Principles of chromosome organization for meiotic recombination.

In meiotic cells, chromosomes are organized as chromatin loop arrays anchored to a protein axis. This organization is essential to regulate meiotic recombination, from DNA double-strand break (DSB) formation to their repair. In mammals, it is unknown how chromatin loops are organized along the genome and how proteins participating in DSB formation are tethered to the chromosome axes.

Genetic dissection of crossover mutants defines discrete intermediates in mouse meiosis.

Crossovers (COs), the exchange of homolog arms, are required for accurate chromosome segregation during meiosis. Studies in yeast have described the single-end invasion (SEI) intermediate: a stabilized 3' end annealed with the homolog as the first detectible CO precursor. SEIs are thought to differentiate into double Holliday junctions (dHJs) that are resolved by MutLgamma (MLH1/MLH3) into COs.

PRDM9 activity depends on HELLS and promotes local 5-hydroxymethylcytosine enrichment.

Meiotic recombination starts with the formation of DNA double-strand breaks (DSBs) at specific genomic locations that correspond to PRDM9-binding sites. The molecular steps occurring from PRDM9 binding to DSB formation are unknown. Using proteomic approaches to find PRDM9 partners, we identified HELLS, a member of the SNF2-like family of chromatin remodelers.

Reading the epigenetic code for exchanging DNA.

Three independent studies show that a protein called ZCWPW1 is able to recognize the histone modifications that initiate the recombination of genetic information during meiosis.

Sustaining the future of HIV counselling to reach 90-90-90: a regional country analysis.

Introduction: Counselling services are recommended by the World Health Organization and have been partially adopted by national HIV guidelines. In settings with a high HIV burden, patient education and counselling is often performed by lay workers, mainly supported with international funding. There are few examples where ministries of health have been able to absorb lay counsellors into their health systems or otherwise sustain their work.

The uncertain future of lay counsellors: continuation of HIV services in Lesotho under pressure.

Between 2006 and 2011, when antiretroviral therapy (ART) was scaled up in a context of severe human resources shortages, transferring responsibility for elements in human immunodeficiency virus (HIV) care from conventional health workers to lay counsellors (LCs) contributed to increased uptake of HIV services in Lesotho. HIV tests rose from 79 394 in 2006 to 274 240 in 2011 and, in that same period, the number of people on ART increased from 17 352 to 83 624. However, since 2012, the jobs of LCs have been at risk because of financial and organizational challenges.

Reframing HIV care: putting people at the centre of antiretroviral delivery.

The delivery of HIV care in the initial rapid scale-up of HIV care and treatment was based on existing clinic-based models, which are common in highly resourced settings and largely undifferentiated for individual needs. A new framework for treatment based on variable intensities of care tailored to the specific needs of different groups of individuals across the cascade of care is proposed here. Service intensity is characterised by four delivery components: (i) types of services delivered, (ii) location of service delivery, (iii) provider of health services and (iv) frequency of health services.

Sustainability of a community-based anti-retroviral care delivery model - a qualitative research study in Tete, Mozambique.

Introduction: To overcome patients' reported barriers to accessing anti-retroviral therapy (ART), a community-based delivery model was piloted in Tete, Mozambique. Community ART Groups (CAGs) of maximum six patients stable on ART offered cost- and time-saving benefits and mutual psychosocial support, which resulted in better adherence and retention outcomes. To date, Médecins Sans Frontières has coordinated and supported these community-driven activities.

Four-year retention and risk factors for attrition among members of community ART groups in Tete, Mozambique.

Objective: Community ART groups (CAG), peer support groups involved in community ART distribution and mutual psychosocial support, were piloted to respond to staggering antiretroviral treatment (ART) attrition in Mozambique. To understand the impact of CAG on long-term retention, we estimated mortality and lost-to-follow-up (LTFU) rates and assessed predictors for attrition.

Methods: Retrospective cohort study.

Community-supported models of care for people on HIV treatment in sub-Saharan Africa.

Objectives: Further scale-up of antiretroviral therapy (ART) to those in need while supporting the growing patient cohort on ART requires continuous adaptation of healthcare delivery models. We describe several approaches to manage stable patients on ART developed by Médecins Sans Frontières together with Ministries of Health in four countries in sub-Saharan Africa.

Methods: Using routine programme data, four approaches to simplify ART delivery for stable patients on ART were assessed from a patient and health system perspective: appointment spacing for clinical and drug refill visits in Malawi, peer educator-led ART refill groups in South Africa, community ART distribution points in DRC and patient-led community ART groups in Mozambique.

Adapting a community-based ART delivery model to the patients' needs: a mixed methods research in Tete, Mozambique.

Background: To improve retention in antiretroviral therapy (ART), lessons learned from chronic disease care were applied to HIV care, providing more responsibilities to patients in the care of their chronic disease. In Tete--Mozambique, patients stable on ART participate in the ART provision and peer support through Community ART Groups (CAG). This article analyses the evolution of the CAG-model during its implementation process.

A qualitative assessment of a community antiretroviral therapy group model in Tete, Mozambique.

Background: To improve retention on ART, Médecins Sans Frontières, the Ministry of Health and patients piloted a community-based antiretroviral distribution and adherence monitoring model through Community ART Groups (CAG) in Tete, Mozambique. By December 2012, almost 6000 patients on ART had formed groups of whom 95.7% were retained in care.

Nevirapine- and efavirenz-associated hepatotoxicity under programmatic conditions in Kenya and Mozambique.

To describe the frequency, risk factors, and clinical signs and symptoms associated with hepatotoxicity (HT) in patients on nevirapine- or efavirenz-based antiretroviral therapy (ART), we conducted a retrospective cohort analysis of patients attending the ART clinic in Kibera, Kenya, from April 2003 to December 2006 and in Mavalane, Mozambique, from December 2002 to March 2007. Data were collected on 5832 HIV-positive individuals who had initiated nevirapine- or efavirenz-based ART. Median baseline CD4+ count was 125 cells/μL (interquartile range [IQR] 55-196).

Distribution of antiretroviral treatment through self-forming groups of patients in Tete Province, Mozambique.

Background: As antiretroviral treatment cohorts continue to expand, ensuring patient retention over time is an increasingly important concern. This, together with capacity and human resource constraints, has led to the consideration of out-of-clinic models for the delivery of antiretroviral therapy (ART). In 2008, Médecins Sans Frontières and the Provincial authorities launched a model of ART distribution and adherence monitoring by community groups in Tete Province, Mozambique.

Risk factors and true outcomes for lost to follow-up individuals in an antiretroviral treatment programme in Tete, Mozambique.

Scale-up of antiretroviral therapy (ART) in sub-Saharan Africa is a major public health priority, but ensuring long-term adherence to treatment is a growing concern. The objectives of this retrospective study were to determine risk factors and true outcomes for individuals lost to follow-up in a routine HIV/AIDS care programme in Tete, Mozambique. Between May 2002 and August 2007, 2818 individuals were initiated on ART and 594 (21%) considered lost to follow-up were actively traced.

An integrated approach of community health worker support for HIV/AIDS and TB care in Angónia district, Mozambique.

Background: The need to scale up treatment for HIV/AIDS has led to a revival in community health workers to help alleviate the health human resource crisis in sub-Saharan Africa. Community health workers have been employed in Mozambique since the 1970s, performing disparate and fragmented activities, with mixed results.

Methods: A participant-observer description of the evolution of community health worker support to the health services in Angónia district, Mozambique.

Lessons learned during down referral of antiretroviral treatment in Tete, Mozambique.

As sub-Saharan African countries continue to scale up antiretroviral treatment, there has been an increasing emphasis on moving provision of services from hospital level to the primary health care clinic level. Delivery of antiretroviral treatment at the clinic level increases the number of entry points to care, while the greater proximity of services encourages retention in care.In Tete City, Mozambique, patients on antiretrovirals were rapidly down referred from a provincial hospital to four urban clinics in large numbers without careful planning, resulting in a number of patients being lost to follow-up.

Viraemia and HIV-1 drug resistance mutations among patients receiving antiretroviral treatment in Mozambique.

This study was conducted among individuals taking first-line antiretroviral treatment (ART) for at least 12 months under programme conditions in Maputo, Mozambique in order to report on the level of detectable viraemia and the proportion and types of drug resistance mutations among those with detectable viral loads. HIV-1 RNA viral load levels (lower detection limit <50 copies/ml) were measured, and resistance mutations were sequenced. One hundred and forty-nine consecutive patients (69% females, median age 36 years) were included after a mean follow-up time of 23 months.

Tuberculosis treatment in complex emergencies: are risks outweighing benefits?

Tuberculosis (TB) is a major public health problem in complex emergencies. Humanitarian agencies usually postpone the decision to offer TB treatment and opportunities to treat TB patients are often missed. This paper looks at the problem of tuberculosis treatment in these emergencies and questions whether treatment guidelines could be more flexible than international recommendations.