Determinants of drug-resistant tuberculosis in Hunan province, China: a case-control study.

BACKGROUND: Drug-resistant tuberculosis (DR-TB) is a major public health threat in Hunan Province, with an increasing clinical burden in recent years. This study aimed to identify socio-demographic and clinical factors associated with DR-TB in Hunan province, China. METHODS: A case-control study was conducted in Hunan province. Cases were all DR-TB patients who were confirmed by culture and Drug susceptibility testing (DST) and enrolled at the DR-TB treatment center of Hunan Chest Hospital from 2013 to 2018. Controls were all Drug Susceptible TB (DS-TB) patients confirmed by DST and enrolled at the same hospital during the same period. A multivariable logistic regression model was fitted to identify factors significantly associated with DR-TB. RESULTS: A total of 17,808 patients (15,534 DS-TB controls and 2274 DR-TB cases) were included in the study, with a mean age of 42.5 years (standard deviation (SD) ± 17.5 years) for cases and 46.1 years (SD ± 19.1 years) for controls. Age 15-64 years (Adjusted odds ratio (AOR = 1.5, 95% CI; 1.4, 1.8)), ethnic minorities (AOR = 1.5; 95% CI; 1.4, 1.8), and a history of previous TB treatment (AOR) = 1.84; 95% CI: 1.57, 2.15) was significantly associated with DR-TB. Being resident in a province outside Hunan was also a significant risk factor (AOR = 1.67; 1.27, 2.21) for DR-TB. CONCLUSION AND RECOMMENDATIONS: To prevent the occurrence of DR-TB in Hunan Province, interventions should be targeted at high-risk demographic groups such as ethnic minorities, individuals of productive age, and residents living outside the province. Interventions must also be targeted to previously treated cases, suggesting the appropriateness of diagnosis, treatment, and follow-up. Understanding the risk factors at the province level helps design strategies for controlling DR-TB due to variations by socioeconomic differences, quality of health care, and healthcare access.

Risk factors for diagnosis and treatment delay among patients with multidrug-resistant tuberculosis in Hunan Province, China.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is a global health threat associated with high morbidity and mortality rates. Diagnosis and treatment delays are associated with poor treatment outcomes in patients with MDR-TB. However, the risk factors associated with these delays are not robustly investigated, particularly in high TB burden countries such as China. Therefore, this study aimed to measure the length of diagnosis and treatment delays and identify their risk factors among patients with MDR-TB in Hunan province. METHODS: A retrospective cohort study was conducted using MDR-TB data from Hunan province between 2013 and 2018. The main outcomes of the study were diagnosis and treatment delay, defined as more than 14 days from the date of symptom to diagnosis confirmation (i.e., diagnosis delay) and from diagnosis to treatment commencement (i.e., treatment delay). A multivariable logistic regression model was fitted, and an adjusted odds ratio (AOR) with a 95% confidence interval (CI) was used to identify factors associated with diagnosis and treatment delay. RESULTS: In total, 1,248 MDR-TB patients were included in this study. The median length of diagnosis delays was 27 days, and treatment delays were one day. The proportion of MDR-TB patients who experienced diagnosis and treatment delay was 62.82% (95% CI: 60.09-65.46) and 30.77% (95% CI: 28.27-33.39), respectively. The odds of experiencing MDR-TB diagnosis delay among patients coming through referral and tracing was reduced by 41% (AOR = 0.59, 95% CI: 0.45-0.76) relative to patients identified through consultations due to symptoms. The odds of experiencing diagnosis delay among ≥ 65 years were 65% (AOR = 0.35, 0.14-0.91) lower than under-15 children. The odds of developing treatment delay among foreign nationalities and people from other provinces were double (AOR = 2.00, 95% CI: 1.31-3.06) compared to the local populations. Similarly, the odds of experiencing treatment delay among severely ill patients were nearly 2.5 times higher (AOR = 2.49, 95% CI: 1.41-4.42) compared to patients who were not severely ill. On the other hand, previously treated TB cases had nearly 40% (AOR = 0.59, 95% CI: 0.42-0.85) lower odds of developing treatment delay compared with new MDR-TB cases. Similarly, other ethnic minority groups had nearly 40% (AOR = 0.57, 95% CI: 0.34-0.96) lower odds of experiencing treatment delay than the Han majority. CONCLUSIONS: Many MDR-TB patients experience long diagnosis and treatment delays in Hunan province. Strengthening active case detection can significantly reduce diagnosis delays among MDR-TB patients. Moreover, giving attention to patients who are new to MDR-TB treatment, are severely ill, or are from areas outside Hunan province will potentially reduce the burden of treatment delay among MDR-TB patients.

The Prevalence of HIV Infection in Minority Indigenous Populations of the South-East Asia and Western Pacific Regions: A Systematic Review and Meta-analysis.

A random effects meta-analysis was used to estimate the pooled prevalence of HIV infection within minority indigenous populations of the South-East Asia (SEAR) and Western Pacific Regions (WPR). Sub-group analyses were conducted, and the sources of heterogeneity explored through meta-regression. The majority of studies were undertaken in high HIV risk subpopulations. There was a paucity of data for many countries with data from China representing 70% of the comparative studies. Within minority indigenous populations the pooled prevalence of HIV infection was 13.7% (95% CI 8.9, 19) and 8.4% (95% CI 6.3, 10.7) among other populations. The prevalence differential between populations was significant in the WPR (adjusted odds ratio 1.1, 95% CI 1.0, 1.2). Across both regions, in contrast to other populations, minority indigenous did not experience any significant reduction in HIV prevalence over the years of data collection. There was large heterogeneity in the prevalence of HIV across studies.

Liver and cardiometabolic markers and conditions in a cross-sectional study of three Australian communities living with environmental per- and polyfluoroalkyl substances contamination.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) have been associated with higher cholesterol and liver function markers in some studies, but the evidence for specific cardiometabolic conditions has been inconclusive. OBJECTIVES: We quantified the associations of single and combined PFAS with cardiometabolic markers and conditions in a cross-sectional study of three Australian communities with PFAS-contaminated water from the historical use of aqueous film-forming foam in firefighting activities, and three comparison communities. METHODS: Participants gave blood samples for measurement of nine PFAS, four lipids, six liver function markers, and completed a survey on sociodemographic characteristics and eight cardiometabolic conditions. We estimated differences in mean biomarker concentrations per doubling in single PFAS concentrations (linear regression) and per interquartile range increase in the PFAS mixture (Bayesian kernel machine regression). We estimated prevalence ratios of biomarker concentrations outside reference limits and self-reported cardiometabolic conditions (Poisson regression). RESULTS: We recruited 881 adults in exposed communities and 801 in comparison communities. We observed higher mean total cholesterol with higher single and mixture PFAS concentrations in blood serum (e.g., 0.18 mmol/L, 95% credible interval -0.06 to 0.42, higher total cholesterol concentrations with an interquartile range increase in all PFAS concentrations in Williamtown, New South Wales), with varying certainty across communities and PFAS. There was less consistency in direction of associations for liver function markers. Serum perfluorooctanoic acid (PFOA) concentrations were positively associated with the prevalence of self-reported hypercholesterolemia in one of three communities, but PFAS concentrations were not associated with self-reported type II diabetes, liver disease, or cardiovascular disease. DISCUSSION: Our study is one of few that has simultaneously quantified the associations of blood PFAS concentrations with multiple biomarkers and cardiometabolic conditions in multiple communities. Our findings for total cholesterol were consistent with previous studies; however, substantial uncertainty in our estimates and the cross-sectional design limit causal inference.

Risk factors associated with unsuccessful tuberculosis treatment outcomes in Hunan Province, China.

OBJECTIVES: Globally, China has the third highest number of tuberculosis (TB) cases despite high rates (85.6%) of effective treatment coverage. Identifying risk factors associated with unsuccessful treatment outcomes is an important component of maximising the efficacy of TB control programmes. METHODS: Retrospective cohort study to evaluate the outcomes of 306,860 drug-susceptible TB patients who underwent treatment in Hunan Province, China between 2013 and 2018. Univariable and multivariable logistic regression models were used to identify factors associated with unsuccessful TB treatment outcomes. RESULTS: A successful treatment outcome was recorded for 98.6% of patients, defined as the sum of patients who were cured (36.2%) and completed treatment (62.4%). An unsuccessful treatment outcome was recorded for 1.8% of patients, defined as the sum of treatment failure (1.1%), deaths (0.5%) and lost to follow up (0.2%). The odds of an unsuccessful treatment outcome showed an increasing trend in more recent years of registration (2018 adjusted odds ratio (AOR): 1.43; 95% Confidence Interval (CI) 1.31, 1.57 relative to 2013). Other significant risk factors were male sex (AOR: 1.17; 95% CI 1.10, 1.25); increasing age (AOR:1.02 per year increase; 95% CI 1.02,1.02); being severely ill (AOR: 1.50; 95% CI 1.33, 1.70); having a history of TB treatment (AOR: 2.93; 95% CI 2.69, 3.20); not being under systematic management (AOR: 16.10 (14.49, 17.88) and treatment regimens that differed from full course management. CONCLUSIONS: The increasing likelihood of an unsuccessful treatment outcome over time necessitates the need for further research.

The impact of ethnic minority status on tuberculosis diagnosis and treatment delays in Hunan Province, China.

BACKGROUND: Tuberculosis (TB) continues to be a major public health challenge in China. Understanding TB management delays within the context of China's unique ethnic diversity may be of value in tackling the disease. This study sought to evaluate the impact of ethnic minority status on TB diagnosis and treatment delays. METHODS: This retrospective cohort study was conducted on patients diagnosed with TB in Hunan Province, China between 2013 and 2018. Diagnosis delay was defined as the time interval between the onset of symptoms and the date of diagnosis. Treatment delay was defined as the time interval between diagnosis and treatment commencement. Univariable and multivariable logistic regression models were used to identify factors associated with TB diagnosis and treatment delay, including ethnic minority status. Adjusted odds ratios (AOR) with 95% confidence intervals (CI) were calculated to assess the strength of association between the dependant and independent variables. RESULTS: A total of 318,792 TB patients were included in the study with a mean age of 51.7 years (SD 17.7). The majority of patients were male (72.6%) and Han ethnicity (90.6%). The odds of experiencing diagnosis delay (> 21 days) were significantly higher for Tujia (AOR: 1.46, 95% CI: 1.41, 1.51), Miao (AOR: 1.31, 95% CI: 1.26, 1.37), Dong (AOR: 1.97, 95% CI: 1.85, 2.11), Yao (AOR: 1.27, 95% CI: 1.17, 1.37), and Bai (AOR: 1.45, 95% CI: 1.22, 1.74) ethnic minorities compared to the Han majority. The odds of experiencing treatment delay (> 15 days) were significantly lower for five of the seven ethnic minority groups relative to the Han majority: Tujia (AOR 0.92, 95% CI 0.88, 0.96), Miao (AOR 0.74, 95% CI 0.70, 0.79), Dong (AOR 0.87, 95% CI 0.81, 0.95), Yao (AOR 0.20, 95% CI 0.17, 0.24) and 'other' (ethnic minorities that individually represented < 0.1% of the patient population) (AOR 0.70, 955 CI 0.51, 0.97). CONCLUSIONS: This study shows ethnic minority status to be a significant risk factor in diagnosis delay, but for it to reduce the odds of treatment delay. Further research is required to determine the underlying causes of diagnosis delay within ethnic minority populations.

Neglected tropical diseases in Australia: a narrative review.

•Neglected tropical diseases (NTDs) represent a threat to the health, wellbeing and economic prosperity of billions of people worldwide, often causing serious disease or death. •Commonly considered diseases of low and middle-income nations, the presence of NTDs in high income countries such as Australia is often overlooked. •Seven of the 20 recognised NTDs are endemic in Australia: scabies, soil-transmitted helminths and strongyloidiasis, echinococcosis, Buruli ulcer, leprosy, trachoma, and snakebite envenoming. •Dengue, while not currently endemic, poses a risk of establishment in Australia. There are occasional outbreaks of dengue fever, with local transmission, due to introductions in travellers from endemic regions. •Similarly, the risk of introduction of other NTDs from neighbouring countries is a concern. Many NTDs are only seen in Australia in individuals travelling from endemic areas, but they need to be recognised in health settings as the potential consequences of infection can be severe. •In this review, we consider the status of NTDs in Australia, explore the risk of introducing and contracting these infections, and emphasise the negative impact they have on the health of Australians, especially Aboriginal and Torres Strait Islander peoples.

Schistosomiasis in the People's Republic of China - down but not out.

Schistosomiasis has been subjected to extensive control efforts in the People's Republic of China (China) which aims to eliminate the disease by 2030. We describe baseline results of a longitudinal cohort study undertaken in the Dongting and Poyang lakes areas of central China designed to determine the prevalence of Schistosoma japonicum in humans, animals (goats and bovines) and Oncomelania snails utilizing molecular diagnostics procedures. Data from the Chinese National Schistosomiasis Control Programme (CNSCP) were compared with the molecular results obtained.Sixteen villages from Hunan and Jiangxi provinces were surveyed; animals were only found in Hunan. The prevalence of schistosomiasis in humans was 1.8% in Jiangxi and 8.0% in Hunan determined by real-time polymerase chain reaction (PCR), while 18.3% of animals were positive by digital droplet PCR. The CNSCP data indicated that all villages harboured S. japonicum-infected individuals, detected serologically by indirect haemagglutination assay (IHA), but very few, if any, of these were subsequently positive by Kato-Katz (KK).Based on the outcome of the IHA and KK results, the CNSCP incorporates targeted human praziquantel chemotherapy but this approach can miss some infections as evidenced by the results reported here. Sensitive molecular diagnostics can play a key role in the elimination of schistosomiasis in China and inform control measures allowing for a more systematic approach to treatment.

Has COVID19 derailed Bhutan's national malaria elimination goal? A commentary.

The COVID-19 pandemic has resulted in massive global disruptions with considerable impact on the delivery of health services and national health programmes. Since the detection of the first COVID-19 case on 5th March 2020, the Royal Government of Bhutan implemented a number of containment measures including border closure and national lockdowns. Against the backdrop of this global COVID-19 pandemic response, there was a sudden surge of locally-transmitted malaria cases between June to August 2020. There were 20 indigenous cases (zero Plasmodium falciparum and 20 Plasmodium vivax) from a total of 49 cases (seven P. falciparum and 42 P. vivax) in 2020 compared to just two from a total of 42 in 2019. Over 80% of the cases were clustered in malaria endemic district of Sarpang. This spike of malaria cases was attributed to the delay in the delivery of routine malaria preventive interventions due to the COVID-19 pandemic. As a result, Bhutan is unlikely to achieve the national goal of malaria elimination by 2020.

Spatial prediction of malaria prevalence in Papua New Guinea: a comparison of Bayesian decision network and multivariate regression modelling approaches for improved accuracy in prevalence prediction.

BACKGROUND: Considerable progress towards controlling malaria has been made in Papua New Guinea through the national malaria control programme's free distribution of long-lasting insecticidal nets, improved diagnosis with rapid diagnostic tests and improved access to artemisinin combination therapy. Predictive prevalence maps can help to inform targeted interventions and monitor changes in malaria epidemiology over time as control efforts continue. This study aims to compare the predictive performance of prevalence maps generated using Bayesian decision network (BDN) models and multilevel logistic regression models (a type of generalized linear model, GLM) in terms of malaria spatial risk prediction accuracy. METHODS: Multilevel logistic regression models and BDN models were developed using 2010/2011 malaria prevalence survey data collected from 77 randomly selected villages to determine associations of Plasmodium falciparum and Plasmodium vivax prevalence with precipitation, temperature, elevation, slope (terrain aspect), enhanced vegetation index and distance to the coast. Predictive performance of multilevel logistic regression and BDN models were compared by cross-validation methods. RESULTS: Prevalence of P. falciparum, based on results obtained from GLMs was significantly associated with precipitation during the 3 driest months of the year, June to August (ß = 0.015; 95% CI = 0.01-0.03), whereas P. vivax infection was associated with elevation (ß = - 0.26; 95% CI = - 0.38 to - 3.04), precipitation during the 3 driest months of the year (ß = 0.01; 95% CI = - 0.01-0.02) and slope (ß = 0.12; 95% CI = 0.05-0.19). Compared with GLM model performance, BDNs showed improved accuracy in prediction of the prevalence of P. falciparum (AUC = 0.49 versus 0.75, respectively) and P. vivax (AUC = 0.56 versus 0.74, respectively) on cross-validation. CONCLUSIONS: BDNs provide a more flexible modelling framework than GLMs and may have a better predictive performance when developing malaria prevalence maps due to the multiple interacting factors that drive malaria prevalence in different geographical areas. When developing malaria prevalence maps, BDNs may be particularly useful in predicting prevalence where spatial variation in climate and environmental drivers of malaria transmission exists, as is the case in Papua New Guinea.

Clinical features and outcomes of COVID-19 and dengue co-infection: a systematic review.

BACKGROUND: Dengue is the most common arboviral disease in the tropical and sub-tropical regions of the world. Like other regions, dengue-endemic areas have faced the additional public health and socio-economic impact of the ongoing coronavirus disease 2019 (COVID-19) pandemic. COVID-19 and dengue co-infections have been reported, with complicated patient management and care requirements. This review aimed to collate and synthesise current knowledge on the clinical features and outcomes of COVID-19 and dengue virus co-infection, a potentially important new dimension to be considered in public health management of the COVID-19 pandemic. METHODS: A systematic literature review was conducted using PubMed, Web of Science and Scopus databases from 1st January to 21st November 2020. The key search terms used were "dengue" and "coronavirus". Descriptive analysis with graphical illustrations were used to present the clinical and laboratory parameters of the co-infection. RESULTS: Thirteen published papers and four news articles were included in the review. Most studies were case reports with a detailed description of the clinical and laboratory characteristics of the co-infection. All cases were in adults with the exception of a six-year old child. The common symptoms of co-infection were fever, dyspnea, headache, and cough. Common laboratory results included thrombocytopenia, lymphocytopenia, elevated transaminases, and leukopenia. Serious outcomes of co-infection included septic shock, acute respiratory disease syndrome and multi-organ failure, leading to death in some patients. CONCLUSIONS: COVID-19 and dengue co-infection was associated with severe disease and fatal outcomes. The correct diagnosis and treatment of co-infection poses a substantial challenge due to the overlapping clinical and laboratory parameters. Therefore, confirmative diagnostic tests are necessary for accurate and timely diagnosis and patient management.

Correction: Quantification of glucose-6-phosphate dehydrogenase activity by spectrophotometry: A systematic review and meta-analysis.

[This corrects the article DOI: 10.1371/journal.pmed.1003084.].

Quantification of glucose-6-phosphate dehydrogenase activity by spectrophotometry: A systematic review and meta-analysis.

BACKGROUND: The radical cure of Plasmodium vivax and P. ovale requires treatment with primaquine or tafenoquine to clear dormant liver stages. Either drug can induce haemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, necessitating screening. The reference diagnostic method for G6PD activity is ultraviolet (UV) spectrophotometry; however, a universal G6PD activity threshold above which these drugs can be safely administered is not yet defined. Our study aimed to quantify assay-based variation in G6PD spectrophotometry and to explore the diagnostic implications of applying a universal threshold. METHODS AND FINDINGS: Individual-level data were pooled from studies that used G6PD spectrophotometry. Studies were identified via PubMed search (25 April 2018) and unpublished contributions from contacted authors (PROSPERO: CRD42019121414). Studies were excluded if they assessed only individuals with known haematological conditions, were family studies, or had insufficient details. Studies of malaria patients were included but analysed separately. Included studies were assessed for risk of bias using an adapted form of the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. Repeatability and intra- and interlaboratory variability in G6PD activity measurements were compared between studies and pooled across the dataset. A universal threshold for G6PD deficiency was derived, and its diagnostic performance was compared to site-specific thresholds. Study participants (n = 15,811) were aged between 0 and 86 years, and 44.4% (7,083) were women. Median (range) activity of G6PD normal (G6PDn) control samples was 10.0 U/g Hb (6.3-14.0) for the Trinity assay and 8.3 U/g Hb (6.8-15.6) for the Randox assay. G6PD activity distributions varied significantly between studies. For the 13 studies that used the Trinity assay, the adjusted male median (AMM; a standardised metric of 100% G6PD activity) varied from 5.7 to 12.6 U/g Hb (p < 0.001). Assay precision varied between laboratories, as assessed by variance in control measurements (from 0.1 to 1.5 U/g Hb; p < 0.001) and study-wise mean coefficient of variation (CV) of replicate measures (from 1.6% to 14.9%; p < 0.001). A universal threshold of 100% G6PD activity was defined as 9.4 U/g Hb, yielding diagnostic thresholds of 6.6 U/g Hb (70% activity) and 2.8 U/g Hb (30% activity). These thresholds diagnosed individuals with less than 30% G6PD activity with study-wise sensitivity from 89% (95% CI: 81%-94%) to 100% (95% CI: 96%-100%) and specificity from 96% (95% CI: 89%-99%) to 100% (100%-100%). However, when considering intermediate deficiency (<70% G6PD activity), sensitivity fell to a minimum of 64% (95% CI: 52%-75%) and specificity to 35% (95% CI: 24%-46%). Our ability to identify underlying factors associated with study-level heterogeneity was limited by the lack of availability of covariate data and diverse study contexts and methodologies. CONCLUSIONS: Our findings indicate that there is substantial variation in G6PD measurements by spectrophotometry between sites. This is likely due to variability in laboratory methods, with possible contribution of unmeasured population factors. While an assay-specific, universal quantitative threshold offers robust diagnosis at the 30% level, inter-study variability impedes performance of universal thresholds at the 70% level. Caution is advised in comparing findings based on absolute G6PD activity measurements across studies. Novel handheld quantitative G6PD diagnostics may allow greater standardisation in the future.

Evaluation of the malaria reporting system supported by the District Health Information System 2 in Solomon Islands.

BACKGROUND: District Health Information Systems 2 (DHIS2) is used for supporting health information management in 67 countries, including Solomon Islands. However, there have been few published evaluations of the performance of DHIS2-enhanced disease reporting systems, in particular for monitoring infectious diseases such as malaria. The aim of this study was to evaluate DHIS2 supported malaria reporting in Solomon Islands and to develop recommendations for improving the system. METHODS: The evaluation was conducted in three administrative areas of Solomon Islands: Honoria City Council, and Malaita and Guadalcanal Provinces. Records of nine malaria indicators including report submission date, total malaria cases, Plasmodium falciparum case record, Plasmodium vivax case record, clinical malaria, malaria diagnosed with microscopy, malaria diagnosed with (rapid diagnostic test) (RDT), record of drug stocks and records of RDT stocks from 1st January to 31st December 2016 were extracted from the DHIS2 database. The indicators permitted assessment in four core areas: availability, completeness, timeliness and reliability. To explore perceptions and point of view of the stakeholders on the performance of the malaria case reporting system, focus group discussions were conducted with health centre nurses, whilst in-depth interviews were conducted with stakeholder representatives from government (province and national) staff and World Health Organization officials who were users of DHIS2. RESULTS: Data were extracted from nine health centres in Honoria City Council and 64 health centres in Malaita Province. The completeness and timeliness from the two provinces of all nine indicators were 28.2% and 5.1%, respectively. The most reliable indicator in DHIS2 was 'clinical malaria' (i.e. numbers of clinically diagnosed malaria cases) with 62.4% reliability. Challenges to completeness were a lack of supervision, limited feedback, high workload, and a lack of training and refresher courses. Health centres located in geographically remote areas, a lack of regular transport, high workload and too many variables in the reporting forms led to delays in timely reporting. Reliability of reports was impacted by a lack of technical professionals such as statisticians and unavailability of tally sheets and reporting forms. CONCLUSION: The availability, completeness, timeliness and reliability of nine malaria indicators collected in DHIS2 were variable within the study area, but generally low. Continued onsite support, supervision, feedback and additional enhancements, such as electronic reporting will be required to further improve the malaria reporting system.

Efficacy of Anthelminthic Drugs and Drug Combinations Against Soil-transmitted Helminths: A Systematic Review and Network Meta-analysis.

Background: Periodic mass distribution of benzimidazole anthelminthic drugs is the key strategy to control soil-transmitted helminths (STHs) globally. However, benzimidazoles have low efficacy against Trichuris trichiura, and there are concerns about benzimidazole resistance potentially emerging in humans. Therefore, identifying alternative drug regimens is a pressing priority. We present a systematic review and network meta-analysis comparing the efficacy of 21 different anthelminthic drug regimens, including standard, novel, and combination treatments. Methods: We searched PubMed, Medline, Embase, Web of Science, and Cochrane databases and identified studies comparing anthelminthic treatments to each other or placebo. The outcomes calculated were relative risk (RR) of cure and difference in egg reduction rates (dERR). We used an automated generalized pairwise modeling framework to generate mixed treatment effects against a common comparator, the current standard treatment (single-dose albendazole). Results: Our search identified 4876 studies, of which 114 were included in the meta-analysis. Results identified several drug combinations with higher efficacy than single-dose albendazole for T. trichiura, including albendazole-ivermectin (RR of cure, 3.22 [95% confidence interval {CI}, 1.84-5.63]; dERR, 0.97 [95% CI, .21-1.74]), albendazole-oxantel pamoate (RR, 5.07 [95% CI, 1.65-15.59]; dERR, 0.51 [95% CI, .50-.52]), mebendazole-ivermectin (RR, 3.37 [95% CI, 2.20-5.16]), and tribendimidine-oxantel pamoate (RR, 4.06 [95% CI, 1.30-12.64]). Conclusions: There are several promising drug combinations that may enhance the impact of STH control programs on T. trichiura, without compromising efficacy against Ascaris lumbricoides and hookworm. We suggest further, large-scale trials of these drug combinations and consideration of their use in STH control programs where T. trichiura is present. International Prospective Register of Systematic Reviews Registration: CRD42016050739.

Forest cover and climate as potential drivers for dengue fever in Sumatra and Kalimantan 2006-2016: a spatiotemporal analysis.

OBJECTIVES: To describe and quantify spatiotemporal trends of dengue fever at district level in Sumatra and Kalimantan, Indonesia in relation to forest cover and climatic factors. METHODS: A spatial ecological study design was used to analyse monthly surveillance data of notified dengue fever cases from January 2006 to December 2016 in the 154 districts of Sumatra and 56 districts of Kalimantan. A multivariate, zero-inflated Poisson regression model was developed with a conditional autoregressive prior structure with posterior parameters estimated using Bayesian Markov chain Monte Carlo simulation with Gibbs sampling. RESULTS: There were 230 745 cases in Sumatra and 132 186 cases in Kalimantan during the study period. In Sumatra, the risk of dengue fever decreased by 9% (95% credible interval [CrI] 8.5-9.5%) for a 1% increase in forest cover and by 12.2% (95% CrI 11.9-12.6%) for a 1% increase in relative humidity. In Kalimantan, dengue fever risk fell by 17.6% (95% CrI 17.1-18.1%) for a 1% increase in relative humidity and rose by 7.6% (95% CrI 6.9-8.4%) for a 1 °C increase in minimum temperature. There was no significant residual spatial clustering in Sumatra after accounting for climate and demographic variables. In Kalimantan, high residual risk areas were primarily centred in North and East of the island. CONCLUSIONS: Dengue fever in Sumatra and Kalimantan was highly seasonal and associated with climate factors and deforestation. Incorporation of climate indicators into risk-based surveillance might be warranted for dengue fever in Indonesia.

OBJECTIFS: Décrire et quantifier les tendances spatiotemporelles de la fièvre dengue au niveau du district à Sumatra et à Kalimantan, en Indonésie, en relation avec la couverture forestière et les facteurs climatiques. MÉTHODES: Un schéma d'étude écologique spatiale a été utilisé pour analyser les données de surveillance mensuelles des cas notifiés de fièvre dengue de janvier 2006 à décembre 2016 dans les 154 districts de Sumatra et 56 districts de Kalimantan. Un modèle de régression de Poisson multivarié à inflation de zéro a été développé avec une structure antérieure autorégressive conditionnelle avec des paramètres postérieurs estimés à l'aide de la simulation bayésienne de Monte Carlo à chaîne de Markov avec échantillonnage de Gibbs. RÉSULTATS: Il y avait 230.745 cas à Sumatra et 132.186 cas à Kalimantan au cours de la période de l'étude. A Sumatra, le risque de fièvre dengue a diminué de 9% (intervalle de confiance à 95% [IC] de 8,5 à 9,5%) pour une augmentation de 1% de la couverture forestière et de 12,2% (IC95%: 11,9-12,6%) pour une augmentation de 1% de l'humidité relative. A Kalimantan, le risque de fièvre dengue a diminué de 17,6% (IC95%: 17,1-18,1%) pour une augmentation de 1% de l'humidité relative et a augmenté de 7,6% (IC95%: 6,9-8,4%) pour une augmentation de 1°C de la température minimale. Après la prise en compte des variables climatiques et démographiques, aucun regroupement spatial résiduel n'était significatif à Sumatra. A Kalimantan, les zones à risque résiduel élevé étaient principalement situées dans le nord et dans l'est de l'île. CONCLUSIONS: La fièvre dengue à Sumatra et à Kalimantan était très saisonnière et associée aux facteurs climatiques et à la déforestation. L'intégration d'indicateurs climatiques dans la surveillance fondée sur les risques pourrait être justifiée pour la fièvre dengue en Indonésie.

Diversity of infectious aetiologies of acute undifferentiated febrile illnesses in south and Southeast Asia: a systematic review.

BACKGROUND: Acute undifferentiated febrile illness (AUFI) is caused by a multitude of diverse pathogens, with significant morbidity and mortality in the developing world. The objective of this review was to characterise the diversity and relative importance of common infectious aetiologies of AUFI in South and Southeast Asia. METHODS: We conducted a comprehensive literature review to identify common aetiologies of AUFI in Asian countries. Four medical and life sciences databases including PubMed, Medline, Embase and Cochrane Central, and Google Scholar were searched for articles published from January 1998 to March 2019. RESULTS: Forty-three studies met the inclusion criteria. Among AUFI cases, viral aetiologies at 18.5% (14888) were more common than bacterial aetiologies (12.9% [10384]). From 80,554 cases, dengue fever was the most common aetiology (11.8%, 9511), followed by leptospirosis (4.4%, 3549), typhoid (4.0%, 3258), scrub typhus (4.0%, 3243) and influenza other than H1N1 (3.1%, 2514). In both adults and children: dengue fever was the leading cause of AUFI with 16.6% (1928) and 18.7% (1281) of the total cases. In admitted patients, dengue fever was the main cause of AUFI at 16.4% (2377), however leptospirosis at 13.9% (2090) was the main cause of AUFI for outpatients. In South Asia, dengue fever was the main cause of AUFI, causing 12.0% (6821) of cases, whereas in Southeast Asia, leptospirosis was the main diagnosis, causing 12.1% (2861) of cases. CONCLUSIONS: In this study the most common causes of AUFI were viral, followed by bacterial and protozoal (malaria) infections. Dengue was the commonest virus that caused AUFI while leptospirosis and typhoid were important bacterial infectious causes. Therefore, it is imperative to maintain a sound epidemiological knowledge of AUFI so that evidence-based diagnostic criteria and treatment guidelines can be developed.

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 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 .

Comparison of influenza disease burden in older populations of Hong Kong and Brisbane: the impact of influenza and pneumococcal vaccination.

BACKGROUND: Influenza and pneumococcal vaccine uptake in the older population aged 65 years or over of Hong Kong dramatically increased since the 2003 SARS outbreak. This study is aimed to evaluate the impact of increased coverage of influenza and pneumococcal vaccines by comparing the change of disease burden in the older population of Hong Kong, with the burden in the older population of Brisbane with relatively high vaccine coverage in the past fifteen years. METHODS: Time series segmented regression models were applied to weekly numbers of cause-specific mortality or hospitalization of Hong Kong and Brisbane. Annual excess rates of mortality or hospitalization associated with influenza in the older population were estimated for the pre-SARS (reference period), post-SARS and post-pandemic period, respectively. The rate ratios (RRs) between these periods were also calculated to assess the relative change of disease burden. RESULTS: Compared to the pre-SARS period, excess rates of mortality associated with influenza during the post-SARS period in Hong Kong decreased for cardiorespiratory diseases (RR = 0.90, 95% CI 0.80, 1.01), stroke (RR = 0.74, 95% CI 0.50, 1.09), and ischemic heart diseases (RR = 0.45, 95% CI 0.34, 0.58). The corresponding RRs in Brisbane were 0.79 (95% CI 0.54, 1.15), 0.33 (0.13, 0.80), and 1.09 (0.62, 1.90), respectively. Only the mortality of ischemic heart diseases showed a greater reduction in Hong Kong than in Brisbane. During the post-pandemic period, excess rates of all-cause mortality increased in Hong Kong, but to a lesser extent than in Brisbane (RR = 1.41 vs 2.39). CONCLUSION: A relative decrease (or less of an increase) of influenza disease burden was observed in the older population of Hong Kong after increased coverage of influenza and pneumococcal vaccines in this population, as compared to those of Brisbane where vaccination rates remained stable. The lack of significant findings in some disease categories highlights the challenges of evaluating the benefits of vaccination at the population level.