Adaptive geostatistical design and analysis for prevalence surveys

Non-adaptive geostatistical designs (NAGDs) offer standard ways of collecting and analysing geostatistical data in which sampling locations are fixed in advance of any data collection. In contrast, adaptive geostatistical designs (AGDs) allow collection of geostatistical data over time to depend on information obtained from previous information to optimise data collection towards the analysis objective. AGDs are becoming more important in spatial mapping, particularly in poor resource settings where uniformly precise mapping may be unrealistically costly and the priority is often to identify critical areas where interventions can have the most health impact. Two constructions are: singleton and batch adaptive sampling. In singleton sampling, locations xi are chosen sequentially and at each stage, xk+1 depends on data obtained at locations x1,…,xk. In batch sampling, locations are chosen in batches of size b>1, allowing each new batch, {x(k+1),…,x(k+b)}, to depend on data obtained at locations x1,…,xkb. In most settings, batch sampling is more realistic than singleton sampling. We propose specific batch AGDs and assess their efficiency relative to their singleton adaptive and non-adaptive counterparts using simulations. We then show how we are applying these findings to inform an AGD of a rolling Malaria Indicator Survey, part of a large-scale, five-year malaria transmission reduction project in Malawi

Inhibitory geostatistical designs for spatial prediction taking account of uncertain covariance structure

The problem of choosing spatial sampling designs for investigating an unobserved spatial phenomenon S arises in many contexts, for example in identifying households to select for a prevalence survey to study disease burden and heterogeneity in a study region D. We studied randomised inhibitory spatial sampling designs to address the problem of spatial prediction whilst taking account of the need to estimate covariance structure. Two specific classes of design are inhibitory designs and inhibitory designs plus close pairs. In an inhibitory design, any pair of sample locations must be separated by at least an inhibition distance δ. In an inhibitory plus close pairs design, n − k sample locations in an inhibitory design with inhibition distance δ are augmented by k locations each positioned close to one of the randomly selected n − k locations in the inhibitory design, uniformly distributed within a disc of radius ζ. We present simulation results for the Mat´ern class of covariance structures. When the nugget variance is non-negligible, inhibitory plus close pairs designs demonstrate improved predictive efficiency over designs without close pairs. We illustrate how these findings can be applied to the design of a rolling Malaria Indicator Survey that forms part of an ongoing large-scale, five-year malaria transmission reduction project in Malawi

Delayed acquisition of Plasmodium falciparum antigen-specific CD4+ T cell responses in HIV-exposed uninfected Malawian children receiving daily cotrimoxazole prophylaxis

BACKGROUND: Cotrimoxazole (CTX) prophylaxis, recommended in HIV-exposed uninfected (HEU) children primarily against HIV-related opportunistic infections, has been shown to have some efficacy against Plasmodium falciparum malaria. The effects of CTX prophylaxis on the acquisition of P. falciparum antigen specific CD4(+) T cells-mediated immunity in HEU children is still not fully understood. METHODS: Peripheral blood was collected from HEU and HIV-unexposed uninfected (HUU) children at 6, 12 and 18 months of age. Proportion of CD4(+) T cells subsets were determined by immunophenotyping. P. falciparum antigen-specific CD4(+) T cells responses were measured by intracellular cytokine staining assay. RESULTS: There were no differences in the proportions of naïve, effector and memory CD4(+) T cell subsets between HEU and HUU children at all ages. There was a trend showing acquisition of P. falciparum-specific IFN-γ and TNF-producing CD4(+) T cells with age in both HUU and HEU children. There was, however, lower frequency of P. falciparum-specific IFN-γ-producing CD4(+) T cells in HEU compared to HUU at 6 and 12 months, which normalized 6 months after stopping CTX prophylaxis. CONCLUSION: The results demonstrate that there is delayed acquisition of P. falciparum-specific IFN-γ-producing CD4(+) T cells in HEU children on daily cotrimoxazole prophylaxis, which is evident at 6 and 12 months of age in comparison to HUU age-matched controls. However, whether this delayed acquisition of P. falciparum-specific IFN-γ-producing CD4(+) T cells leads to higher risk to malaria disease remains unknown and warrants further investigation

Inhibitory geostatistical designs for spatial prediction taking account of uncertain covariance structure

The problem of choosing spatial sampling designs for investigating an unobserved spatial phenomenon S arises in many contexts, for example, in identifying households to select for a prevalence survey to study disease burden and heterogeneity in a study region D. We studied randomized inhibitory spatial sampling designs to address the problem of spatial prediction while taking account of the need to estimate covariance structure. Two specific classes of design are inhibitory designs and inhibitory designs plus close pairs. In an inhibitory design, any pair of sample locations must be separated by at least an inhibition distance δ. In an inhibitory plus close pairs design, n − k sample locations in an inhibitory design with inhibition distance δ are augmented by k locations each positioned close to one of the randomly selected n − k locations in the inhibitory design, uniformly distributed within a disk of radius ζ. We present simulation results for the Matérn class of covariance structures. When the nugget variance is non-negligible, inhibitory plus close pairs designs demonstrate improved predictive efficiency over designs without close pairs. We illustrate how these findings can be applied to the design of a rolling Malaria Indicator Survey that forms part of an ongoing large-scale, 5-year malaria transmission reduction project in Malawi

Iron for Africa-Report of an Expert Workshop.

Scientific experts from nine countries gathered to share their views and experience around iron interventions in Africa. Inappropriate eating habits, infections and parasitism are responsible for significant prevalence of iron deficiency, but reliable and country-comparable prevalence estimates are lacking: improvements in biomarkers and cut-offs values adapted to context of use are needed. Benefits of iron interventions on growth and development are indisputable and outweigh risks, which exist in populations with a high infectious burden. Indeed, pathogen growth may increase with enhanced available iron, calling for caution and preventive measures where malaria or other infections are prevalent. Most African countries programmatically fortify flour and supplement pregnant women, while iron deficiency in young children is rather addressed at individual level. Coverage and efficacy could improve through increased access for target populations, raised awareness and lower cost. More bioavailable iron forms, helping to decrease iron dose, or prebiotics, which both may lower risk of infections are attractive opportunities for Africa. Fortifying specific food products could be a relevant route, adapted to local context and needs of population groups while providing education and training. More globally, partnerships involving various stakeholders are encouraged, that could tackle all aspects of the issue

Malaria research and its influence on antimalarial drug policy in Malawi : a case study

BACKGROUND : In 1993, Malawi changed its first-line anti-malarial treatment for uncomplicated malaria from chloroquine to sulfadoxine-pyrimethamine (SP), and in 2007, it changed from SP to lumefantrine-artemether. The change in 1993 raised concerns about whether it had occurred timely and whether it had potentially led to early development of Plasmodium falciparum resistance to SP. This case study examined evidence from Malawi in order to assess if the policy changes were justifiable and supported by evidence. METHODS : A systematic review of documents and published evidence between 1984 and 1993, when chloroquine was the first-line drug, and 1994 and 2007, when SP was the first-line drug, was conducted herein. The review was accompanied with key informant interviews. RESULTS : A total of 1287 publications related to malaria drug policy changes in sub-Saharan Africa were identified. Using the inclusion criteria, four articles from 1984 to 1993 and eight articles from 1994 to 2007 were reviewed. Between 1984 and 1993, three studies reported on chloroquine poor efficacy prompting policy change according to WHO’s recommendation. From 1994 to 2007, four studies conducted in the early years of policy change reported a high SP efficacy of above 80%, retaining it as a first-line drug. Unpublished sentinel site studies between 2005 and 2007 showed a reduced efficacy of SP, influencing policy change to lumefantrine-artemether. The views of key informants indicate that the switch from chloroquine to SP was justified based on local evidence despite unavailability of WHO’s policy recommendations, while the switch to lumefantrine-artemether was uncomplicated as the country was following the recommendations from WHO. CONCLUSION : Ample evidence from Malawi influenced and justified the policy changes. Therefore, locally generated evidence is vital for decision making during policy change.The University of Pretoria Centre for Sustainable Malaria Control (UP CSMC)http://www.health-policy-systems.comam2016School of Health Systems and Public Health (SHSPH

Changing the policy for intermittent preventive treatment with sulfadoxine–pyrimethamine during pregnancy in Malawi

BACKGROUND : The growing resistance of Plasmodium falciparum to sulfadoxine–pyrimethamine (SP) treatment for uncomplicated malaria led to a recommendation by the World Health Organization for the use of artemisinin-based combination therapy. Inevitably, concerns were also raised surrounding the use of SP for intermittent prevention treatment of malaria during pregnancy (IPTp) amidst the lack of alternative drugs. Malawi was the first country to adopt intermittent prevention treatment with SP in 1993, and updated in 2013. This case study examines the policy updating process and the contribution of research and key stakeholders to this process. The findings support the development of a malaria research-to-policy framework in Malawi. METHODS : Documents and evidence published from 1993 to 2012 were systematically reviewed in addition to key informant interviews. RESULTS : The online search identified 170 potential publications, of which eight from Malawi met the inclusion criteria. Two published studies from Malawi were instrumental in the WHO policy recommendation which in turn led to the updating of national policies. The updated policy indicates that more than two SP doses, as informed by research, overcome the challenges of the first policy of two SP doses only because of ineffectiveness by P. falciparum resistance and the global lack of replacement drugs to SP for IPTp. CONCLUSION : International WHO recommendations facilitated a smooth policy change driven by motivated local leadership with technical and financial support from development partners. Policy development and implementation should include key stakeholders and use local malaria research in a research-to-policy framework.University of Pretoria Institute for Sustainable Malaria Control (UP ISMC) and MRC Collaborating Centre for malaria research.http://www.malariajournal.comam2017School of Health Systems and Public Health (SHSPH

A cohort analysis of survival and outcomes in severely anaemic children with moderate to severe acute malnutrition in Malawi

Introduction Moderate to severe acute malnutrition (SAM/MAM) and severe anaemia are important and associated co-morbidities in children aged less than five years. Independently, these two morbidities are responsible for high risk of in-hospital and post-discharge deaths and hospital readmissions. The primary objective of this study is to investigate the risk of death among severely anaemic children with moderate to severe acute malnutrition compared to children with severe anaemia alone. Methods This was a retrospective analysis of data collected from a large prospective study that was investigating severe anaemia in children aged less than 5 years old. The study was conducted at Queen Elizabeth Central Hospital in Blantyre and Chikhwawa district hospital in southern Malawi. Children aged less than five years old; with severe anaemia were screened and enrolled. Each child was followed up for eighteen months at one, three, six, twelve and eighteen months after enrolment. Data were analysed using STATA 15. Results Between July 2002 and July 2004, 382 severely anaemic children were enrolled in the main study. A total of 52 children were excluded due to missing anthropometric data. Out of the 330 included, 53 children were moderately to severely malnourished and 277 were not. At the end of the 18-month follow period, 28.3% of children with MAM/SAM died compared to 13% of children without MAM/SAM (RR 2.1, CI 0.9–4.2, p = 0.03). Similarly, children with moderate to severe malnutrition reported a significantly higher number of malaria infection cases (33.9%) compared to children with severe anaemia alone (27.9%, p = 0.02). However, the number of hospitalizations and recurrence of severe anaemia was similar and not statistically significant between the two groups (RR 0.8 (0.4–1.4), p = 0.6 and RR 1.1 (0.3–2.8), p = 0.8). Conclusion Among children with severe anaemia, those who also had moderate to severe malnutrition had a twofold higher risk of dying compared to those who did not. It is therefore crucial to investigate acute malnutrition among severely anaemic children, as this might be treatable factor associated with high mortality