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.
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.
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.
Summary 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.
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.
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.
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.
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.
Typhoid fever caused by Salmonella enterica serovar Typhi (S. Typhi) remains a serious burden of disease, especially in developing countries of Asia and Africa. It is estimated that it causes 200,000 ...deaths per year, mainly in children. S. Typhi is an obligate pathogen of humans and although it has a relatively complex life cycle with a long lived carrier state, the absence of non-human hosts suggests that well targeted control methods should have a major impact on disease. Newer control methods including new generations of vaccines offer hope but their implementation would benefit from quantitative models to guide the most cost effective strategies. This paper presents a quantitative model of Typhoid disease, immunity and transmission as a first step in that process.
A stochastic agent-based model has been developed that incorporates known features of the biology of typhoid including probability of infection, the consequences of infection, treatment options, acquisition and loss of immunity as a result of infection and vaccination, the development of the carrier state and the impact of environmental or behavioral factors on transmission. The model has been parameterized with values derived where possible from the literature and where this was not possible, feasible parameters space has been determined by sensitivity analyses, fitting the simulations to age distribution of field data. The model is able to adequately predict the age distribution of typhoid in two settings.
The modeling highlights the importance of variations in the exposure/resistance of infants and young children to infection in different settings, especially as this impacts on design of control programs; it predicts that naturally induced clinical and sterile immunity to typhoid is long lived and highlights the importance of the carrier state especially in areas of low transmission.
Abstract
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/
.
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.
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.
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.
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.
Registered with The Pan African Clinical Trials Registry on 3 March 2016, trial number PACTR201604001501493.
Trials of intermittent preventive treatment in infants (IPTi) and children (IPTc) have shown promising results in reducing malaria episodes but with varying efficacy and cost-effectiveness. The ...effects of different intervention and setting characteristics are not well known. We simulate the effects of the different target age groups and delivery channels, seasonal or year-round delivery, transmission intensity, seasonality, proportions of malaria fevers treated and drug characteristics.
We use a dynamic, individual-based simulation model of Plasmodium falciparum malaria epidemiology, antimalarial drug action and case management to simulate DALYs averted and the cost per DALY averted by IPTi and IPTc. IPT cost components were estimated from economic studies alongside trials.
IPTi and IPTc were predicted to be cost-effective in most of the scenarios modelled. The cost-effectiveness is driven by the impact on DALYs, particularly for IPTc, and the low costs, particularly for IPTi which uses the existing delivery strategy, EPI. Cost-effectiveness was predicted to decrease with low transmission, badly timed seasonal delivery in a seasonal setting, short-acting and more expensive drugs, high frequencies of drug resistance and high levels of treatment of malaria fevers. Seasonal delivery was more cost-effective in seasonal settings, and year-round in constant transmission settings. The difference was more pronounced for IPTc than IPTi due to the different proportions of fixed costs and also different assumed drug spacing during the transmission season. The number of DALYs averted was predicted to decrease as a target five-year age-band for IPTc was shifted from children under 5 years into older ages, except at low transmission intensities.
Modelling can extend the information available by predicting impact and cost-effectiveness for scenarios, for outcomes and for multiple strategies where, for practical reasons, trials cannot be carried out. Both IPTi and IPTc are generally cost-effective but could be rendered cost-ineffective by characteristics of the setting, drug or implementation.
We report a major project to develop integrated mathematical models for predicting the epidemiologic and economic effects of malaria vaccines both at the individual and population level. The project ...has developed models of the within-host dynamics of Plasmodium falciparum that have been fitted to parasite density profiles from malaria therapy patients, and simulations of P. falciparum epidemiology fitted to field malariologic datasets from a large ensemble of settings across Africa. The models provide a unique platform for predicting both the short- and long-term effects of malaria vaccines on the burden of disease, allowing for the temporal dynamics of effects on immunity and transmission. We discuss how the models can be used to obtain robust cost-effectiveness estimates for a wide range of malaria vaccines and vaccination delivery strategies in different eco-epidemiologic settings. This paper outlines for a non-mathematical audience the approach we have taken and its underlying rationale.
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