Rationing tests for drug-resistant tuberculosis - who are we prepared to miss?

BACKGROUND: Early identification of patients with drug-resistant tuberculosis (DR-TB) increases the likelihood of treatment success and interrupts transmission. Resource-constrained settings use risk profiling to ration the use of drug susceptibility testing (DST). Nevertheless, no studies have yet quantified how many patients with DR-TB this strategy will miss. METHODS: A total of 1,545 subjects, who presented to Lima health centres with possible TB symptoms, completed a clinic-epidemiological questionnaire and provided sputum samples for TB culture and DST. The proportion of drug resistance in this population was calculated and the data was analysed to demonstrate the effect of rationing tests to patients with multidrug-resistant TB (MDR-TB) risk factors on the number of tests needed and corresponding proportion of missed patients with DR-TB. RESULTS: Overall, 147/1,545 (9.5%) subjects had culture-positive TB, of which 32 (21.8%) had DR-TB (MDR, 13.6%; isoniazid mono-resistant, 7.5%; rifampicin mono-resistant, 0.7%). A total of 553 subjects (35.8%) reported one or more MDR-TB risk factors; of these, 506 (91.5%; 95% CI, 88.9-93.7%) did not have TB, 32/553 (5.8%; 95% CI, 3.4-8.1%) had drug-susceptible TB, and only 15/553 (2.7%; 95% CI, 1.5-4.4%) had DR-TB. Rationing DST to those with an MDR-TB risk factor would have missed more than half of the DR-TB population (17/32, 53.2%; 95% CI, 34.7-70.9). CONCLUSIONS: Rationing DST based on known MDR-TB risk factors misses an unacceptable proportion of patients with drug-resistance in settings with ongoing DR-TB transmission. Investment in diagnostic services to allow universal DST for people with presumptive TB should be a high priority

Efficacy of antimalarial treatment in Guinea: in vivo study of two artemisinin combination therapies in Dabola and molecular markers of resistance to sulphadoxine-pyrimethamine in N'Zérékoré

BACKGROUND: In the last five years, countries have been faced with changing their malaria treatment policy to an artemisinin-based combination therapy (ACT), many with no national data on which to base their decision. This is particularly true for a number of West African countries, including Guinea, where these studies were performed. Two studies were conducted in 2004/2005 in programmes supported by Medecins Sans Frontieres, when chloroquine was still national policy, but artesunate (AS)/sulphadoxine-pyrimethamine (SP) had been used in refugee camps for two years. METHODS: In Dabola (central Guinea), 220 children aged 6-59 months with falciparum malaria were randomized to receive either AS/amodiaquine (AQ) or AS/SP. In vivo efficacy was assessed following the 2003 World Health Organization guidelines. In a refugee camp in Laine (south of Guinea), where an in vivo study was not feasible due to the unstable context, a molecular genotyping study in 160 patients assessed the prevalence of mutations in the dihydrofolate reductase (dhfr) (codons 108, 51, 59) and dihydropteroate synthase (dhps) (codons 436, 437, 540) genes of Plasmodium falciparum, which have been associated with resistance to pyrimethamine and sulphadoxine, respectively. RESULTS: In Dabola, after 28 days of follow-up, Polymerase Chain Reaction (PCR)-adjusted failure rates were 1.0% (95%CI 0-5.3) for AS/AQ and 1.0% (95%CI 0-5.5) for AS/SP. In the refugee camp in Laine, the molecular genotyping study found three dhfr mutations in 85.6% (95%CI 79.2-90.7) patients and quintuple dhfr/dhps mutations in 9.6% (95%CI 5.2-15.9). CONCLUSION: Both AS/AQ and AS/SP are highly efficacious in Dabola, whereas there is molecular evidence of established SP resistance in Laine. This supports the choice of the national programme of Guinea to adopt AS/AQ as first line antimalarial treatment. The results highlight the difficulties faced by control programmes, which have gone through the upheaval of implementing ACTs, but cannot predict how long their therapeutic life will be, especially in countries which have chosen drugs also available as monotherapies

Poor quality vital anti-malarials in Africa - an urgent neglected public health priority

BACKGROUND: Plasmodium falciparum malaria remains a major public health problem. A vital component of malaria control rests on the availability of good quality artemisinin-derivative based combination therapy (ACT) at the correct dose. However, there are increasing reports of poor quality anti-malarials in Africa. METHODS: Seven collections of artemisinin derivative monotherapies, ACT and halofantrine anti-malarials of suspicious quality were collected in 2002/10 in eleven African countries and in Asia en route to Africa. Packaging, chemical composition (high performance liquid chromatography, direct ionization mass spectrometry, X-ray diffractometry, stable isotope analysis) and botanical investigations were performed. RESULTS: Counterfeit artesunate containing chloroquine, counterfeit dihydroartemisinin (DHA) containing paracetamol (acetaminophen), counterfeit DHA-piperaquine containing sildenafil, counterfeit artemether-lumefantrine containing pyrimethamine, counterfeit halofantrine containing artemisinin, and substandard/counterfeit or degraded artesunate and artesunate+amodiaquine in eight countries are described. Pollen analysis was consistent with manufacture of counterfeits in eastern Asia. These data do not allow estimation of the frequency of poor quality anti-malarials in Africa. CONCLUSIONS: Criminals are producing diverse harmful anti-malarial counterfeits with important public health consequences. The presence of artesunate monotherapy, substandard and/or degraded and counterfeit medicines containing sub-therapeutic amounts of unexpected anti-malarials will engender drug resistance. With the threatening spread of artemisinin resistance to Africa, much greater investment is required to ensure the quality of ACTs and removal of artemisinin monotherapies. The International Health Regulations may need to be invoked to counter these serious public health problems

Mosquito Abundance, Bed net Coverage and Other Factors Associated with Variations in Sporozoite Infectivity Rates in Four Villages of Rural Tanzania.

Entomological surveys are of great importance in decision-making processes regarding malaria control strategies because they help to identify associations between vector abundance both species-specific ecology and disease intervention factors associated with malaria transmission. Sporozoite infectivity rates, mosquito host blood meal source, bed net coverage and mosquito abundance were assessed in this study. A longitudinal survey was conducted in four villages in two regions of Tanzania. Malaria vectors were sampled using the CDC light trap and pyrethrum spray catch methods. In each village, ten paired houses were selected for mosquitoes sampling. Sampling was done in fortnight case and study was undertaken for six months in both Kilimanjaro (Northern Tanzania) and Dodoma (Central Tanzania) regions. A total of 6,883 mosquitoes were collected including: 5,628 (81.8%) Anopheles arabiensis, 1,100 (15.9%) Culex quinquefasciatus, 89 (1.4%) Anopheles funestus, and 66 (0.9%) Anopheles gambiae s.s. Of the total mosquitoes collected 3,861 were captured by CDC light trap and 3,022 by the pyrethrum spray catch method. The overall light trap: spray catch ratio was 1.3:1. Mosquito densities per room were 96.5 and 75.5 for light trap and pyrethrum spray catch respectively. Mosquito infectivity rates between villages that have high proportion of bed net owners and those without bed nets was significant (P < 0.001) and there was a significant difference in sporozoite rates between households with and without bed nets in these four villages (P < 0.001). Malaria remains a major problem in the study areas characterized as low transmission sites. Further studies are required to establish the annual entomological inoculation rates and to observe the annual parasitaemia dynamics in these communities. Outdoor mosquitoes collection should also be considered

Murder, Capital Punishment, and Deterrence: A Review of the Evidence and an Examination of Police Killings.

This paper reviews and assesses the empirical literature on murder, capital punishment, and deterrence. There is a large body of evidence regarding these issues, with studies yielding a rather consistent pattern of nondeterrence. However, most investigations are limited because they rely upon the general homicide rate as the criterion variable, although both legally and theoretically, different types of murder may be differentially subject to deterrence. As an example of how deterrence investigations may benefit from examining different types of homicide, we conduct a monthly time-series analysis of the possible deterrent effect of the provision for capital punishment, levels of execution, and the amount and type of television news coverage executions receive on overall and different types of police killings for 1976-1989. The analysis reveals no evidence that police are afforded an added measure of protection against death by capital punishment

Drivers of Innovation Using BIM in Architecture, Engineering, and Construction Firms

This material may be downloaded for personal use only. Any other use requires prior permission of the American Society of Civil Engineers. This material may be found at https://doi.org/10.1061/9780784482889.023[Otros] Architecture, engineering, and construction (AEC) firms need to innovate in order to increase their business¿ competitiveness. Many companies around the world are considering the possibility of implementing building information modelling (BIM) in their projects without knowing its actual benefits for the business. The current literature recognizes certain barriers to BIM implementation; therefore, considering these barriers, this work proposes a holistic model that allows managers to explain how BIM can play an important role for the success of the AEC companies. The pillars of the model are a collaborative culture and training of employees in order to break down technological barriers. This way, BIM can help AEC companies to innovate. This proposal takes into consideration the three phases of the infrastructure life-cycle. In the design phase, the model considers 3D shape, scheduling (4D), costs (5D), and sustainability (6D). In the construction phase, the model focuses on supply chain and quality management. During the operation phase, the model is related to the virtual management of maintenance activities. Drivers of innovation should consider several facets: marketing, technology, organization, processes, and products. This model aims to enlighten the positive effects of a good strategic management using BIM on innovation activities in each of the phases of the infrastructure life-cycleVillena, F.; García-Segura, T.; Pellicer, E. (2020). Drivers of Innovation Using BIM in Architecture, Engineering, and Construction Firms. American Society of Civil Engineers. 210-222. https://doi.org/10.1061/9780784482889.023S210222Aibinu, A., & Venkatesh, S. (2014). 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Technology Analysis & Strategic Management, 17(2), 121-146. doi:10.1080/09537320500088666Hong Y. Hammad A. Sepasgozar S. and Akbarnezhad A. (2019). "BIM adoption model for small and medium construction organizations in Australia" Engineering Construction and Architectural Management 26(2) 154-183. https://doi.org/10.1108/ECAM-04-2017-006410.1108/ECAM-04-2017-0064Hurley, R. F., & Hult, G. T. M. (1998). Innovation, Market Orientation, and Organizational Learning: An Integration and Empirical Examination. Journal of Marketing, 62(3), 42-54. doi:10.1177/002224299806200303Khosrowshahi, F., & Arayici, Y. (2012). Roadmap for implementation of BIM in the UK construction industry. Engineering, Construction and Architectural Management, 19(6), 610-635. doi:10.1108/09699981211277531Kleinschmidt, E. J., de Brentani, U., & Salomo, S. (2007). Performance of Global New Product Development Programs: A Resource-Based View. 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"The application and barriers of BIM in sustainable building design" Journal of Facilities Management 15(1):15−34. https://doi.org/10.1108/JFM-03-2016-0008.10.1108/JFM-03-2016-0008Olawumi, T. O., Chan, D. W. M., Wong, J. K. W., & Chan, A. P. C. (2018). Barriers to the integration of BIM and sustainability practices in construction projects: A Delphi survey of international experts. Journal of Building Engineering, 20, 60-71. doi:10.1016/j.jobe.2018.06.017Ozorhon, B., & Oral, K. (2017). Drivers of Innovation in Construction Projects. Journal of Construction Engineering and Management, 143(4), 04016118. doi:10.1061/(asce)co.1943-7862.0001234Papadonikolaki, E. (2018). Loosely Coupled Systems of Innovation: Aligning BIM Adoption with Implementation in Dutch Construction. Journal of Management in Engineering, 34(6), 05018009. doi:10.1061/(asce)me.1943-5479.0000644Pellicer, E., Yepes, V., Correa, C. L., & Alarcón, L. F. (2014). Model for Systematic Innovation in Construction Companies. 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Linking multiple layers of innovation-oriented corporate culture, product program innovativeness, and business performance: a contingency approach. Journal of the Academy of Marketing Science, 41(3), 283-299. doi:10.1007/s11747-012-0306-5Succar, B., & Kassem, M. (2015). Macro-BIM adoption: Conceptual structures. Automation in Construction, 57, 64-79. doi:10.1016/j.autcon.2015.04.018Succar, B. (2009). Building information modelling framework: A research and delivery foundation for industry stakeholders. Automation in Construction, 18(3), 357-375. doi:10.1016/j.autcon.2008.10.003Taylor, J. E., & Bernstein, P. G. (2009). Paradigm Trajectories of Building Information Modeling Practice in Project Networks. Journal of Management in Engineering, 25(2), 69-76. doi:10.1061/(asce)0742-597x(2009)25:2(69)Tekla Corporation. (2013). Basic concepts [online] [ 16 Enero 2013]. Available from Internet: http://www.tekla.comVillena Manzanares, F., & Galiano Coronil, A. (2017). EL DESARROLLO URBANO SOSTENIBLE Y SUS IMPLICACIONES PARA LAS EMPRESAS Y LOS TERRITORIOS. Revista de Estudios Empresariales. Segunda Época, (1). doi:10.17561/ree.v0i1.3185Volk, R., Stengel, J., & Schultmann, F. (2014). Building Information Modeling (BIM) for existing buildings — Literature review and future needs. Automation in Construction, 38, 109-127. doi:10.1016/j.autcon.2013.10.023Whyte, J., Bouchlaghem, N., Thorpe, A., & McCaffer, R. (2000). From CAD to virtual reality: modelling approaches, data exchange and interactive 3D building design tools. Automation in Construction, 10(1), 43-55. doi:10.1016/s0926-5805(99)00012-6Wischnevsky, J. D., Damanpour, F., & Méndez, F. A. (2011). Influence of Environmental Factors and Prior Changes on the Organizational Adoption of Changes in Products and in Technological and Administrative Processes. British Journal of Management, 22(1), 132-149. doi:10.1111/j.1467-8551.2010.00700.xWong, K., & Fan, Q. (2013). 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Growing Problem of Multidrug-Resistant Enteric Pathogens in Africa

A disproportionate number of low-income persons are affected

Assessing the impact of microfinance programming on children: an evaluation from post-tsunami Aceh

This paper presents an evaluation of the long‐term impact of microfinance programmes on Acehnese children during the post‐tsunami recovery. The study, conducted from June to August 2010, examined the impact of microfinance programming six years after the tsunami. The sample consisted of 185 microfinance participants, with a comparison group of 192 individuals who did not participate in microfinance programmes. All respondents were parents, interviewed through a structured survey. The study used four child protection indicators—diet, health, childcare and education—in contrast to traditional repayment rate indicators. The primary results were insignificant with respect to all four child protection indicators, suggesting that, with respect to these indicators, there was no long‐term difference between the impact of microfinance on beneficiaries' children and non‐beneficiaries' children. These findings signify a need for microfinance actors to move beyond traditional indicators of economic success to evaluate the social changes microfinance programmes are presumed to effect

Effects of Point Mutations in Plasmodium falciparum Dihydrofolate Reductase and Dihydropterate Synthase Genes on Clinical Outcomes and In Vitro Susceptibility to Sulfadoxine and Pyrimethamine

Sulfadoxine-pyrimethamine was a common first line drug therapy to treat uncomplicated falciparum malaria, but increasing therapeutic failures associated with the development of significant levels of resistance worldwide has prompted change to alternative treatment regimes in many national malaria control programs. METHODOLOGY AND FINDING: We conducted an in vivo therapeutic efficacy trial of sulfadoxine-pyrimethamine at two locations in the Peruvian Amazon enrolling 99 patients of which, 86 patients completed the protocol specified 28 day follow up. Our objective was to correlate the presence of polymorphisms in P. falciparum dihydrofolate reductase and dihydropteroate synthase to in vitro parasite susceptibility to sulfadoxine and pyrimethamine and to in vivo treatment outcomes. Inhibitory concentration 50 values of isolates increased with numbers of mutations (single [108N], sextuplet [BR/51I/108N/164L and 437G/581G]) and septuplet (BR/51I/108N/164L and 437G/540E/581G) with geometric means of 76 nM (35-166 nM), 582 nM (49-6890- nM) and 4909 (3575-6741 nM) nM for sulfadoxine and 33 nM (22-51 nM), 81 nM (19-345 nM), and 215 nM (176-262 nM) for pyrimethamine. A single mutation present in the isolate obtained at the time of enrollment from either dihydrofolate reductase (164L) or dihydropteroate synthase (540E) predicted treatment failure as well as any other single gene alone or in combination. Patients with the dihydrofolate reductase 164L mutation were 3.6 times as likely to be treatment failures [failures 85.4% (164L) vs 23.7% (I164); relative risk = 3.61; 95% CI: 2.14 - 6.64] while patients with the dihydropteroate synthase 540E were 2.6 times as likely to fail treatment (96.7% (540E) vs 37.5% (K540); relative risk = 2.58; 95% CI: 1.88 - 3.73). Patients with both dihydrofolate reductase 164L and dihydropteroate synthase 540E mutations were 4.1 times as likely to be treatment failures [96.7% vs 23.7%; RR = 4.08; 95% CI: 2.45 - 7.46] compared to patients having both wild forms (I164 and K540).In this part of the Amazon basin, it may be possible to predict treatment failure with sulfadoxine-pyrimethamine equally well by determination of either of the single mutations dihydrofolate reductase 164L or dihydropteroate synthase 540E.ClinicalTrials.gov NCT00951106

Multilocus genotyping reveals high heterogeneity and strong local population structure of the Plasmodium vivax population in the Peruvian Amazon

<p>Abstract</p> <p>Background</p> <p>Peru is one of the Latin American countries with the highest malaria burden, mainly due to <it>Plasmodium vivax </it>infections. However, little is known about <it>P. vivax </it>transmission dynamics in the Peruvian Amazon, where most malaria cases occur. The genetic diversity and population structure of <it>P. vivax </it>isolates collected in different communities around Iquitos city, the capital of the Peruvian Amazon, was determined.</p> <p>Methods</p> <p><it>Plasmodium vivax </it>population structure was determined by multilocus genotyping with 16 microsatellites on 159 <it>P. vivax </it>infected blood samples (mono-infections) collected in four sites around Iquitos city. The population characteristics were assessed only in samples with monoclonal infections (n = 94), and the genetic diversity was determined by calculating the expected heterozygosity and allelic richness. Both linkage disequilibrium and the genetic differentiation (<it>θ</it>) were estimated.</p> <p>Results</p> <p>The proportion of polyclonal infections varied substantially by site (11% - 70%), with the expected heterozygosity ranging between 0.44 and 0.69; no haplotypes were shared between the different populations. Linkage disequilibrium was present in all populations (<it>I</it>_A^S0.14 - 0.61) but was higher in those with fewer polyclonal infections, suggesting inbreeding and a clonal population structure. Strong population differentiation (<it>θ </it>= 0.45) was found and the Bayesian inference cluster analysis identified six clusters based on distinctive allele frequencies.</p> <p>Conclusion</p> <p>The <it>P. vivax </it>populations circulating in the Peruvian Amazon basin are genetically diverse, strongly differentiated and they have a low effective recombination rate. These results are in line with the low and clustered pattern of malaria transmission observed in the region around Iquitos city.</p