Burden and Trends of Symptomatic Sexually Transmitted Infections in Malawi From 2000 to 2021: Comparative Analysis of Survey and Case Report Data.

BACKGROUND: In settings without etiologic testing for sexually transmitted infections (STIs), programs rely on STI symptom data to inform priorities. To evaluate whether self-reported STI symptoms in household surveys consistently represent the STI burden, we compared symptomatic infection rates between survey self-reporting and health facility case reporting in Malawi. METHODS: We analyzed self-reported symptoms and treatment seeking in the past year among sexually active adults from 4 Malawi Demographic and Health Surveys between 2000 and 2015. Bayesian mixed-effects models were used to estimate temporal trends, spatial variation, and sociodemographic determinants. Survey reporting was compared with health facility syndromic diagnoses between 2014 and 2021. RESULTS: In surveys, 11.0% (95% confidence interval, 10.7%-11.4%) of adults reported STI or STI-related symptoms in the last year, of whom 54.2% (52.8%-55.7%) sought treatment. In facilities, the mean annual symptomatic case diagnosis rate was 3.3%. Survey-reported treatment in the last year was 3.8% (95% credible interval, 2.3%-6.1%) for genital ulcer, 3.8% (2.0%-6.7%) for vaginal discharge, and 2.6% (1.2%-4.7%) for urethral discharge. Mean annual diagnosis rates at facilities were 0.5% for genital ulcer, 2.2% for vaginal discharge, and 2.0% for urethral discharge. Both data sources indicated a higher burden of symptoms among women, individuals older than 25 years, and those in Southern Malawi. CONCLUSIONS: Survey and facility case reports indicated similar spatial and demographic patterns of STI symptom burden and care seeking, but implied large differences in the magnitude and relative burden of symptoms, particularly genital ulcer, which could affect program priorities. Targeted etiologic surveillance would improve interpretation of these data to enable more comprehensive STI surveillance.

Age-disparate and intergenerational sex partnerships and HIV: the role of gender norms among adolescent girls and young women in Malawi.

BACKGROUND: Age-mixing (age-disparate [5-9 years difference] and intergenerational [≥ 10 years difference]) partnerships are hypothesized drivers of HIV in adolescent girls and young women (AGYW; 15-24 years). These partnerships are often associated with increased gender inequities which undermine women's agency and assertiveness. We assessed whether age-mixing partnerships were associated with HIV in Malawi and if endorsement of inequitable gender norms modifies this relationship. METHODS: We analyzed data from the Malawi Population-based HIV Impact Assessment, a nationally representative household survey conducted in 2015-2016. Participants underwent HIV testing and completed questionnaires related to actively endorsed gender norms and sexual risk behavior. We used multivariate logistic regression and multiplicative interaction to assess associations among AGYW who reported the age of their primary sex partner from the last year. RESULTS: The analysis included 1,958 AGYW (mean age = 19.9 years, SD = 0.1), 459 (23.4%) and 131 (6.7%) of whom reported age-disparate and intergenerational partnerships, respectively. AGYW in age-mixing partnerships accounted for 13% of all AGYW and were older, more likely to reside in urban areas, to be married or cohabitating with a partner, and to have engaged in riskier sexual behavior compared with AGYW in age-concordant partnerships (p < 0.05). HIV prevalence among AGYW in age-disparate and intergenerational partnerships was 6.1% and 11.9%, respectively, compared with 3.2% in age-concordant partnerships (p < 0.001). After adjusting for residence, age, education, employment, wealth quintile, and ever been married or cohabitated as married, AGYW in age-disparate and intergenerational partnerships had 1.9 (95% CI: 1.1-3.5) and 3.4 (95% CI: 1.6-7.2) greater odds of HIV, respectively, compared with AGYW in age-concordant partnerships. Among the 614 (31% of the study group) who endorsed inequitable gender norms, AGYW in age-disparate and intergenerational partnerships had 3.5 (95% CI: 1.1-11.8) and 6.4 (95% CI: 1.5-27.8) greater odds of HIV, respectively, compared with AGYW in age-concordant partnerships. CONCLUSIONS: In this Malawi general population survey, age-mixing partnerships were associated with increased odds of HIV among AGYW. These findings highlight inequitable gender norms as a potential focus for HIV prevention and could inform interventions targeting structural, cultural, and social constraints of this key group.

Awareness of and willingness to use oral pre-exposure prophylaxis (PrEP) for HIV prevention among sexually active adults in Malawi: results from the 2020 Malawi population-based HIV impact assessment.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Mesenchymal Stem Cells from COPD Patients Are Capable of Restoring Elastase-Induced Emphysema in a Murine Experimental Model.

COPD is a chronic lung disease that affects millions of people, declining their lung function and impairing their life quality. Despite years of research and drug approvals, we are still not capable of halting progression or restoring normal lung function. Mesenchymal stem cells (MSC) are cells with extraordinary repair capacity, and MSC-based therapy brings future hope for COPD treatment, although the best source and route of administration are unclear. MSC from adipose tissue (AD-MSC) represents an option for autologous treatment; however, they could be less effective than donor MSC. We compared in vitro behavior of AD-MSC from COPD and non-COPD individuals by migration/proliferation assay, and tested their therapeutic potential in an elastase mouse model. In addition, we tested intravenous versus intratracheal routes, inoculating umbilical cord (UC) MSC and analyzed molecular changes by protein array. Although COPD AD-MSC have impaired migratory response to VEGF and cigarette smoke, they were as efficient as non-COPD in reducing elastase-induced lung emphysema. UC-MSC reduced lung emphysema regardless of the administration route and modified the inflammatory profile in elastase-treated mice. Our data demonstrate equal therapeutic potential of AD-MSC from COPD and non-COPD subjects in the pre-clinical model, thus supporting their autologous use in disease.

The National Evaluation of Malawi's PMTCT Program (NEMAPP) study: 24-month HIV-exposed infant outcomes from a prospective cohort study.

OBJECTIVES: Data on long-term HIV-free survival in breastfeeding, HIV-exposed infants (HEIs) are limited. The National Evaluation of Malawi's Prevention of Mother-to-Child Transmission (PMTCT) Program (NEMAPP), conducted between 2014 and 2018, evaluated mother-to-child transmission (MTCT) and infant outcomes up to 24 months postpartum. METHODS: We enrolled a nationally representative cohort of HEIs at 54 health facilities across four regional strata in Malawi and used multivariable Cox regression analysis to investigate the risk of adverse outcomes (HIV transmission, infant death and loss to follow-up) to 24 months postpartum. Models, controlling for survey design, were fitted for the total cohort (n = 3462) and for a subcohort that received maternal viral load (VL) monitoring (n = 1282). RESULTS: By 24 months, in 3462 HEIs, weighted cumulative MTCT was 4.9% [95% confidence interval (CI) 3.7-6.4%], 1.3% (95% CI 0.8-2.2%) of HEIs had died, 26.2% (95% CI 24.0-28.6%) had been lost to follow-up and 67.5% (95% CI 65.0-70.0%) were alive and HIV-free. Primiparity [weighted adjusted hazard ratio (aHR) 1.6; 95% CI 1.1-2.2; parity 2-3: weighted aHR 1.5; 95% CI 1.2-1.9], the mother not disclosing her HIV status to her partner (no disclosure: weighted aHR 1.3; 95% CI 1.1-1.6; no partner: weighted aHR 0.7; 95% CI 0.5-0.9), unknown maternal ART start (weighted aHR 2.0; 95% CI 1.0-3.9) and poor adherence (missed ≥ 2 days of ART in the last month: weighted aHR 1.7; 95% CI 1.2-2.2; not on ART: weighted aHR 1.7; 95% CI 1.0-2.7) were associated with adverse outcomes by 24 months. In the subcohort analysis, risk of HIV transmission or infant death was higher among HEIs whose mothers started ART post-conception (during pregnancy: weighted aHR 3.2; 95% CI 1.3-7.7; postpartum: weighted aHR 12.4; 95% CI 1.5-99.6) or when maternal viral load at enrolment was > 1000 HIV-1 RNA copies/mL (weighted aHR 15.7; 95% CI 7.8-31.3). CONCLUSIONS: Infant positivity and infant mortality at 24 months were low for a breastfeeding population. Starting ART pre-conception had the greatest impact on HIV-free survival in HEIs. Further population-level reduction in MTCT may require additional intervention during breastfeeding for women new to PMTCT programmes. Pre-partum diagnosis and linkage to ART, followed by continuous engagement in care during breastfeeding can further reduce MTCT but are challenging to implement.

Factors associated with HIV viral suppression among children and adults receiving antiretroviral therapy in Malawi in 2021: Evidence from the Laboratory Management Information System.

OBJECTIVE: To describe the prevalence of HIV viral suppression and assess the factors associated with HIV viral suppression among persons receiving antiretroviral therapy (ART) in Malawi in 2021. METHODS: Implementation study using routinely collected patient-level HIV RNA-PCR test result data extracted from the national Laboratory Management Information System (LIMS) database managed by the Department of HIV/AIDS in 2021. We calculated frequencies, proportions and odds ratios (OR) of HIV viral suppression with their associated 95% confidence intervals (95%CIs). We performed a random-effects logistic regression to determine the risk factors associated with HIV viral suppression among ART patients, controlling for the spatial autocorrelation between districts and adjusting for other variables. RESULTS: We evaluated 515,797 adults and children receiving ART and having a viral load test in 2021. Of these, 92.8% had HIV viral suppression. ART patients living in urban areas had lower likelihood of HIV viral suppression than those living in rural areas (adjusted OR [aOR] = 0.95, 95%CI: 0.92-0.99, p = 0.01). There was an increasing trend in HIV viral suppression with increasing ART duration. Routine VL monitoring samples were 39% more likely to have suppressed VL values than confirmatory HIV VL monitoring samples (aOR = 1.39; 95%CI: 1.34-1.43, p < 0.001). CONCLUSION: This is the first national analysis of Malawi HIV VL data from LIMS. Our findings show the need to particularly consider the urban residents, those below 20 years, males, those on ART for less than a year as well as those on specific ARV regimens in order to persistently suppress HIV VL and consequently achieve the goal of achieving HIV VL suppression by 2030.

Geospatial Transmission Hotspots of Recent HIV Infection - Malawi, October 2019-March 2020.

Persons infected with HIV are more likely to transmit the virus during the early stages (acute and recent) of infection, when viral load is elevated and opportunities to implement risk reduction are limited because persons are typically unaware of their status (1,2). Identifying recent HIV infections (acquired within the preceding 12 months)* is critical to understanding the factors and geographic areas associated with transmission to strengthen program intervention, including treatment and prevention (2). During June 2019, a novel recent infection surveillance initiative was integrated into routine HIV testing services in Malawi, a landlocked country in southeastern Africa with one of the world's highest prevalences of HIV infection.† The objectives of this initiative were to collect data on new HIV diagnoses, characterize the epidemic, and guide public health response (2). New HIV diagnoses were classified as recent infections based on a testing algorithm that included results from the rapid test for recent infection (RTRI)§ and HIV viral load testing (3,4). Among 9,168 persons aged ≥15 years with a new HIV diagnosis who received testing across 103 facilities during October 2019-March 2020, a total of 304 (3.3%) were classified as having a recent infection. Higher proportions of recent infections were detected among females, persons aged <30 years, and clients at maternal and child health and youth clinics. Using a software application that analyzes clustering in spatially referenced data, transmission hotspots were identified with rates of recent infection that were significantly higher than expected. These near real-time HIV surveillance data highlighted locations across Malawi, allowing HIV program stakeholders to assess program gaps and improve access to HIV testing, prevention, and treatment services. Hotspot investigation information could be used to tailor HIV testing, prevention, and treatment to ultimately interrupt transmission.

Analysis of AI-Based Single-View 3D Reconstruction Methods for an Industrial Application.

Machine learning (ML) is a key technology in smart manufacturing as it provides insights into complex processes without requiring deep domain expertise. This work deals with deep learning algorithms to determine a 3D reconstruction from a single 2D grayscale image. The potential of 3D reconstruction can be used for quality control because the height values contain relevant information that is not visible in 2D data. Instead of 3D scans, estimated depth maps based on a 2D input image can be used with the advantage of a simple setup and a short recording time. Determining a 3D reconstruction from a single input image is a difficult task for which many algorithms and methods have been proposed in the past decades. In this work, three deep learning methods, namely stacked autoencoder (SAE), generative adversarial networks (GANs) and U-Nets are investigated, evaluated and compared for 3D reconstruction from a 2D grayscale image of laser-welded components. In this work, different variants of GANs are tested, with the conclusion that Wasserstein GANs (WGANs) are the most robust approach among them. To the best of our knowledge, the present paper considers for the first time the U-Net, which achieves outstanding results in semantic segmentation, in the context of 3D reconstruction tasks. Unlike the U-Net, which uses standard convolutions, the stacked dilated U-Net (SDU-Net) applies stacked dilated convolutions. Of all the 3D reconstruction approaches considered in this work, the SDU-Net shows the best performance, not only in terms of evaluation metrics but also in terms of computation time. Due to the comparably small number of trainable parameters and the suitability of the architecture for strong data augmentation, a robust model can be generated with only a few training data.

[Transient Ischemia of One Leg in a Very Low Birthweight Infant]. / Transiente Ischämie eines Beines bei einem Frühgeborenen der 31+0 Schwangerschaftswoche.

Ischemias in the extremities are rather rare in the neonatal period. Both intrauterine and postnatal factors can cause ischemias. We present the diagnostic procedure and the course in a female very low birthweight (VLBW) infant with transient ischemia in the lower extremity.

Treatment-adjusted prevalence to assess HIV testing programmes.

Scale-up of human immunodeficiency virus (HIV) testing and antiretroviral therapy (ART) for people living with HIV has been increasing in sub-Saharan Africa. As a result, areas with high HIV prevalence are finding a declining proportion of people testing positive in their national testing programmes. In eastern and southern Africa, where there are settings with adult HIV prevalence of 12% and above, the positivity from national HIV testing services has dropped to below 5%. Identifying those in need of ART is therefore becoming more costly for national HIV programmes. Annual target-setting assumes that national testing positivity rates approximate that of population prevalence. This assumption has generated an increased focus on testing approaches which achieve higher rates of HIV positivity. This trend is a departure from the provider-initiated testing and counselling strategy used early in the global HIV response. We discuss a new indicator, treatment-adjusted prevalence, that countries can use as a practical benchmark for estimating the expected adult positivity in a testing programme when accounting for both national HIV prevalence and ART coverage. The indicator is calculated by removing those people receiving ART from the numerator and denominator of HIV prevalence. Treatment-adjusted prevalence can be readily estimated from existing programme data and population estimates, and in 2019, was added to the World Health Organization guidelines for HIV testing and strategic information. Using country examples from Kenya, Malawi, South Sudan and Zimbabwe we illustrate how to apply this indicator and we discuss the potential public health implications of its use from the national to facility level.

Le dépistage du virus de l'immunodéficience humaine (VIH) et le traitement antirétroviral (TAR) pour les personnes vivant avec le VIH ont connu un véritable essor en Afrique subsaharienne. Par conséquent, les régions touchées par une forte prévalence du VIH détectent un pourcentage moins élevé de personnes testées positives dans leurs programmes de dépistage nationaux. En Afrique orientale et australe, là où certains endroits affichent une prévalence du VIH chez l'adulte égale ou supérieure à 12%, le taux de positivité des services de dépistage nationaux est passé sous la barre des 5%. Identifier les personnes nécessitant un TAR devient donc plus coûteux pour les programmes nationaux consacrés au VIH. Pour définir les objectifs annuels, on part du principe que les taux de positivité nationaux se rapprochent du taux de prévalence au sein de la population. Cette supposition a orienté les démarches vers des méthodes de dépistage permettant d'obtenir des taux de positivité plus élevés; une tendance qui s'écarte de la stratégie des services de dépistage et de conseil à l'initiative des prestataires, utilisée à l'aube de la lutte mondiale contre le VIH. Dans le présent document, nous nous intéressons à un nouvel indicateur, la prévalence ajustée sur le traitement. Cet indicateur peut servir de référence concrète pour les pays qui souhaitent évaluer le taux de positivité attendu chez l'adulte dans un programme de dépistage, en tenant compte de la prévalence du VIH au niveau national ainsi que de la portée du TAR. Le calcul consiste à enlever les personnes recevant un TAR du numérateur et du dénominateur de la prévalence du VIH. La prévalence ajustée sur le traitement peut aisément être déterminée en fonction des données de programme et estimations de population existantes. En 2019, elle a également été ajoutée aux lignes directrices de l'Organisation mondiale de la Santé pour l'information stratégique et le dépistage du VIH. En nous inspirant d'exemples issus du Kenya, du Malawi, du Soudan du Sud et du Zimbabwe, nous expliquons comment employer cet indicateur et abordons les potentielles implications liées à son utilisation en matière de santé publique, en partant du niveau national jusqu'aux établissements.

La ampliación de las pruebas de detección del virus de la inmunodeficiencia humana (VIH) y del tratamiento antirretrovírico (TAR) para las personas infectadas por el VIH ha aumentado en el África subsahariana. En consecuencia, el porcentaje de personas que dan positivo en las pruebas de detección del VIH en los programas nacionales está disminuyendo en las zonas con alta prevalencia del virus. En África meridional y oriental, donde hay entornos con una prevalencia del VIH en adultos del 12 % o superior, la tasa de positividad de los servicios nacionales de pruebas de detección del VIH ha descendido a menos del 5 %. Por lo tanto, la identificación de las personas que necesitan TAR es cada vez más costosa para los programas nacionales de VIH. El establecimiento de objetivos anuales supone que las tasas de positividad de las pruebas nacionales se aproximan a las de la prevalencia de la población. Esta suposición ha generado una mayor atención a los enfoques de las pruebas que logran tasas más altas de positividad del VIH. Esta tendencia se aleja de la estrategia del asesoramiento y las pruebas que iniciaron los proveedores y que se utilizó al principio de la respuesta mundial al VIH. Se analiza un nuevo indicador, la prevalencia ajustada según el tratamiento, que los países pueden emplear como punto de referencia práctico para estimar la tasa de positividad esperada en adultos en un programa de pruebas de detección cuando se tiene en cuenta tanto la prevalencia nacional del VIH como la cobertura del TAR. El indicador se calcula eliminando del numerador y el denominador de la prevalencia del VIH a las personas que reciben TAR. La prevalencia ajustada según el tratamiento se puede estimar con facilidad a partir de los datos de los programas existentes y de las estimaciones de población, además, en 2019, se incluyó en las directrices de la Organización Mundial de la Salud para las pruebas de detección del VIH y en la información estratégica. A través de ejemplos de países como Kenia, Malaui, Sudán meridional y Zimbabue, se demuestra cómo aplicar este indicador y se discuten las posibles implicaciones para la salud pública de su uso desde el nivel nacional hasta el de los centros.

Emerging priorities for HIV service delivery.

Nathan Ford and co-authors discuss global priorities in the provision of HIV prevention and treatment services.

The missed potential of CD4 and viral load testing to improve clinical outcomes for people living with HIV in lower-resource settings.

In a Policy Forum, Peter Ehrenkranz and colleagues discuss the contribution of CD4 and viral load testing to outcomes for people with HIV in low- and middle-income countries.

Timing of combination antiretroviral therapy (cART) initiation is not associated with stillbirth among HIV-infected pregnant women in Malawi.

OBJECTIVE: To assess the association between timing of maternal combination ART (cART) initiation and stillbirth among HIV-infected pregnant women in Malawi's Option B+ programme. METHODS: Cohort study of HIV-infected pregnant women delivering singleton live or stillborn babies at ≥28 weeks of gestation using routine data from maternity registers between 1 January 2012 and 30 June 2015. We defined stillbirth as death of a foetus at ≥28 weeks of gestation. We report proportions of stillbirth according to timing of maternal cART initiation (before pregnancy, 1st or 2nd trimester, or 3rd trimester or labour). We used logistic regression, with robust standard errors to account for clustering of women within health facilities, to investigate the association between timing of cART initiation and stillbirth. RESULTS: Of 10 558 mother-infant pairs abstracted from registers, 8380 (79.4%) met inclusion criteria. The overall rate of stillbirth was 25 per 1000 deliveries (95% confidence interval 22-29). We found no significant association between timing of maternal cART initiation and stillbirth. In multivariable models, older maternal age, male sex of the infant, breech vaginal delivery, delivery at < 34 weeks of gestation and experience of any maternal obstetric complication were associated with higher odds of stillbirth. Deliveries managed by a mission hospital or health centre were associated with lower odds of stillbirth. CONCLUSION: Pregnant women's exposure to cART, regardless of time of its initiation, was not associated with increased odds of stillbirth.

OBJECTIF: Evaluer l'association entre le moment d'initiation de l'ART de combinaison (cART) maternel et la mortinaissance chez les femmes enceintes infectées par le VIH dans le programme Option B+ du Malawi. MÉTHODES: Etude de cohorte de femmes enceintes infectées par le VIH qui ont accouché de bébés singletons vivants ou mort-nés à 28 mois ou plus de grossesse, en utilisant les données de routine des registres de maternité entre le 1er janvier 2012 et le 30 juin 2015. Nous avons défini la mortinatalité comme le décès d'un fœtus à 28 semaines ou plus de gestation. Nous rapportons sur les proportions de mortinatalité selon le moment de l'initiation du cART maternel (avant la grossesse, au 1er , 2è ou 3è trimestre ou durant le travail). Nous avons utilisé une régression logistique, avec des erreurs standards robustes, pour prendre en compte le regroupement des femmes par établissements de santé, afin d'investiguer le lien entre le moment d'initiation du cART et la mortinaissance. RÉSULTATS: Sur 10.558 paires mère-enfant extraites des registres, 8.380 (79,4%) répondaient aux critères d'inclusion. Le taux global de mortinatalité était de 25 pour 1.000 accouchements (intervalle de confiance à 95%: 22-29). Nous n'avons trouvé aucune association significative entre le moment de l'initiation du cART maternel et la mortinatalité. Dans les modèles multivariés, l'âge plus élevé de la mère, le sexe masculin du nourrisson, l'accouchement par voie basse, l'accouchement à moins de 34 semaines de gestation et l'expérience de toute complication obstétricale maternelle étaient associés à des probabilités de mortinatalité plus élevées. Les accouchements gérés par un hôpital de la mission ou un centre de santé étaient associés à une probabilité plus faible de mortinatalité. CONCLUSION: L'exposition des femmes enceintes au cART quel que soit le moment de son initiation, n'a pas été associée à une probabilité accrue de mortinatalité.

Fast XANES fluorescence imaging using a Maia detector.

A new fast X-ray absorption spectroscopy scanning method was recently implemented at the Hard X-ray Microprobe endstation P06, PETRA III, DESY, utilizing a Maia detector. Spectromicroscopy maps were acquired with spectra for X-ray absorption near-edge structure (XANES) acquisition in the sub-second regime. The method combines XANES measurements with raster-scanning of the sample through the focused beam. The order of the scanning sequence of the axes, one beam energy axis and two (or more) spatial axes, is a variable experimental parameter and, depending on it, the dwell at each location can be either single and continuous (if the energy axis is the inner loop) or in shorter discontinuous intervals (if a spatial axis is innermost). The combination of improved spatial and temporal resolution may be necessary for rapidly changing samples, e.g. for following in operando chemical reactions or samples highly susceptible to beam damage where the rapid collection of single XANES spectra avoids issues with the emergence of chemical changes developing from latent damage. This paper compares data sets collected on a specially designed test pattern and a geological thin-section scanning the energy as inner, middle and outer axis in the sequence. The XANES data of all three scanning schemes is found to show excellent agreement down to the single-pixel level.

Bone marrow characterization in COPD: a multi-level network analysis.

BACKGROUND: Bone marrow (BM) produces hematopoietic and progenitor cells that contribute to distant organ inflammation and repair. Chronic obstructive pulmonary disease (COPD) is characterized by defective lung repair. Yet, BM composition has not been previously characterized in COPD patients. METHODS: In this prospective and controlled study, BM was obtained by sternum fine-needle aspiration in 35 COPD patients and 25 healthy controls (10 smokers and 15 never-smokers). BM cell count and immunophenotype were determined by microscopy and flow cytometry, respectively. Circulating inflammatory (C-reactive protein, IL-6, IL-8) and repair markers (HGF, IGF, TGF-ß, VEGF) were quantified by ELISA. Results were integrated by multi-level network correlation analysis. RESULTS: We found that: (1) there were no major significant pair wise differences between COPD patients and controls in the BM structural characteristics; (2) multi-level network analysis including patients and controls identifies a relation between immunity, repair and lung function not previously described, that remains in the COPD network but is absent in controls; and (3) this novel network identifies eosinophils as a potential mediator relating immunity and repair, particularly in patients with emphysema. CONCLUSIONS: Overall, these results suggest that BM is activated in COPD with impaired repair capacity in patients with more emphysema and/or higher circulating eosinophils.

HIV and tuberculosis in prisons in sub-Saharan Africa.

Given the dual epidemics of HIV and tuberculosis in sub-Saharan Africa and evidence suggesting a disproportionate burden of these diseases among detainees in the region, we aimed to investigate the epidemiology of HIV and tuberculosis in prison populations, describe services available and challenges to service delivery, and identify priority areas for programmatically relevant research in sub-Saharan African prisons. To this end, we reviewed literature on HIV and tuberculosis in sub-Saharan African prisons published between 2011 and 2015, and identified data from only 24 of the 49 countries in the region. Where data were available, they were frequently of poor quality and rarely nationally representative. Prevalence of HIV infection ranged from 2·3% to 34·9%, and of tuberculosis from 0·4 to 16·3%; detainees nearly always had a higher prevalence of both diseases than did the non-incarcerated population in the same country. We identified barriers to prevention, treatment, and care services in published work and through five case studies of prison health policies and services in Zambia, South Africa, Malawi, Nigeria, and Benin. These barriers included severe financial and human-resource limitations and fragmented referral systems that prevent continuity of care when detainees cycle into and out of prison, or move between prisons. These challenges are set against the backdrop of weak health and criminal-justice systems, high rates of pre-trial detention, and overcrowding. A few examples of promising practices exist, including routine voluntary testing for HIV and screening for tuberculosis upon entry to South African and the largest Zambian prisons, reforms to pre-trial detention in South Africa, integration of mental health services into a health package in selected Malawian prisons, and task sharing to include detainees in care provision through peer-educator programmes in Rwanda, Zimbabwe, Zambia, and South Africa. However, substantial additional investments are required throughout sub-Saharan Africa to develop country-level policy guidance, build human-resource capacity, and strengthen prison health systems to ensure universal access to HIV and tuberculsosis prevention, treatment, and care of a standard that meets international goals and human rights obligations.

Adherence to Antiretroviral Therapy During and After Pregnancy: Cohort Study on Women Receiving Care in Malawi's Option B+ Program.

BACKGROUND: Adherence to antiretroviral therapy (ART) is crucial to preventing mother-to-child transmission of human immunodeficiency virus (HIV) and ensuring the long-term effectiveness of ART, yet data are sparse from African routine care programs on maternal adherence to triple ART. METHODS: We analyzed data from women who started ART at 13 large health facilities in Malawi between September 2011 and October 2013. We defined adherence as the percentage of days "covered" by pharmacy claims. Adherence of ≥90% was deemed adequate. We calculated inverse probability of censoring weights to adjust adherence estimates for informative censoring. We used descriptive statistics, survival analysis, and pooled logistic regression to compare adherence between pregnant and breastfeeding women eligible for ART under Option B+, and nonpregnant and nonbreastfeeding women who started ART with low CD4 cell counts or World Health Organization clinical stage 3/4 disease. RESULTS: Adherence was adequate for 73% of the women during pregnancy, for 66% in the first 3 months post partum, and for about 75% during months 4-21 post partum. About 70% of women who started ART during pregnancy and breastfeeding adhered adequately during the first 2 years of ART, but only about 30% of them had maintained adequate adherence at every visit. Risk factors for inadequate adherence included starting ART with an Option B+ indication, at a younger age, or at a district hospital or health center. CONCLUSIONS: One-third of women retained in the Option B+ program adhered inadequately during pregnancy and breastfeeding, especially soon after delivery. Effective interventions to improve adherence among women in this program should be implemented.

Scaling-up antiretroviral therapy in Malawi.

PROBLEM: In Malawi, health-system constraints meant that only a fraction of people infected with human immunodeficiency virus (HIV) and in immediate need of antiretroviral treatment (ART) received treatment. APPROACH: In 2004, the Malawian Ministry of Health launched plans to scale-up ART nationwide, adhering to the principle of equity to ensure fair geographical access to therapy. A public health approach was used with standardized training and treatment and regular supervision and monitoring of the programme. LOCAL SETTING: Before the scale-up, an estimated 930 000 people in Malawi were HIV-infected, with 170 000 in immediate need of ART. About 3000 patients were on ART in nine clinics. RELEVANT CHANGES: By December 2015, cumulatively 872 567 patients had been started on ART from 716 clinics, following national treatment protocols and using the standard monitoring system. LESSONS LEARNT: Strong national leadership allowed the ministry of health to implement a uniform system for scaling-up ART and provided benchmarks for implementation on the ground. New systems of training staff and accrediting health facilities enabled task-sharing and decentralization to peripheral health centres and a standardized approach to starting and monitoring ART. A system of quarterly supervision and monitoring, into which operational research was embedded, ensured stocks of drug supplies at facilities and adherence to national treatment guidelines.

The rise and fall of tuberculosis in Malawi: associations with HIV infection and antiretroviral therapy.

OBJECTIVES: Since 1985, Malawi has experienced a dual epidemic of HIV and tuberculosis (TB) which has been moderated recently by the advent of antiretroviral therapy (ART). The aim of this study was to describe the association over several decades between HIV/AIDS, the scale-up of ART and TB case notifications. METHODS: Aggregate data were extracted from annual reports of the National TB Control Programme, the Ministry of Health HIV Department and the National Statistics Office. ART coverage was calculated using the total HIV population as denominator (derived from UNAIDS Spectrum software). RESULTS: In 1970, there were no HIV-infected persons but numbers had increased to a maximum of 1.18 million by 2014. HIV prevalence reached a maximum of 10.8% in 2000, thereafter decreasing to 7.5% by 2014. Numbers alive on ART increased from 2586 in 2003 to 536 527 (coverage 45.3%) by 2014. In 1985, there were 5286 TB cases which reached a maximum of 28 234 in 2003 and then decreased to 17 723 by 2014 (37% decline from 2003). There were increases in all types of new TB between 1998-2003 which then declined by 30% for extrapulmonary TB, by 37% for new smear-positive PTB and by 50% for smear-negative PTB. Previously treated TB cases reached a maximum of 3443 in 2003 and then declined by 42% by 2014. CONCLUSION: The rise and fall of TB in Malawi between 1985 and 2014 was strongly associated with HIV infection and ART scale-up; this has implications for ending the TB epidemic in high HIV-TB burden countries.

B Cell-Activating Factor. An Orchestrator of Lymphoid Follicles in Severe Chronic Obstructive Pulmonary Disease.

RATIONALE: Patients with chronic obstructive pulmonary disease (COPD) have increased pulmonary lymphoid follicle (LF) counts. B cell-activating factor of tumor necrosis factor family (BAFF) regulates B cells in health, but its role in COPD pathogenesis is unclear. OBJECTIVES: To determine whether BAFF expression in pulmonary LFs correlates with COPD severity, LF size or number, and/or readouts of B-cell function in LFs. METHODS: We correlated BAFF immunostaining in LFs in lung explants or biopsies from nonsmoking control subjects (NSC), smokers without COPD (SC), and patients with COPD with the number and size of LFs, and LF B-cell apoptosis, activation, and proliferation. We analyzed serum BAFF levels and BAFF expression in B cells in blood and bronchoalveolar lavage samples from the same subject groups. We assessed whether: (1) cigarette smoke extract (CSE) increases B-cell BAFF expression and (2) recombinant BAFF (rBAFF) rescues B cells from CSE-induced apoptosis by inhibiting activation of nuclear factor-κB (NF-κB). MEASUREMENTS AND MAIN RESULTS: Patients with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage IV COPD had increased numbers and larger pulmonary LFs than patients with GOLD stages I-II COPD and SC. We identified two main types of pulmonary LFs: (1) type A, the predominant type in GOLD stages I-II COPD and SC, characterized by abundant apoptotic but few BAFF-positive cells (mostly B cells); and (2) type B, the main type in GOLD stage IV COPD, characterized by abundant BAFF-positive cells but few apoptotic cells (mostly B cells). BAFF levels were also higher in blood and bronchoalveolar lavage B cells in patients with COPD versus NSC and SC. Surprisingly, rBAFF blocked CSE-induced B-cell apoptosis by inhibiting CSE-induced NF-κB activation. CONCLUSIONS: Our data support the hypothesis that B-cell BAFF expression creates a self-perpetuating loop contributing to COPD progression by promoting pulmonary B-cell survival and LF expansion.