Routine entomological monitoring data are used to quantify the abundance of Ae. aegypti. The public health utility of these indicators is based on the assumption that greater mosquito abundance ...increases the risk of human DENV transmission, and therefore reducing exposure to the vector decreases incidence of infection. Entomological survey data from two longitudinal cohort studies in Iquitos, Peru, linked with 8,153 paired serological samples taken approximately six months apart were analyzed. Indicators of Ae. aegypti density were calculated from cross-sectional and longitudinal entomological data collected over a 12-month period for larval, pupal and adult Ae. aegypti. Log binomial models were used to estimate risk ratios (RR) to measure the association between Ae. aegypti abundance and the six-month risk of DENV seroconversion. RRs estimated using cross-sectional entomological data were compared to RRs estimated using longitudinal data. Higher cross-sectional Ae. aegypti densities were not associated with an increased risk of DENV seroconversion. Use of longitudinal entomological data resulted in RRs ranging from 1.01 (95% CI: 1.01, 1.02) to 1.30 (95% CI: 1.17, 1.46) for adult stage density estimates and RRs ranging from 1.21 (95% CI: 1.07, 1.37) to 1.75 (95% CI: 1.23, 2.5) for categorical immature indices. Ae. aegypti densities calculated from longitudinal entomological data were associated with DENV seroconversion, whereas those measured cross-sectionally were not. Ae. aegypti indicators calculated from cross-sectional surveillance, as is common practice, have limited public health utility in detecting areas or populations at high risk of DENV infection.
Large cross-sectional household surveys are common for measuring indicators of neglected tropical disease control programs. As an alternative to standard paper-based data collection, we utilized ...novel paperless technology to collect data electronically from over 12,000 households in Ethiopia.
We conducted a needs assessment to design an Android-based electronic data collection and management system. We then evaluated the system by reporting results of a pilot trial and from comparisons of two, large-scale surveys; one with traditional paper questionnaires and the other with tablet computers, including accuracy, person-time days, and costs incurred.
The electronic data collection system met core functions in household surveys and overcame constraints identified in the needs assessment. Pilot data recorders took 264 (standard deviation (SD) 152 sec) and 260 sec (SD 122 sec) per person registered to complete household surveys using paper and tablets, respectively (P = 0.77). Data recorders felt a lack of connection with the interviewee during the first days using electronic devices, but preferred to collect data electronically in future surveys. Electronic data collection saved time by giving results immediately, obviating the need for double data entry and cross-correcting. The proportion of identified data entry errors in disease classification did not differ between the two data collection methods. Geographic coordinates collected using the tablets were more accurate than coordinates transcribed on a paper form. Costs of the equipment required for electronic data collection was approximately the same cost incurred for data entry of questionnaires, whereas repeated use of the electronic equipment may increase cost savings.
Conducting a needs assessment and pilot testing allowed the design to specifically match the functionality required for surveys. Electronic data collection using an Android-based technology was suitable for a large-scale health survey, saved time, provided more accurate geo-coordinates, and was preferred by recorders over standard paper-based questionnaires.
Glaucoma is the leading cause of irreversible blindness, affecting 76 million globally. It is characterized by irreversible damage to the optic nerve. Pharmacotherapy manages intraocular pressure ...(IOP) and slows disease progression. However, non-adherence to glaucoma medications remains problematic, with 41-71% of patients being non-adherent to their prescribed medication. Despite substantial investment in research, clinical effort, and patient education protocols, non-adherence remains high. Therefore, we aimed to determine if there is a substantive genetic component behind patients' glaucoma medication non-adherence. We assessed glaucoma medication non-adherence with prescription refill data from the Marshfield Clinic Healthcare System's pharmacy dispensing database. Two standard measures were calculated: the medication possession ratio (MPR) and the proportion of days covered (PDC). Non-adherence on each metric was defined as less than 80% medication coverage over 12 months. Genotyping was done using the Illumina HumanCoreExome BeadChip in addition to exome sequencing on the 230 patients (1) to calculate the heritability of glaucoma medication non-adherence and (2) to identify SNPs and/or coding variants in genes associated with medication non-adherence. Ingenuity pathway analysis (IPA) was utilized to derive biological meaning from any significant genes in aggregate. Over 12 months, 59% of patients were found to be non-adherent as measured by the MPR80, and 67% were non-adherent as measured by the PDC80. Genome-wide complex trait analysis (GCTA) suggested that 57% (MPR80) and 48% (PDC80) of glaucoma medication non-adherence could be attributed to a genetic component. Missense mutations in
,
,
,
,
,
,
,
, and
were all found to be significantly associated with glaucoma medication non-adherence by whole exome sequencing after Bonferroni correction (
< 10
) (PDC80). While missense mutations in
,
,
, and
were found to be significantly associated with medication non-adherence by whole exome sequencing after Bonferroni correction (
< 10
) (MPR80). The same coding SNP in
which functions in Alzheimer's disease pathophysiology was significant by both measures and increased risk for glaucoma medication non-adherence by three-fold (95% CI, 1.62-5.8). Although our study was underpowered for genome-wide significance, SNP rs6474264 within ZMAT4 (
5.54 × 10
) was found to be nominally significant, with a decreased risk for glaucoma medication non-adherence (OR, 0.22; 95% CI, 0.11-0.42)). IPA demonstrated significant overlap, utilizing, both standard measures including opioid signaling, drug metabolism, and synaptogenesis signaling. CREB signaling in neurons (which is associated with enhancing the baseline firing rate for the formation of long-term potentiation in nerve fibers) was shown to have
associations. Our results suggest a substantial heritable genetic component to glaucoma medication non-adherence (47-58%). This finding is in line with genetic studies of other conditions with a psychiatric component (e.g., post-traumatic stress disorder (PTSD) or alcohol dependence). Our findings suggest both risk and protective statistically significant genes/pathways underlying glaucoma medication non-adherence for the first time. Further studies investigating more diverse populations with larger sample sizes are needed to validate these findings.
Routine childhood vaccination is among the most cost-effective, successful public health interventions available. Amid substantial investments to expand vaccine delivery throughout Africa and ...strengthen administrative reporting systems, most countries still require robust measures of local routine vaccine coverage and changes in geographical inequalities over time.
This analysis drew from 183 surveys done between 2000 and 2016, including data from 881 268 children in 49 African countries. We used a Bayesian geostatistical model calibrated to results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2017, to produce annual estimates with high-spatial resolution (5 × 5 km) of diphtheria-pertussis-tetanus (DPT) vaccine coverage and dropout for children aged 12–23 months in 52 African countries from 2000 to 2016.
Estimated third-dose (DPT3) coverage increased in 72·3% (95% uncertainty interval UI 64·6–80·3) of second-level administrative units in Africa from 2000 to 2016, but substantial geographical inequalities in DPT coverage remained across and within African countries. In 2016, DPT3 coverage at the second administrative (ie, district) level varied by more than 25% in 29 of 52 countries, with only two (Morocco and Rwanda) of 52 countries meeting the Global Vaccine Action Plan target of 80% DPT3 coverage or higher in all second-level administrative units with high confidence (posterior probability ≥95%). Large areas of low DPT3 coverage (≤50%) were identified in the Sahel, Somalia, eastern Ethiopia, and in Angola. Low first-dose (DPT1) coverage (≤50%) and high relative dropout (≥30%) together drove low DPT3 coverage across the Sahel, Somalia, eastern Ethiopia, Guinea, and Angola.
Despite substantial progress in Africa, marked national and subnational inequalities in DPT coverage persist throughout the continent. These results can help identify areas of low coverage and vaccine delivery system vulnerabilities and can ultimately support more precise targeting of resources to improve vaccine coverage and health outcomes for African children.
Bill & Melinda Gates Foundation.
Background Onchocerciasis is a disease caused by infection with Onchocerca volvulus, which is transmitted to humans via the bite of several species of black fly, and is responsible for permanent ...blindness or vision loss, as well as severe skin disease. Predominantly endemic in parts of Africa and Yemen, preventive chemotherapy with mass drug administration of ivermectin is the primary intervention recommended for the elimination of its transmission. Methods A dataset of 18,116 geo-referenced prevalence survey datapoints was used to model annual 2000-2018 infection prevalence in Africa and Yemen. Using Bayesian model-based geostatistics, we generated spatially continuous estimates of all-age 2000-2018 onchocerciasis infection prevalence at the 5 x 5-km resolution as well as aggregations to the national level, along with corresponding estimates of the uncertainty in these predictions. Results As of 2018, the prevalence of onchocerciasis infection continues to be concentrated across central and western Africa, with the highest mean estimates at the national level in Ghana (12.2%, 95% uncertainty interval UI 5.0-22.7). Mean estimates exceed 5% infection prevalence at the national level for Cameroon, Central African Republic, Democratic Republic of the Congo (DRC), Guinea-Bissau, Sierra Leone, and South Sudan. Conclusions Our analysis suggests that onchocerciasis infection has declined over the last two decades throughout western and central Africa. Focal areas of Angola, Cameroon, the Democratic Republic of the Congo, Ethiopia, Ghana, Guinea, Mali, Nigeria, South Sudan, and Uganda continue to have mean microfiladermia prevalence estimates exceeding 25%. At and above this level, the continuation or initiation of mass drug administration with ivermectin is supported. If national programs aim to eliminate onchocerciasis infection, additional surveillance or supervision of areas of predicted high prevalence would be warranted to ensure sufficiently high coverage of program interventions. Keywords: Onchocerciasis, Geospatial model, Neglected tropical diseases
There remains a lack of epidemiological data on the geographical distribution of trachoma to support global mapping and scale up of interventions for the elimination of trachoma. The Global Atlas of ...Trachoma (GAT) was launched in 2011 to address these needs and provide standardised, updated and accessible maps. This paper uses data included in the GAT to describe the geographical distribution and burden of trachoma in Africa.
Data assembly used structured searches of published and unpublished literature to identify cross-sectional epidemiological data on the burden of trachoma since 1980. Survey data were abstracted into a standardised database and mapped using geographical information systems (GIS) software. The characteristics of all surveys were summarized by country according to data source, time period, and survey methodology. Estimates of the current population at risk were calculated for each country and stratified by endemicity class.
At the time of writing, 1342 records are included in the database representing surveys conducted between 1985 and 2012. These data were provided by direct contact with national control programmes and academic researchers (67%), peer-reviewed publications (17%) and unpublished reports or theses (16%). Prevalence data on active trachoma are available in 29 of the 33 countries in Africa classified as endemic for trachoma, and 1095 (20.6%) districts have representative data collected through population-based prevalence surveys. The highest prevalence of active trachoma and trichiasis remains in the Sahel area of West Africa and Savannah areas of East and Central Africa and an estimated 129.4 million people live in areas of Africa confirmed to be trachoma endemic.
The Global Atlas of Trachoma provides the most contemporary and comprehensive summary of the burden of trachoma within Africa. The GAT highlights where future mapping is required and provides an important planning tool for scale-up and surveillance of trachoma control.
Podoconiosis is a type of elephantiasis characterised by swelling of the lower legs. It is often confused with other causes of tropical lymphedema and its global distribution is uncertain. Here we ...synthesise the available information on the presence of podoconiosis to produce evidence consensus maps of its global geographical distribution.
We systematically searched available data on podoconiosis in SCOPUS and MEDLINE from inception, updated to 10 May, 2019, and identified observational and population-based studies reporting podoconiosis. To establish existence of podoconiosis, we used the number of cases reported in studies and prevalence data with geographical locations. We then developed an index to assess evidence quality and reliability, assigning each country an evidence consensus score. Using these summary scores, we then developed a contemporary global map of national-level podoconiosis status. There is evidence of podoconiosis in 17 countries (12 in Africa, three in Latin America, and two in Asia) and consensus on presence in six countries (all in Africa). We have identified countries where surveillance is required to further define the presence or absence of podoconiosis. We have highlighted areas where evidence is currently insufficient or conflicting, and from which more evidence is needed.
The global distribution of podoconiosis is not clearly known; the disease extent and limits provided here inform the best contemporary map of the distribution of podoconiosis globally from available data. These results help identify surveillance needs, direct future mapping activities, and inform prevention plans and burden estimation of podoconiosis.
The transmission assessment survey (TAS) is recommended to determine whether cessation of mass drug administration (MDA) for lymphatic filariasis (LF) is warranted. Ministries of health typically ...implement TASs in evaluation units (EUs) that have had more than five rounds of annual MDA. Under TAS guidelines, sample size calculations determine a decision value: if the number of individuals testing positive exceeds this threshold, then MDA continues in the EU. The objective of this study was to determine whether fine scale geospatial covariates could be used to identify predictors of TAS failure. We geo-referenced 746 TAS EUs, of which 65 failed and extracted geospatial covariates using R to estimate odds of failure. We implemented stepwise backward elimination to select covariates for inclusion in a logistic regression to estimate the odds of TAS failure. Covariates included environmental predictors (aridity, distance to fresh water, elevation, and enhanced vegetation index), cumulative rounds of MDA, measures of urbanicity and access, LF species, and baseline prevalence. Presence of
was significantly associated with TAS failure (odds ratio OR: 4.79, 95% CI: 2.52-9.07), as was population density (OR: 2.91, 95% CI: 1.06-7.98). The presence of nighttime lights was highly protective against failure (OR: 0.22, 95% CI: 0.10-0.50), as was an increase in elevation (OR: 0.36, 95% CI: 0.18-0.732). This work identifies predictors associated with TAS failure at the EU areal level, given the data presently available, and also identifies the need for more granular data to conduct a more robust assessment of these predictors.
To eliminate blinding trachoma, the World Health Organization emphasizes implementing the SAFE strategy, which includes annual mass drug administration (MDA) with azithromycin to the whole population ...of endemic districts. Prevalence surveys to assess impact at the district level are recommended after at least 3 years of intervention. The decision to stop MDA is based on a prevalence of trachomatous inflammation follicular (TF) among children aged 1-9 years below 5% at the sub-district level, as determined by an additional round of surveys limited within districts where TF prevalence is below 10%. We conducted impact surveys powered to estimate prevalence simultaneously at the sub-district and district in two zones of Amhara, Ethiopia to determine whether MDA could be stopped.
Seventy-two separate population-based, sub-district surveys were conducted in 25 districts. In each survey all residents from 10 randomly selected clusters were screened for clinical signs of trachoma. Data were weighted according to selection probabilities and adjusted for correlation due to clustering.
Overall, 89,735 residents were registered from 21,327 households of whom 72,452 people (80.7%) were examined. The prevalence of TF in children aged 1-9 years was below 5% in six sub-districts and two districts. Sub-district level prevalence of TF in children aged 1-9 years ranged from 0.9-76.9% and district-level from 0.9-67.0%. In only one district was the prevalence of trichiasis below 0.1%.
The experience from these zones in Ethiopia demonstrates that impact assessments designed to give a prevalence estimate of TF at sub-district level are possible, although the scale of the work was challenging. Given the assessed district-level prevalence of TF, sub-district-level surveys would have been warranted in only five districts. Interpretation was not as simple as stopping MDA in sub-districts below 5% given programmatic challenges of exempting sub-districts from a highly regarded program and the proximity of hyper-endemic sub-districts.
Trachoma prevalence surveys provide the evidence base for district and community-wide implementation of the SAFE strategy, and are used to evaluate the impact of trachoma control interventions. An ...economic analysis was performed to estimate the cost of trachoma prevalence surveys conducted between 2006 and 2010 from 8 national trachoma control programs in Africa.
Data were collected retrospectively from reports for 165 districts surveyed for trachoma prevalence using a cluster random sampling methodology in Ethiopia, Ghana, Mali, Niger, Nigeria, Sudan, Southern Sudan and The Gambia. The median cost per district survey was $4,784 (inter-quartile range IQR = $3,508-$6,650) while the median cost per cluster was $311 (IQR = $119-$393). Analysis by cost categories (personnel, transportation, supplies and other) and cost activity (training, field work, supervision and data entry) revealed that the main cost drivers were personnel and transportation during field work.
Population-based cluster random surveys are used to provide the evidence base to set objectives and determine when elimination targets have been reached for several neglected tropical diseases, including trachoma. The cost of conducting epidemiologically rigorous prevalence surveys should not be a barrier to program implementation or evaluation.
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