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

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

Collateral-flow measurements in humans by myocardial contrast echocardiography: validation of coronary pressure-derived collateral-flow assessment

AIMS: Myocardial blood flow (MBF) is the gold standard to assess myocardial blood supply and, as recently shown, can be obtained by myocardial contrast echocardiography (MCE). The aims of this human study are (i) to test whether measurements of collateral-derived MBF by MCE are feasible during elective angioplasty and (ii) to validate the concept of pressure-derived collateral-flow assessment. METHODS AND RESULTS: Thirty patients with stable coronary artery disease underwent MCE of the collateral-receiving territory during and after angioplasty of 37 stenoses. MCE perfusion analysis was successful in 32 cases. MBF during and after angioplasty varied between 0.060-0.876 mL min(-1) g(-1) (0.304+/-0.196 mL min(-1) g(-1)) and 0.676-1.773 mL min(-1) g(-1) (1.207+/-0.327 mL min(-1) g(-1)), respectively. Collateral-perfusion index (CPI) is defined as the rate of MBF during and after angioplasty varied between 0.05 and 0.67 (0.26+/-0.15). During angioplasty, simultaneous measurements of mean aortic pressure, coronary wedge pressure, and central venous pressure determined the pressure-derived collateral-flow index (CFI(p)), which varied between 0.04 and 0.61 (0.23+/-0.14). Linear-regression analysis demonstrated an excellent agreement between CFI(p) and CPI (y=0.88 x +0.01; r(2)=0.92; P<0.0001). CONCLUSION: Collateral-derived MBF measurements by MCE during angioplasty are feasible and proved that the pressure-derived CFI exactly reflects collateral relative to normal myocardial perfusion in humans

Cost of community-led larval source management and house improvement for malaria control: a cost analysis within a cluster-randomized trial in a rural district in Malawi

Background House improvement (HI) to prevent mosquito house entry, and larval source management (LSM) targeting aquatic mosquito stages to prevent development into adult forms, are promising complementary interventions to current malaria vector control strategies. Lack of evidence on costs and cost-effectiveness of community-led implementation of HI and LSM has hindered wide-scale adoption. This study presents an incremental cost analysis of community-led implementation of HI and LSM, in a cluster-randomized, factorial design trial, in addition to standard national malaria control interventions in a rural area (25,000 people), in southern Malawi. Methods In the trial, LSM comprised draining, filling, and Bacillus thuringiensis israelensis-based larviciding, while house improvement (henceforth HI) involved closing of eaves and gaps on walls, screening windows/ventilation spaces with wire mesh, and doorway modifications. Communities implemented all interventions. Costs were estimated retrospectively using the ‘ingredients approach’, combining ‘bottom-up’ and ‘top-down approaches’, from the societal perspective. To estimate the cost of independently implementing each intervention arm, resources shared between trial arms (e.g. overheads) were allocated to each consuming arm using proxies developed based on share of resource input quantities consumed. Incremental implementation costs (in 2017 US$) are presented for HI-only, LSM-only and HI + LSM arms. In sensitivity analyses, the effect of varying costs of important inputs on estimated costs was explored. Results The total economic programme costs of community-led HI and LSM implementation was$626,152. Incremental economic implementation costs of HI, LSM and HI + LSM were estimated as $27.04,$25.06 and $33.44, per person per year, respectively. Project staff, transport and labour costs, but not larvicide or screening material, were the major cost drivers across all interventions. Costs were sensitive to changes in staff costs and population covered. Conclusions In the trial, the incremental economic costs of community-led HI and LSM implementation were high compared to previous house improvement and LSM studies. Several factors, including intervention design, year-round LSM implementation and low human population density could explain the high costs. The factorial trial design necessitated use of proxies to allocate costs shared between trial arms, which limits generalizability where different designs are used. Nevertheless, costs may inform planners of similar intervention packages where cost-effectiveness is known

Procjena mikrostrukture alatnog čelika za hladni rad nakon pretaljivanja pulsirajućim laserom

The aim of this study is the investigation of micro-structural behaviour of a Mat. No. 1.2379 (EN-X160CrMoV121; AISI D2) cold work tool steel after remelting with a precise pulsed Nd:YAG laser. The investigated steel is one of the most hard to weld tool steels, due to large amount of alloying elements. The analysis was done on single spots remelted with specific laser pulse shape and parameters, assuring crack-less solidification. Re-solidifi ed areas were investigated with microscopy, hardness measurements, X-ray spectroscopy and diffraction method. Laser treatment causes rapid solidification leading into a formation of a fine dendritic microstructures containing high amount of retained austenite causing a significant decrease of hardness.Namjena ove studije je ispitivanje ponašanja mikro strukture alatnoga čelika za rad na hladno Mat. No.1.2379 (ENX160CrMoV121; AISI D2) po pretaljivanju s preciznim pulsiranim Nd:YAG laserom. Zbog velike količine legirnih elemenata istraživani materijal spada u grupu vrlo teško zavarljivih alatnih čelika. Analiza je provedena na pojedinim pretaljenim točkama korištenjem specifi čnog oblika i parametara laserskog impulsa koji osiguravaju skrućivanje bez pukotina. Pretaljena područja su ispitivana mikroskopom, mjerenjem mikro tvrdoće, rendgenskom spektroskopijom i defrakcijskom metodom. Tretman laserom uzrokvao je brzo skrućivanje koja dovodi do formiranja fi ne dendritičke strukture s velikim udjelom zaostalog austenita što uzrokuje bitno smanjivanje tvrdoće

Combining malaria vaccination with chemoprevention: a promising new approach to malaria control.

Malaria control has stalled in a number of African countries and novel approaches to malaria control are needed for these areas. The encouraging results of a recent trial conducted in young children in Burkina Faso and Mali in which a combination of the RTS,S/AS01E malaria vaccine and seasonal malaria chemoprevention led to a substantial reduction in clinical cases of malaria, severe malaria, and malaria deaths compared with the administration of either intervention given alone suggests that there may be other epidemiological/clinical situations in which a combination of malaria vaccination and chemoprevention could be beneficial. Some of these potential opportunities are considered in this paper. These include combining vaccination with intermittent preventive treatment of malaria in infants, with intermittent preventive treatment of malaria in pregnancy (through vaccination of women of child-bearing age before or during pregnancy), or with post-discharge malaria chemoprevention in the management of children recently admitted to hospital with severe anaemia. Other potential uses of the combination are prevention of malaria in children at particular risk from the adverse effects of clinical malaria, such as those with sickle cell disease, and during the final stages of a malaria elimination programme when vaccination could be combined with repeated rounds of mass drug administration. The combination of a pre-erythrocytic stage malaria vaccine with an effective chemopreventive regimen could make a valuable contribution to malaria control and elimination in a variety of clinical or epidemiological situations, and the potential of this approach to malaria control needs to be explored