The effect of community-driven larval source management and house improvement on malaria transmission when added to the standard malaria control strategies in Malawi: a cluster-randomized controlled trial.

BACKGROUND: Current standard interventions are not universally sufficient for malaria elimination. The effects of community-based house improvement (HI) and larval source management (LSM) as supplementary interventions to the Malawi National Malaria Control Programme (NMCP) interventions were assessed in the context of an intensive community engagement programme. METHODS: The study was a two-by-two factorial, cluster-randomized controlled trial in Malawi. Village clusters were randomly assigned to four arms: a control arm; HI; LSM; and HI + LSM. Malawi NMCP interventions and community engagement were used in all arms. Household-level, cross-sectional surveys were conducted on a rolling, 2-monthly basis to measure parasitological and entomological outcomes over 3 years, beginning with one baseline year. The primary outcome was the entomological inoculation rate (EIR). Secondary outcomes included mosquito density, Plasmodium falciparum prevalence, and haemoglobin levels. All outcomes were assessed based on intention to treat, and comparisons between trial arms were conducted at both cluster and household level. RESULTS: Eighteen clusters derived from 53 villages with 4558 households and 20,013 people were randomly assigned to the four trial arms. The mean nightly EIR fell from 0.010 infectious bites per person (95% CI 0.006-0.015) in the baseline year to 0.001 (0.000, 0.003) in the last year of the trial. Over the full trial period, the EIR did not differ between the four trial arms (p = 0.33). Similar results were observed for the other outcomes: mosquito density and P. falciparum prevalence decreased over 3 years of sampling, while haemoglobin levels increased; and there were minimal differences between the trial arms during the trial period. CONCLUSIONS: In the context of high insecticide-treated bed net use, neither community-based HI, LSM, nor HI + LSM contributed to further reductions in malaria transmission or prevalence beyond the reductions observed over two years across all four trial arms. This was the first trial, as far as the authors are aware, to test the potential complementary impact of LSM and/or HI beyond levels achieved by standard interventions. The unexpectedly low EIR values following intervention implementation indicated a promising reduction in malaria transmission for the area, but also limited the usefulness of this outcome for measuring differences in malaria transmission among the trial arms. Trial registration PACTR, PACTR201604001501493, Registered 3 March 2016, https://pactr.samrc.ac.za/ .

The WHO 2016 verbal autopsy instrument: An international standard suitable for automated analysis by InterVA, InSilicoVA, and Tariff 2.0.

BACKGROUND: Verbal autopsy (VA) is a practical method for determining probable causes of death at the population level in places where systems for medical certification of cause of death are weak. VA methods suitable for use in routine settings, such as civil registration and vital statistics (CRVS) systems, have developed rapidly in the last decade. These developments have been part of a growing global momentum to strengthen CRVS systems in low-income countries. With this momentum have come pressure for continued research and development of VA methods and the need for a single standard VA instrument on which multiple automated diagnostic methods can be developed. METHODS AND FINDINGS: In 2016, partners harmonized a WHO VA standard instrument that fully incorporates the indicators necessary to run currently available automated diagnostic algorithms. The WHO 2016 VA instrument, together with validated approaches to analyzing VA data, offers countries solutions to improving information about patterns of cause-specific mortality. This VA instrument offers the opportunity to harmonize the automated diagnostic algorithms in the future. CONCLUSIONS: Despite all improvements in design and technology, VA is only recommended where medical certification of cause of death is not possible. The method can nevertheless provide sufficient information to guide public health priorities in communities in which physician certification of deaths is largely unavailable. The WHO 2016 VA instrument, together with validated approaches to analyzing VA data, offers countries solutions to improving information about patterns of cause-specific mortality.

The effect of mass mosquito trapping on malaria transmission and disease burden (SolarMal): a stepped-wedge cluster-randomised trial.

BACKGROUND: Odour baits can attract host-seeking Anopheles mosquitoes indoors and outdoors. We assessed the effects of mass deployment of odour-baited traps on malaria transmission and disease burden. METHODS: We installed solar-powered odour-baited mosquito trapping systems (SMoTS) to households on Rusinga Island, Lake Victoria, western Kenya (mean population 24 879), in a stepped-wedge cluster-randomised trial. All residents in the completed health and demographic surveillance system were eligible to participate. We used the travelling salesman algorithm to assign all households to a cluster (50 or 51 geographically contiguous households); nine contiguous clusters formed a metacluster. Initially, no cluster had SMoTS (non-intervened). During the course of the intervention roll-out SMoTS were gradually installed cluster by cluster until all clusters had SMoTS installed (intervened). We generated 27 cluster randomisations, with the cluster as unit of randomisation, to establish the order to install the traps in the clusters until all had a SMoTS installed. Field workers and participants were not masked to group allocation. The primary outcome of clinical malaria was monitored through repeated household visits covering the entire population, once before roll-out (baseline) and five times throughout the 2-year roll-out. We measured clinical malaria as fever plus a positive result with a rapid diagnostic test. The SolarMal project was registered on the Dutch Trial Register (NTR 3496). FINDINGS: We enrolled 34 041 participants between April 25, 2012, and March 23, 2015, to 81 clusters and nine metaclusters. 4358 households were provided with SMoTS during roll-out between June 3, 2013, and May 16, 2015. 23 clinical malaria episodes were recorded in intervened clusters and 33 episodes in non-intervened clusters (adjusted effectiveness 40·8% [95% CI -172·8 to 87·1], p=0·5) during the roll-out. Malaria prevalence measured by rapid diagnostic test was 29·8% (95% CI 20·9-38·0) lower in SMoTS clusters (prevalence 23·7%; 1552 of 6550 people) than in non-intervened clusters (prevalence 34·5%; 2002 of 5795 people). INTERPRETATION: The unexpectedly low clinical incidence of malaria during roll-out led to an imprecise estimate of effectiveness from the clinical incidence data. The substantial effect on malaria prevalence is explained by reduction in densities of Anopheles funestus. Odour-baited traps might be an effective malaria intervention. FUNDING: COmON Foundation.

Assessment of the effect of larval source management and house improvement on malaria transmission when added to standard malaria control strategies in southern Malawi: study protocol for a cluster-randomised controlled trial.

BACKGROUND: Due to outdoor and residual transmission and insecticide resistance, long-lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) will be insufficient as stand-alone malaria vector control interventions in many settings as programmes shift toward malaria elimination. Combining additional vector control interventions as part of an integrated strategy would potentially overcome these challenges. Larval source management (LSM) and structural house improvements (HI) are appealing as additional components of an integrated vector management plan because of their long histories of use, evidence on effectiveness in appropriate settings, and unique modes of action compared to LLINs and IRS. Implementation of LSM and HI through a community-based approach could provide a path for rolling-out these interventions sustainably and on a large scale. METHODS/DESIGN: We will implement community-based LSM and HI, as additional interventions to the current national malaria control strategies, using a randomised block, 2 × 2 factorial, cluster-randomised design in rural, southern Malawi. These interventions will be continued for two years. The trial catchment area covers about 25,000 people living in 65 villages. Community participation is encouraged by training community volunteers as health animators, and supporting the organisation of village-level committees in collaboration with The Hunger Project, a non-governmental organisation. Household-level cross-sectional surveys, including parasitological and entomological sampling, will be conducted on a rolling, 2-monthly schedule to measure outcomes over two years (2016 to 2018). Coverage of LSM and HI will also be assessed throughout the trial area. DISCUSSION: Combining LSM and/or HI together with the interventions currently implemented by the Malawi National Malaria Control Programme is anticipated to reduce malaria transmission below the level reached by current interventions alone. Implementation of LSM and HI through a community-based approach provides an opportunity for optimum adaptation to the local ecological and social setting, and enhances the potential for sustainability. TRIAL REGISTRATION: Registered with The Pan African Clinical Trials Registry on 3 March 2016, trial number PACTR201604001501493.

Spatially variable risk factors for malaria in a geographically heterogeneous landscape, western Kenya: an explorative study.

BACKGROUND: Large reductions in malaria transmission and mortality have been achieved over the last decade, and this has mainly been attributed to the scale-up of long-lasting insecticidal bed nets and indoor residual spraying with insecticides. Despite these gains considerable residual, spatially heterogeneous, transmission remains. To reduce transmission in these foci, researchers need to consider the local demographical, environmental and social context, and design an appropriate set of interventions. Exploring spatially variable risk factors for malaria can give insight into which human and environmental characteristics play important roles in sustaining malaria transmission. METHODS: On Rusinga Island, western Kenya, malaria infection was tested by rapid diagnostic tests during two cross-sectional surveys conducted 3 months apart in 3632 individuals from 790 households. For all households demographic data were collected by means of questionnaires. Environmental variables were derived using Quickbird satellite images. Analyses were performed on 81 project clusters constructed by a traveling salesman algorithm, each containing 50-51 households. A standard linear regression model was fitted containing multiple variables to determine how much of the spatial variation in malaria prevalence could be explained by the demographic and environmental data. Subsequently, a geographically-weighted regression (GWR) was performed assuming non-stationarity of risk factors. Special attention was taken to investigate the effect of residual spatial autocorrelation and local multicollinearity. RESULTS: Combining the data from both surveys, overall malaria prevalence was 24%. Scan statistics revealed two clusters which had significantly elevated numbers of malaria cases compared to the background prevalence across the rest of the study area. A multivariable linear model including environmental and household factors revealed that higher socioeconomic status, outdoor occupation and population density were associated with increased malaria risk. The local GWR model improved the model fit considerably and the relationship of malaria with risk factors was found to vary spatially over the island; in different areas of the island socio-economic status, outdoor occupation and population density were found to be positively or negatively associated with malaria prevalence. DISCUSSION: Identification of risk factors for malaria that vary geographically can provide insight into the local epidemiology of malaria. Examining spatially variable relationships can be a helpful tool in exploring which set of targeted interventions could locally be implemented. Supplementary malaria control may be directed at areas, which are identified as at risk. For instance, areas with many people that work outdoors at night may need more focus in terms of vector control. TRIAL REGISTRATION: Trialregister.nl NTR3496-SolarMal, registered on 20 June 2012.

Asymptomatic Plasmodium falciparum infections may not be shortened by acquired immunity.

BACKGROUND: The duration of untreated Plasmodium falciparum infections is a defining characteristic of the parasite's biology. It is not clear whether naturally acquired immunity (NAI) can shorten infections, despite the potential implications for malaria control and elimination as well as for basic research. METHODS: Data on the presence of P. falciparum msp2 genotypes in six blood samples collected over one year was analysed, together with four samples collected over 1 week, from a cohort in Navrongo (Ghana). Mathematical models assuming either exponential, Weibull, gamma, or log-normal infection durations were estimated separately for six age-groups. The method allowed for varying clonal acquisition and detection rates. RESULTS: The best fitting (Weibull) mean durations were 124 days (children <5 years old), 179 days (5-9 years), and 70-90 days (>10 years). This non-monotonic age pattern is not suggestive of an infection-clearing effect of NAI since immunity increases with exposure, and thus, age. Age-related differences in innate immunity are a more plausible explanation. 21% of blood-stage infections terminated within 1 week, in stark contrast to months of persistence in infections induced in neuro-syphilis patients (malariatherapy data). Age independence in this percentage raises the possibility that this clearance may result from innate mechanisms or genetic incompatibility between hosts and parasites, rather than from NAI. CONCLUSION: In all ages of hosts a substantial proportion of infections are cleared in the first days or weeks of appearance in the blood, while others persist for many months. Although cumulative exposure and NAI increase with age, this does apparently not translate into an increased rate of termination of infections.

Distribution of malaria exposure in endemic countries in Africa considering country levels of effective treatment.

BACKGROUND: Malaria prevalence, clinical incidence, treatment, and transmission rates are dynamically interrelated. Prevalence is often considered a measure of malaria transmission, but treatment of clinical malaria reduces prevalence, and consequently also infectiousness to the mosquito vector and onward transmission. The impact of the frequency of treatment on prevalence in a population is generally not considered. This can lead to potential underestimation of malaria exposure in settings with good health systems. Furthermore, these dynamical relationships between prevalence, treatment, and transmission have not generally been taken into account in estimates of burden. METHODS: Using prevalence as an input, estimates of disease incidence and transmission [as the distribution of the entomological inoculation rate (EIR)] for Plasmodium falciparum have now been made for 43 countries in Africa using both empirical relationships (that do not allow for treatment) and OpenMalaria dynamic micro-simulation models (that explicitly include the effects of treatment). For each estimate, prevalence inputs were taken from geo-statistical models fitted for the year 2010 by the Malaria Atlas Project to all available observed prevalence data. National level estimates of the effectiveness of case management in treating clinical attacks were used as inputs to the estimation of both EIR and disease incidence by the dynamic models. RESULTS AND CONCLUSIONS: When coverage of effective treatment is taken into account, higher country level estimates of average EIR and thus higher disease burden, are obtained for a given prevalence level, especially where access to treatment is high, and prevalence relatively low. These methods provide a unified framework for comparison of both the immediate and longer-term impacts of case management and of preventive interventions.

Modelling the cost-effectiveness of mass screening and treatment for reducing Plasmodium falciparum malaria burden.

BACKGROUND: Past experience and modelling suggest that, in most cases, mass treatment strategies are not likely to succeed in interrupting Plasmodium falciparum malaria transmission. However, this does not preclude their use to reduce disease burden. Mass screening and treatment (MSAT) is preferred to mass drug administration (MDA), as the latter involves massive over-use of drugs. This paper reports simulations of the incremental cost-effectiveness of well-conducted MSAT campaigns as a strategy for P. falciparum malaria disease-burden reduction in settings with varying receptivity (ability of the combined vector population in a setting to transmit disease) and access to case management. METHODS: MSAT incremental cost-effectiveness ratios (ICERs) were estimated in different sub-Saharan African settings using simulation models of the dynamics of malaria and a literature-based MSAT cost estimate. Imported infections were simulated at a rate of two per 1,000 population per annum. These estimates were compared to the ICERs of scaling up case management or insecticide-treated net (ITN) coverage in each baseline health system, in the absence of MSAT. RESULTS: MSAT averted most episodes, and resulted in the lowest ICERs, in settings with a moderate level of disease burden. At a low pre-intervention entomological inoculation rate (EIR) of two infectious bites per adult per annum (IBPAPA) MSAT was never more cost-effective than scaling up ITNs or case management coverage. However, at pre-intervention entomological inoculation rates (EIRs) of 20 and 50 IBPAPA and ITN coverage levels of 40 or 60%, respectively, the ICER of MSAT was similar to that of scaling up ITN coverage further. CONCLUSIONS: In all the transmission settings considered, achieving a minimal level of ITN coverage is a "best buy". At low transmission, MSAT probably is not worth considering. Instead, MSAT may be suitable at medium to high levels of transmission and at moderate ITN coverage. If undertaken as a burden-reducing intervention, MSAT should be continued indefinitely and should complement, not replace, case management and vector control interventions.

Modeling the public health impact of malaria vaccines for developers and policymakers.

BACKGROUND: Efforts to develop malaria vaccines show promise. Mathematical model-based estimates of the potential demand, public health impact, and cost and financing requirements can be used to inform investment and adoption decisions by vaccine developers and policymakers on the use of malaria vaccines as complements to existing interventions. However, the complexity of such models may make their outputs inaccessible to non-modeling specialists. This paper describes a Malaria Vaccine Model (MVM) developed to address the specific needs of developers and policymakers, who need to access sophisticated modeling results and to test various scenarios in a user-friendly interface. The model's functionality is demonstrated through a hypothetical vaccine. METHODS: The MVM has three modules: supply and demand forecast; public health impact; and implementation cost and financing requirements. These modules include pre-entered reference data and also allow for user-defined inputs. The model includes an integrated sensitivity analysis function. Model functionality was demonstrated by estimating the public health impact of a hypothetical pre-erythrocytic malaria vaccine with 85% efficacy against uncomplicated disease and a vaccine efficacy decay rate of four years, based on internationally-established targets. Demand for this hypothetical vaccine was estimated based on historical vaccine implementation rates for routine infant immunization in 40 African countries over a 10-year period. Assumed purchase price was $5 per dose and injection equipment and delivery costs were $0.40 per dose. RESULTS: The model projects the number of doses needed, uncomplicated and severe cases averted, deaths and disability-adjusted life years (DALYs) averted, and cost to avert each. In the demonstration scenario, based on a projected demand of 532 million doses, the MVM estimated that 150 million uncomplicated cases of malaria and 1.1 million deaths would be averted over 10 years. This is equivalent to 943 uncomplicated cases and 7 deaths averted per 1,000 vaccinees. In discounted 2011 US dollars, this represents $11 per uncomplicated case averted and $1,482 per death averted. If vaccine efficacy were reduced to 75%, the estimated uncomplicated cases and deaths averted over 10 years would decrease by 14% and 19%, respectively. CONCLUSIONS: The MVM can provide valuable information to assist decision-making by vaccine developers and policymakers, information which will be refined and strengthened as field studies progress allowing further validation of modeling assumptions.

Negative pressure wound therapy with saline instillation: 131 patient case series.

Negative pressure wound therapy combined with timed, cyclical instillation (NPWTi) of topical wound solutions has been recently presented as a new adjunctive modality for treating wounds with signs of infection. Normal saline, antiseptics and antimicrobials all have been proposed in scientific and clinical studies as potentially effective when used with NPWTi for treating heavily infected wounds. This is a prospective clinical study of 131 patients with 131 wounds treated with NPWTi using saline between January 2012 and December 2012 in two orthopaedic centres and one surgical wound healing centre in France. Saline was exclusively used. Results were favourable: in 98% of the cases, the wounds could be closed after debridement and following the use of NPWTi. Mean duration of NPWTi was 12·19 days. This does not preclude the need for treating the biofilm appropriately with more active antibacterial products when biofilm has been documented.

Ensemble modeling of the likely public health impact of a pre-erythrocytic malaria vaccine.

BACKGROUND: The RTS,S malaria vaccine may soon be licensed. Models of impact of such vaccines have mainly considered deployment via the World Health Organization's Expanded Programme on Immunization (EPI) in areas of stable endemic transmission of Plasmodium falciparum, and have been calibrated for such settings. Their applicability to low transmission settings is unclear. Evaluations of the efficiency of different deployment strategies in diverse settings should consider uncertainties in model structure. METHODS AND FINDINGS: An ensemble of 14 individual-based stochastic simulation models of P. falciparum dynamics, with differing assumptions about immune decay, transmission heterogeneity, and treatment access, was constructed. After fitting to an extensive library of field data, each model was used to predict the likely health benefits of RTS,S deployment, via EPI (with or without catch-up vaccinations), supplementary vaccination of school-age children, or mass vaccination every 5 y. Settings with seasonally varying transmission, with overall pre-intervention entomological inoculation rates (EIRs) of two, 11, and 20 infectious bites per person per annum, were considered. Predicted benefits of EPI vaccination programs over the simulated 14-y time horizon were dependent on duration of protection. Nevertheless, EPI strategies (with an initial catch-up phase) averted the most deaths per dose at the higher EIRs, although model uncertainty increased with EIR. At two infectious bites per person per annum, mass vaccination strategies substantially reduced transmission, leading to much greater health effects per dose, even at modest coverage. CONCLUSIONS: In higher transmission settings, EPI strategies will be most efficient, but vaccination additional to the EPI in targeted low transmission settings, even at modest coverage, might be more efficient than national-level vaccination of infants. The feasibility and economics of mass vaccination, and the circumstances under which vaccination will avert epidemics, remain unclear. The approach of using an ensemble of models provides more secure conclusions than a single-model approach, and suggests greater confidence in predictions of health effects for lower transmission settings than for higher ones.

Selection of mosquito life-histories: a hidden weapon against malaria?

BACKGROUND: There has recently been a substantial decline in malaria incidence in much of Africa. While the decline can clearly be linked to increasing coverage of mosquito vector control interventions and effective drug treatment in most settings, the ubiquity of reduction raises the possibility that additional ecological and associated evolutionary changes may be reinforcing the effectiveness of current vector control strategies in previously unanticipated ways. PRESENTATION OF HYPOTHESIS: Here it is hypothesized that the increasing coverage of insecticide-treated bed nets and other vector control methods may be driving selection for a shift in mosquito life history that reduces their ability to transmit malaria parasites. Specifically it is hypothesized that by substantially increasing the extrinsic rate of mortality experienced in vector populations, these interventions are creating a fitness incentive for mosquitoes to re-allocate their resources towards greater short-term reproduction at the expense of longer-term survival. As malaria transmission is fundamentally dependent on mosquito survival, a life history shift in this direction would greatly benefit control. TESTING THE HYPOTHESIS: At present, direct evaluation of this hypothesis within natural vector populations presents several logistical and methodological challenges. In the meantime, many insights can be gained from research previously conducted on wild Drosophila populations. Long-term selection experiments on these organisms suggest that increasing extrinsic mortality by a magnitude similar to that anticipated from the up-scaling of vector control measures generated an increase in their intrinsic mortality rate. Although this increase was small, a change of similar magnitude in Anopheles vector populations would be predicted to reduce malaria transmission by 80%. IMPLICATIONS OF HYPOTHESIS: The hypothesis presented here provides a reminder that evolutionary processes induced by interventions against disease vectors may not always act to neutralize intervention effectiveness. In the search for new intervention strategies, consideration should be given to both the potential disadvantages and advantages of evolutionary processes resulting from their implementation, and attempts made to exploit those with greatest potential to enhance control.

Robot-assisted free toe pulp transfer: feasibility study.

The current tendency of microsurgery is heading toward supermicrosurgery and microsurgery assisted by robotics. The aim of this work was to study the feasibility of a free hallux hemipulp transfer with a surgical robot in a cadaveric model. We used a human body. The intervention was realized by a Da Vinci SI® robot (Intuitive Surgical™, Sunnyvale, CA) in two stages: first taking off the medial hallux hemipulp, then transferring the hallux hemipulp to the radial thumb hemipulp. The intervention lasted 1 hour 59 minutes, exclusively with the Da Vinci SI® robot, without any interruption or outside intervention. Despite the absence of sensory feedback and an intervention 25% longer than in conventional microsurgery, we have demonstrated the feasibility of free hallux hemipulp transfer with a surgical robot. In the future, it is likely that the added benefits of the robot (physiological tremor suppression, user-friendly ergonomics, ultraprecise control of the instruments) will make the robot an indispensable tool for the surgeon.

Cost-effectiveness of the introduction of a pre-erythrocytic malaria vaccine into the expanded program on immunization in sub-Saharan Africa: analysis of uncertainties using a stochastic individual-based simulation model of Plasmodium falciparum malaria.

OBJECTIVE: To evaluate the cost-effectiveness of introducing the RTS,S malaria vaccine into the Expanded Programme on Immunization (EPI) in Sub-Saharan Africa (SSA), the contributions of different sources of uncertainty, and the associated expected value of perfect information (EVPI). METHODS: Vaccination was simulated in populations of 100,000 people at 10 different entomological inoculation rates (EIRs), using an existing stochastic model and a 10-year time horizon. Incremental cost-effectiveness ratios (ICERs) and EVPI were computed from weighted averages of outputs using two different assignments of the EIR distribution in 2007. Uncertainty was evaluated by resampling of epidemiological, vaccination, and health systems model parameters. RESULTS: Health benefits were predicted consistently only at low transmission, and program costs always substantially exceeded case management savings. Optimal cost-effectiveness was at EIR of about 10 infectious bites per annum (ibpa). Main contributors to ICER uncertainty were uncertainty in transmission intensity, price per vaccine dose, decay rate of the vaccine effect, degree of homogeneity in host response, and some epidemiological model parameters. Other health system costs were unimportant. With a ceiling ratio of 207 international dollars per disability-adjusted life-year averted, 52.4% of parameterizations predicted cost-effectiveness in the primary analysis. CONCLUSIONS: Cost-effectiveness of RTS,S will be maximal in low endemicity settings (EIR 2-20 ibpa). Widespread deployment of other transmission-reducing interventions will thus improve cost-effectiveness, suggesting a selective introduction strategy. EVPI is substantial. Accrual of up-to-date information on local endemicity to guide deployment decisions would be highly efficient.

Simulation of the cost-effectiveness of malaria vaccines.

BACKGROUND: A wide range of possible malaria vaccines is being considered and there is a need to identify which vaccines should be prioritized for clinical development. An important element of the information needed for this prioritization is a prediction of the cost-effectiveness of potential vaccines in the transmission settings in which they are likely to be deployed. This analysis needs to consider a range of delivery modalities to ensure that clinical development plans can be aligned with the most appropriate deployment strategies. METHODS: The simulations are based on a previously published individual-based stochastic model for the natural history and epidemiology of Plasmodium falciparum malaria. Three different vaccine types: pre-erythrocytic vaccines (PEV), blood stage vaccines (BSV), mosquito-stage transmission-blocking vaccines (MSTBV), and combinations of these, are considered each delivered via a range of delivery modalities (Expanded Programme of Immunization - EPI-, EPI with booster, and mass vaccination combined with EPI). The cost-effectiveness ratios presented are calculated for four health outcomes, for assumed vaccine prices of US$ 2 or US$ 10 per dose, projected over a 10-year period. RESULTS: The simulations suggest that PEV will be more cost-effective in low transmission settings, while BSV at higher transmission settings. Combinations of BSV and PEV are more efficient than PEV, especially in moderate to high transmission settings, while compared to BSV they are more cost-effective in moderate to low transmission settings. Combinations of MSTBV and PEV or PEV and BSV improve the effectiveness and the cost-effectiveness compared to PEV and BSV alone only when applied with EPI and mass vaccinations. Adding booster doses to the EPI is unlikely to be a cost-effective alternative to delivering vaccines via the EPI for any vaccine, while mass vaccination improves effectiveness, especially in low transmission settings, and is often a more efficient alternative to the EPI. However, the costs of increasing the coverage of mass vaccination over 50% often exceed the benefits. CONCLUSION: The simulations indicate malaria vaccines might be efficient malaria control interventions, and that both transmission setting and vaccine delivery modality are important to their cost-effectiveness. Alternative vaccine delivery modalities to the EPI may be more efficient than the EPI. Mass vaccination is predicted to provide substantial health benefits at low additional costs, although achieving high coverage rates can lead to substantial incremental costs.

Influenza vaccination of pregnant women: Engaging clinicians to reduce missed opportunities for vaccination.

BACKGROUND: Antenatal influenza vaccination (AIV) is an effective intervention for protecting pregnant women and their newborns against influenza. Although the World Health Organization recommends AIV at any stage of pregnancy, in low- and middle-income countries, including India, it is rarely provided. Research suggests that antenatal care (ANC) provider practices explain much of this limited coverage. Our study in urban Pune, India, assessed the feasibility of a two-stage clinician-engagement strategy to reduce missed opportunities for AIV in urban private-practice ANC clinics. METHODS: Clinicians were randomized to intervention and control groups in slum and middle-class study sites. Intervention-group clinicians (active clinicians) were assessed on vaccination-related views and practices, and were presented with authoritative AIV recommendations from global, academic and professional medical organizations. In a second meeting after a community survey, findings concerning vaccination-related views and experiences were explained to active clinicians. Assessments of community vaccination views were not provided to control-group clinicians. Both groups maintained logs of ANC clinic visit vaccination status throughout the 11-month study period to enable identification of missed and taken opportunities for vaccination. Analyses were restricted to visits of women in their third trimester without previous AIV in the current pregnancy. RESULTS: Overall, 30 clinicians participated. After first and second interactions, active clinicians in middle-class communities vaccinated at 12.2% and 37.8%, respectively. Middle-class control clinicians vaccinated at <0.2% throughout the study. This difference in AIV taken opportunities between middle-class active and control clinics was statistically significant (p < 0.05) after first and second interactions. In slum-community sites, active clinicians' AIV activity was minimal throughout. CONCLUSIONS: Our approach for engaging clinicians effectively reduced missed opportunities for AIV in urban middle-class settings of Pune. It may also improve maternal vaccination for other conditions. The absence of any similar effect in slum-based clinics likely reflects critical limitations of vaccine access.

Assessing the population coverage of a health demographic surveillance system using satellite imagery and crowd-sourcing.

Remotely sensed data can serve as an independent source of information about the location of residential structures in areas under demographic and health surveillance. We report on results obtained combining satellite imagery, imported from Bing, with location data routinely collected using the built-in GPS sensors of tablet computers, to assess completeness of population coverage in a Health and Demographic Surveillance System in Malawi. The Majete Malaria Project Health and Demographic Surveillance System, in Malawi, started in 2014 to support a project with the aim of studying the reduction of malaria using an integrated control approach by rolling out insecticide treated nets and improved case management supplemented with house improvement and larval source management. In order to support the monitoring of the trial a Health and Demographic Surveillance System was established in the area that surrounds the Majete Wildlife Reserve (1600 km2), using the OpenHDS data system. We compared house locations obtained using GPS recordings on mobile devices during the demographic surveillance census round with those acquired from satellite imagery. Volunteers were recruited through the crowdcrafting.org platform to identify building structures on the images, which enabled the compilation of a database with coordinates of potential residences. For every building identified on these satellite images by the volunteers (11,046 buildings identified of which 3424 (ca. 30%) were part of the censused area), we calculated the distance to the nearest house enumerated on the ground by fieldworkers during the census round of the HDSS. A random sample of buildings (85 structures) identified on satellite images without a nearby location enrolled in the census were visited by a fieldworker to determine how many were missed during the baseline census survey, if any were missed. The findings from this ground-truthing effort suggest that a high population coverage was achieved in the census survey, however the crowd-sourcing did not locate many of the inhabited structures (52.3% of the 6543 recorded during the census round). We conclude that using auxiliary data can play a useful role in quality assurance in population based health surveillance, but improved algorithms would be needed if crowd-sourced house locations are to be used as the basis of population databases.

Do surveys with paper and electronic devices differ in quality and cost? Experience from the Rufiji Health and demographic surveillance system in Tanzania.

BACKGROUND: Data entry at the point of collection using mobile electronic devices may make data-handling processes more efficient and cost-effective, but there is little literature to document and quantify gains, especially for longitudinal surveillance systems. OBJECTIVE: To examine the potential of mobile electronic devices compared with paper-based tools in health data collection. METHODS: Using data from 961 households from the Rufiji Household and Demographic Survey in Tanzania, the quality and costs of data collected on paper forms and electronic devices were compared. We also documented, using qualitative approaches, field workers, whom we called 'enumerators', and households' members on the use of both methods. Existing administrative records were combined with logistics expenditure measured directly from comparison households to approximate annual costs per 1,000 households surveyed. RESULTS: Errors were detected in 17% (166) of households for the paper records and 2% (15) for the electronic records (p < 0.001). There were differences in the types of errors (p = 0.03). Of the errors occurring, a higher proportion were due to accuracy in paper surveys (79%, 95% CI: 72%, 86%) compared with electronic surveys (58%, 95% CI: 29%, 87%). Errors in electronic surveys were more likely to be related to completeness (32%, 95% CI 12%, 56%) than in paper surveys (11%, 95% CI: 7%, 17%).The median duration of the interviews ('enumeration'), per household was 9.4 minutes (90% central range 6.4, 12.2) for paper and 8.3 (6.1, 12.0) for electronic surveys (p = 0.001). Surveys using electronic tools, compared with paper-based tools, were less costly by 28% for recurrent and 19% for total costs. Although there were technical problems with electronic devices, there was good acceptance of both methods by enumerators and members of the community. CONCLUSIONS: Our findings support the use of mobile electronic devices for large-scale longitudinal surveys in resource-limited settings.

Integrating community-based verbal autopsy into civil registration and vital statistics (CRVS): system-level considerations.

BACKGROUND: Reliable and representative cause of death (COD) statistics are essential to inform public health policy, respond to emerging health needs, and document progress towards Sustainable Development Goals. However, less than one-third of deaths worldwide are assigned a cause. Civil registration and vital statistics (CRVS) systems in low- and lower-middle-income countries are failing to provide timely, complete and accurate vital statistics, and it will still be some time before they can provide physician-certified COD for every death. Proposals: Verbal autopsy (VA) is a method to ascertain the probable COD and, although imperfect, it is the best alternative in the absence of medical certification. There is extensive experience with VA in research settings but only a few examples of its use on a large scale. Data collection using electronic questionnaires on mobile devices and computer algorithms to analyse responses and estimate probable COD have increased the potential for VA to be routinely applied in CRVS systems. However, a number of CRVS and health system integration issues should be considered in planning, piloting and implementing a system-wide intervention such as VA. These include addressing the multiplicity of stakeholders and sub-systems involved, integration with existing CRVS work processes and information flows, linking VA results to civil registration records, information technology requirements and data quality assurance. CONCLUSIONS: Integrating VA within CRVS systems is not simply a technical undertaking. It will have profound system-wide effects that should be carefully considered when planning for an effective implementation. This paper identifies and discusses the major system-level issues and emerging practices, provides a planning checklist of system-level considerations and proposes an overview for how VA can be integrated into routine CRVS systems.

An epidemiologic model of severe morbidity and mortality caused by Plasmodium falciparum.

The intensity of Plasmodium falciparum transmission has multifarious and sometimes counter-intuitive effects on age-specific rates of severe morbidity and mortality in endemic areas. This has led to conflicting speculations about the likely impact of malaria control interventions. We propose a quantitative framework to reconcile the various apparently contradictory observations relating morbidity and mortality rates to malaria transmission. Our model considers two sub-categories of severe malaria episodes. These comprise episodes with extremely high parasite densities in hosts with little previous exposure, and acute malaria episodes accompanied by co-morbidity or other risk factors enhancing susceptibility. In addition to direct malaria mortality from severe malaria episodes, the model also considers the enhanced risk of indirect mortality following acute episodes accompanied by co-morbidity after the parasites have been cleared. We fit this model to summaries of field data from endemic areas of Africa, and show that it can account for the observed age- and exposure-specific patterns of pediatric severe malaria and malaria-associated mortality in children. This model will allow us to make predictions of the long-term impact of potential malaria interventions. Predictions for children will be more reliable than those for older people because there is a paucity of epidemiologic studies of adults and adolescents.