Deliberately infecting healthy volunteers with malaria parasites: Perceptions and experiences of participants and other stakeholders in a Kenyan-based malaria infection study

Controlled human malaria infection (CHMI) studies involve the deliberate infection of healthy volunteers with malaria parasites under controlled conditions to study immune responses and/or test drug or vaccine efficacy. An empirical ethics study was embedded in a CHMI study at a Kenyan research programme to explore stakeholders’ perceptions and experiences of deliberate infection and moral implications of these. Data for this qualitative study were collected through focus group discussions, in-depth interviews and non-participant observation. Sixty-nine participants were involved, including CHMI study volunteers, community representatives and research staff. Data were managed using QSR Nvivo 10 and analysed using an inductive-deductive approach, guided by ethics literature. CHMI volunteers had reasonable understanding of the study procedures. Decisions to join were influenced by study incentives, trust in the research institution, their assessment of associated burdens and motivation to support malaria vaccine development. However, deliberate malaria infection was a highly unusual research strategy for volunteers, community representatives and some study staff. Volunteers’ experiences of physical, emotional and social burdens or harms were often greater than anticipated initially, and fluctuated over time, related to specific procedures and events. Although unlikely to deter volunteers' participation in similar studies in furture, we argue that the dissonance between level of understanding of the burdens involved and actual experiences are morally relevant in relation to community engagement, informed consent processes, and ongoing support for volunteers and research staff. We further argue that ethics oversight of CHMI studies should take account of these issues in deciding whether consent, engagement and the balance of benefits and harms are reasonable in a given context.     

Biological nitrogen fixation for sustainable agriculture: A perspective

The economic and environmental costs of the heavy use of chemical N fertilizers in agriculture are a global concern. Sustainability considerations mandate that alternatives to N fertilizers must be urgently sought. Biological nitrogen fixation (BNF), a microbiological process which converts atmospheric nitrogen into a plant-usable form, offers this alternative. Nitrogen-fixing systems offer an economically attractive and ecologically sound means of reducing external inputs and improving internal resources. Symbiotic systems such as that of legumes and Rhizobium can be a major source of N in most cropping systems and that of Azolla and Anabaena can be of particular value to flooded rice crop. Nitrogen fixation by associative and free-living microorganisms can also be important. However, scientific and socio-cultural constraints limit the utilization of BNF systems in agriculture. While several environmental factors that affect BNF have been studied, uncertainties still remain on how organisms respond to a given situation. In the case of legumes, ecological models that predict the likelihood and the magnitude of response to rhizobial inoculation are now becoming available. Molecular biology has made it possible to introduce choice attributes into nitrogen-fixing organisms but limited knowledge on how they interact with the environment makes it difficult to tailor organisms to order. The difficulty in detecting introduced organisms in the field is still a major obstacle to assessing the success or failure of inoculation. Production-level problems and socio-cultural factors also limit the integration of BNF systems into actual farming situations. Maximum benefit can be realized only through analysis and resolution of major constraints to BNF performance in the field and adoption and use of the technology by farmers.     

Noncommunicable disease outcomes and the effects of vertical and horizontal health aid

Foreign health aid forms a substantial portion of health spending in many low- and middle-income countries (LMICs). It can be either vertical (funds earmarked for specific diseases) or horizontal (funds used for broad health sector strengthening). Historically, most health aid has been disbursed vertically toward key infectious diseases, with minimal allocations to noncommunicable diseases (NCDs). High NCD burden in LMICs underscores a need for increased assistance toward NCD objectives, but evidence on the outcomes of health aid for NCDs is sparse. We obtained annual data on cause-specific deaths and disability-adjusted life years (DALYs) for four leading NCDs across 116 countries, 2000–2016, and evaluated the relationship between these indicators and vertical and horizontal health aid using country fixed-effects models with 1-to-5-year lagged effects. After adjusting for fixed and time-variant country heterogeneity, vertical assistance for NCDs was significantly associated with subsequent reductions in NCD morbidity and mortality, particularly for persons under age 70 and for cardiovascular and chronic respiratory diseases. An additional dollar in per-capita NCD vertical assistance corresponded to reductions in the average annual NCD burden of 7,459 DALYs/281 deaths after one year, 7,728 DALYs/319 deaths after two years, and 8,957 DALYs/346 deaths after three years. The findings suggest that vertical assistance for NCD programs may be an appropriate mechanism for addressing short-term NCD needs in LMICs, where it may help to fill health sector gaps in NCD care, but longer-term evaluation is needed for assessing the role of horizontal assistance.     

Domesticating Islam: exploring academic knowledge production on Islam and Muslims in European societies

The attacks on the Twin Towers in New York in September 2001 and subsequent events not only ignited a ‘war on terror’, but also marked a crucial change in the policies on integration of migrants of Islamic background in Europe. Most countries departed from integration policies based on some sort of recognition of cultural diversity and emphasized national culture as the only legitimate format for citizenship. The result is a strengthening of a frame of governance with the aim to regulate Islamic practices and to mould outlooks, institutional settings and legal arrangements into the nation-state format. This has been referred to as the ‘domestication of Islam’. One of the consequences is the narrowing down of research agendas and academic knowledge production. In this article I explore this process and address important fields of study that tend to be neglected in the study of Islam in Europe.     

Plant-derived pharmaceuticals for the developing world

Plant-produced vaccines and therapeutic agents offer enormous potential for providing relief to developing countries by reducing the incidence of infant mortality caused by infectious diseases. Vaccines derived from plants have been demonstrated to effectively elicit an immune response. Biopharmaceuticals produced in plants are inexpensive to produce, require fewer expensive purification steps, and can be stored at ambient temperatures for prolonged periods of time. As a result, plant-produced biopharmaceuticals have the potential to be more accessible to the rural poor. This review describes current progress with respect to plant-produced biopharmaceuticals, with a particular emphasis on those that target developing countries. Specific emphasis is given to recent research on the production of plant-produced vaccines toward human immunodeficiency virus, malaria, tuberculosis, hepatitis B virus, Ebola virus, human papillomavirus, rabies virus and common diarrheal diseases. Production platforms used to express vaccines in plants, including nuclear and chloroplast transformation, and the use of viral expression vectors, are described in this review. The review concludes by outlining the next steps for plant-produced vaccines to achieve their goal of providing safe, efficacious and inexpensive vaccines to the developing world.     

Individual health and the visibility of village economic inequality: Longitudinal evidence from native Amazonians in Bolivia

Mounting evidence suggests that income inequality is associated with worse individual health. But does the visibility of inequality matter? Using data from a horticultural-foraging society of native Amazonians in Bolivia (Tsimane’), we examined whether village inequality in resources and behaviors with greater cultural visibility is more likely to bear a negative association with health than village inequality in less conspicuous resources. We draw on a nine-year annual panel (2002–2010) from 13 Tsimane’ villages for our main analysis, and an additional survey to gauge the cultural visibility of resources. We measured inequality using the Gini coefficient. We tested the robustness of our results using a shorter two-year annual panel (2008–2009) in another 40 Tsimane’ villages and an additional measure of inequality (coefficient of variation, CV). Behaviors with low cultural visibility (e.g., household farm area planted with staples) were less likely to be associated with individual health, compared to more conspicuous behaviors (e.g., expenditures in durable goods, consumption of domesticated animals). We find some evidence that property rights and access to resources matter, with inequality of privately-owned resources showing a larger effect on health. More inequality was associated with improved perceived health – maybe due to improved health prospects from increasing wealth – and worse anthropometric indicators. For example, a unit increase in the Gini coefficient of expenditures in durable goods was associated with 0.24 fewer episodes of stress and a six percentage-point lower probability of reporting illness. A one-point increase in the CV of village inequality in meat consumption was associated with a 4 and 3 percentage-point lower probability of reporting illness and being in bed due to illness, and a 0.05 SD decrease in age-sex standardized arm-muscle area. In small-scale, rural societies at the periphery of market economies, nominal economic inequality in resources bore an association with individual health, but did not necessarily harm perceived health. Economic inequalities in small-scale societies apparently matter, but a thick cultural tapestry of reciprocity norms and kinship ties makes their effects less predictable than in industrial societies.     

Community mental health care worldwide: current status and further developments

This paper aims to give an overview of the key issues facing those who are in a position to influence the planning and provision of mental health systems, and who need to address questions of which staff, services and sectors to invest in, and for which patients. The paper considers in turn: a) definitions of community mental health care; b) a conceptual framework to use when evaluating the need for hospital and community mental health care; c) the potential for wider platforms, outside the health service, for mental health improvement, including schools and the workplace; d) data on how far community mental health services have been developed across different regions of the world; e) the need to develop in more detail models of community mental health services for low‐ and middle‐income countries which are directly based upon evidence for those countries; f) how to incorporate mental health practice within integrated models to identify and treat people with comorbid long‐term conditions; g) possible adverse effects of deinstitutionalization. We then present a series of ten recommendations for the future strengthening of health systems to support and treat people with mental illness.     

The effectiveness of the peer-delivered Thinking Healthy PLUS (THPP+) Program for maternal depression and child socioemotional development in Pakistan: study protocol for a randomized controlled trial

BackgroundThe negative effects of perinatal depression on the mother and child start early and persist throughout the lifecourse (Lancet 369(9556):145–57, 2007; Am J Psychiatry 159(1):43-7, 2002; Arch Dis Child 77(2):99–101, 1997; J Pak Med Assoc 60(4):329; J Psychosoma Res 49(3):207–16, 2000; Clin Child Fam Psychol Rev 14(1):1–27, 2011). Given that 10–35 % of children worldwide are exposed to perinatal depression in their first year of life (Int Rev Psychiatry 8(1):37–54, 1996), mitigating this intergenerational risk is a global public health priority (Perspect Public Health 129(5):221–7, 2009; Trop Med Int Health 13(4):579–83, 2008; Br Med Bull 101(1):57–79, 2012). However, it is not clear whether intervention with depressed women can have long-term benefits for the mother and/or her child. We describe a study of the effectiveness of a peer-delivered depression intervention delivered through 36 postnatal months, the Thinking Healthy Program Peer-delivered PLUS (THPP+) for women and their children in rural Pakistan.Methods/designThe THPP+ study aims are: (1) to evaluate the effects of an extended 36-month perinatal depression intervention on maternal and index child outcomes using a cluster randomized controlled trial (c-RCT) and (2) to determine whether outcomes among index children of perinatally depressed women in the intervention arm converge with those of index children born to perinatally nondepressed women. The trial is designed to recruit 560 pregnant women who screened positive for perinatal depression (PHQ-9 score ≥10) from 40 village clusters, of which 20 receive the THPP+ intervention. An additional reference group consists of 560 perinatally nondepressed women from the same 40 clusters as the THPP+ trial. The women in the nondepressed group are not targeted to receive the THPP+ intervention; but, by recruiting pregnant women from both intervention and control clusters, we are able to evaluate any carryover effects of the THPP+ intervention on the women and their children. Perinatally depressed women in the THPP+ intervention arm receive bimonthly group-based sessions. Primary outcomes are 3-year maternal depression and 3-year child development indicators. Analyses are intention-to-treat and account for the clustered design.DiscussionThis trial, together with the reference group, has the potential to further our understanding of the early developmental lifecourse of children of both perinatally depressed and perinatally nondepressed women in rural Pakistan and to determine whether intervening with women’s depression in the perinatal period can mitigate the negative effects of maternal depression on 36-month child development.

Trial registration

THPP-P ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02111915","term_id":"NCT02111915"}}NCT02111915 (registered on 9 April 2014).THPP+ ClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02658994","term_id":"NCT02658994"}}NCT02658994 (registered on 21 January 2016).Sponsor: Human Development Research Foundation (HDRF).

Electronic supplementary material

The online version of this article (doi:10.1186/s13063-016-1530-y) contains supplementary material, which is available to authorized users.     

Neural tube defects, micronutrient deficiencies, and Helicobacter pylori: a new hypothesis

BACKGROUND: Previous findings for the Texas Neural Tube Defects Project suggested that while maternal access to nutrients is adequate, bioavailability of nutrients to the fetus is compromised in NTD-affected pregnancies. Helicobacter pylori could cause nutrient loss to the fetus. Folate, B12, and ferritin are depleted in H. pylori infection; these same deficiencies are related to NTD risk. METHODS: Using H. pylori IgG ELISA Test System, we tested for H. pylori serum antibodies in participants in the population-based case-control study component of the Texas Neural Tube Defect Project conducted along the Texas-Mexico border. Case-women had pregnancies affected by NTD (anencephalus, spina bifida, encephalocele) and resided and delivered in one of the 14 Texas-Mexico border counties from 1995 through 2000. Control-women were study area residents delivering normal live births during the same period. RESULTS: Of 225 case- and 378 control-women, 103 cases and 156 controls provided questionnaire and H. pylori antibody data. H. pylori seropositivity was modestly associated with NTD-affected pregnancies (OR 1.4; 95% CI: 0.8-2.4). ORs of 2.0 or greater were seen in women younger than age 25 and with less than 7 years education. CONCLUSIONS: Our findings intimate that H. pylori could play a role in NTD causation in certain populations. While results did not provide compelling support for this proposal, subgroup findings prompt us to advocate an evaluation of this hypothesis in developing nations among populations with higher prevalence of H. pylori, marginal nutrient intake, and young childbearing age.     

Prevention of bacterial diarrhea by pasteurization of drinking water in Kenya

Diarrheal disease is one of the major causes of morbidity and mortality in developing countries. Drinking water is a primary transmission route of infectious diarrheagenic bacteria in a rural area of Kenya (Microbiol. Immunol. 41: 773-778, 1997). We tried to prevent diarrhea at villages with approximately 1,500 households in Kenya by pasteurizing drinking water. A durable simple thermoindicator which changes color at 70 C was used as an indicator of pasteurization. The number of households in which drinking water was coliform bacteria-free increased from 10.7% to 43.1% after adoption of a pasteurization practice. Consequently, the incidence of severe diarrhea among people drinking pasteurized water was significantly lower than in people taking raw water (odds ratio=0.55, P=0.0016). The reduction ratio of the incidence after pasteurization was nearly equivalent with that after the adoption of a boiling method. Employment of women leaders as fieldworkers and demonstration of bacterial colony disappearance on agar plates by pasteurization also affected reduction of the diarrheal incidence.