We describe 10 patients with nonkeratitis Acanthamoeba infection who reported performing nasal rinsing before becoming ill. All were immunocompromised, 7 had chronic sinusitis, and many used tap water for nasal rinsing. Immunocompromised persons should be educated about safe nasal rinsing to prevent free-living ameba infections.

We describe the isolation of a novel flavivirus, isolated from a pool of mosquitoes identified as Culex (Culex) chidesteri collected in 2010 in the Pantanal region of west-central Brazil. The virus is herein designated Nhumirim virus (NHUV) after the name of the ranch from which the mosquito pool was collected. Flavivirus RNA was detected by real-time RT-PCR of homogenized mosquitoes and from the corresponding C6/36 culture supernatant. Based on full-genome sequencing, the virus isolate was genetically distinct from but most closely related to Barkedji virus (BJV), a newly described flavivirus from Senegal. Phylogenetic analysis demonstrated that NHUV grouped with mosquito-borne flaviviruses forming a clade with BJV. This clade may be genetically intermediate between the Culex-borne flaviviruses amplified by birds and the insect-only flaviviruses.

Electronic cigarette use is growing in popularity and accessibility among youth in the Southeast Asia region. We analyzed data on 6670 students, aged 13-15 years, from the Philippines' 2019 Global Youth Tobacco Survey. Prevalence estimates and 95% confidence intervals (CI) were estimated for current use (i.e., past 30 days), ever use, and awareness of e-cigarettes. Chi-square tests compared prevalence differences between groups. Multiple logistic regression models assessed factors associated with e-cigarette use while controlling for sociodemographic characteristics, current use of other tobacco products, and secondhand smoke exposure. Prevalence of current e-cigarette use was 14.1% (95% CI = 12.4%, 15.8%), ever use was 24.6% (95% CI = 22.4%, 26.9%), and awareness was 75.5% (95% CI = 73.0%, 78.0%). Current use of any other tobacco products and exposure to secondhand smoke at home, school, or other public places were positively associated with current and ever use of e-cigarettes. Boys and youth living in Luzon or Mindanao had higher odds of current e-cigarette use compared to girls and youth in Visayas. Findings indicated that one in four Philippine students aged 13-15 years ever used e-cigarettes and one in seven currently use e-cigarettes. This study highlights the importance of implementing evidence-based strategies, including relevant tobacco control policies.

BACKGROUND: Rapid diagnostic tests (RDTs) are effective tools to diagnose and inform the treatment of malaria in adults and children. The recent development of a highly sensitive rapid diagnostic test (HS-RDT) for Plasmodium falciparum has prompted questions over whether it could improve the diagnosis of malaria in pregnancy and pregnancy outcomes in malaria endemic areas. METHODS: This landscape review collates studies addressing the clinical performance of the HS-RDT. Thirteen studies were identified comparing the HS-RDT and conventional RDT (co-RDT) to molecular methods to detect malaria in pregnancy. Using data from five completed studies, the association of epidemiological and pregnancy-related factors on the sensitivity of HS-RDT, and comparisons with co-RDT were investigated. The studies were conducted in 4 countries over a range of transmission intensities in largely asymptomatic women. RESULTS: Sensitivity of both RDTs varied widely (HS-RDT range 19.6 to 85.7%, co-RDT range 22.8 to 82.8% compared to molecular testing) yet HS-RDT detected individuals with similar parasite densities across all the studies including different geographies and transmission areas [geometric mean parasitaemia around 100 parasites per µL (p/µL)]. HS-RDTs were capable of detecting low-density parasitaemias and in one study detected around 30% of infections with parasite densities of 0-2 p/µL compared to the co-RDT in the same study which detected around 15%. CONCLUSION: The HS-RDT has a slightly higher analytical sensitivity to detect malaria infections in pregnancy than co-RDT but this mostly translates to only fractional and not statistically significant improvement in clinical performance by gravidity, trimester, geography or transmission intensity. The analysis presented here highlights the need for larger and more studies to evaluate incremental improvements in RDTs. The HS-RDT could be used in any situation where co-RDT are currently used for P. falciparum diagnosis, if storage conditions can be adhered to.

BACKGROUND: Multisite musculoskeletal pain is common and disabling. This study aimed to prospectively investigate distribution of musculoskeletal pain anatomically, and explore risk factors for increases/reductions in the number of painful sites. METHODS: Using data from participants working in 45 occupational groups in 18 countries, we explored changes in reporting pain at 10 anatomical sites on two occasions 14 months apart. We used descriptive statistics to explore consistency over time in the number of painful sites, and their anatomical distribution. Baseline risk factors for increases/reductions by ≥3 painful sites were explored by random intercept logistic regression that adjusted for baseline number of painful sites. RESULTS: Amongst 8,927 workers, only 20% reported no pain at either time point, and 16% reported ≥3 painful sites both times. After 14 months, the anatomical distribution of pain often changed but there was only an average increase of 0.17 painful sites. Some 14% workers reported a change in painful sites by ≥ 3. Risk factors for an increase of ≥ 3 painful sites included female sex, lower educational attainment, having a physically demanding job, and adverse beliefs about the work-relatedness of musculoskeletal pain. Also predictive were: older age, somatising tendency, and poorer mental health (each of which was also associated with lower odds of reductions of ≥ 3 painful sites). CONCLUSIONS: Longitudinally, the number of reported painful sites was relatively stable but the anatomical distribution varied considerably. These findings suggest an important role for central pain sensitisation mechanisms, rather than localised risk factors, among working adults.

OBJECTIVES: To explore the association of sickness absence ascribed to pain at specific anatomical sites with wider propensity to musculoskeletal pain. METHODS: As part of the CUPID (Cultural and Psychosocial Influences on Disability) study, potential risk factors for sickness absence from musculoskeletal pain were determined for 11 922 participants from 45 occupational groups in 18 countries. After approximately 14 months, 9119 (78%) provided follow-up information about sickness in the past month because of musculoskeletal pain, including 8610 who were still in the same job. Associations with absence for pain at specific anatomical sites were assessed by logistic regression and summarised by ORs with 95% CIs. RESULTS: 861 participants (10%) reported absence from work because of musculoskeletal pain during the month before follow-up. After allowance for potential confounders, risk of absence ascribed entirely to low back pain (n=235) increased with the number of anatomical sites other than low back that had been reported as painful in the year before baseline (ORs 1.6 to 1.7 for >/=4 vs 0 painful sites). Similarly, associations with wider propensity to pain were observed for absence attributed entirely to pain in the neck (ORs up to 2.0) and shoulders (ORs up to 3.4). CONCLUSIONS: Sickness absence for pain at specific anatomical sites is importantly associated with wider propensity to pain, the determinants of which extend beyond established risk factors such as somatising tendency and low mood. Better understanding of why some individuals are generally more prone to musculoskeletal pain might point to useful opportunities for prevention.

BACKGROUND: Previous research has indicated that wide international variation in the prevalence of disabling low back pain among working populations is largely driven by factors predisposing to musculoskeletal pain more generally. This paper explores whether the same applies to disabling wrist/hand pain (WHP). METHODS: Using data from the Cultural and Psychosocial Influences on Disability (CUPID) study, we focused on workers from 45 occupational groups (office workers, nurses and other workers) in 18 countries. Among 11,740 participants who completed a baseline questionnaire about musculoskeletal pain and potential risk factors, 9082 (77%) answered a further questionnaire after a mean interval of 14 months, including 1373 (15%) who reported disabling WHP in the month before follow-up. Poisson regression was used to assess associations of this outcome with baseline risk factors, including the number of anatomical sites other than wrist/hand that had been painful in the 12 months before baseline (taken as an index of general propensity to pain). RESULTS: After allowance for other risk factors, the strongest associations were with general pain propensity (prevalence rate ratio for an index >/=6 vs. 0: 3.6, 95% confidence interval 2.9-4.4), and risk rose progressively as the index increased. The population attributable fraction for a pain propensity index > 0 was 49.4%. The prevalence of disabling WHP by occupational group ranged from 0.3 to 36.2%, and correlated strongly with mean pain propensity index (correlation coefficient 0.86). CONCLUSION: Strategies to prevent disability from WHP among working populations should explore ways of reducing general propensity to pain, as well as improving the ergonomics of occupational tasks.

Zika virus (ZIKV) was first discovered in 1947 in Uganda but was not considered a public health threat until 2007 when it found to be the source of epidemic activity in Asia. Epidemic activity spread to Brazil in 2014 and continued to spread throughout the tropical and subtropical regions of the Americas. Despite ZIKV being zoonotic in origin, information about transmission, or even exposure of non-human vertebrates and mosquitoes to ZIKV in the Americas, is lacking. Accordingly, from February 2017 to March 2018, we sought evidence of sylvatic ZIKV transmission by sampling whole blood from approximately 2000 domestic and wild vertebrates of over 100 species in West-Central Brazil within the active human ZIKV transmission area. In addition, we collected over 24,300 mosquitoes of at least 17 genera and 62 species. We screened whole blood samples and mosquito pools for ZIKV RNA using pan-flavivirus primers in a real-time reverse-transcription polymerase chain reaction (RT-PCR) in a SYBR Green platform. Positives were confirmed using ZIKV-specific envelope gene real-time RT-PCR and nucleotide sequencing. Of the 2068 vertebrates tested, none were ZIKV positive. Of the 23,315 non-engorged mosquitoes consolidated into 1503 pools tested, 22 (1.5%) with full data available showed some degree of homology to insect-specific flaviviruses. To identify previous exposure to ZIKV, 1498 plasma samples representing 62 species of domestic and sylvatic vertebrates were tested for ZIKV-neutralizing antibodies by plaque reduction neutralization test (PRNT90). From these, 23 (1.5%) of seven species were seropositive for ZIKV and negative for dengue virus serotype 2, yellow fever virus, and West Nile virus, suggesting potential monotypic reaction for ZIKV. Results presented here suggest no active transmission of ZIKV in non-human vertebrate populations or in alternative vector candidates, but suggest that vertebrates around human populations have indeed been exposed to ZIKV in West-Central Brazil.

STUDY DESIGN: Cross-sectional survey with longitudinal follow-up OBJECTIVES.: To test the hypothesis that pain which is localised to the low back differs epidemiologically from that which occurs simultaneously or close in time to pain at other anatomical sites SUMMARY OF BACKGROUND DATA.: Low back pain (LBP) often occurs in combination with other regional pain, with which it shares similar psychological and psychosocial risk factors. However, few previous epidemiological studies of LBP have distinguished pain that is confined to the low back from that which occurs as part of a wider distribution of pain. METHODS: We analysed data from CUPID, a cohort study that used baseline and follow-up questionnaires to collect information about musculoskeletal pain, associated disability and potential risk factors, in 47 occupational groups (office workers, nurses and others) from 18 countries. RESULTS: Among 12,197 subjects at baseline, 609 (4.9%) reported localised LBP in the past month, and 3,820 (31.3%) non-localised LBP. Non-localised LBP was more frequently associated with sciatica in the past month (48.1% vs. 30.0% of cases), occurred on more days in the past month and past year, was more often disabling for everyday activities (64.1% vs. 47.3% of cases), and had more frequently led to medical consultation and sickness absence from work. It was also more often persistent when participants were followed up after a mean of 14 months (65.6% vs. 54.1% of cases). In adjusted Poisson regression analyses, non-localised LBP was differentially associated with risk factors, particularly female sex, older age and somatising tendency. There were also marked differences in the relative prevalence of localised and non-localised LBP by occupational group. CONCLUSIONS: Future epidemiological studies should distinguish where possible between pain that is limited to the low back and LBP which occurs in association with pain at other anatomical locations. LEVEL OF EVIDENCE: 2.

OBJECTIVES: To assess the differences in the prevalence and incidence of low back pain (LBP) and associated disability among office workers in Costa Rica, Nicaragua and Spain. METHODS: Data were collected at baseline (n=947, 93% response) in November 2007 and at follow-up after 12 months (n=853, 90% response). Six outcome measures were examined: baseline prevalence of (1) LBP in the past 12 months, (2) LBP in the past month and (3) disabling LBP in the past month; and at follow-up: (4) incidence of new LBP in the past month, (5) new disabling LBP and (6) persistent LBP. Differences in prevalence by country were characterised by ORs with 95% CIs, before and after adjustment for covariates. RESULTS: Prevalence of LBP in the past month among office employees in Costa Rica (46.0%) and Nicaragua (44.2%) was higher than in Spain (33.6%). Incidence of new LBP was 37.0% in Nicaragua (OR=2.49; 95% CI 1.57 to 3.95), 14.9% in Costa Rica (OR=0.74; 95% CI 0.41 to 1.34) and 19.0% in Spain (reference). Incidence of new disabling LBP was higher in Nicaragua (17.2%; OR=2.49; 95% CI 1.43 to 4.34) and Costa Rica (13.6%; OR=1.89; 95% CI 1.03 to 3.48) than Spain (7.7%), while persistence of LBP was higher only in Nicaragua. CONCLUSIONS: Prevalence of LBP and disabling LBP was higher in Costa Rican and Nicaraguan office workers than in Spain, but the incidence was higher mainly in Nicaragua. Measured sociodemographic, job-related and health-related variables only partly explained the differences between countries, and further research is needed to explore reasons for the remaining differences.

Somatising tendency, defined as a predisposition to worry about common somatic symptoms, is importantly associated with various aspects of health and health-related behaviour, including musculoskeletal pain and associated disability. To explore its epidemiological characteristics, and how it can be specified most efficiently, we analysed data from an international longitudinal study. A baseline questionnaire, which included questions from the Brief Symptom Inventory about seven common symptoms, was completed by 12,072 participants aged 20-59 from 46 occupational groups in 18 countries (response rate 70%). The seven symptoms were all mutually associated (odds ratios for pairwise associations 3.4 to 9.3), and each contributed to a measure of somatising tendency that exhibited an exposure-response relationship both with multi-site pain (prevalence rate ratios up to six), and also with sickness absence for non-musculoskeletal reasons. In most participants, the level of somatising tendency was little changed when reassessed after a mean interval of 14 months (75% having a change of 0 or 1 in their symptom count), although the specific symptoms reported at follow-up often differed from those at baseline. Somatising tendency was more common in women than men, especially at older ages, and varied markedly across the 46 occupational groups studied, with higher rates in South and Central America. It was weakly associated with smoking, but not with level of education. Our study supports the use of questions from the Brief Symptom Inventory as a method for measuring somatising tendency, and suggests that in adults of working age, it is a fairly stable trait.

OBJECTIVES: To estimate the prevalence and incidence of upper extremity musculoskeletal pain (UEMP) and related disability among office workers in Costa Rica, Nicaragua and Spain. METHODS: Data from the multinational Cultural and Psychosocial Influences on Disability (CUPID) study on 947 (93%) participants at baseline with 90% follow-up after 12 months were employed. Logistic regression was used to estimate the associations (ORs and corresponding 95% CIs) between country and six outcomes: baseline prevalence of (1) UEMP in past 12 months, (2) UEMP in past month and (3) disabling UEMP in past month; (4) incidence of new UEMP at follow-up; (5) incidence of new disabling UEMP at follow-up and (6) persistence of UEMP at follow-up, after adjustment for sociodemographic, job-related and health-related covariates. RESULTS: Baseline prevalence of UEMP in the past month was higher in Costa Rica (53.6%) (OR=1.89; 95% CI 1.36 to 2.62) and Nicaragua (51.9%) (OR=1.74; 95% CI 1.28 to 2.35) than in Spain (38.4%). Compared to Spain (33.2%), the incidence of new UEMP was 50.4% in Costa Rica (OR=2.04; 95% CI 1.34 to 3.12) and 60.2% in Nicaragua (OR=3.04; 95% CI 2.06 to 4.50). The incidence of disabling UEMP was higher in Nicaragua (OR=2.57; 95% CI 1.50 to 4.41) and Costa Rica (OR=2.16; 95% CI 1.22 to 3.84) when compared to Spain. CONCLUSIONS: Prevalence of UEMP was approximately twofold higher and its incidence twofold to threefold higher in Costa Rica and Nicaragua as compared with Spain. Between-country differences were only partially explained by the covariates analysed. Research is needed to explore other aspects of work and cultural attributes that might explain the residual differences in UEMP.

To inform case-definition for neck/shoulder pain in epidemiological research, we compared levels of disability, patterns of association and prognosis for pain that was limited to the neck or shoulders (LNSP) and more generalised musculoskeletal pain that involved the neck or shoulder(s) (GPNS). Baseline data on musculoskeletal pain, disability and potential correlates were collected by questionnaire from 12,195 workers in 47 occupational groups (mostly office workers, nurses, and manual workers) in 18 countries (response rate = 70%). Continuing pain after a mean interval of 14 months was ascertained through a follow-up questionnaire in 9,150 workers from 45 occupational groups. Associations with personal and occupational factors were assessed by Poisson regression and summarised by prevalence rate ratios (PRRs). The one-month prevalence of GPNS at baseline was much greater than that of LNSP (35.1% vs. 5.6%), and it tended to be more troublesome and disabling. Unlike LNSP, the prevalence of GPNS increased with age. Moreover, it showed significantly stronger associations with somatising tendency (PRR 1.6 vs. 1.3) and poor mental health (PRR 1.3 vs. 1.1); greater variation between the occupational groups studied (prevalence ranging from 0% to 67.6%) that correlated poorly with the variation in LNSP; and was more persistent at follow-up (72.1% vs. 61.7%). Our findings highlight important epidemiological distinctions between sub-categories of neck/shoulder pain. In future epidemiological research that bases case definitions on symptoms, it would be useful to distinguish pain which is localised to the neck or shoulder from more generalised pain that happens to involve the neck/shoulder region.

BACKGROUND: Rapid diagnostic tests (RDTs) largely account for the scale-up of malaria diagnosis in endemic settings. However, diversity in labelling including the instructions for use (IFU) limits their interchangeability and user-friendliness. Uniform, easy to follow and consistent labelling, aligned with international standards and appropriate for the level of the end user's education and training, is crucial but a consolidated resource of information regarding best practices for IFU and labelling of RDT devices, packaging and accessories is not available. METHODS: The Roll Back Malaria Partnership (RBM) commissioned the compilation of international standards and regulatory documents and published literature containing specifications and/or recommendations for RDT design, packaging and labelling of in vitro diagnostics (IVD) (which includes RDTs), complemented with a questionnaire based survey of RDT manufacturers and implementers. A summary of desirable RDT labelling characteristics was compiled, which was reviewed and discussed during a RBM Stakeholder consultation meeting and subsequently amended and refined by a dedicated task force consisting of country programme implementers, experts in RDT implementation, IVD regulatory experts and manufacturers. RESULTS: This process led to the development of consensus documents with a list of suggested terms and abbreviations as well as specifications for labelling of box, device packaging, cassettes, buffer bottle and accessories (lancets, alcohol swabs, transfer devices, desiccants). Emphasis was placed on durability (permanent printing or water-resistant labels), legibility (font size, letter type), comprehension (use of symbols) and ease of reference (e.g. place of labelling on the box or cassette packaging allowing quick oversight). A generic IFU template was developed, comprising background information, a template for procedure and reading/interpretation, a selection of appropriate references and a symbol key of internationally recognized symbols together with suggestions about appropriate lay-out, style and readability. CONCLUSIONS: The present document together with its additional files compiled proposes best practices in labelling and IFU for malaria RDTs. It is expected that compliance with these best practices will increase harmonization among the different malaria RDT products available on the market and improve their user-friendliness.

Genome-wide association studies (GWAS) have mapped risk alleles for at least ten distinct cancers to a small region of 63,000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (ASSET) across six distinct cancers in 34,248 cases and 45,036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single nucleotide polymorphisms (SNPs): five in the TERT gene (region 1: rs7726159, P=2.10x10-39; region 3: rs2853677, P=3.30x10-36 and PConditional=2.36x10-8; region 4: rs2736098, P=3.87x10-12 and PConditional=5.19x10-6, region 5: rs13172201, P=0.041 and PConditional=2.04x10-6; and region 6: rs10069690, P=7.49x10-15 and PConditional=5.35x10-7) and one in the neighboring CLPTM1L gene (region 2: rs451360; P=1.90x10-18 and PConditional=7.06x10-16). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele specific effects on DNA methylation were seen for a subset of risk loci indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.

To explore definitions for multisite pain, and compare associations with risk factors for different patterns of musculoskeletal pain, we analysed cross-sectional data from the Cultural and Psychosocial Influences on Disability (CUPID) study. The study sample comprised 12,410 adults aged 20-59 years from 47 occupational groups in 18 countries. A standardised questionnaire was used to collect information about pain in the past month at each of 10 anatomical sites, and about potential risk factors. Associations with pain outcomes were assessed by Poisson regression, and characterised by prevalence rate ratios (PRRs). Extensive pain, affecting 6-10 anatomical sites, was reported much more frequently than would be expected if the occurrence of pain at each site were independent (674 participants vs 41.9 expected). In comparison with pain involving only 1-3 sites, it showed much stronger associations (relative to no pain) with risk factors such as female sex (PRR 1.6 vs 1.1), older age (PRR 2.6 vs 1.1), somatising tendency (PRR 4.6 vs 1.3), and exposure to multiple physically stressing occupational activities (PRR 5.0 vs 1.4). After adjustment for number of sites with pain, these risk factors showed no additional association with a distribution of pain that was widespread according to the frequently used American College of Rheumatology criteria. Our analysis supports the classification of pain at multiple anatomical sites simply by the number of sites affected, and suggests that extensive pain differs importantly in its associations with risk factors from pain that is limited to only a small number of anatomical sites.

To compare the prevalence of disabling low back pain (DLBP) and disabling wrist/hand pain (DWHP) among groups of workers carrying out similar physical activities in different cultural environments, and to explore explanations for observed differences, we conducted a cross-sectional survey in 18 countries. Standardised questionnaires were used to ascertain pain that interfered with everyday activities and exposure to possible risk factors in 12,426 participants from 47 occupational groups (mostly nurses and office workers). Associations with risk factors were assessed by Poisson regression. The 1-month prevalence of DLBP in nurses varied from 9.6% to 42.6%, and that of DWHP in office workers from 2.2% to 31.6%. Rates of disabling pain at the 2 anatomical sites covaried (r = 0.76), but DLBP tended to be relatively more common in nurses and DWHP in office workers. Established risk factors such as occupational physical activities, psychosocial aspects of work, and tendency to somatise were confirmed, and associations were found also with adverse health beliefs and group awareness of people outside work with musculoskeletal pain. However, after allowance for these risk factors, an up-to 8-fold difference in prevalence remained. Systems of compensation for work-related illness and financial support for health-related incapacity for work appeared to have little influence on the occurrence of symptoms. Our findings indicate large international variation in the prevalence of disabling forearm and back pain among occupational groups carrying out similar tasks, which is only partially explained by the personal and socioeconomic risk factors that were analysed.

BACKGROUND: The CUPID (Cultural and Psychosocial Influences on Disability) study was established to explore the hypothesis that common musculoskeletal disorders (MSDs) and associated disability are importantly influenced by culturally determined health beliefs and expectations. This paper describes the methods of data collection and various characteristics of the study sample. METHODS/PRINCIPAL FINDINGS: A standardised questionnaire covering musculoskeletal symptoms, disability and potential risk factors, was used to collect information from 47 samples of nurses, office workers, and other (mostly manual) workers in 18 countries from six continents. In addition, local investigators provided data on economic aspects of employment for each occupational group. Participation exceeded 80% in 33 of the 47 occupational groups, and after pre-specified exclusions, analysis was based on 12,426 subjects (92 to 1018 per occupational group). As expected, there was high usage of computer keyboards by office workers, while nurses had the highest prevalence of heavy manual lifting in all but one country. There was substantial heterogeneity between occupational groups in economic and psychosocial aspects of work; three- to five-fold variation in awareness of someone outside work with musculoskeletal pain; and more than ten-fold variation in the prevalence of adverse health beliefs about back and arm pain, and in awareness of terms such as "repetitive strain injury" (RSI). CONCLUSIONS/SIGNIFICANCE: The large differences in psychosocial risk factors (including knowledge and beliefs about MSDs) between occupational groups should allow the study hypothesis to be addressed effectively.