20 research outputs found
Entomological outcomes of cluster-randomised, community-driven dengue vector-suppression interventions in Kampong Cham province, Cambodia
Cambodia has one of the highest dengue infection rates in Southeast Asia. Here we report quantitative entomological results of a large-scale cluster-randomised trial assessing the impact on vector populations of a package of vector control interventions including larvivorous guppy fish in household water containers, mosquito trapping with gravid-ovitraps, solid waste management, breeding-container coverage through community education and engagement for behavioural change, particularly through the participation of school children. These activities resulted in major reductions in Container Index, House Index, Breteau Index, Pupal Index and Adult Index (all p-values 0.002 or lower) in the Intervention Arm compared with the Control Arm in a series of household surveys conducted over a follow-up period of more than one year, although the project was not able to measure the longer-term sustainability of the interventions. Despite comparative reductions in Adult Index between the study arms, the Adult Index was higher in the Intervention Arm in the final household survey than in the first household survey. This package of biophysical and community engagement interventions was highly effective in reducing entomological indices for dengue compared with the control group, but caution is required in extrapolating the reduction in household Adult Index to a reduction in the overall population of adult Aedes mosquitoes, and in interpreting the relationship between a reduction in entomological indices and a reduction in the number of dengue cases. The package of interventions should be trialled in other locations
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The inclusion of diagnostics in national health insurance schemes in Cambodia, India, Indonesia, Nepal, Pakistan, Philippines and Viet Nam
The Lancet Commission on Diagnostics highlighted a huge gap in access to diagnostic testing even for basic tests, particularly at the primary care level, and emphasised the need for countries to include diagnostics as part of their universal health coverage benefits packages. Despite the poor state of diagnostic-related services in low-income and middle-income countries (LMICs), little is known about the extent to which diagnostics are included in the health benefit packages. We conducted an analysis of seven Asian LMICs - Cambodia, India, Indonesia, Nepal, Pakistan, Philippines, Viet Nam - to understand this issue. We conducted a targeted review of relevant literature and applied a health financing framework to analyse the benefit packages available in each government-sponsored scheme. We found considerable heterogeneity in country approaches to diagnostics. Of the seven countries, only India has developed a national essential diagnostics list. No country presented a clear policy rationale on the inclusion of diagnostics in their scheme and the level of detail on the specific diagnostics which are covered under the schemes was also generally lacking. Government-sponsored insurance expansion in the eligible populations has reduced the out-of-pocket health payment burden in many of the countries but overall, there is a lack of access, availability and affordability for diagnostic-related services
Entomological outcomes of clusterrandomised, community-driven dengue vector-suppression interventions in Kampong Cham province, Cambodia
Cambodia has one of the highest dengue infection rates in Southeast Asia. Here we report
quantitative entomological results of a large-scale cluster-randomised trial assessing the
impact on vector populations of a package of vector control interventions including larvivorous guppy fish in household water containers, mosquito trapping with gravid-ovitraps, solid
waste management, breeding-container coverage through community education and
engagement for behavioural change, particularly through the participation of school children. These activities resulted in major reductions in Container Index, House Index, Breteau
Index, Pupal Index and Adult Index (all p-values 0.002 or lower) in the Intervention Arm compared with the Control Arm in a series of household surveys conducted over a follow-up
period of more than one year, although the project was not able to measure the longer-term
sustainability of the interventions. Despite comparative reductions in Adult Index between
the study arms, the Adult Index was higher in the Intervention Arm in the final household survey than in the first household survey. This package of biophysical and community engagement interventions was highly effective in reducing entomological indices for dengue
compared with the control group, but caution is required in extrapolating the reduction in
household Adult Index to a reduction in the overall population of adult Aedes mosquitoes,
and in interpreting the relationship between a reduction in entomological indices and a
reduction in the number of dengue cases. The package of interventions should be trialled in
other locations.The WHO Special Programme for Research and Training in Tropical Diseases (TDR).https://journals.plos.org/plosntdsdm2022UP Centre for Sustainable Malaria Control (UP CSMC
Antibody tests for identification of current and past infection with SARS-CoV-2
Background
The diagnostic challenges associated with the COVIDâ19 pandemic resulted in rapid development of diagnostic test methods for detecting SARSâCoVâ2 infection. Serology tests to detect the presence of antibodies to SARSâCoVâ2 enable detection of past infection and may detect cases of SARSâCoVâ2 infection that were missed by earlier diagnostic tests. Understanding the diagnostic accuracy of serology tests for SARSâCoVâ2 infection may enable development of effective diagnostic and management pathways, inform public health management decisions and understanding of SARSâCoVâ2 epidemiology.
Objectives
To assess the accuracy of antibody tests, firstly, to determine if a person presenting in the community, or in primary or secondary care has current SARSâCoVâ2 infection according to time after onset of infection and, secondly, to determine if a person has previously been infected with SARSâCoVâ2. Sources of heterogeneity investigated included: timing of test, test method, SARSâCoVâ2 antigen used, test brand, and reference standard for nonâSARSâCoVâ2 cases.
Search methods
The COVIDâ19 Open Access Project living evidence database from the University of Bern (which includes daily updates from PubMed and Embase and preprints from medRxiv and bioRxiv) was searched on 30 September 2020. We included additional publications from the Evidence for Policy and Practice Information and Coâordinating Centre (EPPIâCentre) âCOVIDâ19: Living map of the evidenceâ and the Norwegian Institute of Public Health âNIPH systematic and living map on COVIDâ19 evidenceâ. We did not apply language restrictions.
Selection criteria
We included test accuracy studies of any design that evaluated commercially produced serology tests, targeting IgG, IgM, IgA alone, or in combination. Studies must have provided data for sensitivity, that could be allocated to a predefined time period after onset of symptoms, or after a positive RTâPCR test. Small studies with fewer than 25 SARSâCoVâ2 infection cases were excluded. We included any reference standard to define the presence or absence of SARSâCoVâ2 (including reverse transcription polymerase chain reaction tests (RTâPCR), clinical diagnostic criteria, and preâpandemic samples).
Data collection and analysis
We use standard screening procedures with three reviewers. Quality assessment (using the QUADASâ2 tool) and numeric study results were extracted independently by two people. Other study characteristics were extracted by one reviewer and checked by a second. We present sensitivity and specificity with 95% confidence intervals (CIs) for each test and, for metaâanalysis, we fitted univariate randomâeffects logistic regression models for sensitivity by eligible time period and for specificity by reference standard group. Heterogeneity was investigated by including indicator variables in the randomâeffects logistic regression models. We tabulated results by test manufacturer and summarised results for tests that were evaluated in 200 or more samples and that met a modification of UK Medicines and Healthcare products Regulatory Agency (MHRA) target performance criteria.
Main results
We included 178 separate studies (described in 177 study reports, with 45 as preâprints) providing 527 test evaluations. The studies included 64,688 samples including 25,724 from people with confirmed SARSâCoVâ2; most compared the accuracy of two or more assays (102/178, 57%). Participants with confirmed SARSâCoVâ2 infection were most commonly hospital inpatients (78/178, 44%), and preâpandemic samples were used by 45% (81/178) to estimate specificity. Over twoâthirds of studies recruited participants based on known SARSâCoVâ2 infection status (123/178, 69%). All studies were conducted prior to the introduction of SARSâCoVâ2 vaccines and present data for naturally acquired antibody responses. Seventyânine percent (141/178) of studies reported sensitivity by week after symptom onset and 66% (117/178) for convalescent phase infection. Studies evaluated enzymeâlinked immunosorbent assays (ELISA) (165/527; 31%), chemiluminescent assays (CLIA) (167/527; 32%) or lateral flow assays (LFA) (188/527; 36%).
Risk of bias was high because of participant selection (172, 97%); application and interpretation of the index test (35, 20%); weaknesses in the reference standard (38, 21%); and issues related to participant flow and timing (148, 82%). We judged that there were high concerns about the applicability of the evidence related to participants in 170 (96%) studies, and about the applicability of the reference standard in 162 (91%) studies.
Average sensitivities for current SARSâCoVâ2 infection increased by week after onset for all target antibodies. Average sensitivity for the combination of either IgG or IgM was 41.1% in week one (95% CI 38.1 to 44.2; 103 evaluations; 3881 samples, 1593 cases), 74.9% in week two (95% CI 72.4 to 77.3; 96 evaluations, 3948 samples, 2904 cases) and 88.0% by week three after onset of symptoms (95% CI 86.3 to 89.5; 103 evaluations, 2929 samples, 2571 cases). Average sensitivity during the convalescent phase of infection (up to a maximum of 100 days since onset of symptoms, where reported) was 89.8% for IgG (95% CI 88.5 to 90.9; 253 evaluations, 16,846 samples, 14,183 cases), 92.9% for IgG or IgM combined (95% CI 91.0 to 94.4; 108 evaluations, 3571 samples, 3206 cases) and 94.3% for total antibodies (95% CI 92.8 to 95.5; 58 evaluations, 7063 samples, 6652 cases). Average sensitivities for IgM alone followed a similar pattern but were of a lower test accuracy in every time slot.
Average specificities were consistently high and precise, particularly for preâpandemic samples which provide the least biased estimates of specificity (ranging from 98.6% for IgM to 99.8% for total antibodies).
Subgroup analyses suggested small differences in sensitivity and specificity by test technology however heterogeneity in study results, timing of sample collection, and smaller sample numbers in some groups made comparisons difficult. For IgG, CLIAs were the most sensitive (convalescentâphase infection) and specific (preâpandemic samples) compared to both ELISAs and LFAs (P < 0.001 for differences across test methods). The antigen(s) used (whether from the Spikeâprotein or nucleocapsid) appeared to have some effect on average sensitivity in the first weeks after onset but there was no clear evidence of an effect during convalescentâphase infection.
Investigations of test performance by brand showed considerable variation in sensitivity between tests, and in results between studies evaluating the same test. For tests that were evaluated in 200 or more samples, the lower bound of the 95% CI for sensitivity was 90% or more for only a small number of tests (IgG, n = 5; IgG or IgM, n = 1; total antibodies, n = 4). More test brands met the MHRA minimum criteria for specificity of 98% or above (IgG, n = 16; IgG or IgM, n = 5; total antibodies, n = 7). Seven assays met the specified criteria for both sensitivity and specificity.
In a lowâprevalence (2%) setting, where antibody testing is used to diagnose COVIDâ19 in people with symptoms but who have had a negative PCR test, we would anticipate that 1 (1 to 2) case would be missed and 8 (5 to 15) would be falsely positive in 1000 people undergoing IgG or IgM testing in week three after onset of SARSâCoVâ2 infection.
In a seroprevalence survey, where prevalence of prior infection is 50%, we would anticipate that 51 (46 to 58) cases would be missed and 6 (5 to 7) would be falsely positive in 1000 people having IgG tests during the convalescent phase (21 to 100 days postâsymptom onset or postâpositive PCR) of SARSâCoVâ2 infection.
Authors' conclusions
Some antibody tests could be a useful diagnostic tool for those in whom molecularâ or antigenâbased tests have failed to detect the SARSâCoVâ2 virus, including in those with ongoing symptoms of acute infection (from week three onwards) or those presenting with postâacute sequelae of COVIDâ19. However, antibody tests have an increasing likelihood of detecting an immune response to infection as time since onset of infection progresses and have demonstrated adequate performance for detection of prior infection for seroâepidemiological purposes. The applicability of results for detection of vaccinationâinduced antibodies is uncertain
Entomological outcomes of cluster-randomised, community-driven dengue vector-suppression interventions in Kampong Cham province, Cambodia
Dengue is a steadily escalating arboviral threat resulting in almost 400 million annual global infections. Cambodia has one of the highest dengue infection rates in Southeast Asia. The container-breeding mosquito Aedes aegypti is the main vector. No curative medication or suitable vaccine exists so dengue control relies on reduction of vector populations. Here we report on the impact on vector populations of a package of vector control interventions including larvivorous guppy fish in household water containers, mosquito trapping with gravid-ovitraps, solid waste management, breeding-container coverage through community education and engagement for behavioural change, particularly through the participation of school children. These activities resulted in major reductions in Container Index, House Index, Breteau Index, Pupal Index and Adult Index (all p-values 0.002 or lower) in the Intervention Arm compared with the Control Arm over a follow-up period of more than one year, although the project was not able to measure the longer-term sustainability of the interventions. An earlier cluster-randomised trial of similar interventions in the same location was also successful. This package of biophysical and community engagement interventions was highly effective for dengue vector control in a large-scale cluster-randomised trial in Cambodia and should be trialled in other locations
A scoping review on the risk of tuberculosis in specific population groups: can we expand the World Health Organization recommendations?
Since 2015, the World Health Organization (WHO) has recommended prioritising testing and treatment of tuberculosis (TB) infection (TBI) in 11 high-risk groups. With new options emerging for TB preventive treatment, we conducted a scoping review, in consultation with the WHO's Global Tuberculosis Programme, to explore the evidence for other population groups at potentially high risk of progression to active TB. We searched six databases for preprints and articles published between 2000 and August 2022. 18 out of 33 668 screened records were included (six meta-analyses and 12 original research studies). Most were observational studies reporting the incidence of active TB in a risk group versus control. Glomerular diseases had the strongest association with active TB (standardised incidence ratio 23.36, 95% CI 16.76- 31.68) based on an unpublished study. Other conditions associated with increased risk of active TB included hepatitis C, malignancies, diabetes mellitus, rheumatoid arthritis and vitamin D deficiency. Corticosteroid use was also associated with increased risk in several studies, although heterogeneous definitions of exposure and indications for use challenge interpretation. Despite methodological limitations of the identified studies, expanding the recommendations for TBI screening and treatment to new risk groups such as those reported here should be considered. Further group-specific systematic reviews may provide additional data for decision-making