av)(7) was significantly decreased in patients with SSc (47.3 +/- 15.0% vs 57.6 +/- 9.4% in controls, P = 0.007), as was capillary density (12 +/- 6/mm(2) vs 26 +/- 11/mm(2), P < 0.001). Adjustment for capillary density in multivariate regression analysis demonstrated that differences in I(av)(7) between SSc patients and controls were related to differences in capillary density, BMI and high density lipoprotein cholesterol. CONCLUSION: At the level of the ankle decreased capillary permeability was found in SSc patients, related to decreased capillary density. Microvascular involvement in SSc is widespread, but no evidence was established for increased capillary permeability at the level of individual capillaries as a generalized phenomenon.

Susceptibility to Buruli ulcer is associated with the SLC11A1 (NRAMP1) D543N polymorphism.

Similar to other mycobacterial diseases, susceptibility to Buruli ulcer (Mycobacterium ulcerans infection) may be determined by host genetic factors. We investigated the role of SLC11A1 (NRAMP1) in Buruli ulcer because of its associations with both tuberculosis and leprosy. We enrolled 182 Buruli ulcer patients (102 with positive laboratory confirmation) and 191 healthy neighbourhood-matched controls in Ghana, and studied three polymorphisms in the SLC11A1 gene: 3' UTR TGTG ins/del, D543N G/A, and INT4 G/C. Finger prick blood samples from study subjects were dried on filter papers (FTA) and processed. D543N was significantly associated with Buruli ulcer: the odds ratio (adjusted for gender, age, and region of the participant) of the GA genotype versus the GG genotype was 2.89 (95% confidence intervals (CI): 1.41-5.91). We conclude that a genetic polymorphism in the SLC11A1 gene plays a role in susceptibility to develop Buruli ulcer, with an estimated 13% population attributable risk.

Buruli ulcer: differences in treatment outcome between two centres in Ghana.

OBJECTIVES: Assess treatment effects by following up patients treated for Buruli ulcer in two hospitals with different treatment aspects, including widely differing surgical practices. PATIENTS/METHODS: Treated patients were retrospectively identified from hospital records. Between 1994 and July 2000, 136 patients had been admitted for Buruli ulcer in both hospitals, and lived in areas covered in the research period. 78 (57%) Patients were included in the study. Treatment and status of the patient were analysed. RESULTS: 27 (35%) Patients were not healed. Of the 33 patients treated in hospital A, six (18%) were not healed at follow-up, whereas of the 45 patients treated in hospital B, 21 (47%) were not healed. The length of stay in hospital A was significantly longer (P=0.002), and more operations on average were done per patient (P=0.002). In a univariate analysis, treatment in hospital A; the use of rifampicin (P=0.013); and BCG vaccination status (P=0.04) were all significantly associated with ulcer healing. Using a logistic regression model for multivariate analysis, only treatment as given in hospital A, with standard practice of wide surgical excision, appeared to predict ulcer healing independently (P=0.02). CONCLUSIONS: This study shows large differences in treatment outcome between the two hospitals; the results support the hypothesis that extent of surgical treatment influences the chance of healing of Buruli ulcer.

Susceptibility to development of Mycobacterium ulcerans disease: review of possible risk factors.

Mycobacterium ulcerans disease, also known as Buruli ulcer (BU), is a disease of subcutaneous fat tissue. BU is prevalent in riverine and swamp areas of the tropical zone in Africa, Asia and South America, and a few scattered foci in Australia. The mode of transmission of M. ulcerans has not been fully elucidated, but inoculation into the subcutaneous tissues probably occurs through penetrating skin trauma. BU has not been linked with HIV infection. Antimycobacterial drug treatment is ineffective, and treatment is surgical. Patients eventually develop scars and contractures, with resulting disabilities, and the disease imposes a large burden on affected populations. The incidence of BU has dramatically increased in West African countries over the last decade. There is an urgent need for research into host and environmental risk factors for BU in order to develop effective strategies to combat this disease. We review possible genetic host susceptibility factors for BU that are relevant in other mycobacterial diseases: natural resistance-associated macrophage protein-1 (NRAMP-1), HLA-DR, vitamin D3 receptor, mannose binding protein, interferon-gamma (IFN-gamma) receptor, tumour necrosis factor alpha (TNF-alpha), interleukin (IL)-1 alpha, 1 beta and their receptor antagonists; and IL-12. Schistosoma haematobium infection is highly endemic in many BU foci in West Africa, with a striking increase in transmission after river dams were constructed. This observation, and the observations from interaction of schistosomiasis and tuberculosis, have fueled our hypothesis that schistosomiasis is a risk factor for BU by driving the host immune response towards a predominantly Th-2 pattern, away from a Th-1 preponderant protection against mycobacterial infection. If the latter hypothesis is confirmed, enhanced schistosomiasis control should impact on BU.

[Pulmonary hemorrhage with respiratory insufficiency in Henoch- Schoenlein purpura]. / Longbloedingen met respiratoire insufficiëntie bij Henoch-Schönlein-purpura.

A 20-year-old woman presented with abdominal pain, purpura on the extremities, and arthralgia. The diagnosis of Henoch-Schönlein purpura was made based on granular IgA deposits in the vessels in a skin biopsy. Three weeks after onset of these symptoms, she developed glomerulonephritis and diffuse alveolar haemorrhage; she developed respiratory failure and needed mechanical ventilation. She recovered upon treatment with corticosteroids. Diffuse alveolar bleeding has occasionally been reported in adults with Henoch-Schönlein purpura; this is the first report from the Netherlands.