Socioeconomic risk markers of leprosy in high-burden countries: A systematic review and meta-analysis

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infectious disease 5803 relevant data are within the paper and its Supporting Information filesIntroductionLeprosy, a chronic infectious disease caused by Mycobacterium leprae, remains endemic in 13 low and middle-income countries worldwide [[1]].
infectious disease 45251 of those affected.Migration from a relatively higher-burden setting is an important risk factor for infectious disease s transmission and reactivation in lower-burden settings (e.g., as has been previously demonstrated for
leprosy 69 Title: PLoS Neglected Tropical DiseasesSocioeconomic risk markers of leprosy in high-burden countries: A systematic review and meta-analysisAlternative Title: Socioeconomic risk
leprosy 189 high-burden countries: A systematic review and meta-analysisAlternative Title: Socioeconomic risk markers of leprosy Julia Moreira Pescarini (Conceptualization) (Data curation) (Formal analysis) (Investigation) (Methodology)
leprosy 2170 SWITZERLANDPublication date (epub): 7/2018Publication date (collection): 7/2018AbstractOver 200,000 new cases of leprosy are detected each year, of which approximately 7% are associated with grade-2 disabilities (G2Ds). For
leprosy 2291 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.
leprosy 2452 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
leprosy 2646 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,
leprosy 3434 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),
leprosy 3478 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,
leprosy 3718 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
leprosy 3917 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,
leprosy 4140 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
leprosy 4213 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
leprosy 4306 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.SummaryAuthor summaryMany
leprosy 4428 policies to target socially vulnerable groups in high-burden countries.SummaryAuthor summaryMany cases of leprosy still occur in low and middle-income countries, with a considerable proportion of them leading to permanent
leprosy 4898 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
leprosy 4931 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
leprosy 5194 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
leprosy 5330 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
leprosy 5510 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
leprosy 5660 improving living conditions and decreasing inequality in low and middle-income countries to achieve leprosy elimination.Data AvailabilityAll relevant data are within the paper and its Supporting Information filesIntroductionLeprosy,
leprosy 6095 to cure infections, failures in detection and treatment can lead to the development of stigmatizing leprosy -associated grade-2 disabilities (G2Ds) [[1], [2]]. By recent estimates, 7% of the more than 200,000
leprosy 6216 grade-2 disabilities (G2Ds) [[1], [2]]. By recent estimates, 7% of the more than 200,000 new cases of leprosy detected each year occur in individuals who have already developed G2Ds by the time of diagnosis. To
leprosy 6717 level remains a challenge due to a lack of understanding regarding the epidemiological risk markers of leprosy .In recent years, there has been an increased recognition of the social determinants of health and of
leprosy 6938 potential of social interventions to enhance disease treatment and control strategies [[4]]. In the case of leprosy , existing evidence suggests that poor living conditions may be associated with increased risk, while
leprosy 7092 conditions may be associated with increased risk, while the discrimination and fears associated with leprosy may lead to treatment delays, G2Ds, and decreases in individual economic productivity, thereby perpetuating
leprosy 7341 bidirectional association, several countries have made efforts to break the link between poverty and leprosy by incorporating poverty reduction efforts as a major component in health policies promoting leprosy
leprosy 7442 leprosy by incorporating poverty reduction efforts as a major component in health policies promoting leprosy control [[6]]. To better inform these health policies and to address residual gaps in knowledge related
leprosy 7572 better inform these health policies and to address residual gaps in knowledge related to the markers of leprosy risk, this systematic review aims to collate and appraise the published evidence on the effect of social,
leprosy 7724 and appraise the published evidence on the effect of social, demographic, and economic factors and leprosy occurrence in high-burden settings.MethodsSearch strategy and eligibility criteriaThe protocol for the
leprosy 8052 CRD42016051212 [[7]]. To identify studies reporting associations between socioeconomic variables and leprosy outcomes in high-burden countries, we searched MEDLINE, Embase, LILACS, and Web of Science up to 20th
leprosy 8984 residence, housing conditions/crowding, education/occupation, and social deprivation) and diagnosed leprosy disease. Studies were excluded if they: (i) had a qualitative or review design, (ii) exclusively used
leprosy 9153 or review design, (ii) exclusively used Phenolic Glycolipid I (PGL-1) positivity as a biomarker of leprosy exposure [[10]], (iii) lacked a clear description of the study population, or (iv) exclusively analyzed
leprosy 9983 however the quality score was limited to a maximum of 7 points as it was not possible to demonstrate that leprosy was not present at the start of the study and due to the lack of follow up. Specifically, the reviewers
leprosy 10257 location, baseline survey dates, study design, study population, number of participants, method of leprosy ascertainment, and number of leprosy cases) and the measure of association (i.e., socioeconomic characteristics
leprosy 10294 study design, study population, number of participants, method of leprosy ascertainment, and number of leprosy cases) and the measure of association (i.e., socioeconomic characteristics of leprosy cases and the
leprosy 10380 and number of leprosy cases) and the measure of association (i.e., socioeconomic characteristics of leprosy cases and the comparison group, effect sizes, and statistical adjustment for potential confounders).
leprosy 11005 studies included in this review were summarized in two groups defined by whether the risk markers and leprosy outcomes were evaluated in individuals or at a population level. When estimates for a given risk marker
leprosy 11318 its 95% Confidence Intervals (95% CI) by pooling effect sizes using random-effects meta-analyses. As leprosy is a rare disease, odds ratios and hazard ratios were assumed to approximate the same RR [[13]]. Studies
leprosy 11474 were assumed to approximate the same RR [[13]]. Studies conducted only among household contacts of leprosy patients or those with insufficient information to calculate the point estimates and its 95% CIs were
leprosy 12554 for ecological studies). Of the individual studies, one cohort study assessed both the prevalence of leprosy in households containing an index case (cross-sectional) and followed those household contacts without
leprosy 12665 households containing an index case (cross-sectional) and followed those household contacts without leprosy prospectively [[20]]; a second study (case-control) considered two control groups, one proximal and
leprosy 12993 studies.10.1371/journal.pntd.0006622.t001Table 1Observational studies conducted at the individual level of the association of leprosy with socioeconomic risk markers in high-burden countries.RefAuthor (year)CountryNOSStudy periodType
leprosy 15834 Denominator not specified.10.1371/journal.pntd.0006622.t002Table 2Ecological studies of the association of leprosy with socioeconomic risk markers in high-burden countries.RefAuthor (year)CountryStudy periodUnit of
leprosy 19415 adjustment without providing point estimates [[26]]. Out of 16 studies that investigated the association of leprosy with sex, four reported a higher prevalence of leprosy among males [[14], [16], [17], [29]], of which
leprosy 19470 studies that investigated the association of leprosy with sex, four reported a higher prevalence of leprosy among males [[14], [16], [17], [29]], of which only one provided adjusted estimates. One study reported
leprosy 19624 only one provided adjusted estimates. One study reported that contacts of male patients had higher leprosy incidence [[20]], and the others did not report differences between males and females. Eleven studies
leprosy 19809 females. Eleven studies were included in the meta-analysis of the association between male sex and leprosy . The crude overall RR for male sex was 1.33 (95% CI: 1.06, 1.67), with a substantial heterogeneity between
leprosy 20034 studies (I2 = 64.2%) (Fig 3). The effect decreased along the study years. The association between age and leprosy was assessed in 13 studies, of which six found a positive association with increasing age [[18], [24],
leprosy 20221 increasing age [[18], [24], [32], [34], [36]].10.1371/journal.pntd.0006622.g003Fig 3Association between leprosy and socioeconomic markers.Pooled estimates using random-effects meta-analyses are calculated by subgroups
leprosy 20593 statistic and Q-test p-value are reported.Education and occupationThe association between education and leprosy was evaluated in one cohort [[20]], three case-controls [[23], [24], [26]], and four cross-sectional
leprosy 20953 schooling [[20], [23], [24], [32], [34], [40]]. Three out of eight studies pointed to a higher number of leprosy cases among less educated individuals [[23], [32], [33]], and the associations remained significant
leprosy 21234 colleagues, the educational level of the index patient was negatively associated with other prevalent leprosy cases within the family, but not among incident cases [[20]]. Andrade and colleagues (1994) suggested
leprosy 21403 Andrade and colleagues (1994) suggested that a lower level of education was associated with higher leprosy incidence among neighbours, but not among other random groups [[32]]. Occupation status was analyzed
leprosy 21978 meta-analysis for occupation, there was a positive, but not statistically significant, association between leprosy and manual labor (RR = 2.15, 95% CI = 0.97–4.74; I2 = 92.6%) (Fig 3).10.1371/journal.pntd.0006622.t003Table
leprosy 22144 92.6%) (Fig 3).10.1371/journal.pntd.0006622.t003Table 3Adjusted point estimates of the association of leprosy with socioeconomic risk markers in high-burden countries in individualized studies.RefYear MarkerExposed
leprosy 24075 9Higher diversity of food Dietary Diversity Score > 9ORadj0.83 (0.58, 1.18)■■□■■Contact with leprosy patients [[25]]2013ContactHousehold contactSocial contacts outside the neighbourhoodORadj1.09
leprosy 24446 1.11)□■□□■ [[36]]2006Physical proximity (among contacts)Share the same roof and kitchen with a leprosy patientNeighbors of next-door neighbors or social contactsORadj2.44 (1.44, 4.12)□■■□ [[20]]C2011Physical
leprosy 26883 past 5 yearDid not migrate in the past 5 yearsORadj1.51 (1.0, 2.28)■■■■■AHouseholds with leprosy patient compared with neighbor households.BHouseholds with leprosy patient compared with random household
leprosy 26950 2.28)■■■■■AHouseholds with leprosy patient compared with neighbor households.BHouseholds with leprosy patient compared with random household outside the neighborhood.CCross-sectional study assessing prevalence
leprosy 27069 compared with random household outside the neighborhood.CCross-sectional study assessing prevalence of leprosy inside the household with index leprosy case.DCohort study assessing the incidence.E■ Presence or
leprosy 27109 neighborhood.CCross-sectional study assessing prevalence of leprosy inside the household with index leprosy case.DCohort study assessing the incidence.E■ Presence or □ AbsenceSocial deprivation and food securityThe
leprosy 27260 incidence.E■ Presence or □ AbsenceSocial deprivation and food securityThe relationship between income and leprosy was assessed in one cohort [[20]], four case-controls [[23], [24], [26], [27]], and four cross-sectional
leprosy 27654 social score [[34]]). Three studies reported statistically significant associations between poverty and leprosy in univariate analysis [[20], [27], [29]], but the associations attenuated after adjusting for potential
leprosy 28048 consistent across studies, providing evidence of an inverse association between socioeconomic position and leprosy risk.Factors related to food insecurity, an established correlate of poverty [[53]], were studied as
leprosy 28175 related to food insecurity, an established correlate of poverty [[53]], were studied as a risk factor for leprosy in three case-control studies, two of which were carried out in Bangladesh [[24], [27]] and one in Brazil
leprosy 28685 each [[27]]. Low food diversity and low stocks of food were not associated with increased number of leprosy cases, while food expenditure and HFIAS were negatively associated with leprosy [[27]]. In the meta-analysis,
leprosy 28765 increased number of leprosy cases, while food expenditure and HFIAS were negatively associated with leprosy [[27]]. In the meta-analysis, ever food-shortage was significantly associated with higher leprosy risks
leprosy 28863 with leprosy [[27]]. In the meta-analysis, ever food-shortage was significantly associated with higher leprosy risks (RR = 1.39, 95% CI = 1.05–1.85; I2 = 29.3%) (Fig 3).Contact with leprosy patientsSharing a household
leprosy 28944 associated with higher leprosy risks (RR = 1.39, 95% CI = 1.05–1.85; I2 = 29.3%) (Fig 3).Contact with leprosy patientsSharing a household with a current leprosy case was strongly associated with risk of developing
leprosy 28995 = 1.05–1.85; I2 = 29.3%) (Fig 3).Contact with leprosy patientsSharing a household with a current leprosy case was strongly associated with risk of developing the disease in all nine studies that investigated
leprosy 29322 [[40]]). One study conducted by Feenstra and colleagues, which used a score of social interaction with a leprosy patient (i.e., in the household, within the neighborhood, and outside the neighborhood), found that
leprosy 29508 neighborhood), found that contacts in the household and within the neighborhood shared similar risks of leprosy [[25]]. The meta-analysis of the other eight studies estimated a crude RR of 3.40 (95% CI = 2.24–5.18)
leprosy 29805 (Fig 3). Six studies also evaluated the association between being a household or familial contact of a leprosy patient as opposed to any other type of contact, and all found that household or familial contacts had
leprosy 29931 to any other type of contact, and all found that household or familial contacts had higher risk of leprosy than general contacts [[16], [20], [22], [36], [37], [39]].Living conditions and water supplyHousehold
leprosy 30488 residing in private accommodation [[32]], nor house size [[27]] were significantly associated with leprosy after adjusting for factors such as education, work and household food stocks [[27], [32]]. Only one
leprosy 30804 poorer building material (i.e., floor or house walls made of materials different than cement/bricks) and leprosy [[31]]. Crowding was measured as the number of residents in the household in four studies [[17], [20],
leprosy 31092 Although only one individual study found evidence that crowding was significantly associated with higher leprosy risks [[17]], the pooled RR provides evidence that crowding, (i.e., ≥ five individuals living in the
leprosy 31305 same household or ≥ four individuals sharing the same bedroom) may be a significant risk marker for leprosy (RR = 1.32, 95% CI = 1.13–1.53; I2 = 0.0%) (Fig 3). Of note, Kerr-Pontes and colleagues did not find
leprosy 31470 note, Kerr-Pontes and colleagues did not find an association between bed sharing and higher risk of leprosy [[23]].Water and sanitation were investigated in one case-control [[23]] and in five cross-sectional
leprosy 32112 report by Andrade and colleagues found an association between clean water and a lower incidence of leprosy in adjusted estimates, when comparing households with leprosy with a random household, but not with
leprosy 32174 clean water and a lower incidence of leprosy in adjusted estimates, when comparing households with leprosy with a random household, but not with a neighbouring household [[32]]. The presence of waste collection
leprosy 32380 collection services [[26]] and good sanitary conditions score were associated with a lower prevalence of leprosy [[29]]. Cleanliness habits (e.g., sweeping the house, high frequency of changing bed linen) [[23], [32]]
leprosy 32683 were assessed in four studies, of which three found a negative association between cleanliness and leprosy [[23], [33], [35]]. Pooled statistics were calculated for lack of clean water in the household in three
leprosy 32961 CI = 0.65,1.35; I2 = 62.5%) (Fig 3) and provided no evidence that clean water correlates with lower leprosy incidence.Other sociodemographic indicatorsThe studies at the individual level investigated a range
leprosy 33330 limited. For example, in the one case-control study that examined ethnicity and marriage as correlates of leprosy , the authors report no difference between white and black/brown or unmarried and married individuals
leprosy 33485 and black/brown or unmarried and married individuals [[23]]. The relationship between religion and leprosy was evaluated in three studies, one held in Bangladesh [[27]] and two in India [[31], [33]], with higher
leprosy 33598 evaluated in three studies, one held in Bangladesh [[27]] and two in India [[31], [33]], with higher leprosy prevalence among Muslims reported in one [[31]]. In addition, of the three studies evaluating urbanicity
leprosy 33715 prevalence among Muslims reported in one [[31]]. In addition, of the three studies evaluating urbanicity and leprosy [[29], [30], [38]], two found that individuals living in urban (versus rural areas) [[38]] or in rural
leprosy 33883 urban (versus rural areas) [[38]] or in rural villages (versus the rural surrounding areas) have lower leprosy prevalence [[30]]. The distance from the household to health clinics, which can also be a measure of
leprosy 34132 was evaluated by Fisher and colleagues (2008) in Bangladesh, but no relationship was found between leprosy detection rate and proximity to a clinic [[19]]. Recent migration (i.e., in the past 5 years) was evaluated
leprosy 34288 Recent migration (i.e., in the past 5 years) was evaluated once and was positively associated with leprosy [[26]].Ecological trendsEcological studies provide an important line of evidence on the relationship
leprosy 34447 an important line of evidence on the relationship between socioeconomic and demographic factors and leprosy (Tables 2 and 4). Associations of leprosy with increased urbanization [[41], [45], [47]–[50]], illiteracy/lower
leprosy 34489 relationship between socioeconomic and demographic factors and leprosy (Tables 2 and 4). Associations of leprosy with increased urbanization [[41], [45], [47]–[50]], illiteracy/lower education [[30], [41], [48]–[51]]
leprosy 34930 sanitation (i.e., a sewage system or a sanitary facility) [[48], [50]–[52]] reported a lower number of leprosy cases in the all but one of the studies [[44], [48], [50], [52]]. The mean number of individuals per
leprosy 35170 considered in seven studies [[41], [46]–[50], [52]], five of which found it positively associated with leprosy [[46]–[49], [52]]. Socioeconomic deprivation was measured as the percentage of people living in poverty
leprosy 35572 [[43]–[45]]. Half of these studies found a correlation between having better living conditions and lower leprosy burden [[43]–[45], [49]]. Migration, evaluated as the percentage of people born in other regions,
leprosy 35711 Migration, evaluated as the percentage of people born in other regions, was positively associated with leprosy [[47]]. Ecological studies also provided evidence of a correlation between malnutrition and leprosy
leprosy 35811 leprosy [[47]]. Ecological studies also provided evidence of a correlation between malnutrition and leprosy among children [[30], [51]].10.1371/journal.pntd.0006622.t004Table 4Adjusted point estimates of the
leprosy 35934 [[30], [51]].10.1371/journal.pntd.0006622.t004Table 4Adjusted point estimates of the association of leprosy with socioeconomic risk markers in high burden countries in ecological studies.RefYearMarkerExposed
leprosy 38198 Program < 50%RRadj1.29 (1.17, 1.41)[[50]]2015Health and social assistanceNumber of health campaigns for leprosy detection (per unit)RRadj1.02 (0.96, 1.08)[[50]]2015Health and social assistanceNumber of reference
leprosy 38324 unit)RRadj1.02 (0.96, 1.08)[[50]]2015Health and social assistanceNumber of reference units assisted by leprosy control programme (per unit)RRadj1.69 (1.10, 2.62)[[51]]2015Health and social assistanceVaccination
leprosy 39903 general, indicators of social development and policy interventions were negatively associated with leprosy burden. Inequality was measured using Gini Index or Theil’s L index in four studies [[41], [47]–[49]]
leprosy 40351 evidence of an association between increased inequality and/or lower socioeconomic development and higher leprosy risks [[41], [42], [47]–[49]]. On the other hand, the presence of specific campaigns and health services
leprosy 40470 [[41], [42], [47]–[49]]. On the other hand, the presence of specific campaigns and health services for leprosy detection were associated with higher leprosy incidence rates, potentially by enhancing the leprosy
leprosy 40516 presence of specific campaigns and health services for leprosy detection were associated with higher leprosy incidence rates, potentially by enhancing the leprosy detection efficiency [[50]]. While higher coverage
leprosy 40570 leprosy detection were associated with higher leprosy incidence rates, potentially by enhancing the leprosy detection efficiency [[50]]. While higher coverage of primary health care in Brazil was associated with
leprosy 40689 efficiency [[50]]. While higher coverage of primary health care in Brazil was associated with higher leprosy new case detection in two studies [[48], [49]], no associations with leprosy were found using other
leprosy 40766 associated with higher leprosy new case detection in two studies [[48], [49]], no associations with leprosy were found using other metrics for health care access, including: the number of general public health
leprosy 41173 transfer program showed that increased coverage of the program benefits was associated with a reduction in leprosy new case detection rates [[49]].DiscussionThis systematic review points to a consistent relationship
leprosy 41290 detection rates [[49]].DiscussionThis systematic review points to a consistent relationship between leprosy and unfavorable socioeconomic circumstances. For individual level studies, meta-analyses provide evidence
leprosy 41427 circumstances. For individual level studies, meta-analyses provide evidence for increased risks of leprosy in individuals who are male, share homes with leprosy cases, live in crowded conditions, and have experienced
leprosy 41481 meta-analyses provide evidence for increased risks of leprosy in individuals who are male, share homes with leprosy cases, live in crowded conditions, and have experienced food shortages in the past. In ecological level
leprosy 41647 food shortages in the past. In ecological level studies, point estimates for the associations between leprosy and sociodemographic risk markers of crowding, sanitation, and poverty remained largely consistent with
leprosy 41862 individual level studies and across different geographic settings.Overall, males had a greater risk of leprosy . However, the effect diminished in studies that are more recent; the pattern is potentially attributable
leprosy 41998 diminished in studies that are more recent; the pattern is potentially attributable to higher detection of leprosy among women over time and/or to change in exposure level of different risk markers in men and women.
leprosy 42189 in men and women. In most studies, literacy and high levels of education were associated with lower leprosy rates, although pooled estimates for education were not possible due to incomparable categories. Better
leprosy 42502 better work conditions and resources and promote greater autonomy [[54]], which could potentially reduce leprosy infection and transmission.The type of work performed by an individual reflects their socioeconomic
leprosy 42799 especially in large and multicultural ones (e.g., India and Brazil). Pooled estimates between work and leprosy showed high statistical heterogeneity across the different studies, which might suggest that performing
leprosy 43312 shortage, an indicator of extreme poverty and undernourishment [[27]] also appeared to be a risk marker of leprosy . Food-shortage was assessed in places where seasonality can influence work, income, food prices, consequently
leprosy 43726 only once [[23]].Person-to-person contact inside the household is one of the most likely sources for leprosy transmission [[57]]; nevertheless, similarities of social, sanitary, and poverty conditions shared by
leprosy 43884 social, sanitary, and poverty conditions shared by families and neighbors, which can contribute to leprosy transmission, are poorly taken into account. The higher leprosy prevalence among crowded households
leprosy 43948 neighbors, which can contribute to leprosy transmission, are poorly taken into account. The higher leprosy prevalence among crowded households in the meta-analysis support the hypothesis that crowding can both
leprosy 44193 be a general indicator of poverty. Additionally, the association between religion and higher risk of leprosy in the study of Chaturvedi (1988) was mainly attributed to increased household crowding in some religious
leprosy 44589 urban areas, but only ecological studies showed consistent correlations between urbanization and higher leprosy rates. Studies performed at the individual level, showed that household characteristics and basic socio-sanitary
leprosy 44748 showed that household characteristics and basic socio-sanitary conditions were strongly related with leprosy burden. In 2015, only 58% of the global population had access to clean water and 68% to adequate sanitation,
leprosy 44972 marked inequalities between rural/urban and rich/poor areas, including many high-burden countries for leprosy [[58]]. The absence of association between lack of access to clean water and leprosy in the meta-analysis
leprosy 45057 countries for leprosy [[58]]. The absence of association between lack of access to clean water and leprosy in the meta-analysis might derive from high heterogeneity among the living conditions of those affected.Migration
leprosy 45506 result differs from the two studies that evaluated migration history as a potential risk factor for leprosy . Nevertheless, the origin of migrants or the incidence/prevalence in their country or region of origin
leprosy 45778 between the socioeconomic or demographic characteristics (i.e., crowding, sanitation, and poverty) and leprosy in both individualized and ecological studies followed the same direction, suggesting no ecological
leprosy 45959 direction, suggesting no ecological fallacy and strengthening the association between these risk markers and leprosy . Nevertheless, it is important to mention that few studies reported the potential for reverse causality
leprosy 46132 reported the potential for reverse causality in both cross-sectional and ecological investigations (e.g., leprosy → unemployment). Freitas and colleagues (2014) suggested that higher detection rates of leprosy in
leprosy 46230 (e.g., leprosy → unemployment). Freitas and colleagues (2014) suggested that higher detection rates of leprosy in municipalities with greater Family Health Program coverage can also be attributed to preferential
leprosy 46376 Health Program coverage can also be attributed to preferential targeting of municipalities by their leprosy rates [[48]]. Also, there is a possible link between leprosy-associated stigma and loss of employment,
leprosy 46437 preferential targeting of municipalities by their leprosy rates [[48]]. Also, there is a possible link between leprosy -associated stigma and loss of employment, which could further worsen living conditions.Some limitations
leprosy 47152 environmental factors as potential descriptors in the search strategy, some rare factors linked with leprosy burden might have missed. We selected all high burden countries for leprosy since 2001, but endemic
leprosy 47228 rare factors linked with leprosy burden might have missed. We selected all high burden countries for leprosy since 2001, but endemic countries facing civil war in the last 10 years might not have been included
leprosy 48077 could have contributed to higher heterogeneity in the effects between the studied social markers and leprosy . Despite these limitations, this review aggregated sparse evidence from diverse study settings, showing
leprosy 48245 evidence from diverse study settings, showing consistent associations between social determinants and leprosy across studies. Future research should prioritize investigations in low-income countries, address other
leprosy 48726 and in countries, like Brazil, has been incorporated into social programs [[61]]. For instance, high leprosy burden was accounted for in the prioritization of Brazilian municipalities in social protection programs,
leprosy 49083 particularly designed to address social determinants have not been fully considered in the context of leprosy control programs in many countries. Social determinants of leprosy have been poorly studied to date
leprosy 49150 fully considered in the context of leprosy control programs in many countries. Social determinants of leprosy have been poorly studied to date and need to be particularly addressed in those countries where leprosy
leprosy 49254 leprosy have been poorly studied to date and need to be particularly addressed in those countries where leprosy incidence is still high and human development remains low. In agreement with the WHO Global Leprosy
leprosy 49485 which recommends the increase of inter-sectoral collaboration to further reduce the global and local leprosy burden, this review provides additional evidence that elimination of leprosy at the international level
leprosy 49562 reduce the global and local leprosy burden, this review provides additional evidence that elimination of leprosy at the international level requires reduction of social inequalities, improving access of adequate housing
leprosy 49861 conclusion, this study underscores the many ways that poverty can create conditions that perpetuate leprosy risk. In addition, these findings call attention to persistent gaps in knowledge of the associations
leprosy 49978 addition, these findings call attention to persistent gaps in knowledge of the associations between leprosy and socioeconomic risk markers and highlight a lack of studies conducted in low-income countries. Thus,
leprosy 50168 low-income countries. Thus, political commitment must prioritize investments in not only the diagnosis of leprosy , but also in research on the social determinants of this ancient disease, and in the integration of
leprosy 50276 but also in research on the social determinants of this ancient disease, and in the integration of leprosy -specific programs into social policies aiming to eradicate poverty.Supporting informationS1 TextSearch
leprosy 50452 poverty.Supporting informationS1 TextSearch strategy used to study the socioeconomic factors associated with leprosy burden.(DOCX)Click here for additional data file.S1 TableSummary table of the 39 appraised records.(PDF)Click
tuberculosis 45373 transmission and reactivation in lower-burden settings (e.g., as has been previously demonstrated for tuberculosis ) [[59], [60]]. This result differs from the two studies that evaluated migration history as a potential

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