World Health Organization Objective Research Articles

Molecular Determinants of Mouse Adaptation of Rat Hepacivirus.

The lack of robust immunocompetent animal models for hepatitis C virus (HCV) impedes vaccine development and studies of immune responses. Norway rat hepacivirus (NrHV) infection in rats shares HCV-defining characteristics, including hepatotropism, chronicity, immune responses, and aspects of liver pathology. To exploit genetic variants and research tools, we previously adapted NrHV to prolonged infection in laboratory mice. Through intrahepatic RNA inoculation of molecular clones of the identified variants, we here characterized four mutations in the envelope proteins responsible for mouse adaptation, including one disrupting a glycosylation site. These mutations led to high-titer viremia, similar to that observed in rats. In 4-week-old mice, infection was cleared after around 5 weeks compared to 2 to 3 weeks for nonadapted virus. In contrast, the mutations led to persistent but attenuated infection in rats, and they partially reverted, accompanied by an increase in viremia. Attenuated infection in rat but not mouse hepatoma cells demonstrated that the characterized mutations were indeed mouse adaptive rather than generally adaptive across species and that species determinants and not immune interactions were responsible for attenuation in rats. Unlike persistent NrHV infection in rats, acute resolving infection in mice was not associated with the development of neutralizing antibodies. Finally, infection of scavenger receptor B-I (SR-BI) knockout mice suggested that adaptation to mouse SR-BI was not a primary function of the identified mutations. Rather, the virus may have adapted to lower dependency on SR-BI, thereby potentially surpassing species-specific differences. In conclusion, we identified specific determinants of NrHV mouse adaptation, suggesting species-specific interactions during entry. IMPORTANCE A prophylactic vaccine is required to achieve the World Health Organization's objective for hepatitis C virus elimination as a serious public health threat. However, the lack of robust immunocompetent animal models supporting hepatitis C virus infection impedes vaccine development as well as studies of immune responses and viral evasion. Hepatitis C virus-related hepaciviruses were discovered in a number of animal species and provide useful surrogate infection models. Norway rat hepacivirus is of particular interest, as it enables studies in rats, an immunocompetent and widely used small laboratory animal model. Its adaptation to robust infection also in laboratory mice provides access to a broader set of mouse genetic lines and comprehensive research tools. The presented mouse-adapted infectious clones will be of utility for reverse genetic studies, and the Norway rat hepacivirus mouse model will facilitate studies of hepacivirus infection for in-depth characterization of virus-host interactions, immune responses, and liver pathology.

Drones and digital adherence monitoring for community-based tuberculosis control in remote Madagascar: A cost-effectiveness analysis.

Continuing tuberculosis control with current approaches is unlikely to reach the World Health Organization's objective to eliminate TB by 2035. Innovative interventions such as unmanned aerial vehicles (or drones) and digital adherence monitoring technologies have the potential to enhance patient-centric quality tuberculosis care and help challenged National Tuberculosis Programs leapfrog over the impediments of conventional Directly Observed Therapy (DOTS) implementation. A bundle of innovative interventions referred to for its delivery technology as the Drone Observed Therapy System (DrOTS) was implemented in remote Madagascar. Given the potentially increased cost these interventions represent for health systems, a cost-effectiveness analysis was indicated. A decision analysis model was created to calculate the incremental cost-effectiveness of the DrOTS strategy compared to DOTS, the standard of care, in a study population of 200,000 inhabitants in rural Madagascar with tuberculosis disease prevalence of 250/100,000. A mixed top-down and bottom-up costing approach was used to identify costs associated with both models, and net costs were calculated accounting for resulting TB treatment costs. Net cost per disability-adjusted life years averted was calculated. Sensitivity analyses were performed for key input variables to identify main drivers of health and cost outcomes, and cost-effectiveness. Net cost per TB patient identified within DOTS and DrOTS were, respectively, $282 and $1,172. The incremental cost per additional TB patient diagnosed in DrOTS was $2,631 and the incremental cost-effectiveness ratio of DrOTS compared to DOTS was $177 per DALY averted. Analyses suggest that integrating drones with interventions ensuring highly sensitive laboratory testing and high treatment adherence optimizes cost-effectiveness. Innovative technology packages including drones, digital adherence monitoring technologies, and molecular diagnostics for TB case finding and retention within the cascade of care can be cost effective. Their integration with other interventions within health systems may further lower costs and support access to universal health coverage.

Global mental health and trauma exposure: the current evidence for the relationship between traumatic experiences and spirit possession

BackgroundWe present a literature review on trauma exposure and spirit possession in low- and middle-income countries (LMICs). Despite the World Health Organization's objective of culturally appropriate mental health care in the Mental Health Action Plan 2013–2020, and the recommendations of the Inter-Agency Standing Committee to consider local idioms of distress and to collaborate with local resources, this topic still receives very little attention. Pathological spirit possession is commonly defined as involuntary, uncontrollable, and occurring outside of ritual settings. It is often associated with stigmatization, suffering, and dysfunctional behavior. While spirit possession has been discussed as an idiom of distress in anthropological literature, recent quantitative studies have presented support for a strong relationship between traumatic experiences and pathological possession states.ObjectiveThe aim of this review was to investigate this relationship systematically in LMICs, in view of the debate on how to address the mental health gap in LMICs.MethodsTwenty-one articles, published in peer-reviewed English-language journals between 1994 and 2013, were identified and analyzed with regard to prevalence of possessive trance disorders, patients’ sociodemographic characteristics, and its relation to traumatic experiences.ResultsThe review and analysis of 917 patients with symptoms of possessive trance disorders from 14 LMICs indicated that it is a phenomenon occurring worldwide and with global relevance. This literature review suggests a strong relationship between trauma exposure and spirit possession with high prevalence rates found especially in postwar areas in African countries.ConclusionsMore attention for possessive trance disorders in mental health and psychosocial intervention programs in humanitarian emergency settings as well as in societies in transition in LMICs is needed and justified by the results of this systematic literature review.

Commentary: HIV testing in low- and middle-income countries: An urgent need for scaling up

How can national AIDS program managers in low- and middle-income countries improve the coverage of HIV testing? In these countries heavily affected by HIV/AIDS, testing for HIV infection remains indeed critically infrequent with regard to its central role for individual care and control of the epidemic. Only 20 per cent of adults and 28 per cent of infants born from HIV-infected mothers are tested in a timely manner. The expansion of HIV testing is a prerequisite for reaching the World Health Organization's objective of universal access to HIV prevention, treatment, care, and support as well as the Millennium Development Goals related to HIV/AIDS and child mortality. The successful Rwandan experience of scaling up early infant HIV diagnosis brings hope for many countries.

A prescrição medicamentosa ambulatorial no internato: formação e prática

A prescrição correta de medicamentos é tema de extrema relevância na resolutividade dos problemas da saúde. Frente às deficiências constatadas, a Organização Mundial da Saúde incluiu entre seus objetivos o aprimoramento do ensino da farmacoterapia para estudantes de Medicina. Neste contexto, o presente trabalho avalia a prescrição ambulatorial dos alunos do internato do curso de Medicina da Universidade Federal de Alagoas, bem como o processo de formação para a sua elaboração. Trata-se de um estudo transversal e descritivo, que realizou a análise documental de 133 prescrições de medica mentos em situações de simulação e de 67 questionários. Concluiu-se que o assunto não integra o cur rículo formal do curso de maneira explícita e que as deficiências detectadas com relação às prescrições são semelhantes às encontradas na literatura referentes a profissionais graduados. Nas condutas dos alunos, ressaltou-se a preocupação com a adesão ao tratamento, a prioridade dada ao uso de medica mentos genéricos, a seleção dos produtos de acordo com o nível socioeconômico dos pacientes, além do interesse e empenho na prescrição. Evidenciou-se a relevância do ensino da forma correta da prescrição medicamentosa na graduação médica.