Extended Producer Responsibility for the Management of Waste from Mobile Phones

This thesis explores the functionality of Extend Producer Responsibility (EPR) in the management of Electrical and Electronic waste (e-waste) in Kenya using a case study on manufacturer involvement in end-of-life management. To achieve the purpose of the study the analytical framework used incorporates Environmental effectiveness, Economic efficiency, Political acceptability, Administrabilty and Innovative advancement in discussing the EPR policy instrument used by the manufacturer. On the practical front the data on the take-back scheme was discussed under the following factors that affect the efficiency and effectiveness of a take-back scheme: economic incentives, disincentives, convenience, inconvenience and information. On the other hand the thesis provides preliminary insights into the overall ewaste management scenario in Kenya. Literature and practical knowledge were used to explore and establish a picture of the dynamics of EPR in e-waste management under the ICT sector with special focus on mobile telephony and the actors in the sector. Suggested policy directions are based on the gaps identified through an analysis of the materials and information collected while in the field. The research confirms that there is need to develop waste management policies and regulations in Kenya structured and guided by EPR principles. The thesis emphasizes that EPR is a necessity in the management of e-waste in Kenya and the developing countries at large. Further it notes that there is need for knowledge transfer and exchange from the developed countries to the developing countries grappling with e-waste management in formulation of appropriate institutional and legislative frameworks customized to the ground realities

Simplified molecular detection of Leishmania parasites in various clinical samples from patients with leishmaniasis

<p>Abstract</p> <p>Background</p> <p>Molecular methods to detect <it>Leishmania </it>parasites are considered specific and sensitive, but often not applied in endemic areas of developing countries due to technical complexity. In the present study isothermal, nucleic acid sequence based amplification (NASBA) was coupled to oligochromatography (OC) to develop a simplified detection method for the diagnosis of leishmaniasis. NASBA-OC, detecting <it>Leishmania </it>RNA, was evaluated using clinical samples from visceral leishmaniasis patients from East Africa (n = 30) and cutaneous leishmaniasis from South America (n = 70) and appropriate control samples.</p> <p>Results</p> <p>Analytical sensitivity was 10 parasites/ml of spiked blood, and 1 parasite/ml of culture. Diagnostic sensitivity of NASBA-OC was 93.3% (95% CI: 76.5%-98.8%) and specificity was 100% (95% CI: 91.1%-100%) on blood samples, while sensitivity and specificity on skin biopsy samples was 98.6% (95% CI: 91.2%-99.9%) and 100% (95% CI: 46.3%-100%), respectively.</p> <p>Conclusion</p> <p>The NASBA-OC format brings implementation of molecular diagnosis of leishmaniasis in resource poor countries one step closer.</p

Efficacy and Safety of AmBisome in Combination with Sodium Stibogluconate or Miltefosine and Miltefosine Monotherapy for African Visceral Leishmaniasis: Phase II Randomized Trial.

BACKGROUND: SSG&PM over 17 days is recommended as first line treatment for visceral leishmaniasis in eastern Africa, but is painful and requires hospitalization. Combination regimens including AmBisome and miltefosine are safe and effective in India, but there are no published data from trials of combination therapies including these drugs from Africa. METHODS: A phase II open-label, non-comparative randomized trial was conducted in Sudan and Kenya to evaluate the efficacy and safety of three treatment regimens: 10 mg/kg single dose AmBisome plus 10 days of SSG (20 mg/kg/day), 10 mg/kg single dose AmBisome plus 10 days of miltefosine (2.5mg/kg/day) and miltefosine alone (2.5 mg/kg/day for 28 days). The primary endpoint was initial parasitological cure at Day 28, and secondary endpoints included definitive cure at Day 210, and pharmacokinetic (miltefosine) and pharmacodynamic assessments. RESULTS: In sequential analyses with 49-51 patients per arm, initial cure was 85% (95% CI: 73-92) in all arms. At D210, definitive cure was 87% (95% CI: 77-97) for AmBisome + SSG, 77% (95% CI 64-90) for AmBisome + miltefosine and 72% (95% CI 60-85) for miltefosine alone, with lower efficacy in younger patients, who weigh less. Miltefosine pharmacokinetic data indicated under-exposure in children compared to adults. CONCLUSION: No major safety concerns were identified, but point estimates of definitive cure were less than 90% for each regimen so none will be evaluated in Phase III trials in their current form. Allometric dosing of miltefosine in children needs to be evaluated. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov, number NCT01067443

Safety and efficacy of single dose versus multiple doses of AmBisome for treatment of visceral leishmaniasis in eastern Africa: a randomised trial.

BACKGROUND: Anti-leishmanial drug regimens that include a single dose AmBisome could be suitable for eastern African patients with symptomatic visceral leishmaniasis (VL) but the appropriate single dose is unknown. METHODOLOGY: A multi-centre, open-label, non-inferiority, randomized controlled trial with an adaptive design, was conducted to compare the efficacy and safety of a single dose and multiple doses of AmBisome for the treatment of VL in eastern Africa. The primary efficacy endpoint was definitive cure (DC) at 6 months. Symptomatic patients with parasitologically-confirmed, non-severe VL, received a single dose of AmBisome 7.5 mg/kg body weight or multiple doses, 7 times 3 mg/kg on days 1-5, 14, and 21. If interim analyses, evaluated 30 days after the start of treatment following 40 or 80 patients, showed the single dose gave significantly poorer parasite clearance than multiple doses at the 5% significance level, the single dose was increased by 2·5 mg/kg. In a sub-set of patients, parasite clearance was measured by quantitative reverse transcriptase (qRT) PCR. PRINCIPAL FINDINGS: The trial was terminated after the third interim analysis because of low efficacy of both regimens. Based on the intention-to-treat population, DC was 85% (95%CI 73-93%), 40% (95%CI 19-64%), and 58% (95%CI 41-73%) in patients treated with multiple doses (n = 63), and single doses of 7·5 (n = 21) or 10 mg/kg (n = 40), respectively. qRT-PCR suggested superior parasite clearance with multiple doses as early as day 3. Safety data accorded with the drug label. CONCLUSIONS: The tested AmBisome regimens would not be suitable for VL treatment across eastern Africa. An optimal single dose regimen was not identified. TRIALS REGISTRATION: www.clinicaltrials.govNCT00832208

Contribution of PEPFAR-Supported HIV and TB Molecular Diagnostic Networks to COVID-19 Testing Preparedness in 16 Countries.

The US President's Emergency Plan for AIDS Relief (PEPFAR) supports molecular HIV and tuberculosis diagnostic networks and information management systems in low- and middle-income countries. We describe how national programs leveraged these PEPFAR-supported laboratory resources for SARS-CoV-2 testing during the COVID-19 pandemic. We sent a spreadsheet template consisting of 46 indicators for assessing the use of PEPFAR-supported diagnostic networks for COVID-19 pandemic response activities during April 1, 2020, to March 31, 2021, to 27 PEPFAR-supported countries or regions. A total of 109 PEPFAR-supported centralized HIV viral load and early infant diagnosis laboratories and 138 decentralized HIV and TB sites reported performing SARS-CoV-2 testing in 16 countries. Together, these sites contributed to >3.4 million SARS-CoV-2 tests during the 1-year period. Our findings illustrate that PEPFAR-supported diagnostic networks provided a wide range of resources to respond to emergency COVID-19 diagnostic testing in 16 low- and middle-income countries

A successful treatment of a Kenyan case of unresponsive cutaneous leishmaniasis with a combination of pentostam and oral allopurinol: Case Report

A nine year aged male presented with facial lesions and the problem of responding to conventional treatment of leishmaniasis. Multiple injections of antimony and several topical ointments had been administered in hospital but fresh lesions erupted with potential to disfigure. Smears examined from nodular lesions confirmed presence of Leishmania amastigotes and parenteral pentostam was commenced for over eight weeks. A partial clinical outcome was achieved judged by extent of re-epithelialisation. Combined therapy of pentostam and oral allopurinol at a dose of 7mg/kg/ day was started and finalised at 120 days. All facial lesions receded and 100% re-epithelialisation of the lesions established

Comparison of short-term and long-term protocols for stabilization and preservation of RNA and DNA of Leishmania, Trypanosoma, and Plasmodium

Molecular tools continue to be important in the prevention and control of parasitic diseases. However, using these techniques directly in the field remains a major challenge. Therefore, the preservation of clinical samples collected from endemic field areas for later analysis remains an important preanalytical process. This study aimed at identifying a suitable protocol for stabilization and preservation of RNA and DNA in bioclinical specimens for Trypanosoma, Leishmania, and Plasmodium research. Both spiked and unspiked blood samples were preserved in 7 protocols (different media; storage temperatures). Samples were evaluated for possible degradation of DNA and RNA along the storage duration up to the 10th week. Nucleic acid targets were assessed as follows: (i) Trypanosoma and Plasmodium RNA analysis was done using real-time nucleic acid sequence-based amplification (RT-NASBA) for 18S rRNA and for stage-specific Pfs25 mRNA, respectively; (ii) Trypanosoma DNA assessment analysis was conducted by using a conventional PCR for 18S rDNA; (iii) Leishmania RNA analysis was performed with a quantitative NASBA for 18S rRNA and Leishmania DNA assessment with an RT-PCR for 18S rDNA. Findings suggested that a newly developed L3™ buffer proved to be reliable and suitable for both short- and long-term preservation of parasite nucleic acid material. This buffer is envisaged to be suitable for utilization in field situations where resources are limite

Sensitivity and specificity of the Leishmania OligoC-TesT and NASBA-oligochromatography for diagnosis of visceral leishmaniasis in Kenya

Summary Objective To estimate the sensitivity and specificity of the OligoC-TesT and nucleic acid sequence-based amplification coupled to oligochromatography (NASBA-OC) for molecular detection of Leishmania in blood from patients with confirmed visceral leishmaniasis (VL) and healthy endemic controls from Kenya. Methods Blood specimens of 84 patients with confirmed VL and 98 endemic healthy controls from Baringo district in Kenya were submitted to both assays. Results The Leishmania OligoC-TesT showed a sensitivity of 96.4% (95% confidence interval [CI]: 90-98.8%) and a specificity of 88.8% (95% CI: 81-93.6%), while the sensitivity and specificity of the NASBA-OC were 79.8% (95% CI: 67-87%) and 100% (95% CI: 96.3-100%), respectively. Conclusion Our findings indicate high sensitivity of the Leishmania OligoC-TesT on blood while the NASBA-OC is a better marker for active diseas

Targeted Transcriptional Profiling of Kidney Transplant Biopsies

Introduction: Studies are needed to assess the quality of transcriptome analysis in paired human tissue samples preserved by different methods and different gene amplification platforms to enable data comparisons across experimenters. Methods: RNA was extracted from kidney biopsies, either submerged in RNA-stabilizing solution (RSS) or stored in formalin-fixed, paraffin-embedded (FFPE) blocks. RNA quality and integrity were compared. Gene expression of the common rejection module and other immune cell genes were quantified for both tissue preservation methods in the same sample using conventional quantitative polymerase chain reaction (QPCR) by 2 different commercial platforms, (fluidigm [FD]) or barcoded-oligos (nanostring [NS]). Results: RNA quality was inferior in FFPE tissues. Despite this, gene expression for 19 measured genes on the same sample, stored in FFPE or RSS, were strongly correlated on the FD (r = 0.81) or NS platforms (r = 0.82). For the same samples, interplatform gene expression correlations were excellent (r = 0.80) for RSS and moderate (r = 0.66) for FFPE. Significant differences in gene expression were confirmed on both platforms (FD: P = 1.1E-03; NS: P = 2.5E-04) for biopsy-confirmed acute rejection. Conclusion: Our study provided supportive evidence that despite a low RNA quality of archival FFPE kidney transplantation tissue, small quantities of this tissue can be obtained from existing paraffin blocks to provide a viable and rich biospecimen source for focused gene expression assays. In addition, reliable and reproducible gene expression evaluation can be performed on these FFPE tissues using either a QPCR-based or a barcoded-oligo approach, which provides opportunities for collaborative analytics. Keywords: FFPE, gene expression, kidney transplant, nanostring, QPCR, rejectio

Accordance and concordance of PCR and NASBA followed by oligochromatography for the molecular diagnosis of Trypanosoma brucei and Leishmania

Summary Objective To evaluate the repeatability and reproducibility of four simplified molecular assays for the diagnosis of Trypanosoma brucei spp. or Leishmania ssp. in a multicentre ring trial with seven participating laboratories. Methods The tests are based on PCR or NASBA amplification of the parasites nucleic acids followed by rapid read-out by oligochromatographic dipstick (PCR-OC and NASBA-OC). Results On purified nucleic acid specimens, the repeatability and reproducibility of the tests were Tryp-PRC-OC, 91.7% and 95.5%; Tryp-NASBA-OC, 95.8% and 100%; Leish-PCR-OC, 95.9% and 98.1%; Leish-NASBA-OC, 92.3% and 98.2%. On blood specimens spiked with parasites, the repeatability and reproducibility of the tests were Tryp-PRC-OC, 78.4% and 86.6%; Tryp-NASBA-OC, 81.5% and 89.0%; Leish-PCR-OC, 87.1% and 91.7%; Leish-NASBA-OC, 74.8% and 86.2%. Conclusion As repeatability and reproducibility of the tests were satisfactory, further phase II and III evaluations in clinical and population specimens from disease endemic countries are justifie