Compostos carbonílicos α, ß-insaturados e hidrazonas sintéticas como antiparasitários / α, ß-Unsaturated carbonyl compounds and Synthetic hydrazones as antiparasitics

Apesar da grande relevância médica e social, e por serem responsáveis por grande parte das mortes em países subdesenvolvidos e em desenvolvimento as doenças negligenciadas (DN), ainda, não apresentam terapêutica eficaz. Dentre as diversas DN, doenças como a doença de Chagas, a Leishmaniose visceral e a malária, se destacam no cenário nacional, por terem alta incidência e prejuízos sociais. Os fármacos disponíveis para o tratamento destas parasitoses, apresentam alta toxicidade e, em alguns casos, resistência por parte dos parasitas. Assim sendo, faz-se necessário o planejamento e desenvolvimento de novos agentes quimioterápicos mais seguros e eficazes. Dentre as diferentes estratégias de planejamento de fármacos, selecionamos o planejamento de fármacos baseado na estrutura do ligante - LBDD (Ligand-Based Drug Design) - como base para desenvolvimento deste trabalho. Nesta estratégia, utiliza-se o conhecimento de moléculas (ligantes) e de suas atividades biológicas conhecidas previamente determinadas experimentalmente, como protótipos para a busca de novas entidades químicas com atividade biológica semelhante ou melhorada. Sendo assim, o presente trabalho teve como objetivo a síntese e avaliação biológica de moléculas bioativas para o tratamento de doenças parasitárias. Baseando-se no conhecimento prévio da atividade antiparasitária de compostos carbonílicos α,ß-insaturados e hidrazonas, foram sintetizados séries de compostos destas classes químicas na busca de novos agentes quimioterápicos. Os compostos obtidos foram avaliados contra a forma epimastigota de Trypanosoma cruzi, promastigota de Leishmania donovani, amastigota de Leishmania infantum e, também, determinou-se o seu grau de citotoxicidade (CC50) frente a células de macrófago humanos diferenciado (THP-1). As 31 moléculas obtidas foram caracterizadas por técnicas de ponto de fusão, RMN 1H e RMN 13C e avaliada sua pureza por HPLC. Os compostos da classe da cinamoil-hidrazonas apresentaram-se como promissores antiparasitários, mostrando atividade frente a forma promastigota (Leishmania donovani), 4 dos 12 compostos foram ativos (IC50= 1,27 - 13,68 µM) e frente a forma amastigota (Leishmania infantum), 10 dos 12 compostos apresentaram atividade (9,09 - 63,5 µM). Mesmo apresentando citotoxicidade moderada (CC50 = 8,83 - 87,47 µM), os compostos obtiveram valores inferiores ao fármaco de referência (doxorubicina: CC50 = 0,26 µM). Diante do exposto, o planejamento de fármacos realizado por LBDD mostrou-se bem-sucedido, pois a classe de cinamoil-hidrazonas mostrou-se promissora como antiparasitários, visto sua atividade na escala de baixo micromolar e moderada citotoxicidade em células humanas. Esses resultados assinalam que a classe de compostos descrita está passível a continuar sendo investigada no intuito de aprimorar os protótipos obtidos na busca de novos agentes quimioterápicos antiparasitários e desvendar os mecanismos de ação leishmanicida

Despite to the great medical and social relevance and the amount of deaths in underdeveloped and developing countries, neglected diseases (ND) still do not have an effective therapy. Among the various ND, illnesses such as Chagas disease, visceral leishmaniasis and malaria holds a great importance in the Brazilian scenario due to high incidence and social damage. The drugs available for the treatment of these parasitosis present high toxicity and, in some cases, resistance by the pathogens. Thus, the planning and development of new, safer and more effective chemotherapeutic substances are urgent needed. Among the different drug planning strategies, we selected ligand-based drug design (LBDD) as the basis for the development of this work. In this strategy, we use the knowledge of molecules (ligands) and their known biological activities previously determined experimentally, as prototypes to search for new chemical entities with similar or improved biological activity. Therefore, the present work aimed the synthesis and biological evaluation of bioactive molecules for the treatment of parasitic diseases. Based on previous knowledge of the antiparasitic activity of α,ß-unsaturated and hydrazone carbonyl compounds, series of compounds of these chemical classes were synthesized in search of new chemotherapeutic agents. The compounds obtained were evaluated against the epimastigote form of Trypanosoma cruzi, Leishmania donovani promastigote, Leishmania infantum amastigote and their cytotoxicity (CC50) against differentiated human macrophages (THP-1). The 31 molecules obtained were characterized by melting point, 1 H NMR and 13C NMR techniques and their purity were characterized by HPLC. The cinnamoyl hydrazone class compounds showed promising antiparasitic activity, showing activity against promastigote form (L. donovani), 4 of 12 compounds were active (IC50 = 1.27 - 13.68 µM) and amastigote form (L. infantum), 10 of the 12 compounds showed activity (9.09 - 63.5 µM). Even presenting moderate cytotoxicity (CC50 = 8.83 - 87.47 µM), the compounds had values below the reference drug (doxorubicin: CC50 = 0.26 µM). Considering the results, LBDD drug planning proved to be successful and the class of cinnamoyl hydrazones were promising as antiparasitics due to its activity in low micromolar scale and moderate cytotoxicity in human cells. These results indicate that the described class of compounds can be further investigated in order to improve the prototypes obtained in the search for new antiparasitic chemotherapeutic agents and to unravel the mechanisms of action of leishmanicidal molecules

Global incidence of prostate cancer in developing and developed countries with changing age structures.

To investigate the global incidence of prostate cancer with special attention to the changing age structures. Data regarding the cancer incidence and population statistics were retrieved from the International Agency for Research on Cancer in World Health Organization. Eight developing and developed jurisdictions in Asia and the Western countries were selected for global comparison. Time series were constructed based on the cancer incidence rates from 1988 to 2007. The incidence rate of the population aged ≥ 65 was adjusted by the increasing proportion of elderly population, and was defined as the "aging-adjusted incidence rate". Cancer incidence and population were then projected to 2030. The aging-adjusted incidence rates of prostate cancer in Asia (Hong Kong, Japan and China) and the developing Western countries (Costa Rica and Croatia) had increased progressively with time. In the developed Western countries (the United States, the United Kingdom and Sweden), we observed initial increases in the aging-adjusted incidence rates of prostate cancer, which then gradually plateaued and even decreased with time. Projections showed that the aging-adjusted incidence rates of prostate cancer in Asia and the developing Western countries were expected to increase in much larger extents than the developed Western countries.

Residential scene classification for gridded population sampling in developing countries using deep convolutional neural networks on satellite imagery.

BACKGROUND: Conducting surveys in low- and middle-income countries is often challenging because many areas lack a complete sampling frame, have outdated census information, or have limited data available for designing and selecting a representative sample. Geosampling is a probability-based, gridded population sampling method that addresses some of these issues by using geographic information system (GIS) tools to create logistically manageable area units for sampling. GIS grid cells are overlaid to partition a country's existing administrative boundaries into area units that vary in size from 50 m × 50 m to 150 m × 150 m. To avoid sending interviewers to unoccupied areas, researchers manually classify grid cells as "residential" or "nonresidential" through visual inspection of aerial images. "Nonresidential" units are then excluded from sampling and data collection. This process of manually classifying sampling units has drawbacks since it is labor intensive, prone to human error, and creates the need for simplifying assumptions during calculation of design-based sampling weights. In this paper, we discuss the development of a deep learning classification model to predict whether aerial images are residential or nonresidential, thus reducing manual labor and eliminating the need for simplifying assumptions. RESULTS: On our test sets, the model performs comparable to a human-level baseline in both Nigeria (94.5% accuracy) and Guatemala (96.4% accuracy), and outperforms baseline machine learning models trained on crowdsourced or remote-sensed geospatial features. Additionally, our findings suggest that this approach can work well in new areas with relatively modest amounts of training data. CONCLUSIONS: Gridded population sampling methods like geosampling are becoming increasingly popular in countries with outdated or inaccurate census data because of their timeliness, flexibility, and cost. Using deep learning models directly on satellite images, we provide a novel method for sample frame construction that identifies residential gridded aerial units. In cases where manual classification of satellite images is used to (1) correct for errors in gridded population data sets or (2) classify grids where population estimates are unavailable, this methodology can help reduce annotation burden with comparable quality to human analysts.

The daycourse of place.

The present paper aims to contribute to the debate about the temporal relationships between place and health. It explores the notion of 'daycourse of place' echoing the discussion which recently occurred in this journal about the 'lifecourse of place' (Andrews, 2017; Lekkas et al., 2017a, b). When highlighting the importance of time in shaping health within places, most of studies focus either on the trajectories of places over a matter of years or the daily trajectories of people in link with their activity space. However, daily trajectories of places remain a poor cousin in place and health literature. This paper is intended to overcome 'jetlag', which places suffer when they are labelled with frozen attributes over a 24-h period. It explores the values and feasibility of exploring daily trajectories of places to investigate place effects on health or to design area-based interventions for public health action. More than just a metaphor, the 'daycourse of place' appears to be an inspiring framework to elaborate the importance of daily temporal relationalities for research and action in place-based health inequalities.

Income inequality and adolescent fertility in low-income countries.

: The well-known socioeconomic gradient in health does not imply that income inequality by itself has any effect on well-being. However, there is evidence of a positive association between income inequality and adolescent fertility across countries. Nevertheless, this key finding is not focused on low-income countries. This study applies a multilevel logistic regression of country-level adolescent fertility on country-level income inequality plus individual-level income and controls to the Demographic and Health Surveys data. A negative association between income inequality and adolescent fertility was found among low-income countries, controlling for income (OR = 0.981; 95%CI: 0.963-0.999). Different measures and different subsamples of countries show the same results. Therefore, the international association between income inequality and adolescent fertility seems more complex than previously thought.

Preventing gender-based violence victimization in adolescent girls in lower-income countries: Systematic review of reviews.

This systematic review of reviews synthesizes evidence on the impact of interventions to prevent violence against adolescent girls and young women 10-24 years (VAWG) in low- and middle-income countries (LMICs). Theories of women's empowerment and the social ecology of multifaceted violence frame the review. Child abuse, female genital mutilation/cutting (FGMC), child marriage, intimate partner violence (IPV), and sexual violence were focal outcomes. Our review followed the Assessment of Multiple Systematic Reviews (AMSTAR) for the systematic review of reviews, and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) for a systematic review of recent intervention studies. Of 35 reviews identified between June 7 and July 20, 2016, 18 were non-duplicate systematic reviews of medium-to-high quality. Half of these 18 reviews focused on interventions to prevent IPV. Only four focused on adolescents, of which three focused on child marriage and one compared findings across early and late adolescence. None focused on interventions to prevent child abuse or sexual violence in adolescent/young women. From these 18 reviews and the supplemental systematic review of intervention studies, data were extracted on 34 experimental or quasi-experimental intervention studies describing 28 interventions. Almost all intervention studies measured impacts on one form of VAWG. Most studies assessed impacts on child marriage (n = 13), then IPV (n = 8), sexual violence (n = 4), child abuse (n = 3), and FGMC (n = 3). Interventions included 1-6 components, involving skills to enhance voice/agency (n = 17), social networks (n = 14), human resources like schooling (n = 10), economic incentives (n = 9), community engagement (n = 11) and community infrastructure development (n = 6). Bundled individual-level interventions and multilevel interventions had more favorable impacts on VAWG. Interventions involving community engagement, skill-building to enhance voice/agency, and social-network expansion show promise to reduce VAWG. Future interventions should target poly-victimization, compare impacts across adolescence, and include urban, out-of-school, married, and displaced/conflict-affected populations in LMICs, where VAWG may be heightened.

Income inequality and adolescent fertility in low-income countries / Desigualdad de renta y fertilidad en la adolescencia en países de baja renta / Desigualdade de renda e fertilidade na adolescência em países de baixa renda

Abstract: The well-known socioeconomic gradient in health does not imply that income inequality by itself has any effect on well-being. However, there is evidence of a positive association between income inequality and adolescent fertility across countries. Nevertheless, this key finding is not focused on low-income countries. This study applies a multilevel logistic regression of country-level adolescent fertility on country-level income inequality plus individual-level income and controls to the Demographic and Health Surveys data. A negative association between income inequality and adolescent fertility was found among low-income countries, controlling for income (OR = 0.981; 95%CI: 0.963-0.999). Different measures and different subsamples of countries show the same results. Therefore, the international association between income inequality and adolescent fertility seems more complex than previously thought.

Resumen: El conocido gradiente socioeconómico en la salud no significa que la desigualdad de renta, por sí sola, tenga algún efecto sobre el bienestar. Existen evidencias de una asociación positiva entre desigualdad de renta y fertilidad en la adolescencia en diversos países, pero este importante descubrimiento requiere más investigaciones en los países de baja renta. El estudio aplica la regresión logística multivariada al análisis de la fertilidad en la adolescencia y la desigualdad de renta, ambas a nivel nacional, además de la renta individual y controles, utilizando datos de las Encuestas de Demografía y Salud. Se encontró una asociación negativa entre desigualdad de renta y fertilidad en la adolescencia en países de baja renta, después de ajustar por renta (OR = 0,981; IC95%: 0,963-0,999). Los mismos resultados fueron constatados para medidas diferentes y sub-muestras diferentes de estos países. Por tanto, la asociación internacional entre desigualdad de renta y fertilidad en la adolescencia parece ser más compleja de lo que se pensaba anteriormente.

Resumo: O conhecido gradiente socioeconômico na saúde não significa que a desigualdade de renda, por si só, tenha qualquer efeito sobre o bem-estar. Há evidência de uma associação positiva entre desigualdade de renda e fertilidade na adolescência em diversos países, mas esse importante achado requer mais averiguação nos países de baixa renda. O estudo aplica a regressão logística multivariada à análise da fertilidade na adolescência e a desigualdade de renda, ambas em nível nacional, além da renda individual e controles, utilizando dados dos Inquéritos de Demografia e Saúde. Foi encontrada uma associação negativa entre desigualdade de renda e fertilidade na adolescência em países de baixa renda, depois de ajustar para renda (OR = 0,981; IC95%: 0,963-0,999). Os mesmos resultados foram constatados para medidas diferentes e sub-amostras diferentes dos países. Portanto, a associação internacional entre desigualdade de renda e fertilidade na adolescência parece ser mais complexa do que se pensava anteriormente.

Are State-Sponsored New Radiation Therapy Facilities Economically Viable in Low- and Middle-Income Countries?

PURPOSE: The economic viability of establishing a state-funded radiation therapy (RT) infrastructure in low- and middle-income countries (LMICs) in accordance with the World Bank definition has been assessed through computation of a return on investment (ROI). METHODS AND MATERIALS: Of the 139 LMICs, 100 were evaluated according to their RT facilities, gross national income (GNI) per capita, and employment/population ratio. The assumption was an investment of US$5 million for a basic RT center able to treat 1000 patients annually. The national breakeven points and percentage of ROI (%ROI) were calculated according to the GNI per capita and patient survival rates of 10% to 50% at 2 years. It was assumed that 50% of these patients would be of working age and that, if employed and able to work after treatment, they would contribute to the country's GNI for at least 2 years. The cumulative GNI after attaining the breakeven point until the end of the 15-year lifespan of the teletherapy unit was calculated to estimate the %ROI. The recurring and overhead costs were assumed to vary from 5.5% to 15% of the capital investment. RESULTS: The %ROI was dependent on the GNI per capita, employment/population ratio and 2-year patient survival (all P<.001). Accordingly, none of the low-income countries would attain an ROI. If 50% of the patients survived for 2 years, the %ROI in the lower-middle and upper-middle income countries could range from 0% to 159.9% and 11.2% to 844.7%, respectively. Patient user fees to offset recurring and overhead costs could vary from "nil" to US$750, depending on state subsidies. CONCLUSIONS: Countries with a greater GNI per capita, higher employment/population ratio, and better survival could achieve a faster breakeven point, resulting in a higher %ROI. Additional factors such as user fees have also been considered. These can be tailored to the patient's ability to pay to cover the recurring costs. Certain pragmatic steps that could be undertaken to address these issues are discussed in the present study.

Nonsuicidal self-injury in Indian adolescents: Nonexistent or unacknowledged?

Nonsuicidal self-injury (NSSI) has been a neglected entity in low- and middle-income countries (LMICs). In this correspondence (letter to the editor), authors are advocating for greater research in this area in LMICs as it will help to compare and contrast prevalence rates of NSSI in these countries with high-income countries (HICs), identify context-specific risk and protective factors to better understand the pathophysiology of NSSI and devise context-specific interventions resulting in improvement in adolescent mental health worldwide.

Prioritizing countries for interventions to reduce child mortality: tools for maximizing the impact of mass drug administration of azithromycin.

BACKGROUND: As new interventions to reduce childhood mortality are identified, careful consideration must be given to identifying populations that could benefit most from them. Promising reductions in childhood mortality reported in a large cluster randomized trial of mass drug administration (MDA) of azithromycin (AZM) prompted the development of visually compelling, easy-to-use tools that synthesize country-specific data on factors that would influence both potential AZM benefit and MDA implementation success. METHODOLOGY/PRINCIPAL FINDINGS: We assessed the opportunity to reduce mortality and the feasibility of implementing such a program, creating Opportunity and Feasibility Indices, respectively. Countries with high childhood mortality were included. A Country Ranking Index combined key variables from the previous two Indices and applied a scoring system to identify high-priority countries. We compared four scenarios with varying weights given to each variable. Twenty-five countries met inclusion criteria. We created easily visualized tools to display the results of the Opportunity and Feasibility Indices. The Opportunity Index revealed substantial variation in the opportunity for an MDA of AZM program to reduce mortality, even among countries with high overall childhood mortality. The Feasibility Index demonstrated that implementing such a program would be most challenging in the countries that could see greatest benefit. Based on the Country Ranking Index, Equatorial Guinea would benefit the most from the MZA of AZM in three of the four scenarios we tested. CONCLUSIONS/SIGNIFICANCE: These visually accessible tools can be adapted or refined to include other metrics deemed important by stakeholders, and provide a quantitative approach to prioritization for intervention implementation. The need to explicitly state metrics and their weighting encourages thoughtful and transparent decision making. The objective and data-driven approach promoted by the three Indices may foster more efficient use of resources.

Radiation therapy infrastructure and human resources in low- and middle-income countries: present status and projections for 2020.

PURPOSE: Radiation therapy, a key component of cancer management, is required in more than half of new cancer patients, particularly in low- and middle-income countries (LMICs). The projected rise in cancer incidence over the next decades in LMICs will result in an increasing demand for radiation therapy services. Considering the present cancer incidence and that projected for 2020 (as listed in GLOBOCAN), we evaluated the current and anticipated needs for radiation therapy infrastructure and staffing by 2020 for each of the LMICs. METHODS AND MATERIALS: Based on World Bank classification, 139 countries fall in the category of LMICs. Details of teletherapy, radiation oncologists, medical physicists, and radiation therapy technologists were available for 84 LMICs from the International Atomic Energy Agency-Directory of Radiotherapy Centres (IAEA-DIRAC) database. Present requirements and those for 2020 were estimated according to recommendations from the IAEA and European Society for Radiotherapy & Oncology (ESTRO-QUARTS). RESULTS: Only 4 of the 139 LMICs have the requisite number of teletherapy units, and 55 (39.5%) have no radiation therapy facilities at present. Patient access to radiation therapy in the remaining 80 LMICs ranges from 2.3% to 98.8% (median: 36.7%). By 2020, these 84 LMICs would additionally need 9169 teletherapy units, 12,149 radiation oncologists, 9915 medical physicists, and 29,140 radiation therapy technologists. Moreover, de novo radiation therapy facilities would have to be considered for those with no services. CONCLUSIONS: Twelve pragmatic steps are proposed for consideration at national and international levels to narrow the gap in radiation therapy access. Multipronged and coordinated action from all national and international stakeholders is required to develop realistic strategies to curb this impending global crisis.

Hierarchical cluster analysis of labour market regulations and population health: a taxonomy of low- and middle-income countries.

BACKGROUND: An important contribution of the social determinants of health perspective has been to inquire about non-medical determinants of population health. Among these, labour market regulations are of vital significance. In this study, we investigate the labour market regulations among low- and middle-income countries (LMICs) and propose a labour market taxonomy to further understand population health in a global context. METHODS: Using Gross National Product per capita, we classify 113 countries into either low-income (n = 71) or middle-income (n = 42) strata. Principal component analysis of three standardized indicators of labour market inequality and poverty is used to construct 2 factor scores. Factor score reliability is evaluated with Cronbach's alpha. Using these scores, we conduct a hierarchical cluster analysis to produce a labour market taxonomy, conduct zero-order correlations, and create box plots to test their associations with adult mortality, healthy life expectancy, infant mortality, maternal mortality, neonatal mortality, under-5 mortality, and years of life lost to communicable and non-communicable diseases. Labour market and health data are retrieved from the International Labour Organization's Key Indicators of Labour Markets and World Health Organization's Statistical Information System. RESULTS: Six labour market clusters emerged: Residual (n = 16), Emerging (n = 16), Informal (n = 10), Post-Communist (n = 18), Less Successful Informal (n = 22), and Insecure (n = 31). Primary findings indicate: (i) labour market poverty and population health is correlated in both LMICs; (ii) association between labour market inequality and health indicators is significant only in low-income countries; (iii) Emerging (e.g., East Asian and Eastern European countries) and Insecure (e.g., sub-Saharan African nations) clusters are the most advantaged and disadvantaged, respectively, with the remaining clusters experiencing levels of population health consistent with their labour market characteristics. CONCLUSIONS: The labour market regulations of LMICs appear to be important social determinant of population health. This study demonstrates the heuristic value of understanding the labour markets of LMICs and their health effects using exploratory taxonomy approaches.

Bridging the gaps for global sustainable development: a quantitative analysis.

Global human progress occurs in a complex web of interactions between society, technology and the environment as driven by governance and infrastructure management capacity among nations. In our globalizing world, this complex web of interactions over the last 200 years has resulted in the chronic widening of economic and political gaps between the haves and the have-nots with consequential global cultural and ecosystem challenges. At the bottom of these challenges is the issue of resource limitations on our finite planet with increasing population. The problem is further compounded by pleasure-driven and poverty-driven ecological depletion and pollution by the haves and the have-nots respectively. These challenges are explored in this paper as global sustainable development (SD) quantitatively; in order to assess the gaps that need to be bridged. Although there has been significant rhetoric on SD with very many qualitative definitions offered, very few quantitative definitions of SD exist. The few that do exist tend to measure SD in terms of social, energy, economic and environmental dimensions. In our research, we used several human survival, development, and progress variables to create an aggregate SD parameter that describes the capacity of nations in three dimensions: social sustainability, environmental sustainability and technological sustainability. Using our proposed quantitative definition of SD and data from relatively reputable secondary sources, 132 nations were ranked and compared. Our comparisons indicate a global hierarchy of needs among nations similar to Maslow's at the individual level. As in Maslow's hierarchy of needs, nations that are struggling to survive are less concerned with environmental sustainability than advanced and stable nations. Nations such as the United States, Canada, Finland, Norway and others have higher SD capacity, and thus, are higher on their hierarchy of needs than nations such as Nigeria, Vietnam, Mexico and other developing nations. To bridge such gaps, we suggest that global public policy for local to global governance and infrastructure management may be necessary. Such global public policy requires holistic development strategies in contrast to the very simplistic north-south, developed-developing nations dichotomies.

Country development and the association between parity and overweight.

INTRODUCTION: Parity is associated with overweight and obesity in developed countries and has been related to maternal depletion in poor developing countries. However, the literature from developing countries is limited and may not represent current stages of development. METHODS: We analyzed data from 50 Demographic and Reproductive Health Surveys conducted between 1992 and 2003. We examined the association between parity (proxied by number of live births) and overweight (body mass index (BMI)> or =25 kg/m(2)) in relation to level of country wealth and development. RESULTS: The odds ratio (OR) for overweight comparing women with at least four live births to women with one live birth was >1.0 in 38 of the 50 countries studied. The median OR was >1.0 in all regions studied and highest in North Africa/West Asia, where all countries had OR >1.0. Country wealth and development were both positively associated with the ORs. CONCLUSIONS: The importance of parity as a predictor of overweight increases with national economic development and wealth. Policy implications might include the development and implementation of programs to prevent excessive gestational weight gain and promote postpartum weight loss via dietary change and physical activity, concomitant with exclusive breastfeeding.

The causes of stalling fertility transitions.

An examination of fertility trends in countries with multiple DHS surveys found that in the 1990s fertility stalled in midtransition in seven countries: Bangladesh, Colombia, Dominican Republic, Ghana, Kenya, Peru, and Turkey. In each of these countries fertility was high (more than six births per woman) in the 1950s and declined to fewer than five births per woman in the early or mid-1990s, before stalling. The level of stalling varied from 4.7 births per woman in Kenya to 2.5 births per woman in Turkey. An analysis of trends in the determinants of fertility revealed a systematic pattern of leveling off or near leveling in a number of determinants, including contraceptive use, the demand for contraception, and number of wanted births. The stalling countries did not experience significant increases in unwanted births or in the unmet need for contraception during the late 1990s, and program effort scores improved slightly, except in the Dominican Republic. These findings suggest no major deterioration in contraceptive access during the stall, but levels of unmet need and unwanted births are relatively high, and improvements in access to family planning methods would, therefore, be desirable. No significant link was found between the presence of a stall and trends in socioeconomic development, but at the onset of the stall the level of fertility was low relative to the level of development in all but one of the stalling countries.

The impact of immunization control activities on measles outbreaks in middle and low income countries.

BACKGROUND: The World Health Organization recommended strategy for responding to measles outbreaks in developing countries does not promote the use of immunization campaigns due to their high cost, disruptive nature and limited impact. Given the substantial morbidity and mortality associated with such outbreaks, a literature review was conducted as a basis for re-evaluating this policy. METHODS: Reports of supplementary immunization activities that were performed to control measles outbreaks in middle or low income countries were identified. The impact of the immunization activities on the course of each outbreak was evaluated by examining the data provided. RESULTS: Of 66 reports detailing a measles outbreak in a middle or low income country, 17 described supplementary immunization activities which included seven 'non-selective' immunization campaigns, three 'selective' campaigns and one use of an early 2-dose schedule. Eight of the reports commented on the impact of the response, five of which reported a reduction in outbreak morbidity. Only one of the reports, from an isolated island outbreak, provided sufficient data to support a possible reduction in outbreak-associated morbidity. CONCLUSIONS: There are limited data on the impact of measles outbreak immunization activities from developing countries. The available data do not support a change in the WHO recommended strategy for conducting a limited, if any, immunization response to such outbreaks. Immunization strategies which aim to prevent outbreaks may be more effective than campaigns to interrupt transmission of an outbreak which has already begun.

PIP: Because of their high cost, disruptive nature, and limited impact, immunization campaigns are not recommended by the World Health Organization (WHO) in response to measles outbreaks in developing countries. The authors reviewed the available literature to assess whether that WHO policy should stand or be changed. 66 reports were identified detailing a measles outbreak in middle- or low-income countries. 17 of those reports described supplementary immunization activities to control measles outbreaks which included seven nonselective immunization campaigns, three selective campaigns, and one use of an early two-dose schedule. Eight reports commented upon the impact of the intervention, five of which reported a reduction in outbreak morbidity. Only one report, from an isolated island outbreak, provided sufficient data to support a possible reduction in outbreak-associated morbidity. The available data therefore do not support a change in the WHO-recommended strategy. Immunization strategies to prevent outbreaks may be more effective than campaigns to interrupt transmission of an outbreak which has already begun.