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1.  Exercise-Induced Bronchospasm and Atopy in Ghana: Two Surveys Ten Years Apart 
PLoS Medicine  2007;4(2):e70.
Background
Asthma and allergic diseases have increased in the developed countries. It is important to determine whether the same trends are occurring in the developing countries in Africa. We aimed to determine the time trend in the prevalence of exercise-induced bronchospasm (EIB) and atopic sensitisation over a ten-year period in Ghanaian schoolchildren.
Methods and Findings
Two surveys conducted using the same methodology ten years apart (1993 and 2003) among schoolchildren aged 9–16 years attending urban rich (UR), urban poor (UP), and rural (R) schools. Exercise provocation consisted of free running for six minutes. Children were skin tested to mite, cat, and dog allergen. 1,095 children were exercised in 1993 and 1,848 in 2003; 916 were skin tested in 1993 and 1,861 in 2003. The prevalence of EIB increased from 3.1% (95% CI 2.2%–4.3%) to 5.2% (4.3%–6.3%); absolute percentage increase 2.1% (95% CI 0.6%–3.5%, p < 0.01); among UR, UP, and R children EIB had approximately doubled from 4.2%, 1.4%, and 2.2% to 8.3%, 3.0% and 3.9% respectively. The prevalence of sensitisation had also doubled from 10.6%, 4.7%, and 4.4% to 20.2%, 10.3%, and 9.9% (UR, UP, and R respectively). Mite sensitisation remained unchanged (5.6% versus 6.4%), but sensitisation to cat and dog increased considerably from 0.7% and 0.3% to 4.6% and 3.1%, respectively. In the multiple logistic regression analysis, sensitisation (odds ratio [OR] 1.77, 95% CI 1.12–2.81), age (OR 0.88, 95% CI 0.79–0.98), school (the risk being was significantly lower in UP and R schools: OR 0.40, 95% CI 0.23–0.68 and OR 0.54, 95% CI 0.34–0.86, respectively) and year of the study (OR 1.73, 95% CI 1.13–2.66) remained significant and independent associates of EIB.
Conclusions
The prevalence of both EIB and sensitisation has approximately doubled over the ten-year period amongst 9- to 16-year-old Ghanaian children irrespective of location, with both EIB and atopy being more common among the UR than the UP and R children.
The prevalence of both exercise-induced bronchospasm and sensitisation has approximately doubled over the ten-year period amongst 9- to 16-year-old Ghanaian children
Editors' Summary
Background.
The proportion of children with asthma is thought to be increasing worldwide, and particularly among children that live in more developed countries. However, it is not clear why this is, since many different aspects of lifestyle and the environment have been linked with the onset of asthma. In Africa, asthma has typically been thought of as being very uncommon, and indeed in many African dialects there is no word for asthma or the symptoms, such as wheezing, that asthmatic children experience. However, some research studies have suggested that asthma might be becoming more common in Africa and that this could be linked to ongoing economic and social changes.
Why Was This Study Done?
The researchers here wanted to understand whether the trend for childhood asthma to be on the increase worldwide was also the case in Africa. Economic growth is bringing about rapid changes in lifestyle in many developing countries, and at the same time the burden of disease is changing. In order to make sure that health systems are appropriately resourced, it's important to anticipate future changes in the burden of different diseases.
What Did the Researchers Do and Find?
This study was based on a comparison between two surveys, carried out ten years apart, of children attending three schools in Ghana's second largest city, Kumasi. The surveys were done in 1993 and 2003, and the schools surveyed were a rich city school, a poor city school, and a school in the nearby countryside. The same methods were used in the two different surveys. Importantly, the researchers used an exercise test as an indicator for asthma, because language differences meant they could not find out whether children were indeed asthmatic. In the exercise test, the schoolchildren ran outdoors for six minutes, and the researchers measured how fast the children could breathe out before and after exercise (their “peak flow”). Children whose drop in peak flow was more than 12.5% were classified as having exercise-induced bronchospasm, which is thought to predict asthma. The children were also tested for their response to extracts that commonly cause allergic reactions, such as from dust mites and cat and dog hair. 1,095 children were studied in 1993 and 1,848 in 2003, paralleling the growth of the city, which also meant that by 2003 the rural school had become incorporated into the city. Over this period of time, the proportion of children with exercise-induced bronchospasm increased in all three schools; overall this proportion went up from 3.1% to 5.2%. Children from the rich city school were most likely to have exercise-induced bronchospasm at either survey date. However, children from the poor city school experienced the biggest change over the time period studied, with more than double the proportion of children having exercise-induced bronchospasm in 2003 as compared to 1993. The researchers also saw similar trends in children who had allergic reactions to common substances.
What Do These Findings Mean?
The researchers observed substantial increases in the rate of exercise-induced bronchospasm, and allergic reactions, between the two survey dates. This finding suggests that asthma is likely to have become much more common in that time. However, exercise-induced bronchospasm is not an exact indicator of asthma so it is not possible to be certain about this. These changes are likely to be linked with the adoption of westernized lifestyles, but which precise factors are responsible for the increase is not clear. Factors linked to the development of asthma include a lower rate of childhood infections, a lower rate of breast-feeding, environmental pollution, and many others. Links between the increase in exercise-induced bronchospasm and any of these factors were not examined in this study. However, these results suggest that if the findings here are common to other African cities as well, a greater proportion of African health budgets will need to be devoted to asthma care in the future.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040070.
Wikipedia has an entry on asthma (Wikipedia is an internet encyclopedia anyone can edit)
The World Health Organization's Ghana minisite has information on this country
Patient information from NHS Direct on asthma
An accompanying PLoS Medicine Essay by Matthias Wjst and Daniel Boakye discusses research on asthma in Africa
doi:10.1371/journal.pmed.0040070
PMCID: PMC1808098  PMID: 17326711
2.  Association of Adenotonsillectomy with Asthma Outcomes in Children: A Longitudinal Database Analysis 
PLoS Medicine  2014;11(11):e1001753.
Rakesh Bhattacharjee and colleagues use data from a US private health insurance database to compare asthma severity measures in children one year before and one year after they underwent adenotonsillectomy with asthma measures in those who did not undergo adenotonsillectomy.
Please see later in the article for the Editors' Summary
Background
Childhood asthma and obstructive sleep apnea (OSA), both disorders of airway inflammation, were associated in recent observational studies. Although childhood OSA is effectively treated by adenotonsillectomy (AT), it remains unclear whether AT also improves childhood asthma. We hypothesized that AT, the first line of therapy for childhood OSA, would be associated with improved asthma outcomes and would reduce the usage of asthma therapies in children.
Methods and Findings
Using the 2003–2010 MarketScan database, we identified 13,506 children with asthma in the United States who underwent AT. Asthma outcomes during 1 y preceding AT were compared to those during 1 y following AT. In addition, 27,012 age-, sex-, and geographically matched children with asthma without AT were included to examine asthma outcomes among children without known adenotonsillar tissue morbidity. Primary outcomes included the occurrence of a diagnostic code for acute asthma exacerbation (AAE) or acute status asthmaticus (ASA). Secondary outcomes included temporal changes in asthma medication prescriptions, the frequency of asthma-related emergency room visits (ARERs), and asthma-related hospitalizations (ARHs). Comparing the year following AT to the year prior, AT was associated with significant reductions in AAE (30.2%; 95% CI: 25.6%–34.3%; p<0.0001), ASA (37.9%; 95% CI: 29.2%–45.6%; p<0.0001), ARERs (25.6%; 95% CI: 16.9%–33.3%; p<0.0001), and ARHs (35.8%; 95% CI: 19.6%–48.7%; p = 0.02). Moreover, AT was associated with significant reductions in most asthma prescription refills, including bronchodilators (16.7%; 95% CI: 16.1%–17.3%; p<0.001), inhaled corticosteroids (21.5%; 95% CI: 20.7%–22.3%; p<0.001), leukotriene receptor antagonists (13.4%; 95% CI: 12.9%–14.0%; p<0.001), and systemic corticosteroids (23.7%; 95% CI: 20.9%–26.5%; p<0.001). In contrast, there were no significant reductions in these outcomes in children with asthma who did not undergo AT over an overlapping follow-up period. Limitations of the MarketScan database include lack of information on race and obesity status. Also, the MarketScan database does not include information on children with public health insurance (i.e., Medicaid) or uninsured children.
Conclusions
In a very large sample of privately insured children, AT was associated with significant improvements in several asthma outcomes. Contingent on validation through prospectively designed clinical trials, this study supports the premise that detection and treatment of adenotonsillar tissue morbidity may serve as an important strategy for improving asthma control.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The global burden of asthma has been rising steadily over the past few decades. Nowadays, about 200–300 million adults and children worldwide are affected by asthma, a chronic condition caused by inflammation of the airways (the tubes that carry air in and out of the lungs). Although asthma can develop at any age, it is often diagnosed in childhood—asthma is one of the commonest chronic diseases in children. In the US, for example, asthma affects around 7.1 million children under the age of 18 years and is the third leading cause of hospitalization of children under the age of 15 years. In people with asthma, the airways can react very strongly to allergens such as animal fur or to irritants such as cigarette smoke. Exercise, cold air, and infections can trigger asthma attacks, which can be fatal. The symptoms of asthma include wheezing, coughing, chest tightness, and shortness of breath. Asthma cannot be cured, but drugs can relieve its symptoms and prevent acute asthma attacks.
Why Was This Study Done?
Recent studies have found an association between severe childhood asthma and obstructive sleep apnea (OSA). In OSA, airway inflammation promotes hypertrophy (excess growth) of the adenoids and the tonsils, immune system tissues in the upper airway. During sleep, the presence of hypertrophic adenotonsillar tissues predisposes the walls of the throat to collapse, which results in apnea—a brief interruption in breathing. People with OSA often snore loudly and frequently wake from deep sleep as they struggle to breathe. Childhood OSA, which affects 2%–3% of children, can be effectively treated by removal of the adenoids and tonsils (adenotonsillectomy). Given the association between childhood OSA and severe asthma and given the involvement of airway inflammation in both conditions, might adenotonsillectomy also improve childhood asthma? Here, the researchers analyze data from the MarketScan database, a large database of US patients with private health insurance, to investigate whether adenotonsillectomy is associated with improvements in asthma outcomes and with reductions in the use of asthma therapies in children.
What Did the Researchers Do and Find?
The researchers used the database to identify 13,506 children with asthma who had undergone adenotonsillectomy and to obtain information about asthma outcomes among these children for the year before and the year after the operation. Because asthma severity tends to decrease with age, the researchers also used the database to identify 27,012 age-, sex-, and geographically matched children with asthma who did not have the operation so that they could examine asthma outcomes over an equivalent two-year period in the absence of complications related to adenotonsillar hypertrophy. Comparing the year after adenotonsillectomy with the year before the operation, adenotonsillectomy was associated with a 30% reduction in acute asthma exacerbations, a 37.9% reduction in acute status asthmaticus (an asthma attack that is unresponsive to the drugs usually used to treat attacks), a 25.6% reduction in asthma-related emergency room visits, and a 35.8% reduction in asthma-related hospitalizations. By contrast, among the control children, there was only a 2% reduction in acute asthma exacerbations and only a 7% reduction in acute status asthmaticus over an equivalent two-year period. Adenotonsillectomy was also associated with significant reductions (changes unlikely to have occurred by chance) in prescription refills for most types of drugs used to treat asthma, whereas there were no significant reductions in prescription refills among children with asthma who had not undergone adenotonsillectomy. The study was limited by the lack of measures of race and obesity, which are both associated with severity of asthma.
What Do These Findings Mean?
These findings show that in a large sample of privately insured children in the US, adenotonsillectomy was associated with significant improvements in several asthma outcomes. These results do not show, however, that adenotonsillectomy caused a reduction in the severity of childhood asthma. It could be that the children who underwent adenotonsillectomy (but not those who did not have the operation) shared another unknown factor that led to improvements in their asthma over time. To prove a causal link, it will be necessary to undertake a randomized controlled trial in which the outcomes of groups of children with asthma who are chosen at random to undergo or not undergo adenotonsillectomy are compared. However, with the proviso that there are some risks associated with adenotonsillectomy, these findings suggest that the detection and treatment of adenotonsillar hypertrophy may help to improve asthma control in children.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001753.
The US Centers for Disease Control and Prevention provides information on asthma, including videos, games, and links to other resources for children with asthma
The American Lung Association provides detailed information about asthma and a fact sheet on asthma in children; it also has information about obstructive sleep apnea
The National Sleep Foundation provides information on snoring and obstructive sleep apnea in children
The UK National Health Service Choices website provides information (including some personal stories) about asthma, about asthma in children, and about obstructive sleep apnea
The “Global Asthma Report 2014” will be available in October 2014
MedlinePlus provides links to further information on asthma, on asthma in children, on sleep apnea, and on tonsils and adenoids (in English and Spanish)
doi:10.1371/journal.pmed.1001753
PMCID: PMC4219664  PMID: 25369282
3.  Live Attenuated Influenza Vaccine, Trivalent, Is Safe in Healthy Children 18 Months to 4 Years, 5 to 9 Years, and 10 to 18 Years of Age in a Community-Based, Nonrandomized, Open-Label Trial 
Pediatrics  2005;116(3):e397-e407.
Objective
Influenza-associated deaths in healthy children that were reported during the 2003–2004 influenza season heightened the public awareness of the seriousness of influenza in children. In 1996–1998, a pivotal phase III trial was conducted in children who were 15 to 71 months of age. Live attenuated influenza vaccine, trivalent (LAIV-T), was shown to be safe and efficacious. In a subsequent randomized, double-blind, placebo-controlled LAIV-T trial in children who were 1 to 17 years of age, a statistically significant increase in asthma encounters was observed for children who were younger than 59 months. LAIV-T was not licensed to children who were younger than 5 years because of the concern for asthma. We report on the largest safety study to date of the recently licensed LAIV-T in children 18 months to 4 years, 5 to 9 years, and 10 to 18 years of age in a 4-year (1998–2002) community-based trial that was conducted at Scott & White Memorial Hospital and Clinic (Temple, TX).
Methods
An open-label, nonrandomized, community-based trial of LAIV-T was conducted before its licensure. Medical records of all children were surveyed for serious adverse events (SAEs) 6 weeks after vaccination. Health care utilization was evaluated by determining the relative risk (RR) of medically attended acute respiratory illness (MAARI) and asthma rates at 0 to 14 and 15 to 42 days after vaccination compared with the rates before vaccination. Medical charts of all visits coded as asthma were reviewed for appropriate classification of events: acute asthma or other. We evaluated the risk for MAARI (health care utilization for acute respiratory illness) 0 to 14 and 15 to 42 days after LAIV-T by a method similar to the postlicensure safety analysis conducted on measles, mumps, and rubella and on diphtheria, tetanus, and whole-cell pertussis vaccines.
Results
All children regardless of age were administered a single intranasal dose of LAIV-T in each vaccine year. In the 4 years of the study, we administered 18 780 doses of LAIV-T to 11 096 children. A total of 4529, 7036, and 7215 doses of LAIV-T were administered to children who were 18 months to 4 years, 5 to 9 years, and 10 to 18 years of age, respectively. In vaccination years 1, 2, 3, and 4, we identified 10, 15, 11, and 6 SAEs, respectively. None of the SAEs was attributed to LAIV-T. In vaccination years 1, 2, 3, and 4, we identified 3, 2, 1, and 0 pregnancies, respectively, among adolescents. All delivered healthy infants. The RR for MAARI from 0 to 14 and 15 to 42 days after LAIV-T was assessed in vaccinees during the 4 vaccine years. Compared with the prevaccination period, there was no significant increase in risk in health care utilization attributed to MAARI from 0 to 14 and 15 to 42 days after vaccination in children who were 18 months to 4 years, 5 to 9 years, and 10 to 18 years of age in the 4 vaccine years. In children who were 18 months to 4 years of age, there was no significant increase in the risk in health care utilization for MAARI, MAARI subcategories (otitis media/sinusitis, upper respiratory tract illness, and lower respiratory tract illness), and asthma during the 0 to 14 days after vaccination compared with the prevaccination period. No significant increase in the risk in health care utilization for MAARI, MAARI subcategories, and asthma was detected when the risk period was extended to 15 to 42 days after vaccination, except for asthma events in vaccine year 1. A RR of 2.85 (95% confidence interval [CI]: 1.01–8.03) for asthma events was detected in children who were 18 months to 4 years of age but was not significantly increased for the other 3 vaccine years (vaccine year 2, RR: 1.42 [95% CI: 0.59–3.42]; vaccine year 3, RR: 0.47 [95% CI: 0.12–1.83]; vaccine year 4, RR: 0.20 [95% CI: 0.03–1.54]). No significant increase in the risk in health care utilization for MAARI or asthma was observed in children who were 18 months to 18 years of age and received 1, 2, 3, or 4 annual sequential doses of LAIV-T. Children who were 18 months to 4 years of age and received 1, 2, 3, or 4 annual doses of LAIV-T did not experience a significant increase in the RR for MAARI 0 to 14 days after vaccination; this was also true for children who were 5 to 9 and 10 to 18 years of age.
Conclusions
We observed no increased risk for asthma events 0 to 14 days after vaccination in children who were 18 months to 4 years, 5 to 9 years, and 10 to 18 years of age, In vaccine year 1, children who were 18 months to 4 years of age did have a significantly higher RR (2.85; 95% CI: 1.01–8.03) for asthma events 15 to 42 days after vaccination. In vaccine year 2, the formulation of LAIV-T was identical to the vaccine formulation used in vaccine year 1; however, in children who were 18 months to 4 years of age, no statistically significant increased risk was detected for asthma events 15 to 42 days after vaccination. Similarly, in vaccine years 3 and 4, children who were 18 months to 4 years of age did not have a statistically significant increased risk for asthma events 15 to 42 days after vaccination. Also, LAIV-T did not increase the risk for asthma in children who received 1, 2, 3, or 4 annual doses of LAIV-T. Although the possibility for a true increased risk for asthma was observed in 1 of 4 years in children who were 18 months to 4 years at 15 to 42 days after vaccination, it is more likely that the association is a chance effect because of the 190 comparisons made without adjustment for multiple comparisons. We conclude that LAIV-T is safe in children who are 18 months to 4 years, 5 to 9 years, and 10 to 18 years of age. The hypothesis that LAIV-T is associated with an increase in asthma events in children who are younger than 5 years is not supported by our data. Reassessment of the lower age limit for use of LAIV-T in children is indicated.
doi:10.1542/peds.2004-2258
PMCID: PMC1361119  PMID: 16140685
asthma exacerbation; children and adolescents; health service utilization; influenza vaccine; outcome assessment; RSV, respiratory syncytial virus; LAIV-T, live attenuated influenza vaccine, trivalent; MAARI, medically attended acute respiratory illness; FDA, Food and Drug Administration; SAE, serious adverse event; SWHP, Scott & White Health Plan; RR, relative risk; ICD-9, International Classification of Diseases, Ninth Revision; CI, confidence interval
4.  Effects of BMI, Fat Mass, and Lean Mass on Asthma in Childhood: A Mendelian Randomization Study 
PLoS Medicine  2014;11(7):e1001669.
In this study, Granell and colleagues used Mendelian randomization to investigate causal effects of BMI, fat mass, and lean mass on current asthma at age 7½ years in the Avon Longitudinal Study of Parents and Children (ALSPAC) and found that higher BMI increases the risk of asthma in mid-childhood.
Please see later in the article for the Editors' Summary
Background
Observational studies have reported associations between body mass index (BMI) and asthma, but confounding and reverse causality remain plausible explanations. We aim to investigate evidence for a causal effect of BMI on asthma using a Mendelian randomization approach.
Methods and Findings
We used Mendelian randomization to investigate causal effects of BMI, fat mass, and lean mass on current asthma at age 7½ y in the Avon Longitudinal Study of Parents and Children (ALSPAC). A weighted allele score based on 32 independent BMI-related single nucleotide polymorphisms (SNPs) was derived from external data, and associations with BMI, fat mass, lean mass, and asthma were estimated. We derived instrumental variable (IV) estimates of causal risk ratios (RRs). 4,835 children had available data on BMI-associated SNPs, asthma, and BMI. The weighted allele score was strongly associated with BMI, fat mass, and lean mass (all p-values<0.001) and with childhood asthma (RR 2.56, 95% CI 1.38–4.76 per unit score, p = 0.003). The estimated causal RR for the effect of BMI on asthma was 1.55 (95% CI 1.16–2.07) per kg/m2, p = 0.003. This effect appeared stronger for non-atopic (1.90, 95% CI 1.19–3.03) than for atopic asthma (1.37, 95% CI 0.89–2.11) though there was little evidence of heterogeneity (p = 0.31). The estimated causal RRs for the effects of fat mass and lean mass on asthma were 1.41 (95% CI 1.11–1.79) per 0.5 kg and 2.25 (95% CI 1.23–4.11) per kg, respectively. The possibility of genetic pleiotropy could not be discounted completely; however, additional IV analyses using FTO variant rs1558902 and the other BMI-related SNPs separately provided similar causal effects with wider confidence intervals. Loss of follow-up was unlikely to bias the estimated effects.
Conclusions
Higher BMI increases the risk of asthma in mid-childhood. Higher BMI may have contributed to the increase in asthma risk toward the end of the 20th century.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The global burden of asthma, a chronic (long-term) condition caused by inflammation of the airways (the tubes that carry air in and out of the lungs), has been rising steadily over the past few decades. It is estimated that, nowadays, 200–300 million adults and children worldwide are affected by asthma. Although asthma can develop at any age, it is often diagnosed in childhood—asthma is the most common chronic disease in children. In people with asthma, the airways can react very strongly to allergens such as animal fur or to irritants such as cigarette smoke, becoming narrower so that less air can enter the lungs. Exercise, cold air, and infections can also trigger asthma attacks, which can be fatal. The symptoms of asthma include wheezing, coughing, chest tightness, and shortness of breath. Asthma cannot be cured, but drugs can relieve its symptoms and prevent acute asthma attacks.
Why Was This Study Done?
We cannot halt the ongoing rise in global asthma rates without understanding the causes of asthma. Some experts think obesity may be one cause of asthma. Obesity, like asthma, is increasingly common, and observational studies (investigations that ask whether individuals exposed to a suspected risk factor for a condition develop that condition more often than unexposed individuals) in children have reported that body mass index (BMI, an indicator of body fat calculated by dividing a person's weight in kilograms by their height in meters squared) is positively associated with asthma. Observational studies cannot prove that obesity causes asthma because of “confounding.” Overweight children with asthma may share another unknown characteristic (confounder) that actually causes both obesity and asthma. Moreover, children with asthma may be less active than unaffected children, so they become overweight (reverse causality). Here, the researchers use “Mendelian randomization” to assess whether BMI has a causal effect on asthma. In Mendelian randomization, causality is inferred from associations between genetic variants that mimic the effect of a modifiable risk factor and the outcome of interest. Because gene variants are inherited randomly, they are not prone to confounding and are free from reverse causation. So, if a higher BMI leads to asthma, genetic variants associated with increased BMI should be associated with an increased risk of asthma.
What Did the Researchers Do and Find?
The researchers investigated causal effects of BMI, fat mass, and lean mass on current asthma at age 7½ years in 4,835 children enrolled in the Avon Longitudinal Study of Parents and Children (ALSPAC, a long-term health project that started in 1991). They calculated an allele score for each child based on 32 BMI-related genetic variants, and estimated associations between this score and BMI, fat mass and lean mass (both measured using a special type of X-ray scanner; in children BMI is not a good indicator of “fatness”), and asthma. They report that the allele score was strongly associated with BMI, fat mass, and lean mass, and with childhood asthma. The estimated causal relative risk (risk ratio) for the effect of BMI on asthma was 1.55 per kg/m2. That is, the relative risk of asthma increased by 55% for every extra unit of BMI. The estimated causal relative risks for the effects of fat mass and lean mass on asthma were 1.41 per 0.5 kg and 2.25 per kg, respectively.
What Do These Findings Mean?
These findings suggest that a higher BMI increases the risk of asthma in mid-childhood and that global increases in BMI toward the end of the 20th century may have contributed to the global increase in asthma that occurred at the same time. It is possible that the observed association between BMI and asthma reported in this study is underpinned by “genetic pleiotropy” (a potential limitation of all Mendelian randomization analyses). That is, some of the genetic variants included in the BMI allele score could conceivably also increase the risk of asthma. Nevertheless, these findings suggest that public health interventions designed to reduce obesity may also help to limit the global rise in asthma.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001669.
The US Centers for Disease Control and Prevention provides information on asthma and on all aspects of overweight and obesity (in English and Spanish)
The World Health Organization provides information on asthma and on obesity (in several languages)
The UK National Health Service Choices website provides information about asthma, about asthma in children, and about obesity (including real stories)
The Global Asthma Report 2011 is available
The Global Initiative for Asthma released its updated Global Strategy for Asthma Management and Prevention on World Asthma Day 2014
Information about the Avon Longitudinal Study of Parents and Children is available
MedlinePlus provides links to further information on obesity in children, on asthma, and on asthma in children (in English and Spanish
Wikipedia has a page on Mendelian randomization (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
doi:10.1371/journal.pmed.1001669
PMCID: PMC4077660  PMID: 24983943
5.  Protection against Mycobacterium ulcerans Lesion Development by Exposure to Aquatic Insect Saliva 
PLoS Medicine  2007;4(2):e64.
Background
Buruli ulcer is a severe human skin disease caused by Mycobacterium ulcerans. This disease is primarily diagnosed in West Africa with increasing incidence. Antimycobacterial drug therapy is relatively effective during the preulcerative stage of the disease, but surgical excision of lesions with skin grafting is often the ultimate treatment. The mode of transmission of this Mycobacterium species remains a matter of debate, and relevant interventions to prevent this disease lack (i) the proper understanding of the M. ulcerans life history traits in its natural aquatic ecosystem and (ii) immune signatures that could be correlates of protection. We previously set up a laboratory ecosystem with predatory aquatic insects of the family Naucoridae and laboratory mice and showed that (i) M. ulcerans-carrying aquatic insects can transmit the mycobacterium through bites and (ii) that their salivary glands are the only tissues hosting replicative M. ulcerans. Further investigation in natural settings revealed that 5%–10% of these aquatic insects captured in endemic areas have M. ulcerans–loaded salivary glands. In search of novel epidemiological features we noticed that individuals working close to aquatic environments inhabited by insect predators were less prone to developing Buruli ulcers than their relatives. Thus we set out to investigate whether those individuals might display any immune signatures of exposure to M. ulcerans-free insect predator bites, and whether those could correlate with protection.
Methods and Findings
We took a two-pronged approach in this study, first investigating whether the insect bites are protective in a mouse model, and subsequently looking for possibly protective immune signatures in humans. We found that, in contrast to control BALB/c mice, BALB/c mice exposed to Naucoris aquatic insect bites or sensitized to Naucoris salivary gland homogenates (SGHs) displayed no lesion at the site of inoculation of M. ulcerans coated with Naucoris SGH components. Then using human serum samples collected in a Buruli ulcer–endemic area (in the Republic of Benin, West Africa), we assayed sera collected from either ulcer-free individuals or patients with Buruli ulcers for the titre of IgGs that bind to insect predator SGH, focusing on those molecules otherwise shown to be retained by M. ulcerans colonies. IgG titres were lower in the Buruli ulcer patient group than in the ulcer-free group.
Conclusions
These data will help structure future investigations in Buruli ulcer–endemic areas, providing a rationale for research into human immune signatures of exposure to predatory aquatic insects, with special attention to those insect saliva molecules that bind to M. ulcerans.
Saliva from aquatic insects in areas where Buruli ulcer is endemic can protect mice against the disease's characteristic skin lesion and might play a role in natural immunity in humans.
Editors' Summary
Background.
Buruli ulcer disease is a severe skin infection caused by Mycobacterium ulcerans, a bacterium related to those that cause tuberculosis and leprosy. This poorly understood disease affects people living near slow-flowing or standing water in poor rural communities in tropical and subtropical countries. How people become infected with M. ulcerans is unclear but one possibility is that infected aquatic insects transmit it through their bites. The first sign of infection is usually a small painless swelling in the skin. Bacteria inside these swellings produce a toxin that damages nearby soft tissues until eventually the skin sloughs off to leave a large open sore. This usually heals but the resultant scar can limit limb movement. Consequently, 25% of people affected by Buruli ulcers—most of whom are children—are permanently disabled. If the disease is caught early, powerful antibiotics can prevent ulcer formation. But most patients do not seek help until the later stages when the only treatment is to cut out the infection and do a skin graft, a costly and lengthy treatment.
Why Was This Study Done?
There is currently no effective way to prevent Buruli ulcers. To develop an effective preventative strategy, researchers need to determine exactly how the infection is transmitted to people and what makes some individuals resistant to infection. Previous studies have indicated that 5%–10% of some aquatic insect predators that live in areas where Buruli ulcers occur have M. ulcerans in their salivary glands and that aquatic insects carrying M. ulcerans can transmit it to mice through bites. Furthermore, people working close to water inhabited by insect predators are less likely to develop Buruli ulcers than their relatives who do not work near water. In this study, therefore, the researchers investigated whether exposure to noninfected insect saliva provides some protection against M. ulcerans infection.
What Did the Researchers Do and Find?
The researchers let uninfected aquatic insects bite ten mice several times before exposing these mice and ten unbitten mice to M. ulcerans-infected water bugs. Only one pre-bitten mouse developed an M. ulcerans-containing lesion compared with eight control mice. Next, the researchers injected mice with insect salivary gland extracts before challenging them with “naked” M. ulcerans or bacteria coated with salivary gland extract. Most uninjected mice developed lesions when challenged with coated or naked M. ulcerans, as did experimental mice challenged with naked M. ulcerans. However, most experimental mice challenged with coated M. ulcerans remained lesion-free. In both experiments, the blood of the pre-bitten and extract-treated mice (but not the control mice) contained antibodies (immune system proteins that provide protection against infections and foreign proteins) to proteins in insect salivary gland extracts that stick to M. ulcerans. Finally, the researchers measured the blood concentration (the titer) of antibodies that bind insect salivary gland proteins in patients with Buruli ulcer and in healthy people living in the same area. People with high titers of these antibodies, they report, were less likely to have Buruli ulcers than those with low titers.
What Do These Findings Mean?
These findings suggest that exposure to aquatic insect saliva may provide some protection against M. ulcerans lesion development. However, the current results have several limitations. In particular they will only be relevant to human disease if M. ulcerans is normally transmitted by insect bites, and this has not been proven yet. Also, because the human study did not measure the overall immune status of the study participants, the people with Buruli ulcers may have had a general immune deficit rather than simply lacking antibodies against insect salivary gland proteins. However, if the human findings can be repeated and expanded, they suggest that low antibody titers to salivary gland proteins might identify those people who are most susceptible to M ulcerans infections and who would thus benefit most from regular tests for early signs of the disease. Finally, further work on the immune mechanism by which exposure to insect salivary gland proteins protects against M. ulcerans infections may help in the development of vaccines against Buruli ulcer disease.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0040064.
A related PLoS Medicine Perspective article by Manuel T. Silva and others discusses this study and others on insect-borne parasitic diseases
World Health Organization has information on Buruli ulcer disease
US Centers for Disease Control and Prevention has information on Buruli ulcer
The US Armed Forces Institute of Pathology Web site contains pages on Buruli ulcer
Leprosy Relief Emmaus Switzerland offers information on Buruli ulcer
Wikipedia contains pages on Buruli ulcer (note: Wikipedia is an online encyclopedia that anyone can edit)
PLoS Medicine has a detailed review article on Buruli ulcer by Paul D. R. Johnson and colleagues
doi:10.1371/journal.pmed.0040064
PMCID: PMC1808094  PMID: 17326707
6.  Association of breastfeeding with asthma in young Aboriginal children in Canada 
BACKGROUND:
Few studies have investigated the factors associated with asthma in young Aboriginal children.
OBJECTIVE:
To characterize the association of demographic, environmental and early life factors with asthma in young Aboriginal children in Canada.
METHODS:
The 2006 Aboriginal Children’s Survey was conducted among off-reserve Aboriginal children zero to six years of age to obtain information on Aboriginal children’s development and well-being. The prevalence of asthma in Aboriginal children was obtained from the parental report of asthma as diagnosed by a health care professional.
RESULTS:
The prevalence of reported asthma among off-reserve Aboriginal children zero to six years of age (n=14,170) was 9.4%. Asthma prevalence in both exclusively breastfed children (6.8%) and ever but not exclusively breastfed children (9.0%) was significantly lower than that in nonbreastfed children (11.0%). In the multiple logistic regression analysis, exclusive breastfeeding was protective of asthma compared with nonbreastfeeding (OR 0.59 [95% CI 0.44 to 0.78]). Older age groups, male sex, having two or more older siblings, low birth weight, day care attendance and ear infection were significant risk factors for asthma.
CONCLUSIONS:
The prevalence of asthma among young Aboriginal children zero to six years of age living off reserve was slightly lower than that reported for all other Canadian children. Breastfeeding, especially exclusively breastfeeding, was protective of asthma in Aboriginal children, which is consistent with what has been observed in non-Aboriginal children in Canada. Public health interventions intended for reducing asthma incidence in young Aboriginal children should include breastfeeding promotion programs.
PMCID: PMC3603760  PMID: 23248799
Aboriginal; Asthma; Breastfeeding; Children; Prevalence
7.  Key Source Habitats and Potential Dispersal of Triatoma infestans Populations in Northwestern Argentina: Implications for Vector Control 
Background
Triatoma infestans —the principal vector of the infection that causes Chagas disease— defies elimination efforts in the Gran Chaco region. This study identifies the types of human-made or -used structures that are key sources of these bugs in the initial stages of house reinfestation after an insecticide spraying campaign.
Methodology and Principal Findings
We measured demographic and blood-feeding parameters at two geographic scales in 11 rural communities in Figueroa, northwest Argentina. Of 1,297 sites searched in spring, 279 (21.5%) were infested. Bug abundance per site and female fecundity differed significantly among habitat types (ecotopes) and were highly aggregated. Domiciles (human sleeping quarters) had maximum infestation prevalence (38.7%), human-feeding bugs and total egg production, with submaximal values for other demographic and blood-feeding attributes. Taken collectively peridomestic sites were three times more often infested than domiciles. Chicken coops had greater bug abundance, blood-feeding rates, engorgement status, and female fecundity than pig and goat corrals. The host-feeding patterns were spatially structured yet there was strong evidence of active dispersal of late-stage bugs between ecotopes. Two flight indices predicted that female fliers were more likely to originate from kitchens and domiciles, rejecting our initial hypothesis that goat and pig corrals would dominate.
Conclusions and Significance
Chicken coops and domiciles were key source habitats fueling rapid house reinfestation. Focusing control efforts on ecotopes with human-fed bugs (domiciles, storerooms, goat corrals) would neither eliminate the substantial contributions to bug population growth from kitchens, chicken coops, and pig corrals nor stop dispersal of adult female bugs from kitchens. Rather, comprehensive control of the linked network of ecotopes is required to prevent feeding on humans, bug population growth, and bug dispersal simultaneously. Our study illustrates a demographic approach that may be applied to other regions and triatomine species for the design of innovative, improved vector control strategies.
Author Summary
The major vectors of Chagas disease are species of triatomine bugs adapted to human sleeping quarters and peridomestic annexes where they feed on humans and domestic or synanthropic mammals or birds. Knowledge of the demography and nutritional status of Triatominae in real-life settings is still fragmentary, and this affects our ability to prevent or reduce house reinfestation after insecticide spraying. In addition to showing where the bugs are likely to live (occupancy and density information), our observations and analysis of flight dispersal provide insights into where bugs are likely to originate. Data on nymphal and adult sex ratios, nutritional status, and female fecundity point to the key ecotopes and sites driving the population growth of the bugs and fueling house reinfestation. Focusing control efforts on the three ecotopes (human sleeping quarters, storerooms, and goat corrals) that housed reactive, human-fed bugs would neither eliminate the substantial contributions to bug population growth from kitchens, chicken coops, and pig corrals nor stop dispersal of adult female bugs from kitchens. Rather, comprehensive control of the linked network of ecotopes in a typical house compound and community is required to prevent feeding on humans, bug population growth, and bug dispersal simultaneously.
doi:10.1371/journal.pntd.0003238
PMCID: PMC4191936  PMID: 25299653
8.  Asthma in children born after infertility treatment: findings from the UK Millennium Cohort Study 
STUDY QUESTION
Is asthma more common in children born after subfertility and assisted reproduction technologies (ART)?
SUMMARY ANSWER
Yes. Asthma, wheezing in the last year and anti-asthmatic medication were all more common in children born after a prolonged time to conception (TTC). This was driven specifically by an increase in children born after ART.
WHAT IS KNOWN ALREADY
Few studies have investigated any association between ART and asthma in subsequent children, and findings to date have been mixed. A large registry-based study found an increase in asthma medication in ART children but suggests underlying infertility is the putative risk factor. Little is known about asthma in children after unplanned or mistimed conceptions.
STUDY DESIGN, SIZE, DURATION
The Millennium Cohort Study is a UK-wide, prospective study of 18 818 children recruited at 9 months of age. Follow-up is ongoing. This study analyses data from follow-up surveys at 5 and 7 years of age (response rates of 79 and 70%, respectively).
PARTICIPANTS/MATERIALS, SETTING, METHODS
Singleton children whose natural mothers provided follow-up data were included. Mothers reported whether their pregnancy was planned; planners provided TTC and details of any ART. The population was divided into ‘unplanned’ (unplanned and unhappy), ‘mistimed’ (unplanned but happy), ‘planned’ (planned, TTC < 12 months), ‘untreated subfertile’ (planned, TTC >12 months), ‘ovulation induced’ (received clomiphene citrate) and ‘ART’ (IVF or ICSI). The primary analysis used the planned children as the comparison group; secondary analysis compared the treatment groups to the children born to untreated subfertile parents. Outcomes were parent report of asthma and wheezing at 5 and 7 years, derived from validated questions in the International Study of Asthma and Allergies in Childhood, plus use of anti-asthmatic medications. A total of 13 041 (72%) children with full data on asthma and confounders were included at 5 years of age, and 11 585 (64%) at 7 years.
MAIN RESULTS AND THE ROLE OF CHANCE
Compared with planned children, those born to subfertile parents were significantly more likely to experience asthma, wheezing and to be taking anti-asthmatics at 5 years of age [adjusted odds ratio (OR): 1.39 (95% confidence interval (CI): 1.07, 1.80), OR: 1.27 (1.00, 1.63) and OR: 1.90 (1.32,2.74), respectively]. This association was mainly related to an increase among children born after ART (adjusted OR: 2.65 (1.48, 4.76), OR: 1.97, (1.10, 3.53) and OR: 4.67 (2.20, 9.94) for asthma, wheezing and taking anti-asthmatics, respectively). The association was also present, though reduced, at the age of 7 years.
LIMITATIONS, REASONS FOR CAUTION
The number of singletons born after ART was relatively small (n = 104), and as such the findings should be interpreted with caution. However, data on a wide range of possible confounding and mediating factors were available and analysed. The data were weighted for non-response to minimize selection bias.
WIDER IMPLICATIONS OF THE FINDINGS
The findings add to the growing body of evidence suggesting an association between subfertility, ART and asthma in children. Further work is needed to establish causality and elucidate the underlying mechanism. These findings are generalizable to singletons only, and further work on multiples is needed.
STUDY FUNDING/COMPETING INTEREST(S)
This study was funded by a Medical Research Council project grant. No competing interests.
doi:10.1093/humrep/des398
PMCID: PMC3545639  PMID: 23223378
infertility; assisted reproduction techniques; asthma; unplanned pregnancy
9.  Preterm Birth and Childhood Wheezing Disorders: A Systematic Review and Meta-Analysis 
PLoS Medicine  2014;11(1):e1001596.
In a systematic review and meta-analysis, Jasper Been and colleagues investigate the association between preterm birth and the development of wheezing disorders in childhood.
Please see later in the article for the Editors' Summary
Background
Accumulating evidence implicates early life factors in the aetiology of non-communicable diseases, including asthma/wheezing disorders. We undertook a systematic review investigating risks of asthma/wheezing disorders in children born preterm, including the increasing numbers who, as a result of advances in neonatal care, now survive very preterm birth.
Methods and Findings
Two reviewers independently searched seven online databases for contemporaneous (1 January 1995–23 September 2013) epidemiological studies investigating the association between preterm birth and asthma/wheezing disorders. Additional studies were identified through reference and citation searches, and contacting international experts. Quality appraisal was undertaken using the Effective Public Health Practice Project instrument. We pooled unadjusted and adjusted effect estimates using random-effects meta-analysis, investigated “dose–response” associations, and undertook subgroup, sensitivity, and meta-regression analyses to assess the robustness of associations.
We identified 42 eligible studies from six continents. Twelve were excluded for population overlap, leaving 30 unique studies involving 1,543,639 children. Preterm birth was associated with an increased risk of wheezing disorders in unadjusted (13.7% versus 8.3%; odds ratio [OR] 1.71, 95% CI 1.57–1.87; 26 studies including 1,500,916 children) and adjusted analyses (OR 1.46, 95% CI 1.29–1.65; 17 studies including 874,710 children). The risk was particularly high among children born very preterm (<32 wk gestation; unadjusted: OR 3.00, 95% CI 2.61–3.44; adjusted: OR 2.81, 95% CI 2.55–3.12). Findings were most pronounced for studies with low risk of bias and were consistent across sensitivity analyses. The estimated population-attributable risk of preterm birth for childhood wheezing disorders was ≥3.1%.
Key limitations related to the paucity of data from low- and middle-income countries, and risk of residual confounding.
Conclusions
There is compelling evidence that preterm birth—particularly very preterm birth—increases the risk of asthma. Given the projected global increases in children surviving preterm births, research now needs to focus on understanding underlying mechanisms, and then to translate these insights into the development of preventive interventions.
Review Registration
PROSPERO CRD42013004965
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Most pregnancies last around 40 weeks, but worldwide, more than 11% of babies are born before 37 weeks of gestation (the period during which a baby develops in its mother's womb). Preterm birth is a major cause of infant death—more than 1 million babies die annually from preterm birth complications—and the number of preterm births is increasing globally. Multiple pregnancies, infections, and chronic (long-term) maternal conditions such as diabetes can all cause premature birth, but the cause of many preterm births is unknown. The most obvious immediate complication that is associated with preterm birth is respiratory distress syndrome. This breathing problem, which is more common in early preterm babies than in near-term babies, occurs because the lungs of premature babies are structurally immature and lack pulmonary surfactant, a unique mixture of lipids and proteins that coats the inner lining of the lungs and helps to prevent the collapse of the small air sacs in the lungs that absorb oxygen from the air. Consequently, preterm babies often need help with their breathing and oxygen supplementation.
Why Was This Study Done?
Improvements in the management of prematurity mean that more preterm babies survive today than in the past. However, accumulating evidence suggests that early life events are involved in the subsequent development of non-communicable diseases (non-infectious chronic diseases). Given the increasing burden of preterm birth, a better understanding of the long-term effects of preterm birth is essential. Here, the researchers investigate the risks of asthma and wheezing disorders in children who are born preterm by undertaking a systematic review (a study that uses predefined criteria to identify all the research on a given topic) and a meta-analysis (a statistical method for combining the results of several studies). Asthma is a chronic condition that is caused by inflammation of the airways. In people with asthma, the airways can react very strongly to allergens such as animal fur and to irritants such as cigarette smoke. Exercise, cold air, and infections can also trigger asthma attacks, which can sometimes be fatal. The symptoms of asthma include wheezing (a high-pitched whistling sound during breathing), coughing, chest tightness, and shortness of breath. Asthma cannot be cured, but drugs can relieve its symptoms and prevent acute asthma attacks.
What Did the Researchers Do and Find?
The researchers identified 30 studies undertaken between 1995 and the present (a time span chosen to allow for recent changes in the management of prematurity) that investigated the association between preterm birth and asthma/wheezing disorders in more than 1.5 million children. Across the studies, 13.7% of preterm babies developed asthma/wheezing disorders during childhood, compared to only 8.3% of babies born at term. Thus, the risk of preterm babies developing asthma or a wheezing disorder during childhood was 1.71 times higher than the risk of term babies developing these conditions (an unadjusted odds ratio [OR] of 1.71). In analyses that allowed for confounding factors—other factors that affect the risk of developing asthma/wheezing disorders such as maternal smoking—the risk of preterm babies developing asthma or a wheezing disorder during childhood was 1.46 times higher than that of babies born at term (an adjusted OR of 1.46). Notably, compared to children born at term, children born very early (before 32 weeks of gestation) had about three times the risk of developing asthma/wheezing disorders in unadjusted and adjusted analyses. Finally, the population-attributable risk of preterm birth for childhood wheezing disorders was more than 3.1%. That is, if no preterm births had occurred, there would have been more than a 3.1% reduction in childhood wheezing disorders.
What Do These Findings Mean?
These findings strongly suggest that preterm birth increases the risk of asthma and wheezing disorders during childhood and that the risk of asthma/wheezing disorders increases as the degree of prematurity increases. The accuracy of these findings may be affected, however, by residual confounding. That is, preterm children may share other, unknown characteristics that increase their risk of developing asthma/wheezing disorders. Moreover, the generalizability of these findings is limited by the lack of data from low- and middle-income countries. However, given the projected global increases in children surviving preterm births, these findings highlight the need to undertake research into the mechanisms underlying the association between preterm birth and asthma/wheezing disorders and the need to develop appropriate preventative and therapeutic measures.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001596.
The March of Dimes, a nonprofit organization for pregnancy and baby health, provides information on preterm birth (in English and Spanish)
Nemours, another nonprofit organization for child health, also provides information (in English and Spanish) on premature babies and on asthma (including personal stories)
The UK National Health Service Choices website provides information about premature labor and birth and a real story about having a preterm baby; it provides information about asthma in children (including real stories)
The MedlinePlus Encyclopedia has pages on preterm birth, asthma, asthma in children, and wheezing (in English and Spanish); MedlinePlus provides links to further information on premature birth, asthma, and asthma in children (in English and Spanish)
doi:10.1371/journal.pmed.1001596
PMCID: PMC3904844  PMID: 24492409
10.  Barriers to Provider-Initiated Testing and Counselling for Children in a High HIV Prevalence Setting: A Mixed Methods Study 
PLoS Medicine  2014;11(5):e1001649.
Rashida Ferrand and colleagues combine quantitative and qualitative methods to investigate HIV prevalence among older children receiving primary care in Harare, Zimbabwe, and reasons why providers did not pursue testing.
Please see later in the article for the Editors' Summary
Background
There is a substantial burden of HIV infection among older children in sub-Saharan Africa, the majority of whom are diagnosed after presentation with advanced disease. We investigated the provision and uptake of provider-initiated HIV testing and counselling (PITC) among children in primary health care facilities, and explored health care worker (HCW) perspectives on providing HIV testing to children.
Methods and Findings
Children aged 6 to 15 y attending six primary care clinics in Harare, Zimbabwe, were offered PITC, with guardian consent and child assent. The reasons why testing did not occur in eligible children were recorded, and factors associated with HCWs offering and children/guardians refusing HIV testing were investigated using multivariable logistic regression. Semi-structured interviews were conducted with clinic nurses and counsellors to explore these factors. Among 2,831 eligible children, 2,151 (76%) were offered PITC, of whom 1,534 (54.2%) consented to HIV testing. The main reasons HCWs gave for not offering PITC were the perceived unsuitability of the accompanying guardian to provide consent for HIV testing on behalf of the child and lack of availability of staff or HIV testing kits. Children who were asymptomatic, older, or attending with a male or a younger guardian had significantly lower odds of being offered HIV testing. Male guardians were less likely to consent to their child being tested. 82 (5.3%) children tested HIV-positive, with 95% linking to care. Of the 940 guardians who tested with the child, 186 (19.8%) were HIV-positive.
Conclusions
The HIV prevalence among children tested was high, highlighting the need for PITC. For PITC to be successfully implemented, clear legislation about consent and guardianship needs to be developed, and structural issues addressed. HCWs require training on counselling children and guardians, particularly male guardians, who are less likely to engage with health care services. Increased awareness of the risk of HIV infection in asymptomatic older children is needed.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Over 3 million children globally are estimated to be living with HIV (the virus that causes AIDS). While HIV infection is most commonly spread through unprotected sex with an infected person, most HIV infections among children are the result of mother-to-child HIV transmission during pregnancy, delivery, or breastfeeding. Mother-to-child transmission can be prevented by administering antiretroviral therapy to mothers with HIV during pregnancy, delivery, and breast feeding, and to their newborn babies. According to a report by the Joint United Nations Programme on HIV/AIDS published in 2012, 92% of pregnant women with HIV were living in sub-Saharan Africa and just under 60% were receiving antiretroviral therapy. Consequently, sub-Saharan Africa is the region where most children infected with HIV live.
Why Was This Study Done?
If an opportunity to prevent mother-to-child transmission around the time of birth is missed, diagnosis of HIV infection in a child or adolescent is likely to depend on HIV testing in health care facilities. Health care provider–initiated HIV testing and counselling (PITC) for children is important in areas where HIV infection is common because earlier diagnosis allows children to benefit from care that can prevent the development of advanced HIV disease. Even if a child or adolescent appears to be in good health, access to care and antiretroviral therapy provides a health benefit to the individual over the long term. The administration of HIV testing (and counselling) to children relies not only on health care workers (HCWs) offering HIV testing but also on parents or guardians consenting for a child to be tested. However, more than 30% of children in countries with severe HIV epidemics are AIDS orphans, and economic conditions in these countries cause many adults to migrate for work, leaving children under the care of extended families. This study aimed to investigate the reasons for acceptance and rejection of PITC in primary health care settings in Harare, Zimbabwe. By exploring HCW perspectives on providing HIV testing to children and adolescents, the study also sought to gain insight into factors that could be hindering implementation of testing procedures.
What Did the Researchers Do and Find?
The researchers identified all children aged 6 to 15 years old at six primary care clinics in Harare, who were offered HIV testing as part of routine care between 22 January and 31 May 2013. Study fieldworkers collected data on numbers of child attendances, numbers offered testing, numbers who underwent HIV testing, and reasons why HIV testing did not occur. During the study 2,831 children attending the health clinics were eligible for PITC, and just over half (1,534, 54.2%) underwent HIV testing. Eighty-two children tested HIV-positive, and nearly all of them received counselling, medication, and follow-up care. HCWs offered the test to around 75% of those eligible. The most frequent explanation given by HCWs for a diagnostic test not being offered was that the child was accompanied by a guardian not appropriate for providing consent (401 occasions, 59%); Other reasons given were a lack of available counsellors or test kits and counsellors refusing to conduct the test. The likelihood of being offered the test was lower for children not exhibiting symptoms (such as persistent skin problems), older children, or those attending with a male or a younger guardian. In addition, over 100 guardians or parents provided consent but left before the child could be tested.
The researchers also conducted semi-structured interviews with 12 clinic nurses and counsellors (two from each clinic) to explore challenges to implementation of PITC. The researchers recorded the factors associated with testing not taking place, either when offered to eligible children or when HCWs declined to offer the test. The interviewees identified the frequent absence or unavailability of parents or legal guardians as an obstacle, and showed uncertainty or misconceptions around whether testing of the guardian was mandatory (versus recommended) and whether specifically a parent (if one was living) must provide consent. The interviews also revealed HCW concerns about the availability of adequate counselling and child services, and fears that a child might experience maltreatment if he or she tested positive. HCWs also noted long waiting times and test kits being out of stock as practical hindrances to testing.
What Do These Findings Mean?
Prevalence of HIV was high among the children tested, validating the need for PITC in sub-Saharan health care settings. Although 76% of eligible attendees were offered testing, the authors note that this is likely higher than in routine settings because the researchers were actively recording reasons for not offering testing and counselling, which may have encouraged heath care staff to offer PITC more often than usual. The researchers outline strategies that may improve PITC rates and testing acceptance for Zimbabwe and other sub-Saharan settings. These strategies include developing clear laws and guidance concerning guardianship and proxy consent when testing older children for HIV, training HCWs around these policies, strengthening legislation to address discrimination, and increasing public awareness about HIV infection in older children.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001649.
This study is further discussed in a PLOS Medicine Perspective by Davies and Kalk
The Joint United Nations Programme on HIV/AIDS publishes an annual report on the global AIDS epidemic, which provides information on progress towards eliminating new HIV infections
The World Health Organization has more information on mother-to-child transmission of HIV
The World Health Organization's website also has information about treatment for children living with HIV
Personal stories about living with HIV/AIDS, including stories from young people infected with HIV, are available through Avert, through NAM/aidsmap, and through the charity website Healthtalkonline
doi:10.1371/journal.pmed.1001649
PMCID: PMC4035250  PMID: 24866209
11.  Assessing Optimal Target Populations for Influenza Vaccination Programmes: An Evidence Synthesis and Modelling Study 
PLoS Medicine  2013;10(10):e1001527.
Marc Baguelin and colleagues use virological, clinical, epidemiological, and behavioral data to estimate how policies for influenza vaccination programs may be optimized in England and Wales.
Please see later in the article for the Editors' Summary
Background
Influenza vaccine policies that maximise health benefit through efficient use of limited resources are needed. Generally, influenza vaccination programmes have targeted individuals 65 y and over and those at risk, according to World Health Organization recommendations. We developed methods to synthesise the multiplicity of surveillance datasets in order to evaluate how changing target populations in the seasonal vaccination programme would affect infection rate and mortality.
Methods and Findings
Using a contemporary evidence-synthesis approach, we use virological, clinical, epidemiological, and behavioural data to develop an age- and risk-stratified transmission model that reproduces the strain-specific behaviour of influenza over 14 seasons in England and Wales, having accounted for the vaccination uptake over this period. We estimate the reduction in infections and deaths achieved by the historical programme compared with no vaccination, and the reduction had different policies been in place over the period. We find that the current programme has averted 0.39 (95% credible interval 0.34–0.45) infections per dose of vaccine and 1.74 (1.16–3.02) deaths per 1,000 doses. Targeting transmitters by extending the current programme to 5–16-y-old children would increase the efficiency of the total programme, resulting in an overall reduction of 0.70 (0.52–0.81) infections per dose and 1.95 (1.28–3.39) deaths per 1,000 doses. In comparison, choosing the next group most at risk (50–64-y-olds) would prevent only 0.43 (0.35–0.52) infections per dose and 1.77 (1.15–3.14) deaths per 1,000 doses.
Conclusions
This study proposes a framework to integrate influenza surveillance data into transmission models. Application to data from England and Wales confirms the role of children as key infection spreaders. The most efficient use of vaccine to reduce overall influenza morbidity and mortality is thus to target children in addition to older adults.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every winter, millions of people catch influenza, a viral infection of the airways. Most infected individuals recover quickly, but seasonal influenza outbreaks (epidemics) kill about half a million people annually. In countries with advanced health systems, these deaths occur mainly among elderly people and among individuals with long-term illnesses such as asthma and heart disease that increase the risk of complications occurring after influenza virus infection. Epidemics of influenza occur because small but frequent changes in the influenza virus mean that an immune response produced one year through infection provides only partial protection against influenza the following year. Annual immunization with a vaccine that contains killed influenza viruses of the major circulating strains can greatly reduce a person's risk of catching influenza by preparing the immune system to respond quickly when challenged by a live influenza virus. Consequently, many countries run seasonal influenza vaccination programs that, in line with World Health Organization recommendations, target individuals 65 years old and older and people in high-risk groups.
Why Was This Study Done?
Is this approach the best use of available resources? Might, for example, vaccination of children—the main transmitters of influenza—provide more benefit to the whole population than vaccination of elderly people? Vaccination of children would not directly prevent as many influenza-related deaths as vaccination of elderly people, but it might indirectly prevent deaths in elderly adults by inducing herd immunity—vaccination of a large part of a population can protect unvaccinated members of the population by reducing the chances of an infection spreading. Policy makers need to know whether a change to an influenza vaccination program is likely to provide additional population benefits before altering the program. In this evidence synthesis and modeling study, the researchers combine (synthesize) longitudinal influenza surveillance datasets (data collected over time) from England and Wales, develop a mathematical model for influenza transmission based on these data using a Bayesian statistical approach, and use the model to evaluate the impact on influenza infections and deaths of changes to the seasonal influenza vaccination program in England and Wales.
What Did the Researchers Do and Find?
The researchers developed an influenza transmission model using clinical data on influenza-like illness consultations collected in a primary care surveillance scheme for each week of 14 influenza seasons in England and Wales, virological information on respiratory viruses detected in a subset of patients presenting with clinically suspected influenza, and data on vaccination coverage in the whole population (epidemiological data). They also incorporated data on social contacts (behavioral data) and on immunity to influenza viruses in the population (seroepidemiological data) into their model. To estimate the impact of potential changes to the current vaccination strategy in England and Wales, the researchers used their model, which replicated the patterns of disease observed in the surveillance data, to run simulated epidemics for each influenza season and for three strains of influenza virus under various vaccination scenarios. Compared to no vaccination, the current program (vaccination of people 65 years old and older and people in high-risk groups) averted 0.39 infections per dose of vaccine and 1.74 deaths per 1,000 doses. Notably, the model predicted that extension of the program to target 5–16-year-old children would increase the efficiency of the program and would avert 0.70 infections per dose and 1.95 deaths per 1,000 doses.
What Do These Findings Mean?
The finding that the transmission model developed by the researchers closely fit the available surveillance data suggests that the model should be able to predict what would have happened in England and Wales over the study period if an alternative vaccination regimen had been in place. The accuracy of such predictions may be limited, however, because the vaccination model is based on a series of simplifying assumptions. Importantly, given that influenza vaccination for children is being rolled out in England and Wales from September 2013, the model confirms that children are key spreaders of influenza and suggests that a vaccination program targeting children will reduce influenza infections and potentially influenza deaths in the whole population. More generally, the findings of this study support wider adoption of national vaccination strategies designed to block influenza transmission and to target those individuals most at risk from the complications of influenza infection.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371.journal.pmed.1001527.
The UK National Health Service Choices website provides information for patients about seasonal influenza and about vaccination; Public Health England (formerly the Health Protection Agency) provides information on influenza surveillance in the UK, including information about the primary care surveillance database used in this study
The World Health Organization provides information on seasonal influenza (in several languages)
The European Influenzanet is a system to monitor the activity of influenza-like illness with the aid of volunteers via the Internet
The US Centers for Disease Control and Prevention also provides information for patients and health professionals on all aspects of seasonal influenza, including information about vaccination and about the US influenza surveillance system; its website contains a short video about personal experiences of influenza
Flu.gov, a US government website, provides access to information on seasonal influenza and vaccination
MedlinePlus has links to further information about influenza and about immunization (in English and Spanish)
doi:10.1371/journal.pmed.1001527
PMCID: PMC3793005  PMID: 24115913
12.  Predicting Patterns of Long-Term CD4 Reconstitution in HIV-Infected Children Starting Antiretroviral Therapy in Sub-Saharan Africa: A Cohort-Based Modelling Study 
PLoS Medicine  2013;10(10):e1001542.
Using data from the ARROW trial, Joanna Lewis and colleagues investigate the CD4 cell count recovery profiles of children infected with HIV starting antiretroviral therapy in Sub-Saharan Africa.
Please see later in the article for the Editors' Summary
Background
Long-term immune reconstitution on antiretroviral therapy (ART) has important implications for HIV-infected children, who increasingly survive into adulthood. Children's response to ART differs from adults', and better descriptive and predictive models of reconstitution are needed to guide policy and direct research. We present statistical models characterising, qualitatively and quantitatively, patterns of long-term CD4 recovery.
Methods and Findings
CD4 counts every 12 wk over a median (interquartile range) of 4.0 (3.7, 4.4) y in 1,206 HIV-infected children, aged 0.4–17.6 y, starting ART in the Antiretroviral Research for Watoto trial (ISRCTN 24791884) were analysed in an exploratory analysis supplementary to the trial's pre-specified outcomes. Most (n = 914; 76%) children's CD4 counts rose quickly on ART to a constant age-corrected level. Using nonlinear mixed-effects models, higher long-term CD4 counts were predicted for children starting ART younger, and with higher CD4 counts (p<0.001). These results suggest that current World Health Organization–recommended CD4 thresholds for starting ART in children ≥5 y will result in lower CD4 counts in older children when they become adults, such that vertically infected children who remain ART-naïve beyond 10 y of age are unlikely ever to normalise CD4 count, regardless of CD4 count at ART initiation. CD4 profiles with four qualitatively distinct reconstitution patterns were seen in the remaining 292 (24%) children. Study limitations included incomplete viral load data, and that the uncertainty in allocating children to distinct reconstitution groups was not modelled.
Conclusions
Although younger ART-naïve children are at high risk of disease progression, they have good potential for achieving high CD4 counts on ART in later life provided ART is initiated following current World Health Organization (WHO), Paediatric European Network for Treatment of AIDS, or US Centers for Disease Control and Prevention guidelines. In contrast, to maximise CD4 reconstitution in treatment-naïve children >10 y, ART should ideally be considered even if there is a low risk of immediate disease progression. Further exploration of the immunological mechanisms for these CD4 recovery profiles should help guide management of paediatric HIV infection and optimise children's immunological development.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Worldwide, about 3.3 million children under 15 years old are infected with HIV, the virus that causes AIDS. More than 90% of these children live in sub-Saharan Africa, where nearly 600 children become infected with HIV every day, usually acquiring the virus from their mother during pregnancy, birth, or breastfeeding. HIV gradually reduces the numbers of CD4 lymphocytes in the immune system, leaving infected individuals susceptible to other infections. HIV infection can be kept in check but not cured with antiretroviral therapy (ART)—cocktails of drugs that have to be taken every day throughout life. ART reduces the amount of virus in the blood (viral load), which allows the immune system to recover (long-term immune reconstitution). Unfortunately, ART is very expensive, but concerted international efforts over the past decade mean that about a third of children who need ART are now receiving it, including half a million children in sub-Saharan Africa.
Why Was This Study Done?
World Health Organization (WHO) guidelines recommend initiation of ART at age-related CD4 cell count thresholds based on the risk of short-term disease progression. The guidelines recommend that all HIV-positive children under two years old begin ART as soon they receive a diagnosis of HIV infection. For children aged 2–5 years, ART initiation is recommended once the CD4 count drops below 750 cells/µl blood, whereas for older children the threshold for ART initiation is 350 CD4 cells/µl. Because of improved ART coverage, many more HIV-infected children now survive into adulthood than in the past. It is therefore important to know how the timing of ART initiation in childhood affects long-term immune reconstitution. Unfortunately, although several studies have examined the effect of ART on immune reconstitution in adults, the results of these studies cannot be extrapolated to children because of age-related differences in immune reconstitution. In this cohort-based modelling study, the researchers investigate long-term CD4 recovery in a cohort (group) of HIV-infected children initiating ART in Uganda and Zimbabwe, and present statistical models that predict patterns of long-term CD4 status based on age and CD4 count at ART initiation.
What Did the Researchers Do and Find?
To investigate long-term CD4 reconstitution in children, the researchers used CD4 counts collected during the ARROW trial, a study designed to investigate monitoring strategies during first-line ART in 1,206 HIV-positive children. In three-quarters of the children, CD4 reconstitution following ART initiation was asymptotic—CD4 counts increased rapidly immediately after ART initiation, then slowed before eventually reaching a constant level of about 80% of the CD4 count expected in an uninfected child of the same age. Using a nonlinear mixed-effects statistical model that fitted this pattern of immune reconstitution, the researchers predicted CD4 trajectories for children starting ART at different ages and with different CD4 counts. Higher long-term counts were predicted for children starting ART earlier and with higher CD4 counts. Thus, to achieve a CD4 count greater than 700 cells/µl at age 20 years, CD4 counts of at least 96 cells/µl, 130 cells/µl, and 557 cells/µl are needed for children aged two, five, and 12 years, respectively, when they initiate ART. Qualitatively distinct reconstitution patterns were seen in the remaining children in the study.
What Do These Findings Mean?
These findings suggest that young HIV-positive, ART-naïve children can achieve high CD4 counts in later life, provided ART is initiated as recommended in the current WHO guidelines. However, the recommended CD4 count thresholds for ART initiation are unlikely to maximize immune reconstitution in treatment-naïve children over ten years old. Rather, these findings suggest that ART initiation should be considered in these older children when their CD4 count is still high—even though they have a low risk of immediate disease progression—in order to achieve higher long-term CD4 levels. The omission of viral load measurements in the researchers' model may limit the accuracy of these findings. Moreover, although the predictions made by the model apply to children who will go on to experience asymptotic recovery, they are less relevant to those with different recovery profiles, who cannot currently be accurately identified. Further exploration of the immunological mechanisms underlying the CD4 recovery profiles described here should improve our understanding of the factors that determine the response of HIV-positive children to ART and provide information to guide the management of HIV infections in children.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001542.
Information is available from the US National Institute of Allergy and Infectious Diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS and summaries of recent research findings on HIV care and treatment
Information is available from Avert, an international AIDS charity, on many aspects of HIV/AIDS, including information on HIV and AIDS in Africa and on HIV infection in children (in English and Spanish)
The UNAIDS World AIDS Day Report 2012 provides up-to-date information about the AIDS epidemic and efforts to halt it; the UNAIDS's 2013 Progress Report on the Global Plan provides information on progress towards eliminating new HIV infections among children by 2015
The World Health Organization provides information about universal access to AIDS treatment (in several languages); its 2010 guidelines for ART in infants and children can be downloaded
Information about the ARROW trial is available
Personal stories about living with HIV/AIDS, including stories from young people infected with HIV, are available through Avert, through Nam/aidsmap, and through the charity website Healthtalkonline
doi:10.1371/journal.pmed.1001542
PMCID: PMC3812080  PMID: 24204216
13.  Persistence of Buggy Creek Virus (Togaviridae, Alphavirus) for Two Years in Unfed Swallow Bugs (Hemiptera: Cimicidae: Oeciacus vicarius) 
Journal of medical entomology  2010;47(3):436-441.
Alphaviruses (Togaviridae) have rarely been found to persist for long in the adult insects that serve as their vectors. The ectoparasitic swallow bug (Hemiptera: Cimicidae: Oeciacus vicarius Horvath), the vector for Buggy Creek virus (BCRV; Togaviridae, Alphavirus), lives year-round in the mud nests of its host, the cliff swallow (Petrochelidon pyrrhonota Vieillot). We measured the prevalence of BCRV in swallow bugs at sites with cliff swallows present and at the same sites after cliff swallows had been absent for 2 yr. We collected bugs directly from cliff swallow nests in the field and screened bug pools with BCRV-specific real-time-polymerase chain reaction (RT-PCR) and plaque assay. At two colony sites last occupied by birds 2 yr earlier, we found 12.5 and 55.6% of bug pools positive for BCRV RNA by RT-PCR. Infection rates (per 1,000 bugs) for these sites were 1.32 and 7.39. RNA prevalence in the unfed bugs was not significantly different from that in fed bugs 2 yr earlier at the same sites. The RNA-positive samples from unfed bugs failed to yield cytopathic BCRV by Vero-cell plaque assay. However, viral RNA concentrations did not differ between unfed bugs and bugs at active sites, and over 84% of positive bug pools were cytopathic to Vero cells 4–5 wk later, after cliff swallows moved into one of the colony sites. These data demonstrate the persistence of potentially infectious BCRV in unfed swallow bugs for at least 2 yr in nature.
PMCID: PMC2903633  PMID: 20496591
alphavirus; Buggy Creek virus; cliff swallow; Oeciacus vicarius; Petrochelidon pyrrhonota
14.  Horizontal Transfer of Diatomaceous Earth and Botanical Insecticides in the Common Bed Bug, Cimex lectularius L.; Hemiptera: Cimicidae 
PLoS ONE  2013;8(9):e75626.
Background
Horizontal transfer of insecticide occurs when insects contact or ingest an insecticide, return to an aggregation or a nest, and transfer the insecticide to other conspecific insects through contact. This phenomenon has been reported in a number of insects including social insects, however it has not been reported in bed bugs. Since horizontal transfer can facilitate the spread of insecticide into hard to reach spaces, it could contribute greatly to the management of these public health pests.
Methodology/Results
To demonstrate horizontal transfer of diatomaceous earth and botanical insecticides in C. lectularius, an exposed (donor) bed bug, following a 10-minute acquisition period, was placed with unexposed (recipient) bed bugs. Mortality data clearly demonstrates that diatomaceous earth (DE 51) was actively transferred from a single exposed bug to unexposed bugs in a concentration dependent manner. LC50 values varied from 24.4 mg at 48 h to 5.1 mg at 216 h when a single exposed bed bug was placed with 5 unexposed bed bugs. LT50 values also exhibited a concentration response. LT50 values varied from 1.8 days to 8.4 days when a ‘donor’ bug exposed to 20 and 5 mg of dust respectively was placed with 5 ‘recipient’ bugs. Dust was also actively transferred from adult bed bugs to the nymphs. In addition we observed horizontal transfer of botanical insecticides including neem, ryania, and rotenone to varying degrees.
Conclusion/Significance
Our data clearly demonstrate horizontal transfer of diatomaceous earth and botanical insecticides in the common bed bug, C. lectularius. Use of a fluorescent dust provided visual confirmation that contaminated bed bugs transfer dust to untreated bed bugs in harborage. This result is important because bedbugs live in hard-to-reach places and interaction between conspecifics can be exploited for delivery and dissemination of management products directed at this public health pest.
doi:10.1371/journal.pone.0075626
PMCID: PMC3783411  PMID: 24086593
15.  331 Asthma Management in Latin America: Learnings from the Latin America Asthma Insight and Management (LA AIM) Survey of Patients 
The World Allergy Organization Journal  2012;5(Suppl 2):S123-S124.
Background
In 2003, the Asthma Insights and Reality in Latin America (AIRLA) survey assessed, in part, perception, knowledge, and attitudes related to asthma.1 In 2011 the Latin America Asthma Insight and Management (LA AIM) survey was designed to ascertain the realities of living with asthma, disconnect between expectations in asthma management and patient experience, and unmet needs. Using results from our survey, we investigated the advances made in asthma care and the challenges that remain for Latin American patients with asthma.
Methods
Asthma patients aged ≥18 years from 4 Latin American countries (Argentina, Brazil, Mexico, Venezuela) and the Commonwealth of Puerto Rico responded to survey questions during 35-minute face-to-face interviews. A sample size of 2000 patients (400 patients/location) provided an accurate national representation of the opinions of asthma patients. Questions probed respondents' views on topics such as patient-reported levels of asthma control, frequency and duration of exacerbations in the past year, and current and recent use of asthma medications. Participants in both surveys had a diagnosis of asthma, had taken asthma medication, or had an asthma attack within 12 months of the survey.
Results
Results from the LA AIM will be available November 2011. A total of 2184 adults or parents of children with asthma took part in AIRLA by phone or face-to-face interviews.1 In AIRLA, 54.0% of respondents reported their disease as well- or completely controlled. However, only 2.4% met all guideline criteria for asthma control. Further, 6% of AIRLA respondents reported their asthma as severe; however, when guideline criteria were applied, 21% had severe asthma.
Conclusions
The responses in LA AIM shed light on whether there have been meaningful changes since the 2003 AIRLA survey in patient perception of their asthma control and that control as defined by guideline criteria. Because asthma morbidity is largely preventable, additional education is required to teach patients that by more closely following asthma management strategies outlined by current guidelines, more patients can achieve adequate asthma control.
doi:10.1097/01.WOX.0000412094.11096.f5
PMCID: PMC3512921
16.  Strong Host-Feeding Preferences of the Vector Triatoma infestans Modified by Vector Density: Implications for the Epidemiology of Chagas Disease 
Background
Understanding the factors that affect the host-feeding preferences of triatomine bugs is crucial for estimating transmission risks and predicting the effects of control tactics targeting domestic animals. We tested whether Triatoma infestans bugs prefer to feed on dogs vs. chickens and on dogs vs. cats and whether vector density modified host choices and other vital rates under natural conditions.
Methodology
Two host choice experiments were conducted in small caged huts with two rooms between which bugs could move freely. Matched pairs of dog–chicken (six) and dog–cat (three) were assigned randomly to two levels of vector abundance and exposed to starved bugs during three nights. Bloodmeals from 1,160 bugs were tested by a direct enzyme-linked immunosorbent assay.
Principal Findings
Conditional logistic regression showed that dogs were highly preferred over chickens or cats and that vector density modified host-feeding choices. The relative risk of a bug being blood-engorged increased significantly when it fed only on dog rather than chicken or cat. Bugs achieved higher post-exposure weight at higher vector densities and successive occasions, more so if they fed on a dog rather than on a cat.
Conclusions
Our findings strongly refute the hypothesis that T. infestans prefers to blood-feed on chickens rather than dogs. An increase in dog or cat availability or accessibility will increase the rate of bug feeding on them and exert strong non-linear effects on R0. When combined with between-dog heterogeneities in exposure, infection, and infectiousness, the strong bug preference for dogs can be exploited to target dogs in general, and even the specific individuals that account for most of the risk, with topical lotions or insecticide-impregnated collars to turn them into baited lethal traps or use them as transmission or infestation sentinels based on their immune response to Trypanosoma cruzi or bug salivary antigens.
Author Summary
Chagas disease is a complex zoonosis with more than 150 mammalian host species, nearly a dozen blood-sucking triatomine species as main vectors, and 9–11 million people infected with Trypanosoma cruzi (its causal agent) in the Americas. Triatoma infestans, a highly domesticated species and one of the main vectors, feeds more often on domestic animals than on humans in northern Argentina. The question of whether there are host-feeding preferences among dogs, cats, and chickens is crucial to estimating transmission risks and predicting the effects of control tactics targeting them. This article reports the first host choice experiments of triatomine bugs conducted in small huts under natural conditions. The results demonstrate that T. infestans consistently preferred dogs to chickens or cats, with host shifts occurring more frequently at higher vector densities. Combined with earlier findings showing that dogs have high infection rates, are highly infectious, and have high contact rates with humans and domestic bugs, our results reinforce the role of dogs as the key reservoirs of T. cruzi. The strong bug preference for dogs can be exploited to target dogs with topical lotions or insecticide-impregnated collars to turn them into baited lethal traps or use them as transmission or infestation sentinels.
doi:10.1371/journal.pntd.0000447
PMCID: PMC2682203  PMID: 19478849
17.  Head lice 
Clinical Evidence  2009;2009:1703.
Introduction
Head lice can only be diagnosed by finding live lice, as eggs take 7 days to hatch and may appear viable for weeks after death of the egg. Infestation may be more likely in school children, with risks increased in children with more siblings, longer hair, and of lower socioeconomic group.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for head lice? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2008 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 15 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review we present information relating to the effectiveness and safety of the following interventions: dimeticone, herbal and essential oils, insecticide combinations, lindane, malathion, mechanical removal by combing (‘bug busting’), oral trimethoprim-sulfamethoxazone (co-trimoxazole, TMP-SMX), permethrin, phenothrin, and pyrethrum.
Key Points
Head lice can only be diagnosed by finding live lice, as eggs take 7 days to hatch, and may appear viable for weeks after death of the egg. Infestation may be more likely in school children, with risks increased in children with more siblings, longer hair, or of lower socioeconomic group.
Malathion lotion may increase lice eradication compared with phenothrin or permethrin. Current best practice is to treat with two applications 7 days apart, and to check for cure at 14 days. Studies comparingmalathion or permethrin with wet combing have given conflicting results, possibly due to varying insecticide resistance.
Permethrin may be more effective at eradicating lice compared with lindane. Eradication may be increased by adding trimethoprim-sulfamethoxazole (TMP-SMX, co-trimoxazole) to topical permethrin, although this increases adverse effects.
We don't know whether combinations of insecticides are beneficial compared with single agents or other treatments.
Dimeticone may be more effective at eradicating lice compared with malathion. Dimeticone and phenothrin have produced similar results, but this may be due to varying insecticide resistance and the formulation of phenothrin used.
We don't know whether pyrethrum is beneficial compared with other insecticides.
CAUTION: Lindane has been associated with central nervous system toxicity.
We don't know whether herbal and essential oils eradicate lice compared with other treatments.
PMCID: PMC2907830  PMID: 19445766
18.  Head lice 
Clinical Evidence  2011;2011:1703.
Introduction
Head lice can only be diagnosed by finding live lice, as eggs take 7 days to hatch and may appear viable for weeks after death of the egg. Infestation may be more likely in school children, with risks increased in children with more siblings, longer hair, and of lower socioeconomic group.
Methods and outcomes
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for head lice? We searched: Medline, Embase, The Cochrane Library, and other important databases up to June 2010 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
Results
We found 26 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions.
Conclusions
In this systematic review, we present information relating to the effectiveness and safety of the following interventions: benzyl alcohol, dimeticone, herbal and essential oils, insecticide combinations, isopropyl myristate, ivermectin, lindane, malathion, mechanical removal by combing ("bug busting"), oral trimethoprim–sulfamethoxazole (co-trimoxazole, TMP-SMX), permethrin, phenothrin, pyrethrum, and spinosad.
Key Points
Head lice can only be diagnosed by finding live lice, as eggs take 7 days to hatch, and may appear viable for weeks after death of the egg. Infestation may be more likely in school children, with risks increased in children with more siblings, longer hair, or of lower socioeconomic group.
Malathion lotion may increase lice eradication compared with placebo, phenothrin, or permethrin. Current best practice is to treat with two applications 7 days apart, and to check for cure at 14 days. Studies comparing malathion or permethrin with wet combing have given conflicting results, possibly because of varying insecticide resistance. Oral ivermectin may be more effective at eradicating head lice than malathion in people with previous failed treatment with insecticides. However, although tested in a clinical trial, oral ivermectin is not currently licensed for treating head lice, and generally its likely usefulness has been superseded by the introduction of physically acting chemicals that are not affected by resistance and which are generally considered safer.
Permethrin may be more effective at eradicating lice compared with placebo or lindane. Eradication may be increased by adding trimethoprim–sulfamethoxazole (TMP-SMX, co-trimoxazole) to topical permethrin, although this increases adverse effects.
We don't know whether combinations of insecticides are beneficial compared with single agents or other treatments.
Dimeticone may be more effective at eradicating lice compared with malathion or permethrin. Dimeticone and phenothrin have produced similar results, but this may be because of varying insecticide resistance and the formulation of phenothrin used.
We don't know whether pyrethrum is beneficial compared with other insecticides.
CAUTION: Lindane has been associated with central nervous system toxicity.
Some herbal and essential oils may be beneficial to eradicate lice compared with other treatments but this is likely to depend upon the compound(s) or extracts used.
Isopropyl myristate may be more effective at eradicating lice than permethrin.
Benzyl alcohol may be more effective at eradicating lice than placebo. However, we don't know whether benzyl alcohol is more effective than insecticides or other treatments used in routine clinical practice.
Spinosad may be more effective at eliminating lice than permethrin.
PMCID: PMC3275145  PMID: 21575285
19.  Understanding childhood asthma in focus groups: perspectives from mothers of different ethnic backgrounds 
Background
Diagnosing childhood asthma is dependent upon parental symptom reporting but there are problems in the use of words and terms. The purpose of this study was to describe and compare understandings of childhood 'asthma' by mothers from three different ethnic backgrounds who have no personal experience of diagnosing asthma. A better understanding of parents' perceptions of an illness by clinicians should improve communication and management of the illness.
Method
Sixty-six mothers living in east London describing their ethnic backgrounds as Bangladeshi, white English and black Caribbean were recruited to 9 focus groups. Discussion was semi-structured. Three sessions were conducted with each ethnic group. Mothers were shown a video clip of a boy with audible wheeze and cough and then addressed 6 questions. Sessions were recorded and transcribed verbatim. Responses were compared within and between ethnic groups.
Results
Each session, and ethnic group overall, developed a particular orientation to the discussion. Some mothers described the problem using single signs, while others imitated the sound or made comparisons to other illnesses. Hereditary factors were recognised by some, although all groups were concerned with environmental triggers. Responses about what to do included 'normal illness' strategies, use of health services and calls for complementary treatment. All groups were concerned about using medication every day. Expectations about the quality of life were varied, with recognition that restrictions may be based on parental beliefs about asthma, rather than asthma itself.
Conclusion
Information from these focus groups suggests mothers know a great deal about childhood asthma even though they have no personal experience of it. Knowledge of how mothers from these ethnic backgrounds perceive asthma may facilitate doctor – patient communication with parents of children experiencing breathing difficulties.
doi:10.1186/1471-2296-2-4
PMCID: PMC58588  PMID: 11667951
20.  The effects of indoor environmental exposures on pediatric asthma: a discrete event simulation model 
Environmental Health  2012;11:66.
Background
In the United States, asthma is the most common chronic disease of childhood across all socioeconomic classes and is the most frequent cause of hospitalization among children. Asthma exacerbations have been associated with exposure to residential indoor environmental stressors such as allergens and air pollutants as well as numerous additional factors. Simulation modeling is a valuable tool that can be used to evaluate interventions for complex multifactorial diseases such as asthma but in spite of its flexibility and applicability, modeling applications in either environmental exposures or asthma have been limited to date.
Methods
We designed a discrete event simulation model to study the effect of environmental factors on asthma exacerbations in school-age children living in low-income multi-family housing. Model outcomes include asthma symptoms, medication use, hospitalizations, and emergency room visits. Environmental factors were linked to percent predicted forced expiratory volume in 1 second (FEV1%), which in turn was linked to risk equations for each outcome. Exposures affecting FEV1% included indoor and outdoor sources of NO2 and PM2.5, cockroach allergen, and dampness as a proxy for mold.
Results
Model design parameters and equations are described in detail. We evaluated the model by simulating 50,000 children over 10 years and showed that pollutant concentrations and health outcome rates are comparable to values reported in the literature. In an application example, we simulated what would happen if the kitchen and bathroom exhaust fans were improved for the entire cohort, and showed reductions in pollutant concentrations and healthcare utilization rates.
Conclusions
We describe the design and evaluation of a discrete event simulation model of pediatric asthma for children living in low-income multi-family housing. Our model simulates the effect of environmental factors (combustion pollutants and allergens), medication compliance, seasonality, and medical history on asthma outcomes (symptom-days, medication use, hospitalizations, and emergency room visits). The model can be used to evaluate building interventions and green building construction practices on pollutant concentrations, energy savings, and asthma healthcare utilization costs, and demonstrates the value of a simulation approach for studying complex diseases such as asthma.
doi:10.1186/1476-069X-11-66
PMCID: PMC3527278  PMID: 22989068
Asthma; Simulation; Indoor; Housing; Air pollution; Lung function; Allergen; Green building
21.  Prevalence of asthma and risk factors for asthma-like symptoms in Aboriginal and non-Aboriginal children in the northern territories of Canada 
BACKGROUND:
Few studies have investigated the prevalence and risk factors of asthma in Canadian Aboriginal children.
OBJECTIVE:
To determine the prevalence of asthma and asthma-like symptoms, as well as the risk factors for asthma-like symptoms, in Aboriginal and non-Aboriginal children living in the northern territories of Canada.
METHODS:
Data on 2404 children, aged between 0 and 11 years, who participated in the North component of the National Longitudinal Survey of Children and Youth were used in the present study. A child was considered to have an asthma-like symptom if there was a report of ever having had asthma, asthma attacks or wheeze in the past 12 months.
RESULTS:
After excluding 59 children with missing information about race, 1399 children (59.7%) were of Aboriginal ancestry. The prevalence of asthma was significantly lower (P<0.05) in Aboriginal children (5.7%) than non-Aboriginal children (10.0%), while the prevalence of wheeze was similar between Aboriginal (15.0%) and non-Aboriginal (14.5%) children. In Aboriginal children, infants and toddlers had a significantly greater prevalence of asthma-like symptoms (30.0%) than preschool-aged children (21.5%) and school-aged children (11.5%). Childhood allergy and a mother’s daily smoking habit were significant risk factors for asthma-like symptoms in both Aboriginal and non-Aboriginal children. In addition, infants and toddlers were at increased risk of asthma-like symptoms in Aboriginal children. In analyses restricted to specific outcomes, a mother’s daily smoking habit was a significant risk factor for current wheeze in Aboriginal children and for ever having had asthma in non-Aboriginal children.
CONCLUSIONS:
Asthma prevalence appears to be lower in Aboriginal children than in non-Aboriginal children. The association between daily maternal smoking and asthma-like symptoms, which has been mainly reported for children living in urban areas, was observed in Aboriginal and non-Aboriginal children living in northern and remote communities in Canada.
PMCID: PMC2677938  PMID: 18437256
Aboriginals; Asthma; Children; Remote area; Risk factors; Smoking
22.  The Malawi Developmental Assessment Tool (MDAT): The Creation, Validation, and Reliability of a Tool to Assess Child Development in Rural African Settings 
PLoS Medicine  2010;7(5):e1000273.
Melissa Gladstone and colleagues evaluate the reliability and validity of an assessment tool for evaluating child development in rural African settings.
Background
Although 80% of children with disabilities live in developing countries, there are few culturally appropriate developmental assessment tools available for these settings. Often tools from the West provide misleading findings in different cultural settings, where some items are unfamiliar and reference values are different from those of Western populations.
Methods and Findings
Following preliminary and qualitative studies, we produced a draft developmental assessment tool with 162 items in four domains of development. After face and content validity testing and piloting, we expanded the draft tool to 185 items. We then assessed 1,426 normal rural children aged 0–6 y from rural Malawi and derived age-standardized norms for all items. We examined performance of items using logistic regression and reliability using kappa statistics. We then considered all items at a consensus meeting and removed those performing badly and those that were unnecessary or difficult to administer, leaving 136 items in the final Malawi Developmental Assessment Tool (MDAT). We validated the tool by comparing age-matched normal children with those with malnutrition (120) and neurodisabilities (80). Reliability was good for items remaining with 94%–100% of items scoring kappas >0.4 for interobserver immediate, delayed, and intra-observer testing. We demonstrated significant differences in overall mean scores (and individual domain scores) for children with neurodisabilities (35 versus 99 [p<0.001]) when compared to normal children. Using a pass/fail technique similar to the Denver II, 3% of children with neurodisabilities passed in comparison to 82% of normal children, demonstrating good sensitivity (97%) and specificity (82%). Overall mean scores of children with malnutrition (weight for height <80%) were also significantly different from scores of normal controls (62.5 versus 77.4 [p<0.001]); scores in the separate domains, excluding social development, also differed between malnourished children and controls. In terms of pass/fail, 28% of malnourished children versus 94% of controls passed the test overall.
Conclusions
A culturally relevant developmental assessment tool, the MDAT, has been created for use in African settings and shows good reliability, validity, and sensitivity for identification of children with neurodisabilities.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Babies can do very little when they are first born. But, gradually, over the first few years of life, they learn to walk and run (gross motor skills), they learn to manipulate objects with their hands (fine motor skills), they learn to communicate with words and gestures (language skills), and they learn how to interact with other people (social skills). For each of these skill “domains,” experts have identified “developmental milestones,” skills that are acquired by a specific age if development is proceeding normally. So, for example, by one year, a child should be able crawl, put objects into a container, respond to simple verbal requests, and enjoy imitating people during play. Every child attains the various developmental milestones at a slightly different age but their overall development can be monitored using a series of simple tests (items) covering each of the developmental domains. Clinicians and teachers can use these “developmental assessment tools” to identify children whose development deviates significantly from the norm. It is important to identify these children as young as possible because early intervention can help them reach their full developmental potential.
Why Was This Study Done?
In developing countries, poverty, poor health, and malnutrition are responsible for millions of children failing to reach their developmental potential. But because developmental assessment tools have mainly been designed and validated in western, developed countries, they contain many items that are alien to children in non-western cultures (for example, the use of knives and forks for eating and the use of specific gestures). They cannot, therefore, accurately assess whether a child living in, for example, a rural area of Africa, is developing normally. In this study, the researchers describe the creation and testing of a culturally appropriate developmental assessment tool for use in rural Africa—the Malawi Developmental Assessment Tool (MDAT)—from a 162-item draft tool (MDAT Draft I) that they previously developed from Denver II, an assessment tool widely used in developed countries.
What Did the Researchers Do and Find?
The researchers assessed the “face validity” (do the items look acceptable to untrained judges?) and “content validity” (does the tool examine all the domains it is meant to measure?) of MDAT Draft I and modified it to produce MDAT Draft II. After piloting this version on 80 children in rural Malawi, they modified it further to produce MDAT Draft III, which was used to assess 1,426 normal children aged 0–6 years from rural Malawi and to derive age-standardized norms for each item. After statistically analyzing the performance of each item in MDAT Draft III, all the items were considered at a consensus meeting, and items that were badly performing, unnecessary, and difficult to administer were removed, leaving 136 items (MDAT). The researchers then validated MDAT by using it to assess children with neurodisabilities (disorders of the nervous system that impair normal functioning) and children with delayed development because of malnutrition. The tool was reliable (different testers got similar results for individual children and individual testers got similar results when they retested specific children), sensitive (it correctly identified most children with a neurodisability or delayed development), and specific (it correctly identified most children who were developing normally; that is, it did not give false-positive results).
What Do These Findings Mean?
These findings show that MDAT is a culturally relevant assessment tool that reliably identifies children with neurodisabilities and delayed development in rural Malawi. Importantly, they also provide a detailed illustration of how to create and validate a culturally relevant assessment tool. Although MDAT is likely to be applicable in other similar settings, further research is needed to test its generalizability and to test whether it will work in children with more subtle developmental problems. MDAT, the researchers note, should be useful as a clinical tool for the early identification of neurodisabilities and as an outcome measure in clinical trials of interventions designed to improve child development. However, they stress, because developing countries have limited resources available for screening and for helping children whose development is delayed or disrupted, for now tools like MDAT are more likely to be used for research studies than for routine developmental assessments in Malawi and other African countries.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000273.
The World Health Organization has information on disability, prevention, and management in children and adults worldwide
UNICEF has a site on early childhood and in particular, provides information on programming experiences for early child intervention programs worldwide
Disability World is a website for international views and perspectives on disability worldwide. It provides information and links about the worldwide state of disability in children and adults in developing countries
Source, the International Information Support Centre has a good website of information about disability, inclusion, and development in children with links to many other sources of information
Wikipedia has a page on child development (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
The US Centers for Disease Control and Prevention provides information on developmental screening and on developmental milestones
The American Academy of Pediatrics also provides information on developmental stages and on developmental milestones
The UK National Health Service Choices site has an interactive guide to child development
MedlinePlus has links to further resources on infant and toddler development (in English and Spanish)
doi:10.1371/journal.pmed.1000273
PMCID: PMC2876049  PMID: 20520849
23.  Seasonal and Regional Dynamics of M. ulcerans Transmission in Environmental Context: Deciphering the Role of Water Bugs as Hosts and Vectors 
Background
Buruli ulcer, the third mycobacterial disease after tuberculosis and leprosy, is caused by the environmental mycobacterium M. ulcerans. Various modes of transmission have been suspected for this disease, with no general consensus acceptance for any of them up to now. Since laboratory models demonstrated the ability of water bugs to transmit M. ulcerans, a particular attention is focused on the transmission of the bacilli by water bugs as hosts and vectors. However, it is only through detailed knowledge of the biodiversity and ecology of water bugs that the importance of this mode of transmission can be fully assessed. It is the objective of the work here to decipher the role of water bugs in M. ulcerans ecology and transmission, based on large-scale field studies.
Methodology/Principal Findings
The distribution of M. ulcerans-hosting water bugs was monitored on previously unprecedented time and space scales: a total of 7,407 water bugs, belonging to large number of different families, were collected over one year, in Buruli ulcer endemic and non endemic areas in central Cameroon. This study demonstrated the presence of M. ulcerans in insect saliva. In addition, the field results provided a full picture of the ecology of transmission in terms of biodiversity and detailed specification of seasonal and regional dynamics, with large temporal heterogeneity in the insect tissue colonization rate and detection of M. ulcerans only in water bug tissues collected in Buruli ulcer endemic areas.
Conclusion/Significance
The large-scale detection of bacilli in saliva of biting water bugs gives enhanced weight to their role in M. ulcerans transmission. On practical grounds, beyond the ecological interest, the results concerning seasonal and regional dynamics can provide an efficient tool in the hands of sanitary authorities to monitor environmental risks associated with Buruli ulcer.
Author Summary
Buruli ulcer, caused by Mycobacterium ulcerans, is a devastating skin disease. Most cases of Buruli ulcer occur in poor rural communities. As a result, treatment is frequently sought too late and about 25% of those infected—particularly children—become permanently disabled. Outbreaks of Buruli ulcer have always been associated with swampy areas. However, the route(s) of bacillus transmission is (are) still unclear. This Mycobacterium species resides in water where it colonizes many ecological niches such as aquatic plants, herbivorous animals and predatory/carnivorous insects. For several years the role of water bugs as hosts and vectors of M. ulcerans was suspected and was demonstrated under laboratory conditions. The aim of this work was to further assess the role of water bugs as hosts and vectors of M. ulcerans in environmental context. This work identifies several water bug families as hosts of M. ulcerans in Buruli ulcer endemic area. The detection of bacilli in saliva of human biting insects provides further evidence for their role in M. ulcerans transmission. Interestingly, three of these insects are good flyers, and as such could participate in M. ulcerans dissemination.
doi:10.1371/journal.pntd.0000731
PMCID: PMC2897839  PMID: 20625552
24.  Bugging Forecast: Unknown, Disliked, Occasionally Intimate. Bed Bugs in Germany Meet Unprepared People 
PLoS ONE  2013;8(1):e51083.
Bed bugs appear to be feared more than vector insects and other household pests. The reasons for this exaggerated fear are not fully understood. One hypothesis is that the folk knowledge on recognising and controlling bed bugs decreased as bed bugs became rarer in the 1960s and led to irrational perceptions. Here, we examine people’s ability to recognise a bed bug and their response what to do in case of an infestation. We found that 13% of a sample of 391 people in four large German cities recognised a bed bug; 15% of all respondents would call a pest controller in case of bed bug infestation. This results in the pessimistic estimate that 97% of all early-stage infestations could go untreated. We discuss additional scenarios. The effectiveness of efforts to educate people about the presence of bed bugs has never been tested, but our sample is useful to guide future studies. We found three sources of information were associated with increased recognition rates of bed bugs: a) previous contacts with bed bugs (60% recognition), b) knowledge from friends or relatives (25%) and school or education courses (15%). By contrast, people who heard of bed bugs from television, print media or the Internet showed reduced recognition rates. We propose that the former factors be tested for educational interventions. In Germany, the bed bug is an estranged creature to many people, a fact that seems to hinder rational approaches to their control.
doi:10.1371/journal.pone.0051083
PMCID: PMC3534700  PMID: 23300947
25.  Gene-Environment Interaction in the Onset of Eczema in Infancy: Filaggrin Loss-of-Function Mutations Enhanced by Neonatal Cat Exposure  
PLoS Medicine  2008;5(6):e131.
Background
Loss-of-function variants in the gene encoding filaggrin (FLG) are major determinants of eczema. We hypothesized that weakening of the physical barrier in FLG-deficient individuals may potentiate the effect of environmental exposures. Therefore, we investigated whether there is an interaction between FLG loss-of-function mutations with environmental exposures (pets and dust mites) in relation to the development of eczema.
Methods and Findings
We used data obtained in early life in a high-risk birth cohort in Denmark and replicated the findings in an unselected birth cohort in the United Kingdom. Primary outcome was age of onset of eczema; environmental exposures included pet ownership and mite and pet allergen levels. In Copenhagen (n = 379), FLG mutation increased the risk of eczema during the first year of life (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.27–4.00, p = 0.005), with a further increase in risk related to cat exposure at birth amongst children with FLG mutation (HR 11.11, 95% CI 3.79–32.60, p < 0.0001); dog exposure was moderately protective (HR 0.49, 95% CI 0.24–1.01, p = 0.05), but not related to FLG genotype. In Manchester (n = 503) an independent and significant association of the development of eczema by age 12 mo with FLG genotype was confirmed (HR 1.95, 95% CI 1.13–3.36, p = 0.02). In addition, the risk increased because of the interaction of cat ownership at birth and FLG genotype (HR 3.82, 95% CI 1.35–10.81, p = 0.01), with no significant effect of the interaction with dog ownership (HR 0.59, 95% CI 0.16–2.20, p = 0.43). Mite-allergen had no effects in either cohort. The observed effects were independent of sensitisation.
Conclusions
We have demonstrated a significant interaction between FLG loss-of-function main mutations (501x and 2282del4) and cat ownership at birth on the development of early-life eczema in two independent birth cohorts. Our data suggest that cat but not dog ownership substantially increases the risk of eczema within the first year of life in children with FLG loss-of-function variants, but not amongst those without. FLG-deficient individuals may need to avoid cats but not dogs in early life.
In two independent cohorts of children, Hans Bisgaard and colleagues show an association between mutations in the filaggrin gene (FLG) and ownership of cats, but not dogs, with development of eczema.
Editors' Summary
Background.
Eczema is a skin condition characterized by dry, red, and itchy patches on the skin. Eczema is associated with asthma and allergy, though allergy rarely plays a role in development or severity of eczema. Eczema usually begins during infancy, typically on the face, scalp, neck, extensor sides of the forearms, and legs. Up to one in five infants develops eczema, but in more than half of them, the condition improves or disappears completely before they are 15 years old. If eczema persists into adulthood, it usually affects the face and the skin inside the knees and elbows. There is no cure for eczema but it can be controlled by avoiding anything that makes its symptoms worse. These triggers include irritants such as wool, strong soaps, perfumes, and dry environments. A good skin-care routine and frequent moisturizing can also help to keep eczema under control, but in many cases, corticosteroid creams and ointments may be necessary to reduce inflammation.
Why Was This Study Done?
Eczema tends to run in families. This suggests that eczema is caused by genetic factors as well as by environmental factors. Recently, researchers discovered that two common “loss-of-function” variants in the gene encoding filaggrin (FLG) predispose people to eczema. People who inherit one or two defective genes make no filaggrin, a protein that normally forms a physical barrier in the skin that protects the body from potentially harmful substances in the environment. Might the weakening of this barrier in filaggrin-deficient individuals affect their responses to environmental substances to which the skin is exposed? In this study, the researchers test this potential explanation for how genetic and environmental factors (in particular, exposure to pets) might interact to determine an individual's chances of developing eczema.
What Did the Researchers Do and Find?
To test their hypothesis, the researchers studied two independent groups of infants during their first year of life—a high-risk group consisting of infants born in Copenhagen, Denmark to mothers with asthma and a group of infants born to women from the general population in Manchester, United Kingdom. The researchers determined which FLG variants each child had inherited and classified those with either one or two defective copies of FLG as having an FLG mutation. They determined pet exposure in early life by asking whether a dog or a cat was living in the parental home when the child was born (“pet ownership”) and then analyzed how these genetic and environmental factors affected the age of onset of eczema. In both groups, children with FLG mutations were twice as likely to develop eczema during the first year of life as children without FLG mutations. For children without FLG mutations, cat ownership at birth had no effect on eczema risk but for children with FLG mutations, cat ownership at birth (but not dog ownership) further increased the risk of developing eczema.
What Do These Findings Mean?
These findings show that FLG mutations and cat ownership at birth interact to determine the chances of a child developing eczema during the first year of life. They provide support, therefore, for the researchers' suggestion that the weakening of the skin's protective barrier that is caused by filaggrin deficiency increases the child's susceptibility to factors associated with cat exposure. Only a small number of children in this study carried FLG mutations and were exposed to cats from birth, so these findings need confirming in independent studies. In addition, it is still not clear how exposure to cats drives the development of eczema. Allergy was not the mechanism as the FLG-deficient children exposed to cat and who developed eczema did not develop cat-specific immunoglobin E antibodies. Nevertheless, these findings suggest that, to reduce their risk of developing eczema, filaggrin-deficient individuals should avoid cats (but not dogs) during the first few months of life.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050131.
The MedlinePlus Encyclopedia has a page on eczema (in English and Spanish); links to further information are provided by MedlinePlus
EczemaNet is a comprehensive online information resource about eczema provided by the American Academy of Dermatologists
The US National Institute of Arthritis and Musculoskeletal and Skin Diseases provides information on eczema
The UK National Health Service Direct health encyclopedia provides information for patients on eczema (in several languages)
The Copenhagen Studies on Asthma in Childhood (COPSAC) and Manchester Asthma and Allergy Study (MAAS) Web sites provide more information about the children involved in this research
doi:10.1371/journal.pmed.0050131
PMCID: PMC2504043  PMID: 18578563

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