Cost of digital technologies and family-observed DOT for a shorter MDR-TB regimen: a modelling study in Ethiopia, India and Uganda.

BACKGROUND: In 2017, the WHO recommended the use of digital technologies, such as medication monitors and video observed treatment (VOT), for directly observed treatment (DOT) of drug-susceptible TB. The WHO's 2020 guidelines extended these recommendations to multidrug-resistant tuberculosis (MDR-TB), based on low evidence. The impact of COVID on health systems and patients underscored the need to use digital technologies in the management of MDR-TB. METHODS: A decision-tree model was developed to explore the costs of several potential DOT alternatives: VOT, 99DOTS (Directly-observed Treatment, Short-course) and family-observed DOT. Assuming a 9-month, all-oral regimen (as evaluated within the STREAM trial), we constructed base-case cost models for the standard-of-care DOTs in Ethiopia, India, and Uganda, as well as for the three alternative DOT approaches. The models were populated with STREAM Stage 2 clinical trial outcome and cost data, supplemented with market prices data for the digital DOT strategies. Sensitivity analyses were conducted on key parameters. RESULTS: Modelling suggested that the standard-of-care DOT approach is the most expensive DOT strategy from a societal perspective in all three countries evaluated (Ethiopia, India, Uganda), with considerable direct- and indirect-costs incurred by patients. The second most expensive DOT approach is VOT, with high health-system costs, largely caused by up-front technology expenditure. Each of VOT, 99DOTS and family-observed DOT would reduce by more than 90% patients' direct and indirect costs compared to standard of care DOT. Results were robust to the sensitivity analyses. CONCLUSIONS: While data on the costs and efficacy of alternative DOT approaches in the context of shorter MDR-TB treatment is limited, our modelling suggests alternative DOT approaches can significantly reduce patient costs in all three countries. Health system costs are higher for VOT and lower for 99DOTS and family-observed therapy when compared to standard of care DOT, as low smartphone penetration and internet availability requires the VOT health system to fund the cost of making them available to patients.

TB training in Kenya: building capacity for care and prevention.

BACKGROUND: Devolution of healthcare services in Kenya resulted in a large number of newly recruited tuberculosis (TB) coordinators. We describe a unique collaboration between a national tuberculosis program (NTP), a local, and an international non-governmental organization to build human resource capacity in TB care and prevention. METHODS: From 2016 to 2021, the Kenya Division of National Tuberculosis, Leprosy and Lung Disease Program, Centre for Health Solutions-Kenya, and the International Union Against Tuberculosis and Lung Disease developed and conducted a series of 7-day training courses. A key focus of training was the introduction of TBData4Action, an approach involving the local use of routinely available data to strengthen decision-making and support supervision. RESULTS: Implementation outcomes included training 331 (96%) coordinators out of 344, representing all 47 counties, 37 national officers and 21 other stakeholders using the country-tailored curriculum, including hands-on group work by county teams and field practicals. Thirty-five national facilitators were identified and mentored as local faculty. Training costs were reduced by 75% compared with international alternatives. CONCLUSION: The collaboration resulted in the training of the majority of the coordinators in a standardized approach to TB care. A sustainable approach to capacity building in local data use was found feasible; the model could be adapted by other NTPs.

CONTEXTE: La décentralisation des services de santé au Kenya a conduit au recrutement d'un grand nombre de nouveaux coordinateurs TB. Nous décrivons une collaboration unique entre un programme national de lutte contre la TB (NTP), une organisation non gouvernementale locale et une organisation non gouvernementale internationale visant à renforcer les capacités humaines en matière de prévention et de soins de la TB. MÉTHODES: De 2016 à 2021, la division kényane du programme national de lutte contre la tuberculose, la lèpre et les maladies respiratoires, le Centre for Health Solutions-Kenya et l'Union internationale contre la tuberculose et les maladies respiratoires ont développé et dispensé une série de formations en 7 jours. La formation mettait l'accent sur l'introduction de l'approche TBData4Action, qui promeut une utilisation locale des données disponibles en routine afin de renforcer la prise de décision et d'épauler les activités de supervision. RÉSULTATS: Les résultats de la mise en place de cette formation comprenaient la formation de 331 (96%) coordinateurs sur 344, représentant l'ensemble des 47 pays, 37 administrateurs nationaux et 21 autres acteurs formés à l'aide du programme adapté aux besoins du pays concerné (dont travail de groupe pratique par les équipes nationales et travaux pratiques sur le terrain). Trente-cinq facilitateurs nationaux ont été identifiés et formés comme enseignants locaux. Les coûts de la formation ont été réduits de 75% par rapport aux alternatives internationales. CONCLUSION: La collaboration a permis de former la majorité des coordinateurs à l'aide d'une approche standardisée de soins de la TB. Une approche durable de renforcement des capacités en matière d'utilisation des données locales s'est avérée réalisable. Ce modèle peut être adapté à d'autres NTP.

T4 lysozyme fused with cellulose-binding module for antimicrobial cellulosic wound dressing materials.

AIMS: Bacterial infection is a major challenge in wound care. Antimicrobial wound dressings are of great value for treating wound infections. Endolysins are evolving as a new class of antimicrobials with multiple applications. This study describes the production and evaluation of T4 lysozyme (T4Lyz), product of gene e of the T4 bacteriophage, fused with Cellulose Binding Module (CBM) for facile immobilization to cellulosic wound dressing. METHODS AND RESULTS: Genes encoding T4Lyz-CBM and T4Lyz were cloned and expressed in Escherichia coli and the enzymes were purified by cation exchange chromatography. While the CBM tag did not alter the optimum pH and stability features of T4Lyz, the lytic activity of the fusion protein was lowered. The bactericidal activity of T4Lyz-CBM, determined by viable count plating assay after 1 h incubation with Micrococcus lysodeikticus was 97·5% with 10 µg ml(-1) , and 99·96% and 95% for E. coli and Pseudomonas mendocina, respectively, with 200 µg ml(-1) enzyme. T4Lyz-CBM was immobilized to wound dressing gauze with a capacity of 5·5 µg mg(-1) matrix, whereas the unmodified T4Lyz did not exhibit any binding. The immobilized protein retained its bactericidal activity against Gram-positive and Gram-negative bacteria. Both free and immobilized T4Lyz-CBM, after heat denaturation, retained their bactericidal activities against Gram-negative bacteria only. The immobilized enzyme exhibited higher stability than the free enzyme when stored in dry form or in the presence of polyol stabilizers. CONCLUSION: Tagging T4Lyz with CBM provides a facile, irreversible binding to cellulosic wound dressing while retaining its activity. This approach may be suitable even for other antimicrobial enzymes and -peptides. SIGNIFICANCE AND IMPACT OF THE STUDY: The spread of antibiotic resistance requires innovative strategies for discovery and development of effective antimicrobial alternatives. This report presents a novel strategy for producing antimicrobial wound dressing materials.

High temperature simultaneous saccharification and fermentation of starch from inedible wild cassava (Manihot glaziovii) to bioethanol using Caloramator boliviensis.

The thermoanaerobe, Caloramator boliviensis was used to ferment starch hydrolysate from inedible wild cassava to ethanol at 60°C. A raw starch degrading α-amylase was used to hydrolyse the cassava starch. During fermentation, the organism released CO2 and H2 gases, and Gas Endeavour System was successfully used for monitoring and recording formation of these gaseous products. The bioethanol produced in stoichiometric amounts to CO2 was registered online in Gas Endeavour software and correlated strongly (R(2)=0.99) with values measured by HPLC. The organism was sensitive to cyanide that exists in cassava flour. However, after acclimatisation, it was able to grow and ferment cassava starch hydrolysate containing up to 0.2ppm cyanide. The reactor hydrogen partial pressure had influence on the bioethanol production. In fed-batch fermentation by maintaining the hydrogen partial pressure around 590Pa, the organism was able to ferment up to 76g/L glucose and produced 33g/L ethanol.

Strain diversity of mycobacteria isolated from pulmonary tuberculosis patients at Debre Birhan Hospital, Ethiopia.

BACKGROUND: Ethiopia ranks seventh in the list of 22 high tuberculosis (TB) burden countries, with an incidence rate of 379 cases per 100,000 population for TB all forms. However, information on the genomic diversity of Mycobacterium tuberculosis in Ethiopia is limited. OBJECTIVE: To investigate the molecular characteristics of M. tuberculosis strains implicated in pulmonary TB in the study area. METHODS AND RESULTS: A cross-sectional study was conducted using socio-demographic, clinical and culture data combined with molecular typing analysis. The proportion of TB and M. tuberculosis isolates was not associated with risk factors (P > 0.05). Of 99 sputum samples, 80.8% were culture-positive. Speciation of isolates showed that 88.8% were M. tuberculosis. Further characterisation led to the identification of 27 different spoligotype patterns of M. tuberculosis; the most dominant shared types were SIT149, SIT53 and SIT54. Of the 27 strains, three strains were new and were reported to the SITVIT database. More than two thirds of the strains belonged to the Euro-American lineage. CONCLUSION: This study shows the presence of several clusters and new strains of M. tuberculosis circulating in pulmonary TB patients in the study area, suggesting recent transmission. Nationwide studies are recommended to map the population structure of M. tuberculosis and set control measures.

IgA response to ESAT-6/CFP-10 and Rv2031 antigens varies in patients with culture-confirmed pulmonary tuberculosis, healthy Mycobacterium tuberculosis-infected and non-infected individuals in a tuberculosis endemic setting, Ethiopia.

Little attention has been given to the role of antibodies against Mycobacterium tuberculosis (Mtb) infection. We have compared the levels of IgA and IgG against ESAT-6/CFP-10 and Rv2031c antigens in sera of patients with culture-confirmed pulmonary tuberculosis (PTB), healthy Mtb-infected and non-infected individuals in endemic TB settings. Venous blood samples were collected from 166 study participants; sera were separated and assayed by an enzyme-linked immunosorbent assay (ELISA). QuantiFERON-TB Gold In-Tube (QFTGIT) assay was used for the screening of latent TB infection. The mean optical density (OD) values of IgA against ESAT-6/CFP-10 and Rv2031 were significantly higher in sera of patients with culture-confirmed PTB compared with healthy Mtb-infected and non-infected individuals (P < 0.001). The mean OD values of IgG against ESAT-6/CFP-10 and Rv2031 were also significantly higher in sera of patients with culture-confirmed PTB compared with healthy Mtb-infected and non-infected individuals (P < 0.05). The mean OD values of IgA against both antigens were also higher in sera of healthy Mtb-infected cases compared with non-infected individuals. There were positive correlations (P < 0.05) between the level of IFN-γ induced in QFTGIT assay and the OD values of serum IgA against both antigens in healthy Mtb-infected subjects. This study shows the potential of IgA response against ESAT-6/CFP-10 and Rv2031 antigens in discriminating clinical TB from healthy Mtb-infected and non-infected cases. Nevertheless, further well-designed cohort study is needed to fully realize the full potential of this diagnostic marker.

Spoligotyping of multidrug-resistant Mycobacterium tuberculosis isolates in Ethiopia.

SETTING: St Peter Tuberculosis (TB) Specialized Hospital and the Aklilu Lemma Institute of Pathobiology, Addis Ababa, Ethiopia. OBJECTIVE: To genotype multidrug-resistant tuberculosis (MDR-TB) isolates and assess the magnitude of their clustering. DESIGN: A total of 183 consecutive MDR-TB isolates collected between September 2009 and February 2012 were characterised using molecular typing. Prior to the study, the isolates were confirmed as MDR-TB using GenoType MTBDRplus. Recent transmission index was used to analyse the clusters. RESULTS: Spoligotyping identified 43 different patterns, of which 17 consisted of at least two isolates forming clusters, while 26 had only a single isolate. The most frequent patterns were spoligo international typing (SIT) number 21 and 149. Twenty-four patterns did not match existing patterns in the SpolDB4 database. The strains belonged to three lineages, the predominant lineages being Euro-American and Indo-Oceanic, each consisting of 65 isolates. High proportions (86%) of patients were infected with clustered strains, suggesting probable recent transmission of MDR-TB in the study area. CONCLUSION: The observation of cluster formation of the spoligotype patterns of MDR-TB isolates could suggest transmission of MDR-TB strains among the population, thus warranting further attention.

Utilization of agricultural residues for poly(3-hydroxybutyrate) production by Halomonas boliviensis LC1.

AIMS: Utilization of cheap and readily available agricultural residues as cheap carbon sources for poly(3-hydroxybutyrate) (PHB) production by Halomonas boliviensis. METHODS AND RESULTS: Wheat bran was hydrolysed by a crude enzyme preparation from Aspergillus oryzae NM1 to provide a mixture of reducing sugars composed mainly of glucose, mannose, xylose and arabinose. Growth of H. boliviensis using a mixture of glucose (0.75% w/v) and xylose (0.25% w/v) in the medium led to a PHB content and concentration of 45 wt% and 1 g l(-1), respectively, after 30 h. A similar PHB concentration was attained when H. boliviensis was grown on wheat bran hydrolysate but with a lower PHB content, 34 wt%. In a batch cultivation mode in a fermentor, using 1.8% (w/v) reducing sugars, the maximum PHB accumulation by H. boliviensis was attained in 20 h, but was reduced to about 30 wt%. By adding butyric acid (0.8% v/v), sodium acetate (0.8% w/v) and decreasing the reducing sugars concentration to 1 x 0% w/v in the medium, PHB accumulation and concentration were increased to 50 wt% and 4 g l(-1), respectively, after 20 h. Butyric acid and sodium acetate for PHB production could also be provided by anaerobic digestion of solid potato waste. CONCLUSIONS: Cheap and readily available agricultural residues can be used as substrates to produce PHB. The production of PHB by H. boliviensis using wheat bran hydrolysate as source of carbon is expected to reduce the production cost and motivates further studies. SIGNIFICANCE AND IMPACT OF THE STUDY: Large-scale commercial utilization of PHB is mainly hampered by its high production cost. Carbon source for PHB production accounts up to 50% of the total production costs. Thus, the use of waste agricultural residues can substantially reduce the substrate cost (and in turn even provide value to the waste), and can downsize the production costs. This improves the market competitiveness. Studies on PHB production by moderate halophiles were recently initiated with H. boliviensis and findings show that it has potential for commercial exploitation. PHB production by H. boliviensis using wheat bran and potato waste is hence interesting.

Modified techniques of S3 foramen localization and lead implantation in S3 neuromodulation.

INTRODUCTION: We describe a reproducible and less invasive surgical approach to sacral neuromodulation (InterStim Therapy) in the treatment of voiding dysfunction. Twenty patients underwent modified lead implantation (mean operative time 45 minutes) without any difficulties or complications, with a mean follow-up of 8 months (range 1 to 14).Technical Considerations. The highlights of these modifications include (a) fluoroscopy to localize the S3 foramen; (b) paramedian incision; (c) use of a cutoff S3 finder needle and a 14-gauge Angiocath to direct permanent lead into the S3 foramen without dissection; (d) use of lateral fluoroscopy to determine the depth of the Angiocath insertion; and (e) anchoring the lead to the lumbodorsal fascia (superficial to the sacral periosteum) using a moveable lead anchor system. These modifications simplify and minimize the invasiveness of this therapy without compromising the efficacy. CONCLUSIONS: Because of the simplicity of these modifications, we are currently using an implanted lead, rather than the temporary percutaneous lead, to assess patients' clinical response before implanting a pulse generator.

Pubovaginal sling technique utilizing a unique bone anchor instrumentation system.

INTRODUCTION: In the past, the pubovaginal sling (PVS) technique was originally delegated for the treatment of intrinsic sphincter deficiency syndrome (ISD). Today, it has not only undergone a revitalization, but is being recommended for the treatment of all forms of stress urinary incontinence (SUI) as well as the ISD syndrome. In an attempt to combine the best features of the traditional approach plus add the benefits of simplicity, reduction of costs, morbidity, and rapid return to patient normality, a new variation of the PVS has been developed. The technique utilizes pre-threaded bone anchors to which either a natural fascia or pre-prepared cadaveric fascia can be anchored. MATERIAL AND METHODS: This study consists of 78 female patients treated between September 1997 and December 1998 with our PVS procedure. The patient population spans the spectrum of pure stress incontinence, with or without associated pelvic relaxation defects, pure ISD group and lastly, those individuals who suffered from both anatomical incontinence and overactive bladder syndrome. In our 72 evaluable patients, the results as of this publication are: an overall cure rate of 86% with an additional 11% improved and 3% failure. The following text describes in detail the patient population, the surgical technique, the final results, complications, and patient satisfaction scores. Also included is a short review of the literature documenting several other techniques utilizing bone anchoring fixation devices. CONCLUSION: A simplification of the true-and-tried PVS is described which provides the surgeon with a new and exciting methodology for the treatment of all forms of hypermobility, i.e. stress incontinence, as well as the intrinsic sphincter deficiency syndrome. At the same time the surgical learning curve, patient morbidity, and hospital stay are decreased; without compromising total surgical outcome.

Immobilization of alkaliphilic Bacillus sp. cells for xylanase production using batch and continuous culture.

Agar-immobilized alkaliphilic Bacillus sp. AR-009 cells were used for xylanase production using batch and continuous culture. In a batch culture, maximum enzyme production was observed after 48 h and remained high up to 72 h. In repeated batch cultivation, immobilized cells produced an appreciable level of xylanase activity in seven consecutive batches without any significant decline in productivity. For continuous xylanase production, immobilized cells were packed in a jacketed glass column and sterile medium was continuously pumped. A stable continuous production of xylanase was observed over a period of 1 mo. The volumetric productivity of the continuous culture was 17-fold higher than the batch culture using free cells.

Production of raw-starch digesting amyloglucosidase by Aspergillussp GP-21 in solid state fermentation.

Aspergillus sp GP-21 produced a raw-starch digesting amyloglucosidase which showed optimum activity at 65 degrees C and pH 5.0-5.5. At 50 degrees C the enzyme converted about 40% of raw corn starch to glucose within 48 h. Enzyme production was studied in solid state fermentation using wheat bran. Productivity was affected by the level of moisture, incubation temperature and the presence or absence of supplements. Maximum enzyme production was observed at a moisture level of 75% and at 30 degrees C. Enzyme production was stimulated by supplementing wheat bran with 0.25% proteose peptone, 1% trace mineral solution, 0.01% CaCl2 and 0.01% MgSO4.

Locked-in syndrome (LIS).

Two young female patients, who were admitted to Tikur Anbessa Hospital in September 1993 and January 1994, respectively, with locked-in syndrome are reported and literature is reviewed.

Cryptococcal prostatic abscess associated with the acquired immunodeficiency syndrome.

A case of cryptococcal prostatic abscess in a 28-year old man with the acquired immunodeficiency syndrome is presented. This is a unique presentation of a cryptococcal prostatic infection and of a prostatic abscess. The diagnosis and management are discussed, and the literature is reviewed.

Early catheter removal vs. conventional practice in patients undergoing transurethral resection of prostate.

A retrospective analysis of 127 of 146 consecutive patients undergoing transurethral resection of the prostate from February 1985 to January 1988 (3-year period) was performed. The catheter was removed on postoperative day 1 in 66 patients (group I) and on postoperative day 2 in 61 patients (group II). There were no significant differences between the two groups in terms of population age, weight of resected glands, operative time, and management. Both groups I and II had 8 complications following catheter removal. Postoperative hospital stay was reduced by an average of 1.37 days in group I. Total hospital cost was reduced by approximately $466.00. We conclude that catheter removal on postoperative day 1 is safe with no added morbidity while having the advantage of reduced hospital costs.