Relapse and regression to severe wasting in children under 5 years: A theoretical framework.

Systematic reviews have highlighted that repeated severe wasting after receiving treatment is likely to be common, but standardised measurement is needed urgently. The Council of Research & Technical Advice for Acute Malnutrition (CORTASAM) released recommendations on standard measurement of relapse (wasting within 6 months after exiting treatment as per recommended discharge criteria), regression (wasting within 6 months after exiting treatment before reaching recommended discharge criteria) and reoccurrence (wasting after 6 months of exit from treatment as per recommended discharge criteria). We provide a theoretical framework of post-treatment relapse and regression to severe wasting to guide discussions, risk factor analyses, and development and evaluations of interventions. This framework highlights that there are factors that may impact risk of relapse and regression in addition to the impact of contextual factors associated with incidence and reoccurrence of severe wasting more generally. Factors hypothesised to be associated with relapse and regression relate specifically to the nutrition and health status of the child on admission to, during and exit from treatment and treatment interventions, platforms and approaches as well as type of exit from treatment (e.g., before reaching recommended criteria). These factors influence whether children reach full recovery, and poorer nutritional and immunological status at exit from treatment are more proximate determinants of risk of severe wasting after treatment, although post-treatment interventions may modify risks. The evidence base for many of these factors is weak. Our framework can guide research to improve our understanding of risks of relapse and regression and how to prevent them and inform programmes on what data to collect to evaluate relapse. Implementation research is needed to operationalise results in programmes and reduce post-treatment severe wasting at scale.

A new tool to measure approaches to supervision from the perspective of community health workers: a prospective, longitudinal, validation study in seven countries.

BACKGROUND: The global scale-up of community health workers (CHWs) depends on supportive management and supervision of this expanding cadre. Existing tools fail to incorporate the perspective of the CHW (i.e. perceived supervision) in terms of supportive experiences with their supervisor. Aligned to the WHO's strategy on human resources for health, we developed and validated a simple tool to measure perceived supervision across seven low and middle-income countries. METHODS: Phase 1 was carried out with 327 CHWs in Sierra Leone. Twelve questions, informed by the extant literature on health worker supervision, were reduced to six questions using confirmatory factor analysis. Phase 2 employed structural equation modelling with 741 CHWs in six countries (Bangladesh, Ethiopia, Indonesia, Kenya, Malawi, Mozambique), to assess the factorial validity, predictive validity, and internal reliability of the questions at three time-points, over 8-months. RESULTS: We developed a robust, 6-item measure of perceived supervision (PSS), capturing regular contact, two-way communication, and joint problem-solving elements as being critical from the perspective of CHWs. When assessed across the six countries, over time, the PSS was also found to have good validity and internal reliability. PSS scores at baseline positively and significantly predicted a range of performance-related outcomes at follow-up. CONCLUSION: The PSS is the first validated tool that measures supervisory experience from the perspective of CHWs and is applicable across multiple, culturally-distinct global health contexts with a wide range of CHW typologies. Simple, quick to administer, and freely available in 11 languages, the PSS could assist practitioners in the management of community health programmes.

The EPICS Trial: Enabling Parents to Increase Child Survival through the introduction of community-based health interventions in rural Guinea Bissau.

BACKGROUND: Guinea-Bissau is a small country in West Africa with a population of 1.7 million. The WHO and UNICEF reported an under-five child mortality of 203 per 1000, the 10th highest amongst 192 countries. The aim of the trial is to assess whether an intervention package that includes community health promotion campaign and education through health clubs, intensive training and mentoring of village health workers to diagnose and provide first-line treatment for children's diseases within the community, and improved outreach services can generate a rapid and cost-effective reduction in under-five child mortality in rural regions of Guinea-Bissau. Effective Intervention plans to expand the project to a much larger region if there is good evidence after two and a half years that the project is generating a cost-effective, sustainable reduction in child mortality. METHODS/DESIGN: This trial is a cluster-randomised controlled trial involving 146 clusters. The trial will run for 2.5 years. The interventions will be introduced in two stages: seventy-three clusters will receive the interventions at the start of the project, and seventy-three control clusters will receive the interventions 2.5 years after the first clusters have received all interventions if the research shows that the interventions are effective. The impact of the interventions and cost-effectiveness will be measured during the first stage.The package of interventions includes a community health promotion campaign and education through health clubs, and intensive training and mentoring of village health workers to diagnose and provide first-line treatment for common children's diseases within the community. It also includes improved outreach services to encourage provision of antenatal and post natal care and provide ongoing monitoring for village health workers.The primary outcome of the trial will be the proportion of children that die under 5 years of age during the trial. Secondary outcomes will include age at and cause of child deaths, neonatal mortality, infant mortality, maternal mortality, health knowledge, health seeking behaviour, morbidity and costs. DISCUSSION: The trial will be run by research and service delivery teams that act independently, overseen by a trial steering committee. A data monitoring committee will be appointed to monitor the outcome and any adverse effects. TRIAL REGISTRATION: Current Controlled Trials ISRCTN52433336.

Aquaculture practices and potential human health risks: current knowledge and future priorities.

Annual global aquaculture production has more than tripled within the past 15 years, and by 2015, aquaculture is predicted to account for 39% of total global seafood production by weight. Given that lack of adequate nutrition is a leading contributor to the global burden of disease, increased food production through aquaculture is a seemingly welcome sign. However, as production surges, aquaculture facilities increasingly rely on the heavy input of formulated feeds, antibiotics, antifungals, and agrochemicals. This review summarizes our current knowledge concerning major chemical, biological and emerging agents that are employed in modern aquaculture facilities and their potential impacts on public health. Findings from this review indicate that current aquaculture practices can lead to elevated levels of antibiotic residues, antibiotic-resistant bacteria, persistent organic pollutants, metals, parasites, and viruses in aquacultured finfish and shellfish. Specific populations at risk of exposure to these contaminants include individuals working in aquaculture facilities, populations living around these facilities, and consumers of aquacultured food products. Additional research is necessary not only to fully understand the human health risks associated with aquacultured fish versus wild-caught fish but also to develop appropriate interventions that could reduce or prevent these risks. In order to adequately understand, address and prevent these impacts at local, national and global scales, researchers, policy makers, governments, and aquaculture industries must collaborate and cooperate in exchanging critical information and developing targeted policies that are practical, effective and enforceable.

Polymorphisms in Nef associated with different clinical outcomes in HIV type 1 subtype C-infected children.

The human immunodeficiency virus type 1 (HIV-1) negative factor, or Nef, has a variety of functions that are important in viral pathogenesis. Sequence analysis has identified nef mutations that are linked to the rate of disease progression in adults and children infected with HIV-1 subtype B. Here we have sequenced and analyzed HIV-1 subtype C nef sequences from 34 children with rapid (RP) or slow progressing (SP) disease and identified polymorphisms associated with disease stage including motifs involved in specific pathogenic functions. Unlike subtype B, insertions and deletions in the N-terminal variable region were observed exclusively in SP children (8 out of 25). Strong positive selection pressures were found in sites of known functional importance among SP sequences, whereas RP had strong negative selection across the gene. A lineage analysis of selection pressures indicated weaker pressure across the nef gene in SP sequences bearing a deletion in region 8-12, suggesting this deletion has functional importance in vivo. Together these results suggest a differential adaptation of certain Nef functions related to disease progression, some of which may be attributable to immune-imposed pressures. These data broadly reflect previous studies on subtype B, corroborate the decreased cytopathicity of SP viruses, but also highlight potential subtype differences that require further investigation.

What do we feed to food-production animals? A review of animal feed ingredients and their potential impacts on human health.

OBJECTIVE: Animal feeding practices in the United States have changed considerably over the past century. As large-scale, concentrated production methods have become the predominant model for animal husbandry, animal feeds have been modified to include ingredients ranging from rendered animals and animal waste to antibiotics and organoarsenicals. In this article we review current U.S. animal feeding practices and etiologic agents that have been detected in animal feed. Evidence that current feeding practices may lead to adverse human health impacts is also evaluated. DATA SOURCES: We reviewed published veterinary and human-health literature regarding animal feeding practices, etiologic agents present in feed, and human health effects along with proceedings from animal feed workshops. DATA EXTRACTION: Data were extracted from peer-reviewed articles and books identified using PubMed, Agricola, U.S. Department of Agriculture, Food and Drug Administration, and Centers for Disease Control and Prevention databases. DATA SYNTHESIS: Findings emphasize that current animal feeding practices can result in the presence of bacteria, antibiotic-resistant bacteria, prions, arsenicals, and dioxins in feed and animal-based food products. Despite a range of potential human health impacts that could ensue, there are significant data gaps that prevent comprehensive assessments of human health risks associated with animal feed. Limited data are collected at the federal or state level concerning the amounts of specific ingredients used in animal feed, and there are insufficient surveillance systems to monitor etiologic agents "from farm to fork." CONCLUSIONS: Increased funding for integrated veterinary and human health surveillance systems and increased collaboration among feed professionals, animal producers, and veterinary and public health officials is necessary to effectively address these issues.

Genotypic and phenotypic characterization of viral isolates from HIV-1 subtype C-infected children with slow and rapid disease progression.

The genotypes and biological phenotypes of HIV-1 isolates obtained from 40 perinatally infected children in South Africa were analyzed. This included 15 infants who had HIV-related symptoms, most of whom died within 2 years of birth (rapid progressors), and 25 children who survived between 4 and 9 years with varying signs of disease (slow progressors). Heteroduplex mobility assays and sequence analysis confirmed that within the env and gag regions, all isolates were HIV-1 subtype C. Viral isolates from 14 of the 15 rapid progressors used the CCR5 coreceptor, whereas 1 (02ZARP1) used both the CXCR4 and CCR5 coreceptors. Among the 25 slow progressors, 22 isolates used CCR5 only, 2 used CXCR4 only, and 1 used both CCR5 and CXCR4. Two of the slow-progressing children who harbored CXCR4-using viruses had AIDS. All four CXCR4-using viruses had genotypic changes in the V3 region previously shown to be associated with CXCR4 usage. This cross-sectional study shows that HIV-1 subtype C viruses from both rapid- and slow-progressing perinatally infected children used predominantly CCR5. Similar to adults, CXCR4 usage was uncommon among HIV-1 subtype C isolates from pediatric infections.

Effects of community health interventions on under-5 mortality in rural Guinea-Bissau (EPICS): a cluster-randomised controlled trial.

BACKGROUND: Evidence suggests that community-based interventions that promote improved home-based practices and care-seeking behaviour can have a large impact on maternal and child mortality in regions where rates are high. We aimed to assess whether an intervention package based on the WHO Integrated Management of Childhood Illness handbook and community mobilisation could reduce under-5 mortality in rural Guinea-Bissau, where the health service infrastructure is weak. METHODS: We did a non-masked cluster-randomised controlled trial (EPICS) in the districts of Tombali and Quinara in Guinea-Bissau. Clusters of rural villages were stratified by ethnicity and distance from a regional health centre, and randomly assigned (1:1) to intervention or control using a computerised random number generator. Women were eligible if they lived in one of the clusters at baseline survey prior to randomisation and if they were aged 15-49 years or were primary caregivers of children younger than 5 years. Their children were eligible if they were younger than 5 years or were liveborn after intervention services could be implemented on July 1, 2008. In villages receiving the intervention, community health clubs were established, community health workers were trained in case management, and traditional birth attendants were trained to care for pregnant women and newborn babies, and promote facility-based delivery. Registered nurses supervised community health workers and offered mobile clinic services. Health centres were not improved. The control group received usual services. The primary outcome was the proportion of children dying under age 5 years, and was analysed in all eligible children up to final visits to villages between Jan 1 and March 31, 2011. This trial is registered with ISRCTN, number ISRCTN52433336. FINDINGS: On Aug 30, 2007, we randomly assigned 146 clusters to intervention (73 clusters, 5669 women, and 4573 children) or control (73 clusters, 5840 women, and 4675 children). From randomisation until the end of the trial (last visit by June 30, 2011), the intervention clusters had 3093 livebirths and the control clusters had 3194. 6729 children in the intervention group and 6894 in the control group aged 0-5 years on July 1, 2008, or liveborn subsequently were analysed for mortality outcomes. 311 (4·6%) of 6729 children younger than 5 years died in the intervention group compared with 273 (4·0%) of 6894 in the control group (relative risk 1·16 [95% CI 0·99-1·37]). INTERPRETATION: Our package of community-based interventions did not reduce under-5 mortality in rural Guinea-Bissau. The short timeframe and other trial limitations might have affected our results. Community-based health promotion and basic first-line services in fragile contexts with weak secondary health service infrastructure might be insufficient to reduce child deaths. FUNDING: Effective Intervention.

Comparative population dynamics of HIV-1 subtypes B and C: subtype-specific differences in patterns of epidemic growth.

The human immunodeficiency virus (HIV) pandemic continues to grow at an alarming rate, with a further 5 million new infections in 2003. Some 3.5 million of these were in sub-Saharan Africa, where approximately 70% of the world's HIV-positive population resides. In contrast, the spread of HIV in high-income countries has slowed since its discovery in the 1980s, and in regions such as Western Europe prevalence has decreased. Here, we employ coalescent methods to compare the epidemic growth rates of two subtypes of HIV-1 with differing epidemiological profiles: subtype C, which is dominant in sub-Saharan Africa and associated with heterosexual transmission, and subtype B, the main cause of AIDS in Western Europe and North America, and which was primarily transmitted through homosexual sex and injecting drug use. We show that although both subtypes emerged at approximately the same time ( approximately 1960), they have widely differing patterns of exponential population growth. At its current growth rate the epidemic of subtype C in sub-Saharan Africa is doubling every 2.4 years, which is approximately half the rate observed during the early stages of the subtype B epidemic in Western Europe and North America. However, the subtype C growth rate is still 5-10 times greater than that estimated for the blood-borne hepatitis C virus, supporting the hypothesis that sexual transmission has been primarily responsible for the HIV epidemic in sub-Saharan Africa.

How sustainable agriculture can address the environmental and human health harms of industrial agriculture.

The industrial agriculture system consumes fossil fuel, water, and topsoil at unsustainable rates. It contributes to numerous forms of environmental degradation, including air and water pollution, soil depletion, diminishing biodiversity, and fish die-offs. Meat production contributes disproportionately to these problems, in part because feeding grain to livestock to produce meat--instead of feeding it directly to humans--involves a large energy loss, making animal agriculture more resource intensive than other forms of food production. The proliferation of factory-style animal agriculture creates environmental and public health concerns, including pollution from the high concentration of animal wastes and the extensive use of antibiotics, which may compromise their effectiveness in medical use. At the consumption end, animal fat is implicated in many of the chronic degenerative diseases that afflict industrial and newly industrializing societies, particularly cardiovascular disease and some cancers. In terms of human health, both affluent and poor countries could benefit from policies that more equitably distribute high-protein foods. The pesticides used heavily in industrial agriculture are associated with elevated cancer risks for workers and consumers and are coming under greater scrutiny for their links to endocrine disruption and reproductive dysfunction. In this article we outline the environmental and human health problems associated with current food production practices and discuss how these systems could be made more sustainable.

High specificity of V3 serotyping among human immunodeficiency virus type-1 subtype C infected patients with varying disease status and viral phenotype.

V3 serotyping is a technique for determining HIV-1 genetic subtype based on the binding of antibodies from patient sera or plasma to synthetic V3 peptides derived from subtype consensus sequences. Variation in the performance of this assay has been attributed to V3 sequence heterogeneity, the degree of which varies with patient disease progression, virus co-receptor usage, and genetic subtype. This study assessed the performance of a competitive peptide enzyme immunoassay (cPEIA) in samples from HIV-1 subtype C infected patients with varying disease profiles, including those with syncytium (SI) and non-syncytium-inducing (NSI) viruses. Out of 90 sera tested, 94.4% reacted strongly against the subtype C peptide. There was no significant difference in assay sensitivity among samples from advanced AIDS patients in which humoral immune response may be lower, nor among SI viruses which carry changes in the V3 sequence. Four samples were found to be cross-reactive with other subtypes and one acutely infected patient sample was non-reactive due to low anti-gp120 antibody titers. A significantly higher number of samples showed secondary reactivity to subtype A, compared to other subtypes (P < 0.005). In conclusion, the assay was able to identify HIV-1 subtype C infection with a high level of sensitivity (94%) irrespective of the stage of disease and therefore provides a valuable resource for the large-scale epidemiological monitoring of the spread of HIV-1 subtypes in South Africa.

Public health implications of meat production and consumption.

The high level of meat and saturated fat consumption in the USA and other high-income countries exceeds nutritional needs and contributes to high rates of chronic diseases such as cardiovascular disease, diabetes mellitus and some cancers. Affluent citizens in middle- and low-income countries are adopting similar high-meat diets and experiencing increased rates of these same chronic diseases. The industrial agricultural system, now the predominant form of agriculture in the USA and increasingly world-wide, has consequences for public health owing to its extensive use of fertilisers and pesticides, unsustainable use of resources and environmental pollution. In industrial animal production there are public health concerns surrounding feed formulations that include animal tissues, arsenic and antibiotics as well as occupational health risks and risks for nearby communities. It is of paramount importance for public health professionals to become aware of and involved in how our food is produced.

Plasmodium chabaudi: rosetting in a rodent malaria model.

Rosetting is a property of many malaria parasite species that has been linked to virulence in the major species infecting humans, Plasmodium falciparum. Here, the basic properties of rosettes in the rodent malaria laboratory model, P. chabaudi, were studied with a view to future studies on the role of rosetting in malaria parasite virulence and transmission. Rosetting occurred in 14 out of the 15 P. chabaudi clones studied, varied consistently between clones, and ranged between 9 and 37% at full parasite maturity. Rosetting frequency markedly declined after the mouse reached peak parasitemia, possibly due to host immunity. Consistent with P. falciparum and P. vivax, rosettes in P. chabaudi were disrupted by treatment with trypsin and EDTA. However, P. chabaudi rosettes were insensitive to sulfated glycoconjugates (heparin, heparan sulfate and fucoidan). The molecular basis of rosetting in P. chabaudi is unknown at present, but the results suggest that the molecules involved may differ from those in human-infecting species.

A test of the California competency-based differentiated role model.

To address the incongruence between the expectations of nursing service and education in California, the Education Industry Interface Task Force of the California Strategic Planning Committee for Nursing developed descriptions to assist employers and educators in clearly differentiating practice and educational competencies. The completion of the Competency-Based Role Differentiation Model resulted in the need to test the model for its utility in the service setting, in education, and for career planning for nurses. Three alpha demonstration sites were selected based on representative geographical regions of California. The sites were composed of tri-partnerships consisting of a medical center, an associate degree in nursing program, and a baccalaureate nursing program. Observers rated senior students and new graduates in medical-surgical units on their behaviors in teacher and leadership care provider and care coordinator roles. The alpha demonstration study results were as expected. That is, senior students practice predominantly at a novice level in teacher and management/leadership care provider functions and new graduates practice predominately at the competent level. New graduates are more likely to take on novice and competent care coordinator roles. The CBRDM may be useful for practice and education settings to evaluate student and nurse performance, to define role expectations, and to identify the preparation necessary for the roles. It is useful for all of nursing as it continues to define its levels of practice and their relationship to on-the-job performance, curriculum development, and carrier planning.

Testing the model for testing competency.

The pilot study to demonstrate the utility of the CBRDM in the practice setting was successful. Using a matrix evaluation tool based on the model's competencies, evaluators were able to observe specific performance behaviors of senior nursing students and new graduates at either the novice or competent levels. The study faced the usual perils of pilot studies, including small sample size, a limited number of items from the total CBRDM, restricted financial resources, inexperienced researchers, unexpected barriers, and untested evaluation tools. It was understood from the beginning of the study that the research would be based on a program evaluation model, analyzing both processes and outcomes. However, the meager data findings led to the desire to continue to study use of the model for practice setting job expectations, career planning for nurses, and curriculum development for educators. Although the California Strategic Planning Committee for Nursing no longer has funding, we hope that others interested in role differentiation issues will take the results of this study and test the model in other practice settings. Its ability to measure higher levels of competency as well as novice and competent should be studied, i.e., proficient, expert, and advanced practice. The CBRDM may be useful in evaluating student and nurse performance, defining role expectations, and identifying the preparation necessary for the roles. The initial findings related to the two functions as leader and teacher in the care provider and care coordinator roles led to much discussion about helping students and nurses develop competence. Additional discussion focused on the roles as they apply to settings such as critical care or primary health care. The model is useful for all of nursing as it continues to define its levels of practice and their relationship to on-the-job performance, curriculum development, and career planning.