A coded aperture microscope for X-ray fluorescence full-field imaging

The design and construction of an instrument for full-field imaging of the X-ray fluorescence emitted by a fully illuminated sample are presented. The aim is to produce an X-ray microscope with a few micrometers spatial resolution, which does not need to scan the sample. Since the fluorescence from a spatially inhomogeneous sample may contain many fluorescence lines, the optic which will provide the magnification of the emissions must be achromatic, i.e. its optical properties must be energy-independent. The only optics which fulfill this requirement in the X-ray regime are mirrors and pinholes. The throughput of a simple pinhole is very low, so the concept of coded apertures is an attractive extension which improves the throughput by having many pinholes, and retains the achromatic property. Modified uniformly redundant arrays (MURAs) with 10 mu m openings and 50% open area have been fabricated using gold in a lithographic technique, fabricated on a 1 mu m-thick silicon nitride membrane. The gold is 25 mu m thick, offering good contrast up to 20keV. The silicon nitride is transparent down into the soft X-ray region. MURAs with various orders, from 19 up to 73, as well as their respective negative (a mask where open and closed positions are inversed compared with the original mask), have been made. Having both signs of mask will reduce near-field artifacts and make it possible to correct for any lack of contrast

Temporal changes in prevalence of molecular markers mediating antimalarial drug resistance in a high malaria transmission setting in Uganda.

Standard therapy for malaria in Uganda changed from chloroquine to chloroquine + sulfadoxine-pyrimethamine in 2000, and artemether-lumefantrine in 2004, although implementation of each change was slow. Plasmodium falciparum genetic polymorphisms are associated with alterations in drug sensitivity. We followed the prevalence of drug resistance-mediating P. falciparum polymorphisms in 982 samples from Tororo, a region of high transmission intensity, collected from three successive treatment trials conducted during 2003-2012, excluding samples with known recent prior treatment. Considering transporter mutations, prevalence of the mutant pfcrt 76T, pfmdr1 86Y, and pfmdr1 1246Y alleles decreased over time. Considering antifolate mutations, the prevalence of pfdhfr 51I, 59R, and 108N, and pfdhps 437G and 540E were consistently high; pfdhfr 164L and pfdhps 581G were uncommon, but most prevalent during 2008-2010. Our data suggest sequential selective pressures as different treatments were implemented, and they highlight the importance of genetic surveillance as treatment policies change over time

Diagnostics to Support Elimination of Lymphatic Filariasis-Development of Two Target Product Profiles

As lymphatic filariasis (LF) programs move closer to established targets for validation elimination of LF as a public health problem, diagnostic tools capable of supporting the needs of the programs are critical for success. Known limitations of existing diagnostic tools make it challenging to have confidence that program endpoints have been achieved. In 2019, the World Health Organization (WHO) established a Diagnostic Technical Advisory Group (DTAG) for Neglected Tropical Diseases tasked with prioritizing diagnostic needs including defining use-cases and target product profiles (TPPs) for needed tools. Subsequently, disease-specific DTAG subgroups, including one focused on LF, were established to develop TPPs and use-case analyses to be used by product developers. Here, we describe the development of two priority TPPs for LF diagnostics needed for making decisions for stopping mass drug administration (MDA) of a triple drug regimen and surveillance. Utilizing the WHO core TPP development process as the framework, the LF subgroup convened to discuss and determine attributes required for each use case. TPPs considered the following parameters: Product use, design, performance, product configuration and cost, and access and equity. Version 1.0 TPPs for two use cases were published by WHO on 12 March 2021 within the WHO Global Observatory on Health Research and Development. A common TPP characteristic that emerged in both use cases was the need to identify new biomarkers that would allow for greater precision in program delivery. As LF diagnostic tests are rarely used for individual clinical diagnosis, it became apparent that reliance on population-based surveys for decision making requires consideration of test performance in the context of such surveys. In low prevalence settings, the number of false positive test results may lead to unnecessary continuation or resumption of MDA, thus wasting valuable resources and time. Therefore, highly specific diagnostic tools are paramount when used to measure low thresholds. The TPP process brought to the forefront the importance of linking use case, program platform and diagnostic performance characteristics when defining required criteria for diagnostic tools

Risk factors for Buruli ulcer disease (Mycobacterium ulcerans infection):Results from a case-control study in Ghana

Background. Morbidity due to Buruli ulcer disease (BUD), a cutaneous infection caused by Mycobacterium ulcerans, has been increasingly recognized in rural West Africa. The source and mode of transmission remain unknown. Methods. To identify BUD risk factors, we conducted a case-control study in 3 BUD-endemic districts in Ghana. We enrolled case patients with clinically diagnosed BUD and obtained skin biopsy specimens. M. ulcerans infection was confirmed by at least I of the following diagnostic methods: histopathologic analysis, culture, polymerase chain reaction, and Ziehl-Neelsen staining of a lesion smear. We compared characteristics of case patients with confirmed BUD with those of age- and community-matched control subjects using conditional logistic regression analysis. Results. Among 121 case patients with confirmed BUD, leg lesions (49%) or arm lesions (36%) were common. Male case patients were significantly more likely than female case patients to have lesions on the trunk (25% vs. 6%; P = .009). Multivariable modeling among 116 matched case-control pairs identified wading in a river as a risk factor for BUD (odds ratio [OR], 2.69; 95% confidence interval [Cl], 1.27-5.68; P = .0096). Wearing a shirt while farming (OR, 0.27; 95% Cl, 0.11-0.70; P = .0071), sharing indoor living space with livestock (OR, 0.36; 95% Cl, 0.15-0.86; P = .022), and bathing with toilet soap (OR, 0.41; 95% Cl, 0.19-0.90; P = .026) appeared to be protective. BUD was not significantly associated with penetrating injuries (P = .14), insect bites near water bodies (P = .84), bacille Calmette-Guerin vaccination (P = .33), or human immunodeficiency virus infection (P = .99). Conclusions. BUD is an environmentally acquired infection strongly associated with exposure to river areas. Exposed skin may facilitate transmission. Until transmission is better defined, control strategies in BUD-endemic areas could include covering exposed skin

HIV care and treatment factors associated with improved survival during TB treatment in Thailand: an observational study

<p>Abstract</p> <p>Background</p> <p>In Southeast Asia, HIV-infected patients frequently die during TB treatment. Many physicians are reluctant to treat HIV-infected TB patients with anti-retroviral therapy (ART) and have questions about the added value of opportunistic infection prophylaxis to ART, the optimum ART regimen, and the benefit of initiating ART early during TB treatment.</p> <p>Methods</p> <p>We conducted a multi-center observational study of HIV-infected patients newly diagnosed with TB in Thailand. Clinical data was collected from the beginning to the end of TB treatment. We conducted multivariable proportional hazards analysis to identify factors associated with death.</p> <p>Results</p> <p>Of 667 HIV-infected TB patients enrolled, 450 (68%) were smear and/or culture positive. Death during TB treatment occurred in 112 (17%). In proportional hazards analysis, factors strongly associated with reduced risk of death were ART use (Hazard Ratio [HR] 0.16; 95% confidence interval [CI] 0.07–0.36), fluconazole use (HR 0.34; CI 0.18–0.64), and co-trimoxazole use (HR 0.41; CI 0.20–0.83). Among 126 patients that initiated ART after TB diagnosis, the risk of death increased the longer that ART was delayed during TB treatment. Efavirenz- and nevirapine-containing ART regimens were associated with similar rates of adverse events and death.</p> <p>Conclusion</p> <p>Among HIV-infected patients living in Thailand, the single most important determinant of survival during TB treatment was use of ART. Controlled clinical trials are needed to confirm our findings that early ART initiation improves survival and that the choice of non-nucleoside reverse transcriptase inhibitor does not.</p

Hepatitis E Epidemic, Uganda

In October 2007, an epidemic of hepatitis E was suspected in Kitgum District of northern Uganda where no previous epidemics had been documented. This outbreak has progressed to become one of the largest hepatitis E outbreaks in the world. By June 2009, the epidemic had caused illness in >10,196 persons and 160 deaths

Frequent capsule switching in 'ultra-virulent' meningococci - Are we ready for a serogroup B ST-11 complex outbreak?

The meningococcal ST-11 complex (cc11) causes large invasive disease outbreaks with high case fatality rates, such as serogroup C (MenC) epidemics in industrialised nations in the 1990s and the serogroup W epidemic currently expanding globally. Glycoconjugate vaccines are available for serogroups A, C, W and Y. Broad coverage protein-based vaccines have recently been licensed against serogroup B meningococci (MenB), however, these do not afford universal MenB protection. Capsular switching from MenC to MenB among cc11 organisms is concerning because a large MenB cc11 (B:cc11) outbreak has the potential to cause significant morbidity and mortality. This study aimed to assess the potential for licensed and developmental non-capsular meningococcal vaccines to protect against B:cc11. The population structure and vaccine antigen distribution was determined for a panel of >800 geo-temporally diverse, predominantly MenC cc11 and B:cc11 genomes. The two licensed vaccines potentially protect against many but not all B:cc11 meningococci. Furthermore, strain coverage by these vaccines is often due to a single vaccine antigen and both vaccines are highly susceptible to vaccine escape owing to the apparent dispensability of key proteins used as vaccine antigens. cc11 strains with MenB and MenC capsules warrant special consideration when formulating future non-capsular meningococcal vaccines

Reproductive Intentions and Outcomes among Women on Antiretroviral Therapy in Rural Uganda: A Prospective Cohort Study

Background: Antiretroviral therapy (ART) may influence the biological, social and behavioral determinants of pregnancy in HIV-infected women. However, there are limited longitudinal data on the reproductive intentions and outcomes among women on ART in Africa. Methodology /Principal Findings: Using a prospective cohort design, we analyzed trends in desire for children and predictors of pregnancy among a cohort of 733 HIV-infected women in rural Uganda who initiated ART between May 2003 and May 2004 and were followed up in their homes until June 2006. Women answered in-depth social and behavioral questionnaires administered every quarter in year 1 after initiating ART, and every 6 to 12 months thereafter. Use of family planning methods was assessed at 18 and 24 months after starting ART. We tested for non-constant pregnancy incidence by using a shape parameter test from the Weibull distribution. We modeled repeated measurements of all variables related to the women’s desire for children over time using a generalized estimating equation (GEE) extension to the logistic regression model. Risk factors for pregnancy were examined using Cox proportional hazards model. 711 women eligible for the study were followed-up for a median time of 2.4 years after starting ART. During this time, less than 7 % of women reported wanting more children at any time point yet 120 (16.9%) women experienced 140 pregnancies and pregnancy incidence increased from 3.46 per 100 women-years (WY) in the first quarter to 9.5 per 100 WY at 24 months (p,0.0001). This wa

Challenges to immunization: the experiences of homeless youth

<p>Abstract</p> <p>Background</p> <p>Homelessness is a critical social issue, both a product of, and contributing to, poor mental and physical health. Over 150,000 young Canadians live on the streets. Homeless youth experience a high incidence of infectious diseases, many of which are vaccine preventable. Early departure from school and limited access to public health services makes them a particularly vulnerable high-risk group. This study explores challenges to obtaining essential vaccines experienced by homeless youth.</p> <p>Methods</p> <p>A qualitative research study to explore knowledge, attitudes, beliefs, and experiences surrounding immunization of hard-to-reach homeless youth was designed. Participants were recruited for focus groups from Phoenix House and Shelter, a non-profit, community-based organization assisting homeless youth in Halifax, Nova Scotia, Canada. An experienced facilitator guided the recorded discussions. Transcripts of audiotapes were analyzed using a constant comparative method until data revealed a set of exemplars and themes that best captured participants’ knowledge, attitudes, beliefs and experiences surrounding immunization and infectious diseases.</p> <p>Results</p> <p>Important themes emerged from our analysis. Considerable variability in knowledge about immunization and vaccine preventable diseases was found. The homeless youth in the study had limited awareness of meningitis in contrast to a greater knowledge about sexually transmitted infections and influenza, gained during the H1N1/09 public health campaign. They recognized their poverty as a risk for contracting infectious diseases, along with their inability to always employ known strategies to prevent infectious diseases, due to circumstances. They showed considerable insight into the detrimental effects of poor hygiene, sleeping locations and risk behaviour. Interviewed homeless youth regarded themselves as good compliers of health professional advice and offered valuable suggestions to improve immunization in their population.</p> <p>Conclusions</p> <p>To provide effective public health interventions, it is necessary to consider the knowledge, attitudes, beliefs, and experiences of hard to reach, high risk groups. Our study shows that homeless youth are interested and capable in discussing immunization. Active targeting of homeless youth for public health immunization programs is needed. Working collaboratively with non-profit organizations that assist homeless youth provides an opportunity to increase their knowledge of infectious risks and to improve immunization strategies in this vulnerable group.</p