Abstract Metacognitive beliefs have been shown to correlate with emotional disorders and more recently have been implicated in health anxiety. Research exploring these beliefs have tended to use the ...Metacognition Questionnaire (MCQ), which is a general measure. To facilitate research on the metacognitive model applied to health anxiety the present study reports on the development and initial evaluation of a new specific metacognitive measure of health anxiety, the Metacognitions Questionnaire-Health Anxiety (MCQ-HA). Principal components analysis identified 14 suitable items to be explored. Subsequent exploratory factor analysis of the MCQ-HA identified three factors: “Beliefs that Thoughts can cause Illness”, “Beliefs about Biased thinking”, and “Beliefs that Thoughts are Uncontrollable”. Confirmatory factor analysis supported the three factor model with all selected goodness-of-fit statistics equivalent to or better than recommended values. Preliminary evidence suggests good internal-consistency, incremental, convergent and discriminant validity in relation to associated measures. The MCQ-HA appears to be a potentially useful predictor of health anxiety.
We hypothesized that mass distribution of a broad-spectrum antibiotic agent to preschool children would reduce mortality in areas of sub-Saharan Africa that are currently far from meeting the ...Sustainable Development Goals of the United Nations.
In this cluster-randomized trial, we assigned communities in Malawi, Niger, and Tanzania to four twice-yearly mass distributions of either oral azithromycin (approximately 20 mg per kilogram of body weight) or placebo. Children 1 to 59 months of age were identified in twice-yearly censuses and were offered participation in the trial. Vital status was determined at subsequent censuses. The primary outcome was aggregate all-cause mortality; country-specific rates were assessed in prespecified subgroup analyses.
A total of 1533 communities underwent randomization, 190,238 children were identified in the census at baseline, and 323,302 person-years were monitored. The mean (±SD) azithromycin and placebo coverage over the four twice-yearly distributions was 90.4±10.4%. The overall annual mortality rate was 14.6 deaths per 1000 person-years in communities that received azithromycin (9.1 in Malawi, 22.5 in Niger, and 5.4 in Tanzania) and 16.5 deaths per 1000 person-years in communities that received placebo (9.6 in Malawi, 27.5 in Niger, and 5.5 in Tanzania). Mortality was 13.5% lower overall (95% confidence interval CI, 6.7 to 19.8) in communities that received azithromycin than in communities that received placebo (P<0.001); the rate was 5.7% lower in Malawi (95% CI, -9.7 to 18.9), 18.1% lower in Niger (95% CI, 10.0 to 25.5), and 3.4% lower in Tanzania (95% CI, -21.2 to 23.0). Children in the age group of 1 to 5 months had the greatest effect from azithromycin (24.9% lower mortality than that with placebo; 95% CI, 10.6 to 37.0). Serious adverse events occurring within a week after administration of the trial drug or placebo were uncommon, and the rate did not differ significantly between the groups. Evaluation of selection for antibiotic resistance is ongoing.
Among postneonatal, preschool children in sub-Saharan Africa, childhood mortality was lower in communities randomly assigned to mass distribution of azithromycin than in those assigned to placebo, with the largest effect seen in Niger. Any implementation of a policy of mass distribution would need to strongly consider the potential effect of such a strategy on antibiotic resistance. (Funded by the Bill and Melinda Gates Foundation; MORDOR ClinicalTrials.gov number, NCT02047981 .).
Trachoma, caused by Chlamydia trachomatis, remains the world's leading infectious cause of blindness. Repeated ocular infection during childhood leads to scarring of the conjunctiva, in-turning of ...the eyelashes (trichiasis) and corneal opacity in later life. There is a growing body of evidence to suggest non-chlamydial bacteria are associated with clinical signs of trachoma, independent of C. trachomatis infection.
We used deep sequencing of the V1-V3 region of the bacterial 16S rRNA gene to characterize the microbiome of the conjunctiva of 220 residents of The Gambia, 105 with healthy conjunctivae and 115 with clinical signs of trachoma in the absence of detectable C. trachomatis infection. Deep sequencing was carried out using the Roche-454 platform. Sequence data were processed and analyzed through a pipeline developed by the Human Microbiome Project.
The microbiome of healthy participants was influenced by age and season of sample collection with increased richness and diversity seen in younger participants and in samples collected during the dry season. Decreased diversity and an increased abundance of Corynebacterium and Streptococcus were seen in participants with conjunctival scarring compared to normal controls. Abundance of Corynebacterium was higher still in adults with scarring and trichiasis compared to adults with scarring only.
Our results indicate that changes in the conjunctival microbiome occur in trachomatous disease; whether these are a cause or a consequence is yet unknown.
Mass azithromycin distributions have been shown to reduce mortality in preschool children, although the factors mediating this mortality reduction are not clear. This study was performed to determine ...whether mass distribution of azithromycin, which has modest antimalarial activity, reduces the community burden of malaria.
In a cluster-randomized trial conducted from 23 November 2014 until 31 July 2017, 30 rural communities in Niger were randomized to 2 years of biannual mass distributions of either azithromycin (20 mg/kg oral suspension) or placebo to children aged 1 to 59 months. Participants, field staff, and investigators were masked to treatment allocation. The primary malaria outcome was the community prevalence of parasitemia on thick blood smear, assessed in a random sample of children from each community at study visits 12 and 24 months after randomization. Analyses were performed in an intention-to-treat fashion. At the baseline visit, a total of 1,695 children were enumerated in the 15 azithromycin communities, and 3,029 children were enumerated in the 15 placebo communities. No communities were lost to follow-up. The mean prevalence of malaria parasitemia at baseline was 8.9% (95% CI 5.1%-15.7%; 52 of 552 children across all communities) in the azithromycin-treated group and 6.7% (95% CI 4.0%-12.6%; 36 of 542 children across all communities) in the placebo-treated group. In the prespecified primary analysis, parasitemia was lower in the azithromycin-treated group at month 12 (mean prevalence 8.8%, 95% CI 5.1%-14.3%; 51 of 551 children across all communities) and month 24 (mean 3.5%, 95% CI 1.9%-5.5%; 21 of 567 children across all communities) than it was in the placebo-treated group at month 12 (mean 15.3%, 95% CI 10.8%-20.6%; 81 of 548 children across all communities) and month 24 (mean 4.8%, 95% CI 3.3%-6.4%; 28 of 592 children across all communities) (P = 0.02). Communities treated with azithromycin had approximately half the odds of parasitemia compared to those treated with placebo (odds ratio OR 0.54, 95% CI 0.30 to 0.97). Parasite density was lower in the azithromycin group than the placebo group at 12 and 24 months (square root-transformed outcome; density estimates were 7,540 parasites/μl lower 95% CI -350 to -12,550 parasites/μl; P = 0.02 at a mean parasite density of 17,000, as was observed in the placebo arm). No significant difference in hemoglobin was observed between the 2 treatment groups at 12 and 24 months (mean 0.34 g/dL higher in the azithromycin arm, 95% CI -0.06 to 0.75 g/dL; P = 0.10). No serious adverse events were reported in either group, and among children aged 1 to 5 months, the most commonly reported nonserious adverse events (i.e., diarrhea, vomiting, and rash) were less common in the azithromycin-treated communities. Limitations of the trial include the timing of the treatments and monitoring visits, both of which took place before the peak malaria season, as well as the uncertain generalizability to areas with different malaria transmission dynamics.
Mass azithromycin distributions were associated with a reduced prevalence of malaria parasitemia in this trial, suggesting one possible mechanism for the mortality benefit observed with this intervention.
The trial was registered on ClinicalTrials.gov (NCT02048007).
•We evaluated the feasibility of delivering MCT for health anxiety and to collect pilot data on the treatment's preliminary efficacy as measured by the whiteley index.•MCT was found to be feasible ...and acceptable for individuals with health anxiety, with clinically significant changes and large effects (Hedges’ g = 3.18).•The results support continued evaluation of MCT in health anxiety and a large-scale randomised trial is supported.
Health anxiety is a pervasive mental health condition, in which people worry about having or developing a serious illness or disease. Cognitive behavioural therapy (CBT) is currently considered the most researched psychological treatment for health anxiety, although several systematic reviews and meta-analysis have shown mixed findings for its efficacy. More efficacious interventions that can be easily integrated within services are required. An alternative to CBT, that has proven more effective in some other disorders, is metacognitive therapy (MCT). The aim was to evaluate the feasibility of delivering MCT for health anxiety and to collect pilot data on the treatment's preliminary efficacy.
Twenty participants with health anxiety were recruited to an open randomized feasibility trial and randomized to MCT or waitlist control. Acceptability and feasibility of MCT was based on recruitment rates, withdrawal, and drop-out, number of MCT sessions attended, completion of questionnaires, and any adverse reactions observed. The study was also used to evaluate initial treatment effects.
MCT was found to be feasible and acceptable for individuals with health anxiety. Recruitment and retention of all participants was high, and no adverse events were observed in either group. Pre to post between group effect sizes on the primary outcome measure The Whiteley Index (Pilowsky, 1967) were large (Hedges’ g = 3.18-Mdiff= 26.2, 95 % CI=18.7–33.6) in favour of MCT. Clinically significant recovery rates were 80 % at post treatment and follow up.
The results suggest that a trial of MCT was acceptable and feasible in individuals with health anxiety and the treatment effects were statistically significant in comparison to the waiting list. Based upon the design used in this study MCT should be compared with active treatments such as medication, treatment as usual or specific cognitive behaviour therapy protocols in a future definitive randomised trial.
Trachoma causes blindness through a conjunctival scarring process initiated by ocular Chlamydia trachomatis infection; however, the rates, drivers and pathophysiological determinants are poorly ...understood. We investigated progressive scarring and its relationship to conjunctival infection, inflammation and transcript levels of cytokines and fibrogenic factors.
We recruited two cohorts, one each in Ethiopia and Tanzania, of individuals with established trachomatous conjunctival scarring. They were followed six-monthly for two years, with clinical examinations and conjunctival swab sample collection. Progressive scarring cases were identified by comparing baseline and two-year photographs, and compared to individuals without progression. Samples were tested for C. trachomatis by PCR and transcript levels of S100A7, IL1B, IL13, IL17A, CXCL5, CTGF, SPARCL1, CEACAM5, MMP7, MMP9 and CD83 were estimated by quantitative RT-PCR. Progressive scarring was found in 135/585 (23.1%) of Ethiopian participants and 173/577 (30.0%) of Tanzanian participants. There was a strong relationship between progressive scarring and increasing inflammatory episodes (Ethiopia: OR 5.93, 95%CI 3.31-10.6, p<0.0001. Tanzania: OR 5.76, 95%CI 2.60-12.7, p<0.0001). No episodes of C. trachomatis infection were detected in the Ethiopian cohort and only 5 episodes in the Tanzanian cohort. Clinical inflammation, but not scarring progression, was associated with increased expression of S100A7, IL1B, IL17A, CXCL5, CTGF, CEACAM5, MMP7, CD83 and reduced SPARCL1.
Scarring progressed in the absence of detectable C. trachomatis, which raises uncertainty about the primary drivers of late-stage trachoma. Chronic conjunctival inflammation appears to be central and is associated with enriched expression of pro-inflammatory factors and altered expression of extracellular matrix regulators. Host determinants of scarring progression appear more complex and subtle than the features of inflammation. Overall this indicates a potential role for anti-inflammatory interventions to interrupt progression and the need for trichiasis disease surveillance and surgery long after chlamydial infection has been controlled at community level.
Malnourished children are at increased risk of mortality from infectious diseases such as diarrhea and respiratory tract infections 6. ...the relationship between malnutrition and infection is ...complex, with undernutrition suppressing the immune system and increasing the risk of infection, and infection causing a reduction in appetite, malabsorption of nutrients, and competition for nutrients 7,8, Provision of antibiotics to malnourished children could lead to clearance of both overt and subclinical infections associated with mortality. Outcomes The outcome for this analysis is mortality, defined as community mortality rate (deaths per 1,000 person-years at risk). Given the fixed design, the prevalence of moderate to severe and severe underweight, and the mortality rates within subgroups, this subgroup analysis had 80% power to detect additive interaction effects of the following sizes, interpreted as the mortality rate among underweight children receiving placebo in excess of the individual effects of underweight or placebo on mortality: 17 deaths per 1,000 person-years for the moderate to severe subgroup and 25 deaths per 1,000 person-years for the severe subgroup 22. Analyses were conducted in R. Participant characteristics, WAZ, and outcomes were summarized by arm using frequency and percentage for categorical variables, mean and standard deviation for continuous variables, and incidence rate (deaths per 1,000 person-years, hereafter referred to as “mortality rate”) and 95% confidence interval for outcomes.
Following one to five years of antibiotic mass drug administration (MDA) for the elimination of trachoma as a public health problem, programmes must conduct impact surveys to inform decisions on ...whether MDA is still needed. These decisions are currently based on the prevalence of trachomatous inflammation-follicular (TF), which, after MDA, correlates poorly with prevalence of ocular Chlamydia trachomatis infection.
Impact surveys in six evaluation units (EUs) of Malawi were used as a platform to explore associations between the prevalence of TF, ocular C. trachomatis infection and anti-Pgp3 antibodies one year after the third annual round of MDA. Participants were examined for trachoma using the World Health Organization simplified grading system. Ocular swabs and dried blood spots (DBS) were collected from children aged 1-9 years. Swabs were tested for C. trachomatis DNA using GeneXpert. DBS were assayed for anti-Pgp3 antibodies using ELISA. EU-level prevalence of TF in children aged 1-9 years ranged from 4.7% (95% CI 3.4-6.3) to 7.2% (95% CI 5.8-8.9). Prevalence of C. trachomatis infection in children ranged from 0.1% (95% CI 0.0-0.6) to 0.7% (95% CI 0.3-1.3) while Pgp3 seroprevalence ranged from 6.9% (95% CI 5.4-8.6) to 12.0% (95% CI 10.1-14.0) and increased with age.
Based on current global policy, the prevalence of TF indicates that a further year of antibiotic MDA is warranted in four of six EUs yet the very low levels of infection cast doubt on the universal applicability of TF-based cut-offs for antibiotic MDA. Pgp3 seroprevalence was similar to that reported following MDA in other settings that have reached the elimination target however the predictive value of any particular level of seropositivity with respect to risk of subsequent infection recrudescence is, as yet, unknown.
Yaws, caused by Treponema pallidum ssp. pertenue, is reportedly endemic in Ghana. Mass distribution of azithromycin is now the cornerstone of the WHO yaws eradication campaign. Mass distribution of ...azithromycin at a lower target dose was previously undertaken in two regions of Ghana for the control of trachoma. Ongoing reporting of yaws raises the possibility that resistance may have emerged in T. pallidum pertenue, or that alternative infections may be responsible for some of the reported cases. We conducted a cross-sectional survey in thirty communities in two districts of Ghana where MDA for trachoma had previously been conducted. Children aged 5-17 years with ulcerative lesions compatible with yaws were enrolled. Samples for treponemal serology and lesion PCR were collected from all children. 90 children with 98 lesions were enrolled. Syphilis serology was negative in all of them. PCR for T. pallidum ssp pertenue was negative in all children, but Haemophilus ducreyi DNA was detected in 9 lesions. In these communities, previously treated for trachoma, we found no evidence of ongoing transmission of yaws. H. ducreyi was associated with a proportion of skin lesions, but the majority of lesions remain unexplained. Integration of diagnostic testing into both pre and post-MDA surveillance systems is required to better inform yaws control programmes.
Ocular infections with
serovars A-C cause the neglected tropical disease trachoma. As infection does not confer complete immunity, repeated infections are common, leading to long-term sequelae such ...as scarring and blindness. Here, we apply a systems serology approach to investigate whether systemic antibody features are associated with susceptibility to infection.
Sera from children in five trachoma endemic villages in the Gambia were assayed for 23 antibody features: IgG responses towards two
antigens and three serovars elementary bodies and major outer membrane protein (MOMP), serovars A-C, IgG responses towards five MOMP peptides (serovars A-C), neutralization, and antibody-dependent phagocytosis. Participants were considered resistant if they subsequently developed infection only when over 70% of other children in the same compound were infected.
The antibody features assayed were not associated with resistance to infection (false discovery rate < 0.05). Anti-MOMP SvA IgG and neutralization titer were higher in susceptible individuals (
< 0.05 before multiple testing adjustment). Classification using partial least squares performed only slightly better than chance in distinguishing between susceptible and resistant participants based on systemic antibody profile (specificity 71%, sensitivity 36%).
Systemic infection-induced IgG and functional antibody responses do not appear to be protective against subsequent infection. Ocular responses, IgA, avidity, or cell-mediated responses may play a greater role in protective immunity than systemic IgG.
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