A research agenda for helminth diseases of humans: health research and capacity building in disease-endemic countries for helminthiases control

Capacity building in health research generally, and helminthiasis research particularly, is pivotal to the implementation of the research and development agenda for the control and elimination of human helminthiases that has been proposed thematically in the preceding reviews of this collection. Since helminth infections affect human populations particularly in marginalised and low-income regions of the world, they belong to the group of poverty-related infectious diseases, and their alleviation through research, policy, and practice is a sine qua non condition for the achievement of the United Nations Millennium Development Goals. Current efforts supporting research capacity building specifically for the control of helminthiases have been devised and funded, almost in their entirety, by international donor agencies, major funding bodies, and academic institutions from the developed world, contributing to the creation of (not always equitable) North-South "partnerships". There is an urgent need to shift this paradigm in disease-endemic countries (DECs) by refocusing political will, and harnessing unshakeable commitment by the countries' governments, towards health research and capacity building policies to ensure long-term investment in combating and sustaining the control and eventual elimination of infectious diseases of poverty. The Disease Reference Group on Helminth Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), was given the mandate to review helminthiases research and identify research priorities and gaps. This paper discusses the challenges confronting capacity building for parasitic disease research in DECs, describes current capacity building strategies with particular reference to neglected tropical diseases and human helminthiases, and outlines recommendations to redress the balance of alliances and partnerships for health research between the developed countries of the "North" and the developing countries of the "South". We argue that investing in South-South collaborative research policies and capacity is as important as their North-South counterparts and is essential for scaled-up and improved control of helminthic diseases and ultimately for regional elimination.     

Donor issues in Indonesia: A developing country in South East Asia

In most developing countries in South East Asia blood services have not been treated properly as an important service to support health program. Indonesia as a large archipelago country in South East Asia has specific obstacles in managing a blood service. To position the country blood service profile especially in term of donor issues, we compared our blood service with that in other South East Asia countries.Indonesia has 17 thousand islands with 220 million inhabitants. Blood services have been mostly run by the Indonesian Red Cross as a government assignment since 1950. Donor recruitment programs have been directed toward 100% of Voluntary Non Remunerated Blood Donor (VNRD), which now have reached 81.3%. Dissemination of information on VNRD, donor recruiter's training and VNRD appreciation programs are strategies to increase and maintain the VNRD.Limited female donors and insufficient blood supply during the fasting month and holidays constitute major challenges. Low hemoglobin level, low body weight and fear are reasons for low number of female donors. Poor management of blood stock during fasting month, long holidays and also poor networking of blood supply are reasons for insufficient blood supply during the year.Considering the great size of Indonesia with different ethnic groups and cultures, worsened by lack of infrastructure, decisive and effective strategies in donor recruitment and retention programs are needed.     

Causality or coincidence: may the slow disappearance of helminths be responsible for the imbalances in immune control mechanisms?

Intestinal infection continues to be a problem worldwide and helminths, which currently infect billions of individuals, are primary culprits. The major burden of disease falls on the populations of developing countries, given that over the last four to five decades helminth infections are disappearing in industrialized societies. In developing countries, a major source of immunomodulatory signals in post-natal life are parasites, particularly helminths, which, unlike most bacteria and viruses, selectively stimulate Th2 function. Helminths and their eggs are probably the most potent stimulators of mucosal Th2 responses. Responses elicited by worms can modulate immune reactions to other parasites, bacterial, viral infections and several unrelated diseases. Bacterial and protozoal infections may also protect against atopy and asthma, through the induction of the Th1 regulatory responses. Today, people in developed countries often live in ultra-hygienic environments, avoiding exposure to viruses, bacteria, ectoparasites and endoparasites, particularly helminths. Perhaps failure to acquire worms and experience mucosal Th2 conditioning predisposes to unrelated diseases. In contrast to this hypothesis it has also been suggested that Th2 responses can make the host more susceptible to other important diseases and to contribute to the spread of them.     

Beyond Attributable Burden: Estimating the Avoidable Burden of Disease Associated with Household Air Pollution

Background

The Global Burden of Disease (GBD) studies have transformed global understanding of health risks by producing comprehensive estimates of attributable disease burden, or the current disease that would be eliminated if a risk factor did not exist. Yet many have noted the greater policy significance of avoidable burden, or the future disease that could actually be eliminated if a risk factor were eliminated today. Avoidable risk may be considerably lower than attributable risk if baseline levels of exposure or disease are declining, or if a risk factor carries lagged effects on disease. As global efforts to deliver clean cookstoves accelerate, a temporal estimation of avoidable risk due to household air pollution (HAP) becomes increasingly important, particularly in light of the rapid uptake of modern stoves and ongoing epidemiologic transitions in regions like South and Southeast Asia.

Methods and Findings

We estimate the avoidable burden associated with HAP using International Futures (IFs), an integrated forecasting system that has been used to model future global disease burdens and risk factors. Building on GBD and other estimates, we integrated a detailed HAP exposure estimation and exposure-response model into IFs. We then conducted a counterfactual experiment in which HAP exposure is reduced to theoretical minimum levels in 2015. We evaluated avoidable mortality and DALY reductions for the years 2015 to 2024 relative to a Base Case scenario in which only endogenous changes occurred. We present results by cause and region, looking at impacts on acute lower respiratory infection (ALRI) and four noncommunicable diseases (NCDs). We found that just 2.6% of global DALYs would be averted between 2015 and 2024, compared to 4.5% of global DALYs attributed to HAP in the 2010 GBD study, due in large part to the endogenous tendency towards declining traditional stove usage in the IFs base case forecast. The extent of diminished impact was comparable for ALRI and affected NCDs, though for different reasons. ALRI impacts diminish due to the declining burden of ALRI in the base case forecast, particularly apparent in South Asia and Southeast Asia. Although NCD burdens are rising in regions affected by HAP, the avoidable risk of NCD nonetheless diminishes due to lagged effects. Because the stove transition and the decline of ALRI are proceeding more slowly in Sub-Saharan Africa, avoidable impacts would also be more persistent (3.9% of total DALY due to HAP) compared to South Asia (3.6%) or Southeast Asia (2.5%).

Conclusions

Our results illustrate how a temporal dynamic calculation of avoidable risk may yield different estimates, compared to a static attributable risk estimate, of the global and regional burden of disease. Our results suggest a window of rising and falling opportunity for HAP interventions that may have already closed in Southeast Asia and may be closing quickly in South Asia, but may remain open longer in Sub-Saharan Africa. A proper accounting of global health priorities should apply an avoidable risk framework that considers the role of ongoing social, economic and health transitions in constantly altering the disease and risk factor landscape.     

Human cysticercosis and Indian scenario: a review

Cysticercosis, caused by Taenia solium larva is a major public health problem, especially in the developing world and neurocysticercosis (NCC) is considered to be the most common parasitic infestation of the central nervous system. NCC is identified as the single most common cause of community acquired active epilepsy; 26.3% to 53.8% active epilepsy cases in the developing world including India and Latin America are due to NCC. It is also becoming more common in the developed world because of increased migration of people with the disease or Taenia solium carriers and frequent travel to the endemic countries. It is estimated that three quarters of the estimated 50 million people with active epilepsy live in the poor countries of the world. Recent Indian studies using neuroimaging techniques suggest that the disease burden in India surpasses many other developing countries. Hence it is important to know the epidemiology, pathogenesis and diagnostic criteria so as to assess the disease burden and adopt interventional strategies for its control. Literature search was done for this review with special emphasis on Indian studies to create awareness about the disease in India, since cysticercosis is preventable and potentially eradicable.     

Cholera Threat to Humans in Ghana Is Influenced by Both Global and Regional Climatic Variability

Cholera, an acute diarrheal illness, is caused by infection of the intestine with the bacterium Vibrio cholerae after ingestion of contaminated water or food. The disease had disappeared from most of the developed countries in the last 50 years, but cholera epidemics remain a major public health problem in many developing countries, most often localized in tropical areas. Cholera is an infectious disease for which a relationship between disease temporal patterns and climate has been demonstrated, but only in an endemic context and for local areas of Asia and South America. Until now, similar studies have not been done in an epidemic context, on the African continent, although the largest number of cholera cases has been reported for those countries by the World Health Organization. The wavelet method was used in order to explore periodicity in (i) a long-time monthly cholera incidence in Ghana, West Africa, (ii) proxy environmental variables, and (iii) climatic indices time series, from 1975 to 1995. Cross-analysis were done to explore links between these time series, i.e., between cholera and climate. Results showed strong statistical association (coherency) from the end of the 1980s, between cholera outbreak resurgences in Ghana and the climatic/environmental parameters under scrutiny. Further examination of the existence of common spatial and temporal patterns in infectious diseases on the continent of Africa will permit development of more effective treatment of disease.     

Is vaccine the magic bullet for malaria elimination? A reality check

Malaria remains a major health burden especially for the developing countries. Despite concerted efforts at using the current control tools, such as bed nets, anti malarial drugs and vector control measures, the disease is accountable for close to a million deaths annually. Vaccines have been proposed as a necessary addition to the armamentarium that could work towards elimination and eventual eradication of malaria in view of their historical significance in combating infectious diseases. However, because malaria vaccines would work differently depending on the targeted parasite stage, this review addresses the potential impact various malaria vaccine types could have on transmission. Further, because of the wide variation in the epidemiology of malaria across the endemic regions, this paper proposes that the ideal approach to malaria control ought to be tailor-made depending on the specific context. Finally, it suggests that although it is highly desirable to anticipate and aim for malaria elimination and eventual eradication, many affected regions should prioritize reduction of mortality and morbidity before aspiring for elimination.     

Neglected infections of poverty in the United States of America

In the United States, there is a largely hidden burden of diseases caused by a group of chronic and debilitating parasitic, bacterial, and congenital infections known as the neglected infections of poverty. Like their neglected tropical disease counterparts in developing countries, the neglected infections of poverty in the US disproportionately affect impoverished and under-represented minority populations. The major neglected infections include the helminth infections, toxocariasis, strongyloidiasis, ascariasis, and cysticercosis; the intestinal protozoan infection trichomoniasis; some zoonotic bacterial infections, including leptospirosis; the vector-borne infections Chagas disease, leishmaniasis, trench fever, and dengue fever; and the congenital infections cytomegalovirus (CMV), toxoplasmosis, and syphilis. These diseases occur predominantly in people of color living in the Mississippi Delta and elsewhere in the American South, in disadvantaged urban areas, and in the US-Mexico borderlands, as well as in certain immigrant populations and disadvantaged white populations living in Appalachia. Preliminary disease burden estimates of the neglected infections of poverty indicate that tens of thousands, or in some cases, hundreds of thousands of poor Americans harbor these chronic infections, which represent some of the greatest health disparities in the United States. Specific policy recommendations include active surveillance (including newborn screening) to ascertain accurate population-based estimates of disease burden; epidemiological studies to determine the extent of autochthonous transmission of Chagas disease and other infections; mass or targeted treatments; vector control; and research and development for new control tools including improved diagnostics and accelerated development of a vaccine to prevent congenital CMV infection and congenital toxoplasmosis.     

Seroprevalence of Taenia solium infections in Croatian patients presenting with epilepsy

Epilepsy is one of the most common neurological disorders, while neurocysticercosis caused by Taenia solium infection of the central nervous system currently represents the leading cause of secondary epilepsy in Central and South America, East and South Asia, and sub-Saharan Africa. As a result of increased migration from these endemic regions, neurocysticercosis and subsequent epilepsy are becoming a growing public health problem in developed countries as well. In order to determine the prevalence of T. solium infection in patients with epilepsy in Croatia, a retrospective serological study was conducted. A total of 770 serum samples were tested for the presence of T. solium IgG antibodies using a commercial qualitative enzyme immunoassay. The Western blot technique was used as a confirmatory test for the diagnosis. The overall seroprevalence rate of T. solium infection in patients with clinically proven epilepsy was 1.5%. Although the results have shown that infection with this tapeworm is rare in Croatia, this study hopes to increase awareness about the importance of preventive measures and benefits of accurate and timely diagnosis. Intervention measures for infection control are crucial, namely sanitation improvement, control of domestic pig-breeding, detailed meat inspection, detection and treatment of tapeworm carriers, hand washing and health education.     

Essential diagnostics--the role of the Department of Biomedical Research of the Royal Tropical Institute in the 21st century

In the light of emerging and overlooked infectious diseases and widespread drug resistance, diagnostics have become increasingly important in supporting surveillance, disease control and outbreak management programs. In many low-income countries the diagnostic service has been a neglected part of health care, often lacking quantity and quality or even non-existing at all. High-income countries have exploited few of their advanced technical abilities for the much-needed development of low-cost, rapid diagnostic tests to improve the accuracy of diagnosis and accelerate the start of appropriate treatment. As is now also recognized by World Health Organization, investment in the development of affordable diagnostic tools is urgently needed to further our ability to control a variety of diseases that form a major threat to humanity. The Royal Tropical Institute's Department of Biomedical Research aims to contribute to the health of people living in the tropics. To this end, its multidisciplinary group of experts focuses on the diagnosis of diseases that are major health problems in low-income countries. In partnership we develop, improve and evaluate simple and cheap diagnostic tests, and perform epidemiological studies. Moreover, we advice and support others--especially those in developing countries--in their efforts to diagnose infectious diseases.     

Global Burden of Human Brucellosis: A Systematic Review of Disease Frequency

Background

This report presents a systematic review of scientific literature published between 1990–2010 relating to the frequency of human brucellosis, commissioned by WHO. The objectives were to identify high quality disease incidence data to complement existing knowledge of the global disease burden and, ultimately, to contribute towards the calculation of a Disability-Adjusted Life Years (DALY) estimate for brucellosis.

Methods/Principal Findings

Thirty three databases were searched, identifying 2,385 articles relating to human brucellosis. Based on strict screening criteria, 60 studies were selected for quality assessment, of which only 29 were of sufficient quality for data analysis. Data were only available from 15 countries in the regions of Northern Africa and Middle East, Western Europe, Central and South America, Sub-Saharan Africa, and Central Asia. Half of the studies presented incidence data, six of which were longitudinal prospective studies, and half presented seroprevalence data which were converted to incidence rates. Brucellosis incidence varied widely between, and within, countries. Although study biases cannot be ruled out, demographic, occupational, and socioeconomic factors likely play a role. Aggregated data at national or regional levels do not capture these complexities of disease dynamics and, consequently, at-risk populations or areas may be overlooked. In many brucellosis-endemic countries, health systems are weak and passively-acquired official data underestimate the true disease burden.

Conclusions

High quality research is essential for an accurate assessment of disease burden, particularly in Eastern Europe, the Asia-Pacific, Central and South America and Africa where data are lacking. Providing formal epidemiological and statistical training to researchers is essential for improving study quality. An integrated approach to disease surveillance involving both human health and veterinary services would allow a better understanding of disease dynamics at the animal-human interface, as well as a more cost-effective utilisation of resources.     

Direct maternal morbidity and the risk of pregnancy-related deaths,stillbirths, and neonatal deaths in South Asia and sub-Saharan Africa: A population-based prospective cohort study in 8 countries

BackgroundMaternal morbidity occurs several times more frequently than mortality, yet data on morbidity burden and its effect on maternal, foetal, and newborn outcomes are limited in low- and middle-income countries. We aimed to generate prospective, reliable population-based data on the burden of major direct maternal morbidities in the antenatal, intrapartum, and postnatal periods and its association with maternal, foetal, and neonatal death in South Asia and sub-Saharan Africa.Methods and findingsThis is a prospective cohort study, conducted in 9 research sites in 8 countries of South Asia and sub-Saharan Africa. We conducted population-based surveillance of women of reproductive age (15 to 49 years) to identify pregnancies. Pregnant women who gave consent were include in the study and followed up to birth and 42 days postpartum from 2012 to 2015. We used standard operating procedures, data collection tools, and training to harmonise study implementation across sites. Three home visits during pregnancy and 2 home visits after birth were conducted to collect maternal morbidity information and maternal, foetal, and newborn outcomes. We measured blood pressure and proteinuria to define hypertensive disorders of pregnancy and woman’s self-report to identify obstetric haemorrhage, pregnancy-related infection, and prolonged or obstructed labour. Enrolled women whose pregnancy lasted at least 28 weeks or those who died during pregnancy were included in the analysis. We used meta-analysis to combine site-specific estimates of burden, and regression analysis combining all data from all sites to examine associations between the maternal morbidities and adverse outcomes.Among approximately 735,000 women of reproductive age in the study population, and 133,238 pregnancies during the study period, only 1.6% refused consent. Of these, 114,927 pregnancies had morbidity data collected at least once in both antenatal and in postnatal period, and 114,050 of them were included in the analysis. Overall, 32.7% of included pregnancies had at least one major direct maternal morbidity; South Asia had almost double the burden compared to sub-Saharan Africa (43.9%, 95% CI 27.8% to 60.0% in South Asia; 23.7%, 95% CI 19.8% to 27.6% in sub-Saharan Africa). Antepartum haemorrhage was reported in 2.2% (95% CI 1.5% to 2.9%) pregnancies and severe postpartum in 1.7% (95% CI 1.2% to 2.2%) pregnancies. Preeclampsia or eclampsia was reported in 1.4% (95% CI 0.9% to 2.0%) pregnancies, and gestational hypertension alone was reported in 7.4% (95% CI 4.6% to 10.1%) pregnancies. Prolonged or obstructed labour was reported in about 11.1% (95% CI 5.4% to 16.8%) pregnancies. Clinical features of late third trimester antepartum infection were present in 9.1% (95% CI 5.6% to 12.6%) pregnancies and those of postpartum infection in 8.6% (95% CI 4.4% to 12.8%) pregnancies. There were 187 pregnancy-related deaths per 100,000 births, 27 stillbirths per 1,000 births, and 28 neonatal deaths per 1,000 live births with variation by country and region. Direct maternal morbidities were associated with each of these outcomes.ConclusionsOur findings imply that health programmes in sub-Saharan Africa and South Asia must intensify their efforts to identify and treat maternal morbidities, which affected about one-third of all pregnancies and to prevent associated maternal and neonatal deaths and stillbirths.Trial registrationThe study is not a clinical trial.     

Strengthening of the clinical research capacity for malaria: a shared responsibility

Malaria remains a major health burden especially for the developing countries. Despite concerted efforts at using the current control tools, such as bed nets, anti malarial drugs and vector control measures, the disease is accountable for close to a million deaths annually. Vaccines have been proposed as a necessary addition to the armamentarium that could work towards elimination and eventual eradication of malaria in view of their historical significance in combating infectious diseases. However, because malaria vaccines would work differently depending on the targeted parasite stage, this review addresses the potential impact various malaria vaccine types could have on transmission. Further, because of the wide variation in the epidemiology of malaria across the endemic regions, this paper proposes that the ideal approach to malaria control ought to be tailor-made depending on the specific context. Finally, it suggests that although it is highly desirable to anticipate and aim for malaria elimination and eventual eradication, many affected regions should prioritize reduction of mortality and morbidity before aspiring for elimination.

     

The PAL+ program, an incentive concerted action about malaria and associated infectious diseases, for developing countries

The French Ministry in charge of Research has launched a multi-institutional incentive concerted action to assist Southern countries on malaria: the PAL+ program. PAL+ aims at bringing out: 1) conditions to promote novel preventive and therapeutic tools adapted to existing situations in the countries concerned; 2) a contribution to help research teams in Southern countries become competitive. PAL+ plans to strengthen cooperative relationships with developing countries (subsaharian Africa, South East Asia and South American countries). Research programs were oriented towards public health needs in malaria-endemic countries and thus mainly focused on: i) development of new antimalarial drugs and new therapeutical strategies: new targets and new leads for drugs, clinical assays for recognition of malaria and optimization of effective treatment or prophylactic drug dosage; ii) pathophysiology of severe malaria: mechanisms of immunity, biology and genome of host and parasite and research leading to vaccine trials; iii) basic and field research on mosquito genetics and biology which may lead to new prevention and control opportunities; iv) social studies on behaviours and habits around prevention and medication of malaria. The objective is to help Southern countries increase their capacity in clinical research, epidemiology, therapeutics, public health and social science (e.g. behaviours and habits accompanying medicine-taking). This means a true partnership and training adapted to specific needs and based on sound science. Research was therefore largely pursued in the laboratories of Southern countries and PAL+ supported the initiative in different ways by: i) providing easier opportunities for scientists from the North to collaborate with scientists from the South; ii) supporting networks of scientist collaborations. This was achieved by setting up a new type of relationships between scientists, based on a continuous dialogue and on bringing them together in small meetings on thematic discussions, the so-called Ateliers de PAL+. The Ateliers should play a major role in increasing the scientific capacity in developing countries. PAL+ program is a commitment to speed up better understanding of the disease by helping endemic countries contribute to research for their own benefit.     

Human T cell lymphotropic viruses (HTLV-I/II) in South America: Should it be a public health concern?

The presence of the human T cell lymphotropic virus (HTLV-I/II) in South America is well established. Its origin and spectrum in the continent still remain a matter of debate. There are signs now that HTLV-I/II was already present in the Amerindian population coming originally from Asia and that HTLV-I was also introduced with African slave trade and with immigration of individuals from endemic areas of Japan. South America has approximately 350 million inhabitants in its 13 countries. The presence of HTLV-I/II has been reported with impressive numbers in most of them and may be considered endemic in this continent. The distribution of HTLV I/II among native Amerindian populations has shown a geographic clustering of type I in the Andean highlands and Brazilian coast, while type II predominates in lowlands of South America. Although comparability between studies conducted among blood donors in different countries may be difficult, the data indicate that the viruses are also circulating among otherwise healthy individuals. Undoubtedly, HTLV-I/II infection and its related diseases should be considered a public health concern in South America and measures to prevent its spread should be emphasized.     

Breast cancer in South Asia: A Bangladeshi perspective

South Asian countries are facing a hidden breast cancer epidemic. A significant proportion of the breast cancer cases occur in premenopausal women. Knowledge of the various aspects of breast cancer in different geographical regions is limited in South Asia. In this article, we review the Bangladeshi perspective of the epidemiology, risk factors, pathology, diagnosis and treatment of breast cancer. As in other developing countries, because of the lack of breast cancer awareness in Bangladeshi population and inadequate access to health care, most patients are diagnosed at an advanced stage of the disease. Early detection has a crucial impact on overall treatment outcomes. To battle against breast cancer in resource-limited countries like Bangladesh, it is not feasible to set up a parallel health service system solely dedicated to cancer. Therefore, a cost-effective public health strategy is needed which could reach a large number of women in the country. Considering all these issues, we propose an innovative female-based primary healthcare approach focused on awareness, screening and early detection of breast cancer in Bangladesh. This preventive strategy could be a model for other resource-limited developing countries.     

Inhibitors of dihydrofolate reductase in Leishmania and trypanosomes

The protozoan diseases leishmaniasis, Chagas' disease and African trypanosomiasis are major health problems in many countries, particularly developing countries, and there are few drugs available to treat these diseases. Dihydrofolate reductase (DHFR) inhibitors have been used successfully in the treatment of a number of other diseases such as cancer, malaria and bacterial infections; however they have not been used for the treatment of these diseases. This article summarises studies on leishmanial and trypanosomal DHFR inhibitor development and evaluation. Possible mechanisms of resistance to DHFR inhibitors are also discussed.     

Mental and Substance Use Disorders in Sub-Saharan Africa: Predictions of Epidemiological Changes and Mental Health Workforce Requirements for the Next 40 Years

The world is undergoing a rapid health transition, with an ageing population and disease burden increasingly defined by disability. In Sub-Saharan Africa the next 40 years are predicted to see reduced mortality, signalling a surge in the impact of chronic diseases. We modelled these epidemiological changes and associated mental health workforce requirements. Years lived with a disability (YLD) predictions for mental and substance use disorders for each decade from 2010 to 2050 for four Sub-Saharan African regions were calculated using Global Burden of Disease 2010 study (GBD 2010) data and UN population forecasts. Predicted mental health workforce requirements for 2010 and 2050, by region and for selected countries, were modelled using GBD 2010 prevalence estimates and recommended packages of care and staffing ratios for low- and middle-income countries, and compared to current staffing from the WHO Mental Health Atlas. Significant population growth and ageing will result in an estimated 130% increase in the burden of mental and substance use disorders in Sub-Saharan Africa by 2050, to 45 million YLDs. As a result, the required mental health workforce will increase by 216,600 full time equivalent staff from 2010 to 2050, and far more compared to the existing workforce. The growth in mental and substance use disorders by 2050 is likely to significantly affect health and productivity in Sub-Saharan Africa. To reduce this burden, packages of care for key mental disorders should be provided through increasing the mental health workforce towards targets outlined in this paper. This requires a shift from current practice in most African countries, involving substantial investment in the training of primary care practitioners, supported by district based mental health specialist teams using a task sharing model that mobilises local community resources, with the expansion of inpatient psychiatric units based in district and regional general hospitals.     

Integrating evidence-based treatments for common mental disorders in routine primary care: feasibility and acceptability of the MANAS intervention in Goa,India

Common mental disorders, such as depression and anxiety, pose a major public health burden in developing countries. Although these disorders are thought to be best managed in primary care settings, there is a dearth of evidence about how this can be achieved in low resource settings. The MANAS project is an attempt to integrate an evidence based package of treatments into routine public and private primary care settings in Goa, India. Before initiating the trial, we carried out extensive preparatory work, over a period of 15 months, to examine the feasibility and acceptability of the planned intervention. This paper describes the systematic development and evaluation of the intervention through this preparatory phase. The preparatory stage, which was implemented in three phases, utilized quantitative and qualitative methods to inform our understanding of the potential problems and possible solutions in implementing the trial and led to critical modifications of the original intervention plan. Investing in systematic formative work prior to conducting expensive trials of the effectiveness of complex interventions is a useful exercise which potentially improves the likelihood of a positive result of such trials.     

Mitochondria and endoplasmic reticulum: Targets for a better insulin sensitivity in skeletal muscle?

Obesity and its associated metabolic disorders represent a major health burden, with economic and social consequences. Although adapted lifestyle and bariatric surgery are effective in reducing body weight, obesity prevalence is still rising. Obese individuals often become insulin-resistant. Obesity impacts on insulin responsive organs, such as the liver, adipose tissue and skeletal muscle, and increases the risk of cardiovascular diseases, type 2 diabetes and cancer. In this review, we discuss the effects of obesity and insulin resistance on skeletal muscle, an important organ for the control of postprandial glucose. The roles of mitochondria and the endoplasmic reticulum in insulin signaling are highlighted and potential innovative research and treatment perspectives are proposed.