The World Health Organization recommends Pre-Exposure Prophylaxis (PrEP) for all populations at substantial risk of HIV infection. Understanding PrEP awareness and interest is crucial for designing ...PrEP programs; however, data are lacking in sub-Saharan Africa. In Malawi, oral PrEP was introduced in 2018. We analyzed data from the 2020 Malawi Population-based HIV Impact Assessment (MPHIA) to assess PrEP awareness and factors associated with PrEP interest in Malawi. MPHIA 2020 was a national cross-sectional household-based survey targeting adults aged 15 + years. Oral PrEP was first described to the survey participants as taking a daily pill to reduce the chance of getting HIV. To assess awareness, participants were asked if they had ever heard of PrEP and to assess interest, were asked if they would take PrEP to prevent HIV, regardless of previous PrEP knowledge. Only sexually active HIV-negative participants are included in this analysis. We used multivariable logistic regression to assess sociodemographic factors and behaviors associated with PrEP interest. All results were weighted. We included 13,995 HIV-negative sexually active participants; median age was 29 years old. Overall, 15.0%, 95% confidence interval (CI): 14.2-15.9% of participants were aware of PrEP. More males (adjusted odds ratio (aOR): 1.3, 95% CI: 1.2-1.5), those with secondary (aOR: 1.5, 95% CI: 1.2-2.0) or post-secondary (aOR: 3.4, 95% CI: 2.4-4.9) education and the wealthiest (aOR: 1.6, 95% CI: 1.2-2.0) were aware of PrEP than female, those without education and least wealthy participants, respectively. Overall, 73.0% (95% CI: 71.8-74.1%) of participants were willing to use PrEP. Being male (aOR: 1.2; 95% CI: 1.1-1.3) and having more than one sexual partner (aOR: 1.7 95% CI: 1.4-1.9), were associated higher willingness to use PrEP. In this survey, prior PrEP knowledge and use were low while PrEP interest was high. High risk sexual behavior was associated with willingness to use PrEP. Strategies to increase PrEP awareness and universal access, may reduce HIV transmission.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
22.
Preparation of nanoparticles by continuous-flow microfluidics Jahn, Andreas; Reiner, Joseph E.; Vreeland, Wyatt N. ...
Journal of nanoparticle research : an interdisciplinary forum for nanoscale science and technology,
08/2008, Letnik:
10, Številka:
6
Journal Article
We review a variety of micro- and nanoparticle formulations produced with microfluidic methods. A diverse variety of approaches to generate microscale and nanoscale particles has been reported. Here ...we emphasize the use of microfluidics, specifically microfluidic systems that operate in a continuous flow mode, thereby allowing continuous generation of desired particle formulations. The generation of semiconductor quantum dots, metal colloids, emulsions, and liposomes is considered. To emphasize the potential benefits of the continuous-flow microfluidic methodology for nanoparticle generation, preliminary data on the size distribution of liposomes formed using the microfluidic approach is compared to the traditional bulk alcohol injection method.
The scale-up of antiretroviral therapy (ART) in Malawi was based on a public health approach adapted to its resource-poor setting, with principles and practices borrowed from the successful ...tuberculosis control framework. From 2004 to 2015, the number of new patients started on ART increased from about 3000 to over 820,000. Despite being a small country, Malawi has made a significant contribution to the 15 million people globally on ART and has also contributed policy and service delivery innovations that have supported international guidelines and scale up in other countries. The first set of global guidelines for scaling up ART released by the World Health Organization (WHO) in 2002 focused on providing clinical guidance. In Malawi, the ART guidelines adopted from the outset a more operational and programmatic approach with recommendations on health systems and services that were needed to deliver HIV treatment to affected populations. Seven years after the start of national scale-up, Malawi launched a new strategy offering all HIV-infected pregnant women lifelong ART regardless of the CD4-cell count, named Option B+. This strategy was subsequently incorporated into a WHO programmatic guide in 2012 and WHO ART guidelines in 2013, and has since then been adopted by the majority of countries worldwide. In conclusion, the Malawi experience of ART scale-up has become a blueprint for a public health response to HIV and has informed international efforts to end the AIDS epidemic by 2030.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
Ligand-based virtual screening experiments are an important task in the early drug discovery stage. An ambitious aim in each experiment is to disclose active structures based on new ...scaffolds. To perform these "scaffold-hoppings" for individual problems and targets, a plethora of different similarity methods based on diverse techniques were published in the last years. The optimal assignment approach on molecular graphs, a successful method in the field of quantitative structure-activity relationships, has not been tested as a ligand-based virtual screening method so far.
Results
We evaluated two already published and two new optimal assignment methods on various data sets. To emphasize the "scaffold-hopping" ability, we used the information of chemotype clustering analyses in our evaluation metrics. Comparisons with literature results show an improved early recognition performance and comparable results over the complete data set. A new method based on two different assignment steps shows an increased "scaffold-hopping" behavior together with a good early recognition performance.
Conclusion
The presented methods show a good combination of chemotype discovery and enrichment of active structures. Additionally, the optimal assignment on molecular graphs has the advantage to investigate and interpret the mappings, allowing precise modifications of internal parameters of the similarity measure for specific targets. All methods have low computation times which make them applicable to screen large data sets.
Isoniazid preventive therapy (IPT) against tuberculosis (TB) is a life-saving intervention for people living with HIV (PLHIV). In September 2017, Malawi began programmatic scale-up of IPT to eligible ...PLHIV in five districts with high HIV and TB burden. We measured the frequency and timeliness of early-phase IPT implementation to inform quality-improvement processes.
We applied a two-stage cluster design with systematic, probability-proportional-to-size sampling of six U.S. Centers for Disease Control and Prevention (CDC)-affiliated antiretroviral therapy (ART) centers operating in the urban areas of Lilongwe and Blantyre, Malawi (November 2017). ART clinic patient volume determined cluster size. Within each cluster, we sequentially sampled approximately 50 PLHIV newly enrolled in ART care. We described a quality-of-care cascade for intensive TB case finding (ICF) and IPT in PLHIV. PLHIV newly enrolled in ART care were eligibility-screened for hepatitis and peripheral neuropathy, as well as for TB disease using a standardized four-symptom screening tool. Among eligible PLHIV, the overall weighted IPT initiation rate was 70% (95% CI: 46%-86%). Weighted IPT initiation among persons aged <15 years (30% 95% CI: 12%-55%) was significantly lower than among persons aged ≥15 years (72% 95% CI: 47%-89%; Rao-Scott chi-square P = 0.03). HIV-positive children aged <5 years had a weighted initiation rate of only 13% (95% CI: 1%-79%). For pregnant women, the weighted initiation rate was 67% (95% CI: 32%-90%), similar to non-pregnant women aged ≥15 years (72% 95% CI: 49%-87%). Lastly, 95% (95% CI: 92%-97%) of eligible PLHIV started ART within one week of HIV diagnosis, and 92% (95% CI: 73%-98%) of patients receiving IPT began on the same day as ART.
Early-phase IPT uptake among adults at ART centers in Malawi was high. Child uptake needed improvement. National programs could adapt this framework to evaluate their ICF-IPT care cascades.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Culture positive bacterial meningitis has fallen over a 12-year period in urban Malawi following Hib vaccination. Hib, NTS, and pneumococcal meningitis have fallen significantly in children. ...Pneumococcal meningitis has not fallen in adults; NTS and pneumococcal meningitis are seasonal.
Background.
We documented bacterial meningitis trends among adults and children presenting to a large teaching hospital in Malawi during introduction of Haemophilus influenzae type b (Hib) vaccination and the rollout of antiretroviral therapy (ART).
Methods.
We analyzed data from 51 000 consecutive cerebrospinal fluid (CSF) samples obtained from adults, adolescents, and children with suspected meningitis admitted to the Queen Elizabeth Central Hospital, Blantyre, Malawi, between 2000 and 2012.
Results.
There was a significant decline in the total number of CSF isolates over 12 years (incident rate ratio IRR, 0.93; 95% CI, .92–.94; P < .001). This decline was entirely in children aged <5 years (IRR, 0.87; 95% CI, .85–.88; P < .001) and coincided with the introduction of Hib vaccination. The number of adult isolates has remained unchanged (IRR, 0.99; 95% CI, .97–1.0; P = .135) despite rapid scale-up of ART provision. In children aged <5 years, Streptococcus pneumoniae, nontyphoidal salmonellae (NTS), and Hib were the most frequently isolated pathogens, and have declined over this time period. Streptococcus pneumoniae was the most frequently isolated pathogen in older children and adults. Estimated incidence of bacterial meningitis in 2012 was 20 per 100 000 cases in children aged <14 years, 6 per 100 000 adolescents, and 10 per 100 000 adults.
Conclusions.
Rates of bacterial meningitis have declined in children, but not adults, coinciding with the introduction of Hib vaccination. The highly successful rollout of ART has not yet resulted in a reduction in the incidence in adults where the burden remains high. Long-term surveillance of bacterial meningitis outside of the epidemic “meningitis belt” in Africa is essential.
Background
The decomposition of a chemical graph is a convenient approach to encode information of the corresponding organic compound. While several commercial toolkits exist to encode molecules as ...so-called fingerprints, only a few open source implementations are available. The aim of this work is to introduce a library for exactly defined molecular decompositions, with a strong focus on the application of these features in machine learning and data mining. It provides several options such as search depth, distance cut-offs, atom- and pharmacophore typing. Furthermore, it provides the functionality to combine, to compare, or to export the fingerprints into several formats.
Results
We provide a Java 1.6 library for the decomposition of chemical graphs based on the open source Chemistry Development Kit toolkit. We reimplemented popular fingerprinting algorithms such as depth-first search fingerprints, extended connectivity fingerprints, autocorrelation fingerprints (e.g. CATS2D), radial fingerprints (e.g. Molprint2D), geometrical Molprint, atom pairs, and pharmacophore fingerprints. We also implemented custom fingerprints such as the all-shortest path fingerprint that only includes the subset of shortest paths from the full set of paths of the depth-first search fingerprint. As an application of jCompoundMapper, we provide a command-line executable binary. We measured the conversion speed and number of features for each encoding and described the composition of the features in detail. The quality of the encodings was tested using the default parametrizations in combination with a support vector machine on the Sutherland QSAR data sets. Additionally, we benchmarked the fingerprint encodings on the large-scale Ames toxicity benchmark using a large-scale linear support vector machine. The results were promising and could often compete with literature results. On the large Ames benchmark, for example, we obtained an AUC ROC performance of 0.87 with a reimplementation of the extended connectivity fingerprint. This result is comparable to the performance achieved by a non-linear support vector machine using state-of-the-art descriptors. On the Sutherland QSAR data set, the best fingerprint encodings showed a comparable or better performance on 5 of the 8 benchmarks when compared against the results of the best descriptors published in the paper of Sutherland et al.
Conclusions
jCompoundMapper is a library for chemical graph fingerprints with several tweaking possibilities and exporting options for open source data mining toolkits. The quality of the data mining results, the conversion speed, the LPGL software license, the command-line interface, and the exporters should be useful for many applications in cheminformatics like benchmarks against literature methods, comparison of data mining algorithms, similarity searching, and similarity-based data mining.
Smear-positive pulmonary TB is the most infectious form of TB. Previous studies on the effect of HIV and antiretroviral therapy on TB treatment outcomes among these highly infectious patients ...demonstrated conflicting results, reducing understanding of important issues.
All adult smear-positive pulmonary TB patients diagnosed between 2008 and 2010 in Malawi's largest public, integrated TB/HIV clinic were included in the study to assess treatment outcomes by HIV and antiretroviral therapy status using logistic regression.
Of 2,361 new smear-positive pulmonary TB patients, 86% had successful treatment outcome (were cured or completed treatment), 5% died, 6% were lost to follow-up, 1% failed treatment, and 2% transferred-out. Overall HIV prevalence was 56%. After adjusting for gender, age and TB registration year, treatment success was higher among HIV-negative than HIV-positive patients (adjusted odds ratio 1.49; 95% CI: 1.14-1.94). Of 1,275 HIV-infected pulmonary TB patients, 492 (38%) received antiretroviral therapy during the study. Pulmonary TB patients on antiretroviral therapy were more likely to have successful treatment outcomes than those not on ART (adjusted odds ratio : 1.83; 95% CI: 1.29-2.60).
HIV co-infection was associated with poor TB treatment outcomes. Despite high HIV prevalence and the integrated TB/HIV setting, only a minority of patients started antiretroviral therapy. Intensified patient education and provider training on the benefits of antiretroviral therapy could increase antiretroviral therapy uptake and improve TB treatment success among these most infectious patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To describe the electronic medical databases used in antiretroviral therapy (ART) programmes in lower-income countries and assess the measures such programmes employ to maintain and improve data ...quality and reduce the loss of patients to follow-up.
In 15 countries of Africa, South America and Asia, a survey was conducted from December 2006 to February 2007 on the use of electronic medical record systems in ART programmes. Patients enrolled in the sites at the time of the survey but not seen during the previous 12 months were considered lost to follow-up. The quality of the data was assessed by computing the percentage of missing key variables (age, sex, clinical stage of HIV infection, CD4+ lymphocyte count and year of ART initiation). Associations between site characteristics (such as number of staff members dedicated to data management), measures to reduce loss to follow-up (such as the presence of staff dedicated to tracing patients) and data quality and loss to follow-up were analysed using multivariate logit models.
Twenty-one sites that together provided ART to 50 060 patients were included (median number of patients per site: 1000; interquartile range, IQR: 72-19 320). Eighteen sites (86%) used an electronic database for medical record-keeping; 15 (83%) such sites relied on software intended for personal or small business use. The median percentage of missing data for key variables per site was 10.9% (IQR: 2.0-18.9%) and declined with training in data management (odds ratio, OR: 0.58; 95% confidence interval, CI: 0.37-0.90) and weekly hours spent by a clerk on the database per 100 patients on ART (OR: 0.95; 95% CI: 0.90-0.99). About 10 weekly hours per 100 patients on ART were required to reduce missing data for key variables to below 10%. The median percentage of patients lost to follow-up 1 year after starting ART was 8.5% (IQR: 4.2-19.7%). Strategies to reduce loss to follow-up included outreach teams, community-based organizations and checking death registry data. Implementation of all three strategies substantially reduced losses to follow-up (OR: 0.17; 95% CI: 0.15-0.20).
The quality of the data collected and the retention of patients in ART treatment programmes are unsatisfactory for many sites involved in the scale-up of ART in resource-limited settings, mainly because of insufficient staff trained to manage data and trace patients lost to follow-up.
Millions of Africans are on dolutegravir-based antiretroviral therapy (ART), but few detailed descriptions of dolutegravir resistance and its clinical management exist. We reviewed HIV drug ...resistance (HIVDR) testing application forms submitted between June 2019 and October 2022, data from the national HIVDR database, and genotypic test results. We obtained standardized ART outcomes and virological results of cases with dolutegravir resistance, and explored associations with dolutegravir resistance among individuals with successful integrase sequencing. All cases were on two nucleoside reverse transcriptase inhibitors (NRTIs)/dolutegravir, and had confirmed virological failure, generally with prolonged viremia. Among 89 samples with successful integrase sequencing, 24 showed dolutegravir resistance. Dolutegravir resistance-associated mutations included R263K (16/24), E138K (7/24), and G118R (6/24). In multivariable logistic regression analysis, older age and the presence of high-level NRTI resistance were significantly associated with dolutegravir resistance. After treatment modification recommendations, four individuals (17%) with dolutegravir resistance died, one self-discontinued ART, one defaulted, and one transferred out. Of the 17 remaining individuals, 12 had follow-up VL results, and 11 (92%) were <1000 copies/mL. Twenty-four cases with dolutegravir resistance among 89 individuals with confirmed virological failure suggests a considerable prevalence in the Malawi HIV program. Successful management of dolutegravir resistance was possible, but early mortality was high. More research on the management of treatment-experienced individuals with dolutegravir resistance is needed.
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