Over 200,000 new cases of leprosy are detected each year, of which approximately 7% are associated with grade-2 disabilities (G2Ds). For achieving leprosy elimination, one of the main challenges will be targeting higher risk groups within endemic communities. Nevertheless, the socioeconomic risk markers of leprosy remain poorly understood. To address this gap we systematically reviewed MEDLINE/PubMed, Embase, LILACS and Web of Science for original articles investigating the social determinants of leprosy in countries with > 1000 cases/year in at least five years between 2006 and 2016. Cohort, case-control, cross-sectional, and ecological studies were eligible for inclusion; qualitative studies, case reports, and reviews were excluded. Out of 1,534 non-duplicate records, 96 full-text articles were reviewed, and 39 met inclusion criteria. 17 were included in random-effects meta-analyses for sex, occupation, food shortage, household contact, crowding, and lack of clean (i.e., treated) water. The majority of studies were conducted in Brazil, India, or Bangladesh while none were undertaken in low-income countries. Descriptive synthesis indicated that increased age, poor sanitary and socioeconomic conditions, lower level of education, and food-insecurity are risk markers for leprosy. Additionally, in pooled estimates, leprosy was associated with being male (RR = 1.33, 95% CI = 1.06–1.67), performing manual labor (RR = 2.15, 95% CI = 0.97–4.74), suffering from food shortage in the past (RR = 1.39, 95% CI = 1.05–1.85), being a household contact of a leprosy patient (RR = 3.40, 95% CI = 2.24–5.18), and living in a crowded household (≥5 per household) (RR = 1.38, 95% CI = 1.14–1.67). Lack of clean water did not appear to be a risk marker of leprosy (RR = 0.94, 95% CI = 0.65–1.35). Additionally, ecological studies provided evidence that lower inequality, better human development, increased healthcare coverage, and cash transfer programs are linked with lower leprosy risks. These findings point to a consistent relationship between leprosy and unfavorable economic circumstances and, thereby, underscore the pressing need of leprosy control policies to target socially vulnerable groups in high-burden countries. Many cases of leprosy still occur in low and middle-income countries, with a considerable proportion of them leading to permanent nerve damage and visible physical deformities. Disease elimination can be achieved with a better understanding of the sociodemographic characteristics of those most affected by the disease and by targeting those with greater risk within endemic countries. To address this question, we reviewed all published studies evaluating the social determinants of leprosy in countries endemic for leprosy. We found 39 studies, most of them conducted in Brazil (i.e., an upper-middle-income country), India or Bangladesh (i.e., lower-middle income countries), and none in low-income countries. Our review found strong evidence that males, household contacts of leprosy patients, individuals living in crowded households, and individuals who suffered food shortage in the past are more affected by leprosy. Evidence also exists that increasing age, poor sanitary and socioeconomic conditions, lower levels of education, and food insecurity are associated with a greater risk of leprosy. Our review underscores the importance of improving living conditions and decreasing inequality in low and middle-income countries to achieve leprosy elimination.

Although leprosy is recognised as a disease of poverty, there is little evidence on the specific socioeconomic factors associated with disease risk. To inform targeted strategies for disease elimination, we investigated socioeconomic markers of leprosy risk in Brazil. Socioeconomic data from the 100 Million Brazilian Cohort were linked to the Brazilian national disease registry (Sistema de Informação de Agravos de Notificação) for leprosy from Jan 1, 2007, to Dec 31, 2014. Using Poisson regression, we assessed the association of socioeconomic factors with risk of incident leprosy in the full cohort and in children (aged 0-15 years), by leprosy subtype and region of residence. In an analysis of 23 899 942 individuals including 18 518 patients with leprosy, increased levels of deprivation were associated with an increased risk of leprosy in Brazil. Directions of effect were consistent in children younger than 15 years and across disease subtypes. Individuals residing in regions with the highest poverty in the country (central-west, north, and northeast regions) had a risk of leprosy incidence five-to-eight times greater than did other individuals. Decreased levels of income and education and factors reflecting unfavourable living conditions were associated with an up to two-times increase in leprosy incidence (incidence rate ratio 1·46, 95% CI 1·32-1·62, for lowest vs highest quartile of income per capita; 2·09, 95% CI 1·62-2·72, for lowest vs highest level of education). Within the poorest half of the Brazilian population, the most deprived individuals have the greatest risk of leprosy. Strategies focusing on early detection and treatment in the poorest populations could contribute substantially to global disease control. Medical Research Council, Wellcome Trust, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (Brazil), the Conselho Nacional das Fundações Estaduais de Amparo à Pesquisa, Economic and Social Research Council, Biotechnology and Biological Sciences Research Council, Conselho Nacional de Desenvolvimento Científico e Tecnológico, and Fundação de Apoio à Pesquisa do Distrito Federal.

Whole-sporozoite vaccines confer sterilizing immunity to malaria-naive individuals by unknown mechanisms. In the first PfSPZ Vaccine trial ever in a malaria-endemic population, Vδ2 γδ T cells were significantly elevated and Vγ9/Vδ2 transcripts ranked as the most upregulated in vaccinees who were protected from Plasmodium falciparum infection. In a mouse model, absence of γδ T cells during vaccination impaired protective CD8 T cell responses and ablated sterile protection. γδ T cells were not required for circumsporozoite protein–specific Ab responses, and γδ T cell depletion before infectious challenge did not ablate protection. γδ T cells alone were insufficient to induce protection and required the presence of CD8α⁺ dendritic cells. In the absence of γδ T cells, CD8α⁺ dendritic cells did not accumulate in the livers of vaccinated mice. Altogether, our results show that γδ T cells were essential for the induction of sterile immunity during whole-organism vaccination.

Prenatal exposure to Zika virus has potential teratogenic effects, with a wide spectrum of clinical presentation referred to as congenital Zika syndrome. Data on survival among children with congenital Zika syndrome are limited. In this population-based cohort study, we used linked, routinely collected data in Brazil, from January 2015 through December 2018, to estimate mortality among live-born children with congenital Zika syndrome as compared with those without the syndrome. Kaplan–Meier curves and survival models were assessed with adjustment for confounding and with stratification according to gestational age, birth weight, and status of being small for gestational age. A total of 11,481,215 live-born children were followed to 36 months of age. The mortality rate was 52.6 deaths (95% confidence interval [CI], 47.6 to 58.0) per 1000 person-years among live-born children with congenital Zika syndrome, as compared with 5.6 deaths (95% CI, 5.6 to 5.7) per 1000 person-years among those without the syndrome. The mortality rate ratio among live-born children with congenital Zika syndrome, as compared with those without the syndrome, was 11.3 (95% CI, 10.2 to 12.4). Among infants born before 32 weeks of gestation or with a birth weight of less than 1500 g, the risks of death were similar regardless of congenital Zika syndrome status. Among infants born at term, those with congenital Zika syndrome were 14.3 times (95% CI, 12.4 to 16.4) as likely to die as those without the syndrome (mortality rate, 38.4 vs. 2.7 deaths per 1000 person-years). Among infants with a birth weight of 2500 g or greater, those with congenital Zika syndrome were 12.9 times (95% CI, 10.9 to 15.3) as likely to die as those without the syndrome (mortality rate, 32.6 vs. 2.5 deaths per 1000 person-years). The burden of congenital anomalies, diseases of the nervous system, and infectious diseases as recorded causes of deaths was higher among live-born children with congenital Zika syndrome than among those without the syndrome. The risk of death was higher among live-born children with congenital Zika syndrome than among those without the syndrome and persisted throughout the first 3 years of life. (Funded by the Ministry of Health of Brazil and others.)

Background Urbanisation has been associated with temporal and geographical differences in asthma prevalence in low-income and middle-income countries (LMICs). However, little is known of the mechanisms by which urbanisation and asthma are associated, perhaps explained by the methodological approaches used to assess the urbanisation-asthma relationship. Objective This review evaluated how epidemiological studies have assessed the relationship between asthma and urbanisation in LMICs, and explored urban/rural differences in asthma prevalence. Methods Asthma studies comparing urban/rural areas, comparing cities and examining intraurban variation were assessed for eligibility. Included publications were evaluated for methodological quality and pooled OR were calculated to indicate the risk of asthma in urban over rural areas. Results Seventy articles were included in our analysis. Sixty-three compared asthma prevalence between urban and rural areas, five compared asthma prevalence between cities and two examined intraurban variation in asthma prevalence. Urban residence was associated with a higher prevalence of asthma, regardless of asthma definition: current-wheeze OR:1.46 (95% CI:1.22 to 1.74), doctor diagnosis OR:1.89 (95% CI:1.47 to 2.41), wheeze-ever OR:1.44 (95% CI:1.15 to 1.81), self-reported asthma OR:1.77 (95% CI:1.33 to 2.35), asthma questionnaire OR:1.52 (95% CI:1.06 to 2.16) and exercise challenge OR:1.96 (95% CI:1.32 to 2.91). Conclusions Most evidence for the relationship between urbanisation and asthma in LMICs comes from studies comparing urban and rural areas. These studies tend to show a greater prevalence of asthma in urban compared to rural populations. However, these studies have been unable to identify which specific characteristics of the urbanisation process may be responsible. An approach to understand how different dimensions of urbanisation, using contextual household and individual indicators, is needed for a better understanding of how urbanisation affects asthma. PROSPERO registration number CRD42017064470.