Impacts of armed conflicts on tuberculosis burden and treatment outcomes: a systematic review.

OBJECTIVES: This systematic review aimed to summarise existing literature on the impacts of armed conflicts on tuberculosis burden and treatment outcomes. DESIGN: A systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. DATA SOURCES: PubMed, Web of Science, Cumulative Index to Nursing and Allied Health Literature Plus, Scopus, ScienceDirect, Embase and medRxiv. DATA EXTRACTION AND SYNTHESIS: Three reviewers independently screened, selected eligible studies and extracted data. A narrative review was undertaken to summarise the findings qualitatively. RESULTS: Eleven studies were included in this review, reporting on tuberculosis incidence rates, prevalence and treatment outcomes, including mortality. Overall, the impact of armed conflicts on case notifications was variable. Six studies reported overall increases in tuberculosis case notifications following the onset of conflicts, while three studies reported overall decreases in tuberculosis case notifications. Factors, including limited access to healthcare services, challenges in surveillance and laboratory confirmation, the destruction of health systems and incapacitating the healthcare workforce, contributed to a decrease in the number of notified cases. The higher tuberculosis notification in some of the studies could be attributed to the disruption of tuberculosis prevention and control programmes as well as increased socioeconomic deprivation, including malnutrition, mass migration, poor living conditions and overcrowding that are worsened during conflicts. Armed conflicts without effective interventions were associated with worse tuberculosis treatment outcomes, including lower proportions of people with treatment success and higher proportions of people with loss to follow-up, mortality and treatment failure. However, implementing various interventions in conflict settings (such as establishing a National Tuberculosis Control Programme) led to higher tuberculosis notification rates and treatment success. CONCLUSION: The impact of armed conflicts on tuberculosis notification is complex and is influenced by multiple factors. The findings of this review underscore the importance of concerted efforts to control tuberculosis in conflict settings using available resources.

Economic burden of multidrug-resistant tuberculosis on patients and households: a global systematic review and meta-analysis.

Multidrug-resistant tuberculosis (MDR-TB) is a major health threat worldwide, causing a significant economic burden to patients and their families. Due to the longer duration of treatment and expensive second-line medicine, the economic burden of MDR-TB is assumed to be higher than drug-susceptible TB. However, the costs associated with MDR-TB are yet to be comprehensively quantified. We conducted this systematic review and meta-analysis to determine the global burden of catastrophic costs associated with MDR-TB on patients and their households. We systematically searched five databases (CINHAL, MEDLINE, Embase, Scopus, and Web of Science) from inception to 2 September 2022 for studies reporting catastrophic costs on patients and affected families of MDR-TB. The primary outcome of our study was the proportion of patients and households with catastrophic costs. Costs were considered catastrophic when a patient spends 20% or more of their annual household income on their MDR-TB diagnosis and care. The pooled proportion of catastrophic cost was determined using a random-effects meta-analysis. Publication bias was assessed using visualization of the funnel plots and the Egger regression test. Heterogeneity was assessed using I2, and sub-group analysis was conducted using study covariates as stratification variables. Finally, we used the Preferred Reporting Items for Reporting Systematic Review and Meta-Analysis-20 (PRISMA-20). The research protocol was registered in PROSPERO (CRD42021250909). Our search identified 6635 studies, of which 11 were included after the screening. MDR-TB patients incurred total costs ranging from $USD 650 to $USD 8266 during treatment. The mean direct cost and indirect cost incurred by MDR-TB patients were $USD 1936.25 (SD ± $USD 1897.03) and $USD 1200.35 (SD ± $USD 489.76), respectively. The overall burden of catastrophic cost among MDR-TB patients and households was 81.58% (95% Confidence Interval (CI) 74.13-89.04%). The catastrophic costs incurred by MDR-TB patients were significantly higher than previously reported for DS-TB patients. MDR-TB patients incurred more expenditure for direct costs than indirect costs. Social protection and financial support for patients and affected families are needed to mitigate the catastrophic economic consequences of MDR-TB.

Protocol for a systematic review of long-term physical sequelae and financial burden of multidrug-resistant and extensively drug-resistant tuberculosis.

INTRODUCTION: Multidrug resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) are major public health threats that are significant causes of physical sequelae and financial consequences for infected people. Treatment for MDR- and XDR-TB are more toxic and take longer duration than for drug-susceptible-TB. As a result, the long-term sequelae are thought to be more common among patients with MDR- and XDR-TB than drug-susceptible-TB, but this is yet to be quantified. Hence, the aim of this systematic review and meta-analysis is to quantify the global burden and types of long-term physical sequelae and financial burden associated with both MDR- and XDR-TB. METHOD AND ANALYSIS: We will search CINHAL, MEDLINE, Embase, Scopus, and Web of science for studies that report physical and financial sequelae associated with rifampicin-resistant (RR), MDR- and XDR-TB or their treatments. The search will be conducted without time, language, and place restrictions. A random-effects meta-analysis will be conducted to estimate the pooled prevalence of each physical sequela. Heterogeneity will be measured using the Higgins I2 statistics. We will assess publication bias visually using the funnel plot and statistically using Egger's test. Adjustments for publication basis will be made using Tweedie's and Duval Trim and Fill analysis. ETHICS AND DISSEMINATION: Since the study is based on published evidence, ethics approval is not required. The findings of the systematic review will be presented at various conferences and will be published in a peer-reviewed journal. PROTOCOL REGISTRATION: The protocol is published in the PROSPERO with registration number CRD42021250909.

Cost analysis for "The Magic Glasses Philippines" health education package to prevent intestinal worm infections among Filipino schoolchildren.

Background: Soil-transmitted helminth (STH) infections are a significant public health problem affecting over 900 million people globally. Health education has been shown to complement mass drug administration (MDA) for the control of these intestinal worms. We reported recently results of a cluster randomised control trial (RCT) showing the positive impact of the "The Magic Glasses Philippines (MGP)" health education package in reducing STH infections among schoolchildren in intervention schools with ≤15% STH baseline prevalence in Laguna province, the Philippines. To inform decision making on the economic implications of the MGP, we evaluated the in-trial costs and then quantified the costs of scaling up the intervention both regionally and nationally. Methods: Costs were determined for the MGP RCT conducted in 40 schools in Laguna province. We estimated the total cost and the costs incurred per student for the actual RCT and the total costs for regional and national scale-up in all schools regardless of STH endemicity. The costs associated with the implementation of standard health education (SHE) activities and mass drug administration (MDA) were determined with a public sector perspective. Findings: The cost per participating student in the MGP RCT was Php 58.65 (USD 1.15) but if teachers instead of research staff had been involved, the estimated cost would have been considerably lower at Php 39.45 (USD 0.77). Extrapolating the costs for regional scale-up, the costs per student were estimated to be Php 15.24 (USD 0.30). As it is scaled up at the national level to include more schoolchildren, the estimated cost was increased at Php 17.46 (USD 0.34). In scenario 2 and 3, consistently, labour/salary costs associated with the delivery of the MGP contributed most to overall programme expenditure. Furthermore, the estimated average cost per student for SHE and MDA were Php 117.34 (USD 2.30) and Php 58.17 (USD 1.14), respectively. Using national scale up estimates, the cost of combining the MGP with SHE and MDA was Php 192.97 (USD 3.79). Interpretation: These findings suggest that the integration of MGP into the school curriculum would be an affordable and scalable approach to respond to the continuous burden of STH infection among schoolchildren in the Philippines. Funding: National and Medical Research Council, Australia, and the UBS-Optimus Foundation, Switzerland.

Soil-transmitted helminth infections and nutritional indices among Filipino schoolchildren.

BACKGROUND: Soil-transmitted helminth (STH) infections are still prevalent among schoolchildren in the Philippines. We evaluated the risk factors associated with STH and the relationship between STH and nutritional indices among schoolchildren aged 9-10 years in Laguna province, the Philippines. METHODS: We used the baseline data from 40 schools enrolled in a randomised controlled trial of the Magic Glasses Philippines health education package. Data on demographic and socio-economic variables, and STH related knowledge, attitudes and practices, were obtained through a questionnaire. Stool samples were collected and assessed for STH egg presence using the Kato-Katz technique. Haemoglobin levels and height and weight of study participants were also determined. The generalized estimating equations approach was used to construct logistic regression models to assess STH-associated risk factors, and the association between any STH infection and anaemia, child stunting, wasting and being underweight. The trial is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12616000508471). FINDINGS: Among 1,689 schoolchildren, the prevalence of any STH was 23%. The prevalence of anaemia, stunting, being underweight and wasting was 13%, 20.2%, 19% and 9.5%, respectively. Age, socio-economic status, rural/urban classification of schools and knowledge of STH were significant risk factors for acquiring a STH infection. Moreover, infections with any STH were significantly associated with stunting (P = <0.001) and being underweight (P = <0.003), but not wasting (P = 0.375) or anaemia (P = 0.462) after controlling for confounding covariates. CONCLUSION: The study findings emphasise the need for sustainable deworming in tandem with other measures such as the provision of health education, improvements in sanitation and hygiene, and nutritional programs in order to control STH infections and improve morbidity outcomes in schoolchildren. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12616000508471).

The prevalence of soil transmitted helminth infections in minority indigenous populations of South-East Asia and the Western Pacific Region: A systematic review and meta-analysis.

INTRODUCTION: Soil transmitted helminth (STH) infections cause one of the most prevalent diseases in man. STHs disproportionately impact socio-economically disadvantaged communities including minority indigenous populations. This systematic review aimed to quantify the prevalence of STH infection within minority indigenous populations of the South-East Asia and Western Pacific Regions. METHODS: The systematic review was conducted in accordance with The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines following a published protocol. A random effects meta-analysis was used to estimate the pooled prevalence of STH infection, and meta-regression analysis was used to quantify associations with study characteristics. Where comparative data were available, sub-group analysis was conducted to evaluate the risk of STH infection in minority indigenous people relative to other population groups. The heterogeneity between studies was evaluated visually using Forest plots and was assessed quantitatively by the index of heterogeneity (I2) and Cochran Q-statistics. RESULTS: From 1,366 unique studies that were identified, 81 were included in the final analysis. The pooled prevalence of infection within minority indigenous populations was 61.4% (95% CI 50.8, 71.4) for overall STH infection; 32.3% (95% CI 25.7, 39.3) for Ascaris.lumbricoides; 43.6% (95% CI 32.6, 54.8) for Trichuris.trichiura; 19.9% (95% CI 15.7, 24.5) for hookworm and 6.3% (95% CI 3.2, 10.2) for Strongyloides.stercoralis. A significant increase in T. trichiura prevalence was observed over time. The stratified analysis showed that the prevalence of infection for STH overall and for each STH species were not significantly different in minority indigenous participants compared to other populations groups. CONCLUSION: The prevalence of STH infection is high within minority indigenous populations across countries at very different levels of socio-economic development. The increasing prevalence of T. trichiura calls for the implementation of more effective therapies and control strategies.

Spatio-temporal patterns of childhood pneumonia in Bhutan: a Bayesian analysis.

Pneumonia is one of the top 10 diseases by morbidity in Bhutan. This study aimed to investigate the spatial and temporal trends and risk factors of childhood pneumonia in Bhutan. A multivariable Zero-inflated Poisson regression model using a Bayesian Markov chain Monte Carlo simulation was undertaken to quantify associations of age, sex, altitude, rainfall, maximum temperature and relative humidity with monthly pneumonia incidence and to identify the underlying spatial structure of the data. Overall childhood pneumonia incidence was 143.57 and 10.01 per 1000 persons over 108 months of observation in children aged < 5 years and 5-14 years, respectively. Children < 5 years or male sex were more likely to develop pneumonia than those 5-14 years and females. Each 1 °C increase in maximum temperature was associated with a 1.3% (95% (credible interval [CrI] 1.27%, 1.4%) increase in pneumonia cases. Each 10% increase in relative humidity was associated with a 1.2% (95% CrI 1.1%, 1.4%) reduction in the incidence of pneumonia. Pneumonia decreased by 0.3% (CrI 0.26%, 0.34%) every month. There was no statistical spatial clustering after accounting for the covariates. Seasonality and spatial heterogeneity can partly be explained by the association of pneumonia risk to climatic factors including maximum temperature and relative humidity.

Dengue risk assessment using multicriteria decision analysis: A case study of Bhutan.

BACKGROUND: Dengue is the most rapidly spreading vector-borne disease globally, with a 30-fold increase in global incidence over the last 50 years. In Bhutan, dengue incidence has been on the rise since 2004, with numerous outbreaks reported across the country. The aim of this study was to identify and map areas that are vulnerable to dengue in Bhutan. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a multicriteria decision analysis (MCDA) using a weighted linear combination (WLC) to obtain a vulnerability map of dengue. Risk factors (criteria) were identified and assigned with membership values for vulnerability according to the available literature. Sensitivity analysis and validation of the model was conducted to improve the robustness and predictive ability of the map. Our study revealed marked differences in geographical vulnerability to dengue by location and season. Low-lying areas and those located along the southern border were consistently found to be at higher risk of dengue. The vulnerability extended to higher elevation areas including some areas in the Capital city Thimphu during the summer season. The higher risk was mostly associated with relatively high population density, agricultural and built-up landscapes and relatively good road connectivity. CONCLUSIONS: Using MCDA, our study identified vulnerable areas in Bhutan during specific seasons when and where the transmission of dengue is most likely to occur. This study provides evidence for the National Vector-borne Disease Control programme to optimize the use of limited public health resources for surveillance and vector control, to mitigate the public health threat of dengue.

A cluster-randomised controlled trial comparing school and community-based deworming for soil transmitted helminth control in school-age children: the CoDe-STH trial protocol.

BACKGROUND: Current guidelines and targets for soil-transmitted helminth (STH) control focus on school-based deworming for school-age children, given the high risk of associated morbidity in this age group. However, expanding deworming to all age groups may achieve improved STH control among both the community in general and school-age children, by reducing their risk of reinfection. This trial aims to compare school-based targeted deworming with community-wide mass deworming in terms of impact on STH infections among school-age children. METHODS: The CoDe-STH (Community Deworming against STH) trial is a cluster-randomised controlled trial (RCT) in 64 primary schools in Dak Lak province, Vietnam. The control arm will receive one round of school-based targeted deworming with albendazole, while in the intervention arm, community-wide mass deworming with albendazole will be implemented alongside school-based deworming. Prevalence of STH infections will be measured in school-age children at baseline and 12 months following deworming. The primary outcome is hookworm prevalence in school-age children at 12 months, by quantitative PCR. Analysis will be intention-to-treat, with outcomes compared between study arms using generalised linear and non-linear mixed models. Additionally, cost-effectiveness of mass and targeted deworming will be calculated and compared, and focus group discussions and interviews will be used to assess acceptability and feasibility of deworming approaches. Individual based stochastic models will be used to predict the impact of mass and targeted deworming strategies beyond the RCT timeframe to assess the likelihood of parasite population 'bounce-back' if deworming is ceased due to low STH prevalence. DISCUSSION: The first large-scale trial comparing mass and targeted deworming for STH control in South East Asia will provide key information for policy makers regarding the optimal design of STH control programs. TRIAL REGISTRATION: ACTRN12619000309189 .

Mapping tuberculosis treatment outcomes in Ethiopia.

BACKGROUND: Tuberculosis (TB) is the leading cause of death from an infectious disease in Ethiopia, killing more than 30 thousand people every year. This study aimed to determine whether the rates of poor TB treatment outcome varied geographically across Ethiopia at district and zone levels and whether such variability was associated with socioeconomic, behavioural, health care access, or climatic conditions. METHODS: A geospatial analysis was conducted using national TB data reported to the health management information system (HMIS), for the period 2015-2017. The prevalence of poor TB treatment outcomes was calculated by dividing the sum of treatment failure, death and loss to follow-up by the total number of TB patients. Binomial logistic regression models were computed and a spatial analysis was performed using a Bayesian framework. Estimates of parameters were generated using Markov chain Monte Carlo (MCMC) simulation. Geographic clustering was assessed using the Getis-Ord Gi* statistic, and global and local Moran's I statistics. RESULTS: A total of 223,244 TB patients were reported from 722 districts in Ethiopia during the study period. Of these, 63,556 (28.5%) were cured, 139,633 (62.4%) completed treatment, 6716 (3.0%) died, 1459 (0.7%) had treatment failure, and 12,200 (5.5%) were lost to follow-up. The overall prevalence of a poor TB treatment outcome was 9.0% (range, 1-58%). Hot-spots and clustering of poor TB treatment outcomes were detected in districts near the international borders in Afar, Gambelia, and Somali regions and cold spots were detected in Oromia and Amhara regions. Spatial clustering of poor TB treatment outcomes was positively associated with the proportion of the population with low wealth index (OR: 1.01; 95%CI: 1.0, 1.01), the proportion of the population with poor knowledge about TB (OR: 1.02; 95%CI: 1.01, 1.03), and higher annual mean temperature per degree Celsius (OR: 1.15; 95% CI: 1.08, 1.21). CONCLUSIONS: This study showed significant spatial variation in poor TB treatment outcomes in Ethiopia that was related to underlying socioeconomic status, knowledge about TB, and climatic conditions. Clinical and public health interventions should be targeted in hot spot areas to reduce poor TB treatment outcomes and to achieve the national End-TB Strategy targets.

A cost analysis of producing vaccines in developing countries.

Developing country vaccine manufacturers (DCVMs) supply over half of the vaccines used in developing country immunisation programs. Decisions by developing countries to establish vaccine manufacturing should be based on economic viability, however reliable assessments of vaccine production costs are lacking. This study aimed to quantify the cost of establishing vaccine manufacturing facilities and producing vaccines in developing countries. This study estimates vaccine production costs in developing countries based on twelve vaccines produced by eight DCVMs. The results were based on estimates of the capital and operating costs required to establish vaccine manufacturing facilities under three hypothetical scenarios of production scale and scope. Cost patterns were then compared to vaccine prices paid by countries in both industrialized and developing country markets. The cost of producing vaccines in developing countries was estimated to be on average US$ 2.18 per dose, ranging between US$ 0.98 and US$ 4.85 for different vaccine types and formulations. Vaccine costs-per-dose decrease as production scale and scope increase. Cost-per-dose is mainly driven by fixed costs, but at a scale of production over 20 million doses per year it becomes driven by variable costs. Under the three hypothetical scenarios used, costs-per-dose of vaccines produced by developing countries were around 47% lower than vaccine prices in developing-country markets and 84% lower than prices in industrialized-country markets. This study has found that local production of vaccines in developing countries exhibits both economies of scale and economies of scope. The lower costs relative to prices suggests that a producer surplus and potential profits may be attainable in both developing and developed country markets, supporting sustainable production.

Determinants of Spatial Heterogeneity of Functional Illiteracy among School-Aged Children in the Philippines: An Ecological Study.

Functional literacy is one of the targets of the Sustainable Development Goals (SDGs) of the United Nations. Functional literacy indicators are likely to vary between locations given the geographical variability of its major determinants. This property poses a challenge to decisions around efficient allocation of population services and resources to mitigate the impact of functional literacy in populations most in need. Using functional literacy indicators of 11,313 school-aged children collected in 2008 during the nationwide survey, the current study examined the association between functional literacy and geographical disparities in socioeconomic status (SES), water supply, sanitation and hygiene, household education stimuli, and environmental variables in all three regions of the Philippines (Luzon, the Visayas, and Mindanao). Three nested fixed-effects multinomial regression models were built to determine associations between functional literacy and a wide array of variables. Our results showed the general prevalence rate of functional illiteracy as being 4.7%, with the highest prevalence rate in the Visayas, followed by Mindanao and Luzon (7.5%, 6.9%, and 3.0%, respectively. Our results indicated that in Luzon prevalence of functional illiteracy was explained by variation in household education stimuli scores, sources of drinking water, and type of toilet facility. In Mindanao and the Visayas prevalence of functional illiteracy was primarily explained by geographical variation in SES, and natural environmental conditions. Our study highlights region-specific determinants of functional literacy and the need for geographically targeted, integrated interventions.

Spatiotemporal transmission and socio-climatic factors related to paediatric tuberculosis in north-western Ethiopia.

The burden of tuberculosis (TB) in children reflects continuing and recent transmission within a population. This study aimed to identify spatiotemporal and socio-climatic factors associated with paediatric TB in north-western Ethiopia. Multivariate Poisson regression models were computed using a Bayesian framework. Estimates of parameters were generated using Markov chain Monte Carlo simulation. A total of 2,240 children aged under 15 years diagnosed with TB during the years 2013- 2016 were included in the analysis. The annual TB incidence rates were 44 and 28 per 100,000 children, for children aged under 15 and 5 years, respectively. Spatial clustering of TB was observed in the border area of north-western Ethiopia. The spatio-temporal transmission of childhood TB was found to be associated with district level socio-climatic factors such as urbanisation [relative risk (RR): 1.8; 95% credible interval (CrI): 1.2, 2.6], lower educational status (RR: 1.5; 95% CrI: 1.0, 2.1), a high percentage of internal migration (RR: 1.3; 95% CrI: 1.0, 1.6), high temperature (RR: 1.3; 95% CrI: 1.0, 1.7) and high rainfall (RR: 1.5; 95% CrI: 1.1, 2.0). We conclude that interventions targeting hotspot districts with a high proportion of childhood TB are important to reduce TB transmission in northwest Ethiopia.

Geographical outcome disparities in infection occurrence after colorectal surgery: An analysis of 58,096 colorectal surgical procedures.

BACKGROUND: Despite improved surgical practices and in-hospital surveillance systems, surgical site infections remain a major public health problem worldwide and often require readmission to hospital. The aim was to apply an advance and innovative spatial analysis approach to identify spatial pattern and clustering (hotspots) of surgical site infection rate (CSIR), and quantifying disparities across communities. METHODS: We used the Admitted Patient Data Collection for patients aged 18 years and over who underwent colorectal surgery in a public hospital between 2002 and 2013 in the Australian State of New South Wales (NSW). The colorectal surgical infection rate (CSIR) was computed. We assessed geographical variation and clustering in CSIR patterning to demonstrate spatial pattern and clustering across communities in NSW, Australia. RESULTS: There were 58,096 colorectal surgical procedures conducted in NSW from 2002 to 2013. The overall occurrence of CSIR was 9.64% (95%CI 9.40-9.88%). We found significant clusters of both high and low CSIR in outer regional and remote areas of NSW. CONCLUSION: Use of advanced spatial analyses allows identification of hotspots/clusters of adverse events that can help policy makers and clinicians better understand national patterns and initiate research to address disparities/geographical variation, and clustering of adverse events after surgery.

An environmental assessment and risk map of Ascaris lumbricoides and Necator americanus distributions in Manufahi District, Timor-Leste.

BACKGROUND: In Timor-Leste there have been intermittent and ineffective soil-transmitted helminth (STH) deworming programs since 2004. In a resource-constrained setting, having information on the geographic distribution of STH can aid in prioritising high risk communities for intervention. This study aimed to quantify the environmental risk factors for STH infection and to produce a risk map of STH in Manufahi district, Timor-Leste. METHODOLOGY/PRINCIPAL FINDINGS: Georeferenced cross-sectional data and stool samples were obtained from 2,194 participants in 606 households in 24 villages in the Manufahi District as part of cross sectional surveys done in the context of the "WASH for Worms" randomised controlled trial. Infection status was determined for Ascaris lumbricoides and Necator americanus using real-time quantitative polymerase chain reaction. Baseline infection data were linked to environmental data obtained for each household. Univariable and multivariable multilevel mixed-effects logistic regression analysis with random effects at the village and household level were conducted, with all models adjusted for age and sex. For A. lumbricoides, being a school-aged child increased the odds of infection, whilst higher temperatures in the coolest quarter of the year, alkaline soils, clay loam/loam soils and woody savannas around households were associated with decreased infection odds. For N. americanus, greater precipitation in the driest month, higher average enhanced vegetation index, age and sandy loam soils increased infection odds, whereas being female and living at higher elevations decreased the odds of infection. Predictive risk maps generated for Manufahi based upon these final models highlight the high predicted risk of N. americanus infection across the district and the more focal nature of A. lumbricoides infection. The predicted risk of any STH infection is high across the entire district. CONCLUSIONS/SIGNIFICANCE: The widespread predicted risk of any STH infection in 6 to 18 year olds provides strong evidence to support strategies for control across the entire geographical area. As few studies include soil texture and pH in their analysis, this study adds to a growing body of evidence suggesting these factors influence STH infection distribution. This study also further supports that A. lumbricoides prefers acidic soils, highlighting a potential relatively unexplored avenue for control. TRIAL REGISTRATION: ClinicalTrials.gov ACTRN12614000680662.

Spatial patterns of multidrug resistant tuberculosis and relationships to socio-economic, demographic and household factors in northwest Ethiopia.

BACKGROUND: Understanding the geographical distribution of multidrug-resistant tuberculosis (MDR-TB) in high TB burden countries such as Ethiopia is crucial for effective control of TB epidemics in these countries, and thus globally. We present the first spatial analysis of multidrug resistant tuberculosis, and its relationship to socio-economic, demographic and household factors in northwest Ethiopia. METHODS: An ecological study was conducted using data on patients diagnosed with MDR-TB at the University of Gondar Hospital MDR-TB treatment centre, for the period 2010 to 2015. District level population data were extracted from the Ethiopia National and Regional Census Report. Spatial autocorrelation was explored using Moran's I statistic, Local Indicators of Spatial Association (LISA), and the Getis-Ord statistics. A multivariate Poisson regression model was developed with a conditional autoregressive (CAR) prior structure, and with posterior parameters estimated using a Bayesian Markov chain Monte Carlo (MCMC) simulation approach with Gibbs sampling, in WinBUGS. RESULTS: A total of 264 MDR-TB patients were included in the analysis. The overall crude incidence rate of MDR-TB for the six-year period was 3.0 cases per 100,000 population. The highest incidence rate was observed in Metema (21 cases per 100,000 population) and Humera (18 cases per 100,000 population) districts; whereas nine districts had zero cases. Spatial clustering of MDR-TB was observed in districts located in the Ethiopia-Sudan and Ethiopia-Eritrea border regions, where large numbers of seasonal migrants live. Spatial clustering of MDR-TB was positively associated with urbanization (RR: 1.02; 95%CI: 1.01, 1.04) and the percentage of men (RR: 1.58; 95% CI: 1.26, 1.99) in the districts; after accounting for these factors there was no residual spatial clustering. CONCLUSION: Spatial clustering of MDR-TB, fully explained by demographic factors (urbanization and percent male), was detected in the border regions of northwest Ethiopia, in locations where seasonal migrants live and work. Cross-border initiatives including options for mobile TB treatment and follow up are important for the effective control of MDR-TB in the region.

Risk assessment of malaria in land border regions of China in the context of malaria elimination.

BACKGROUND: Cross-border malaria transmission poses a challenge for countries to achieve and maintain malaria elimination. Because of a dramatic increase of cross-border population movement between China and 14 neighbouring countries, the malaria epidemic risk in China's land border regions needs to be understood. METHODS: In this study, individual case-based epidemiological data on malaria in the 136 counties of China with international land borders, from 2011 to 2014, were extracted from the National Infectious Disease Information System. The Plasmodium species, seasonality, spatiotemporal distribution and changing features of imported and indigenous cases were analysed using descriptive spatial and temporal methods. RESULTS: A total of 1948 malaria cases were reported, with 1406 (72.2%) imported cases and 542 (27.8%) indigenous cases. Plasmodium vivax is the predominant species, with 1536 malaria cases occurrence (78.9%), following by Plasmodium falciparum (361 cases, 18.5%), and the others (51 cases, 2.6%). The magnitude and geographic distribution of malaria in land border counties shrunk sharply during the elimination period. Imported malaria cases were with a peak of 546 cases in 2011, decreasing yearly in the following years. The number of counties with imported cases decreased from 28 counties in 2011 to 26 counties in 2014. Indigenous malaria cases presented a markedly decreasing trend, with 319 indigenous cases in 2011 reducing to only 33 indigenous cases in 2014. The number of counties with indigenous cases reduced from 26 counties in 2011 to 10 counties in 2014. However, several bordering counties of Yunnan province adjacent to Myanmar reported indigenous malaria cases in the four consecutive years from 2011 to 2014. CONCLUSIONS: The scale and extent of malaria occurrence in the international land border counties of China decreased dramatically during the elimination period. However, several high-risk counties, especially along the China-Myanmar border, still face a persistent risk of malaria introduction and transmission. The study emphasizes the importance and urgency of cross-border cooperation between neighbouring countries to jointly face malaria threats to elimination goals.

Complexities and Perplexities: A Critical Appraisal of the Evidence for Soil-Transmitted Helminth Infection-Related Morbidity.

BACKGROUND: Soil-transmitted helminths (STH) have acute and chronic manifestations, and can result in lifetime morbidity. Disease burden is difficult to quantify, yet quantitative evidence is required to justify large-scale deworming programmes. A recent Cochrane systematic review, which influences Global Burden of Disease (GBD) estimates for STH, has again called into question the evidence for deworming benefit on morbidity due to STH. In this narrative review, we investigate in detail what the shortfalls in evidence are. METHODOLOGY/PRINCIPAL FINDINGS: We systematically reviewed recent literature that used direct measures to investigate morbidity from STH and we critically appraised systematic reviews, particularly the most recent Cochrane systematic review investigating deworming impact on morbidity. We included six systematic reviews and meta-analyses, 36 literature reviews, 44 experimental or observational studies, and five case series. We highlight where evidence is insufficient and where research needs to be directed to strengthen morbidity evidence, ideally to prove benefits of deworming. CONCLUSIONS/SIGNIFICANCE: Overall, the Cochrane systematic review and recent studies indicate major shortfalls in evidence for direct morbidity. However, it is questionable whether the systematic review methodology should be applied to STH due to heterogeneity of the prevalence of different species in each setting. Urgent investment in studies powered to detect direct morbidity effects due to STH is required.

Malaria burden and costs of intensified control in Bhutan, 2006-14: an observational study and situation analysis.

INTRODUCTION: The number of malaria cases has fallen in Bhutan in the past two decades, and the country has a goal of complete elimination of malaria by 2016. The aims of this study are to ascertain the trends and burden of malaria, the costs of intensified control activities, the main donors of funding for the control activities, and the costs of different preventive measures in the pre-elimination phase (2006-14) in Bhutan. METHODS: We undertook a descriptive analysis of malaria surveillance data from 2006 to 2014, using data from the Vector-borne Disease Control Programme (VDCP) run by the Department of Public Health of Bhutan's Ministry of Health. Malaria morbidity and mortality in local Bhutanese people and foreign nationals were analysed. The cost of different control and preventive measures were calculated, and the average numbers of long-lasting insecticidal nests per person were estimated. FINDINGS: A total of 5491 confirmed malaria cases occurred in Bhutan between 2006 and 2014. By 2013, there was an average of one long-lasting insecticidal net for every 1·51 individuals. The cost of procuring long-lasting insecticidal nets accounted for more than 90% of the total cost of prevention measures. The Global Fund to Fight AIDS, Tuberculosis and Malaria was the main international donor, accounting for more than 80% of the total funds. INTERPRETATION: The malaria burden in Bhutan decreased significantly during the study period with high coverage of long-lasting insecticidal nets. The foreseeable challenges that require national attention to maintain a malaria-free status after elimination are importation of malaria, especially from India; continued protection of the population in endemic districts through complete coverage with long-lasting insecticidal nets and indoor residual spraying; and exploration of local funding modalities post-elimination in the event of a reduction in international funding. FUNDING: None.

Cost analysis of the development and implementation of a spatial decision support system for malaria elimination in Solomon Islands.

BACKGROUND: The goal of malaria elimination faces numerous challenges. New tools are required to support the scale up of interventions and improve national malaria programme capacity to conduct detailed surveillance. This study investigates the cost factors influencing the development and implementation of a spatial decision support system (SDSS) for malaria elimination in the two elimination provinces of Isabel and Temotu, Solomon Islands. METHOD: Financial and economic costs to develop and implement a SDSS were estimated using the Solomon Islands programme's financial records. Using an ingredients approach, verified by stakeholders and operational reports, total costs for each province were quantified. A budget impact sensitivity analysis was conducted to investigate the influence of variations in standard budgetary components on the costs and to identify potential cost savings. RESULTS: A total investment of US$ 96,046 (2012 constant dollars) was required to develop and implement the SDSS in two provinces (Temotu Province US$ 49,806 and Isabel Province US$ 46,240). The single largest expense category was for computerized equipment totalling approximately US$ 30,085. Geographical reconnaissance was the most expensive phase of development and implementation, accounting for approximately 62% of total costs. Sensitivity analysis identified different cost factors between the provinces. Reduced equipment costs would deliver a budget saving of approximately 10% in Isabel Province. Combined travel costs represented the greatest influence on the total budget in the more remote Temotu Province. CONCLUSION: This study provides the first cost analysis of an operational surveillance tool used specifically for malaria elimination in the South-West Pacific. It is demonstrated that the costs of such a decision support system are driven by specialized equipment and travel expenses. Such factors should be closely scrutinized in future programme budgets to ensure maximum efficiencies are gained and available resources are allocated effectively.