Field studies often use caregiver-reported diarrhoea and related symptoms to measure child morbidity. There are various vernacular terms to define diarrhoea that vary across the local cultural contexts. The relationship between vernacular definitions of diarrhoea and symptoms-based definitions is not well-documented. This paper describes the association of the vernacular Quechua term k'echalera with the symptoms-based standard definition of diarrhoea in rural Bolivian settings. During a cluster randomized trial in rural Bolivia, both signs and symptoms of diarrhoea and reports of k'echalera were collected for children aged less than five years. Reported k'echalera were found to be associated with important changes in stool frequency, consistency, and presence of blood and mucus. Reported k'echalera were highly related to three of four recorded categories of watery stool. The intermediate (milk-rice) stool consistency, which fits into the definition of watery stool, was not strongly related to k'echalera. Mucus in the stool was also associated with k'echalera; however, its presence in k'echalera-free days accounted for at least 50% of the possible false negatives. The sensitivity and specificity of the term k'echalera were estimated by Bayesian methods, allowing for both symptoms of diarrhoea and reports of k'echalera to be subject to diagnosis error. An average specificity of at least 97% and the sensitivity of at least 50% were obtained. The findings suggest that the use of k'echalera would identify fewer cases of diarrhoea than a symptom-based definition in rural Bolivia.

Background

Serological surveys with multiplex bead assays can be used to assess seroprevalence to multiple pathogens simultaneously. However, multiple methods have been used to generate cut-off values for seropositivity and these may lead to inconsistent interpretation of results. A literature review was conducted to describe the methods used to determine cut-off values for data generated by multiplex bead assays.

Methodology/principal findings

A search was conducted in PubMed that included articles published from January 2010 to January 2020, and 308 relevant articles were identified that included the terms "serology", "cut-offs", and "multiplex bead assays". After application of exclusion of articles not relevant to neglected tropical diseases (NTD), vaccine preventable diseases (VPD), or malaria, 55 articles were examined based on their relevance to NTD or VPD. The most frequently applied approaches to determine seropositivity included the use of presumed unexposed populations, mixture models, receiver operating curves (ROC), and international standards. Other methods included the use of quantiles, pre-exposed endemic cohorts, and visual inflection points.

Conclusions/significance

For disease control programmes, seropositivity is a practical and easily interpretable health metric but determining appropriate cut-offs for positivity can be challenging. Considerations for optimal cut-off approaches should include factors such as methods recommended by previous research, transmission dynamics, and the immunological backgrounds of the population. In the absence of international standards for estimating seropositivity in a population, the use of consistent methods that align with individual disease epidemiological data will improve comparability between settings and enable the assessment of changes over time.

Objectives:We recently completed 3 efficacy trials (Bangladesh, Kenya, Zimbabwe) testing the independent and combined effects of improved complementary feeding (CF) and intensive household water quality, sanitation, and hygiene (WASH) on child diarrhea and length-for-age-Z-score (LAZ) at 18 to 24 mo. Intervention uptake was high. In all three trials: CF increased LAZ but WASH had no effect on LAZ. WASH reduced diarrhea in Bangladesh but not in Kenya or Zimbabwe. We present a synthesis of trial findings and their implications. Methods:Reviews of the literature and reanalyses of trial data were conducted. Results:WASH and stunting: Copious observational studies have demonstrated a strong association between household-level WASH and child LAZ. We conducted an observational anlaysis (nested birth cohort) from our control arms. In adjusted analyses of all three trials, having an improved latrine when the pregnant woman was enrolled was associated with ∼0.2LAZ increase in her child at 18-24 mo. The frequently reported association between household WASH indicators and child growth may be confounded and drawing causal inferance misguided.WASH and diarrhea: Promoters visited intervention households 6 times per month in Bangladesh and monthly in Kenya and Zimbabwe. We conducted a systematic literature review: virtually all evidence that household water chlorination and handwashing reduce diarrhea comes from studies with daily to fortnightly intervention contact. In studies with follow-up after the trial ending, behaviors steeply declined and the effect on child diarrhea disappeared. Household water chlorination and handwashing promotion implemented through sporadic message delivery may not reduce child diarrhea.Enteropathogen transmission: Despite achieving substantial contrast between WASH and non-WASH households, children in the WASH arms still experienced high enteropathogen transmission, illustrating the recalcitrance of pervasive fecal contamination in rural low-income communities to even intense intervention. Conclusions:Household WASH interventions are unlikely to reduce child stunting and may not reduce child diarrhea. We call for substantial investment in research to identify and in programming to deliver much more efficacious interventions. Funding Sources:Bill & Melinda Gates Foundation, USAID, DFID/UKAID, Wellcome Trust.

Rationale

Former smoking history and chronic obstructive pulmonary disease (COPD) are potential risk factors for osteoporosis and fractures. Under existing guidelines for osteoporosis screening, women are included but men are not, and only current smoking is considered.

Objectives

To demonstrate the impact of COPD and smoking history on the risk of osteoporosis and vertebral fracture in men and women.

Methods

Characteristics of participants with low volumetric bone mineral density (vBMD) were identified and related to COPD and other risk factors. We tested associations of sex and COPD with both vBMD and fractures adjusting for age, race, body mass index (BMI), smoking, and glucocorticoid use.

Measurements and main results

vBMD by calibrated quantitative computed tomography (QCT), visually scored vertebral fractures, and severity of lung disease were determined from chest CT scans of 3,321 current and ex-smokers in the COPDGene study. Low vBMD as a surrogate for osteoporosis was calculated from young adult normal values. Male smokers had a small but significantly greater risk of low vBMD (2.5 SD below young adult mean by calibrated QCT) and more fractures than female smokers. Low vBMD was present in 58% of all subjects, was more frequent in those with worse COPD, and rose to 84% among subjects with very severe COPD. Vertebral fractures were present in 37% of all subjects and were associated with lower vBMD at each Global Initiative for Chronic Obstructive Lung Disease stage of severity. Vertebral fractures were most common in the midthoracic region. COPD and especially emphysema were associated with both low vBMD and vertebral fractures after adjustment for steroid use, age, pack-years of smoking, current smoking, and exacerbations. Airway disease was associated with higher bone density after adjustment for other variables. Calibrated QCT identified more subjects with abnormal values than the standard dual-energy X-ray absorptiometry in a subset of subjects and correlated well with prevalent fractures.

Conclusions

Male smokers, with or without COPD, have a significant risk of low vBMD and vertebral fractures. COPD was associated with low vBMD after adjusting for race, sex, BMI, smoking, steroid use, exacerbations, and age. Screening for low vBMD by using QCT in men and women who are smokers will increase opportunities to identify and treat osteoporosis in this at-risk population.