Immunization, urbanization and slums – a systematic review of factors and interventions

Background In 2014, over half (54%) of the world’s population lived in urban areas and this proportion will increase to 66% by 2050. This urbanizing trend has been accompanied by an increasing number of people living in urban poor communities and slums. Lower immunization coverage is found in poorer urban dwellers in many contexts. This study aims to identify factors associated with immunization coverage in poor urban areas and slums, and to identify interventions to improve coverage. Methods We conducted a systematic review, searching Medline, Embase, Global Health, CINAHL, Web of Science and The Cochrane Database with broad search terms for studies published between 2000 and 2016. Results Of 4872 unique articles, 327 abstracts were screened, leading to 63 included studies: 44 considering factors and 20 evaluating interventions (one in both categories) in 16 low or middle-income countries. A wide range of socio-economic characteristics were associated with coverage in different contexts. Recent rural-urban migration had a universally negative effect. Parents commonly reported lack of awareness of immunization importance and difficulty accessing services as reasons for under-immunization of their children. Physical distance to clinics and aspects of service quality also impacted uptake. We found evidence of effectiveness for interventions involving multiple components, especially if they have been designed with community involvement. Outreach programmes were effective where physical distance was identified as a barrier. Some evidence was found for the effective use of SMS (text) messaging services, community-based education programmes and financial incentives, which warrant further evaluation. No interventions were identified that provided services to migrants from rural areas. Conclusion Different factors affect immunization coverage in different urban poor and slum contexts. Immunization services should be designed in collaboration with slum-dwelling communities, considering the local context. Interventions should be designed and tested to increase immunization in migrants from rural areas. Electronic supplementary material The online version of this article (doi:10.1186/s12889-017-4473-7) contains supplementary material, which is available to authorized users.


Background
In 2014, over half (54%) of the world's population lived in urban areas [1]. By 2050 this proportion is expected to increase to 66%, adding approximately 2.5 billion new urban dwellers, of whom 90% will be in Asia and Africa [2]. This trend towards urbanization is closely linked with an increasing population living in urban poor communities and slum environments [2]. Although the proportion of urban residents living in slums has been decreasing, the absolute number has increased substantially, from 689 million in 1990 to 880 million in 2014, and is expected to double by 2030 [3]. In order to meet the outcomes in the New Urban Agenda and Sustainable Development Goals to improve health for slum-dwellers a better understanding is needed of each individual slum environment and the factors contributing to poor health outcomes [4,5].

Immunization and urbanization
Significant disparities exist in immunization coverage in urban areas with lower coverage observed in the urban poor in many countries (Fig. 1).
Although some countries, such as Bangladesh, have achieved immunization equity, these disparities are growing in many others, including Nigeria, Ethiopia, Cameroon and Pakistan [6]. However, Demographic Health Surveys do not sample urban slums specifically Tables 1 and 2. display the results of recent studies that have reported data on immunization coverage in slums in India and in sub-Saharan African countries, showing a wide range of coverage, from 3.0% and 8.5% in rural migrant children in slums in Chandigarh and Nigeria [7,8], to 88.7% and 93.3% in Mumbai and Ouagadougou [9,10].
In addition, vaccine programmes designed for a general population may not be as effective in urban slums, which are characterized by lack of essential infrastructure (such as electricity and water), poor housing quality and where residents may be recent migrants, or have insecure legal or residential status, limiting access to basic health services, if they are available at all [22,23].
Although low immunization coverage is not inevitable amongst the urban poor, there is no current systematic synthesis describing the associated demographic, geographic, and socio-economic factors, nor considering interventions to increase coverage. Therefore, the aim of this study is to identify the factors associated with immunization coverage in low-income urban areas and slums in low and middleincome countries (LMICs), and identify the evidence for interventions to improve coverage.

Methods
We conducted a systematic review in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement [24].

Search strategy
We searched Medline, Embase, Global Health, CINAHL, Web of Science and The Cochrane Database of Systematic Reviews, using the strategy shown in Additional file 1.

Inclusion and exclusion criteria
Studies published between 2000 and July 2016 with the following characteristics were included: Population: any population living in a low-income urban area or slum in a LMIC [25]. Slums have a broad operational definition, so we have included consideration of urban poor communities that have slum-like characteristics, even if they have not been formally designated as a slum [22]. Study design: Observational studies: cross-sectional surveys and cohort studies, designed to identify factors associated with coverage levels.   Intervention studies: randomised controlled trials (RCTs), quasi-experimental (including time-series and before-and-after studies) and ecological designs that evaluated any intervention designed to increase vaccine uptake or coverage, including any associated economic analyses.
In addition, we included primary studies identified from searching the references from other review articles identified in the search that fitted inclusion criteria.

Study selection process
One reviewer screened articles by title and manually deduplicated records. Two reviewers screened potentially relevant abstracts independently. Any disagreement was resolved by discussion, based on the inclusion criteria. Three reviewers agreed the final inclusions.

Factors associated with immunization coverage
The qualitative synthesis of factors identified from 44 studies is presented below, categorized into 4 groups: socio-economic characteristics; migration status; information, beliefs and behavior; and health services. All studies were cross-sectional surveys, aside from one qualitative study [37], and one ecological study [38]. Quantitative synthesis of measures of effect was not able to be performed due to heterogeneity in study design, population and methods.

Socio-economic and demographic characteristics
Socio-economic (SE) status was measured in a variety of ways, including using measures of wealth or income, employment status, education, or surrogate markers like receipt of government payments.
In India, the impact of SE factors has been studied extensively in low-income urban and slum areas. An ecological study using data from the Indian National Family Health Survey showed that the children in the lowest wealth quartile in urban areas have significantly lower coverage (around 40%) than in any other urban wealth group [38]. Another study examined the survey data in more detail to compare a wider range of SE factors and outcomes of 1877 children in less developed Empowered Action Group states with more developed northern counterparts and found that having an illiterate mother or father, poverty, and being a 3rd born child or greater had the greatest effect on immunization coverage [46]. However, studies conducted in individual locations paint a more heterogeneous picture. Mothers' education was associated with lower coverage in some studies [39,49,51], but not in others [45,53]. Similarly, female children had lower coverage in some studies [39,45,51], but no gender difference was found in others [9,49,50]. In one study malnutrition was also found to be much more common in unimmunized slumdwelling children [44].
Elsewhere, a study in a slum in Karachi, Pakistan, found lower coverage in lower SE groups [59]. However, the study reported a much more significant effect of being from a marginalized ethnic group, particularly if associated with illegal or insecure residential status. Another study in Pakistan found mothers' education was a significant predictor of measles containing vaccine (MCV) coverage in urban areas [60]. However, the impact of other SE factors was different in different localities.
The findings from sub-Saharan African countries are similar in their diversity. Across 3 slum populations in Kenya factors associated with immunization coverage included: maternal education, employment and age; child's birth order; number of children, place of birth; and household assets and expenditure [64][65][66]. Ethnic group was a significant predictor of MCV uptake in Nairobi [67]. A paired study conducted in slums in Nairobi and Ouagadougou found that while the SE factors in each slum were similar, children in Nairobi were 11.5 times more likely to be unvaccinated, suggesting a powerful environmental effect [10]. In Jigjiga, Ethiopia, maternal age and literacy, place of residence, tetanus immunization status, place of delivery and household visit by health workers were the most important predictors of completing immunization [72].
In Sao Palo, Brazil, a study of 258 children in a philanthropic day care centre found premature birth, malnourishment, inadequate housing and poor prenatal care to be associated with lower coverage [75]. However, a larger Brazilian study involving 17,000 children found that those in lower SE groups had higher immunization rates than their wealthier peers [76]. Although this association is not fully explained in the paper, the authors found that parents in higher socioeconomic quintiles had higher vaccine refusal rates and hypothesize that progressive reduction in VPD incidence over many years may have led to complacency, alongside unfounded vaccine safety concerns widely reported in other countries.

Migration status
Four studies demonstrated a negative effect of migration status on immunization coverage in India [7,53], China [63], and Nigeria [71]. In India, recent migrants were found to have lower coverage than settled migrants (living in new urban location for >12 months), which then resolved to the slum-area average over time [53]. A study comparing reasons for under-immunization given by migrant and non-migratory parents in an Indian slum cited mother or both parents being too busy; parent returned to home village; parent unaware of place or time of immunization; and lack of awareness for the need for immunization as the main reasons for underimmunization [7]. In Nigeria, children of urban nonmigrant mothers had 67% higher chance of being fully immunized than migrant children, which was attributed to the disrupting force of migration [71]. However, other characteristics, including: children being of higher birth order; being a mother aged <18 years; and lower SE status, also played a significant role, independent of migration status after regression modelling. Thus, there are elements of similarity of the risks of low immunization coverage as faced by all urban poor communities, but these are exacerbated by the disruptive force of migration.
Unfortunately, there are fewer studies available from other countries to make similar comparisons. In two studies conducted in Pakistan, maternal knowledge of immunization was an important factor; [61] and the reasons for under-immunization given by mothers were to do with 'carelessness' or difficulty in accessing services [60]. In Ibadan, Nigeria, a study found fear of sideeffects, maternal awareness, and parents being too busy to attend clinic to be significant; [8] in neonates in Benin City, Nigeria, a study found that SE and education status were associated with delayed immunization; [69] and the 3 main reasons for under-vaccination identified in a study from Bangui, Central African Republic, were the mother being too busy, negative attitude of health workers, and lack of access to information [73].
One qualitative study conducted in a slum in DRC investigated health service access using focus group interviews [37]. It painted a detailed picture of parents conflicting views and beliefs, including concerns over out-of-pocket expenditure and being suspicious of free services (including vaccines), while seeing some services as beneficial, but not acceptable due to lack of information and distrust in the government.

Health services
A study that used mapping techniques to evaluate health service access in Agra, India, found that the presence of a health center within 2 km of the slum doubled the chances of a child being completely immunized [51]. A similar study in Lusaka, Zambia, showed that further distance from service points were associated with lower coverage [74]. Timing of services is also important, where offering services only on one particular day is associated with reduced coverage in neonates in Nigeria [69]. However, slum-dwelling populations may also be less likely to access health services due to fear of costs, risk of lost income, or lack of local knowledge [48]. A study from Nigeria showed that even when services are provided free, urban dwellers consume less than their rural counterparts [70]. However, another study found a high level of payment for services that should have been provided for free, including immunization and pre-natal care. This may be a common experience in LMICs, due to low payments made to health workers, and when present, may affect the long-term effectiveness of vaccine programmes. However, when people do access healthcare higher patient satisfaction and provision of accurate information was shown to lead to increased attendance for repeat vaccine doses in an Indian slum community [58]. Accessing pre-natal care was shown to have a positive impact on immunization coverage in India [41], Ethiopia [72], and Brazil [75].
A missed vaccination opportunity is when health workers interact with a child who is under-immunized and could have been offered a vaccination, but for some reason do not [27]. A study conducted in 6 health facilities in a Nairobi slum found that vaccine coverage could have been increased if all missed vaccination opportunities had been taken [68].

Multi-component interventions
We found evidence of effectiveness for interventions involving multiple components designed to meet the specific needs of a slum-dwelling community, especially if they have been designed and delivered with community involvement.
Two related studies reported on an intervention conducted in Dhaka, Bangladesh. The first is a noncontrolled before-and-after evaluation of the intervention comprising four components: extended services hours; provider training; a screening tool; and a community support group [88]. Analysis of 529 children before and 526 after the intervention showed increased coverage over 12 months, with complete immunization rising from 43% to 99%. The second study calculated the cost of the programme at $20.95 per fully immunized child [87]. A similar programme in low-income areas Table 3 Showing the results of studies examining interventions to increase immunization uptake in urban poor and slum communities in low and middle-income countries Author    of Patna, India, involving enhanced service delivery (outreach; additional nursing staff; task-shifting; geographic monitoring; community mobilization; supervision and communication components) was evaluated using before-and-after analysis of routinely collected data, and showed increases in immunization uptake e.g. DTP3 increased from 21% to 49%, MCV from 23% to 51% [81]. Another study evaluated the Urban Health Programme (combining demand and supply side interventions with increased clinic accessibility and community involvement) in Indore, India, which showed an increase in complete immunization among infants from 32% to 72% [77]. Two studies considered typhoid vaccination specifically. A cluster RCT involving 21,059 children was conducted in squatter communities in Karachi, Pakistan, to evaluate a campaign to increase typhoid vaccine coverage (involving information provision; community involvement; increased services; and staff training), which achieved 74% coverage in the target population, with maintenance of cold-chain [85]. A study in New Delhi, India, undertook economic analyses of different vaccination campaigns against typhoid and concluded that a targeted program for pre-school children was most costeffective (US$14 per case averted), when compared to a school campaign (US$41) or general mass campaign (US$50) [96].
A large study (n = 161,695 children) in urban Nairobi and Nyanza provinces focusing on populations living in low-income, high-density environments demonstrated how the use of community volunteers calling door-to-door and providing standardized information using mobile phone technology can contribute to achieving high coverage (92%) during a planned mass MCV campaign [92].
A study conducted in Ulaanbaatar City, Mongolia, reports a before-and-after analysis following the implementation of the 'Reaching Every District' (RED) strategy by the ministry of health in an urban poor community, which reached an additional 477 children at risk of underimmunization, 15% of the total eligible population in the entire district, and also improved organizational structures and staff motivation [95].

Outreach programmes
Two related studies reported on the Growth Monitoring Program Plus programme, which involved providing monthly outreach services implemented in periurban areas of Lusaka, Zambia [74,90]. Comparing early implementation sites with late implementers, immunization coverage was shown to significantly increase in both areas, from 52.6% to 68.8% (early) and 43.1% to 56.7% (late), even after controlling for socioeconomic characteristics.
A study on an outreach services provided in Aligarh City, India, as part of a campaign reported success in immunizing over 2500 children in a low-income district and improving overall complete immunization coverage, demonstrating both feasibility and acceptability [78]. Another study in India provided descriptive evidence for the feasibility of providing vaccinations through a mobile health clinic in slum communities in Delhi, at the cost of RS66.14 per vaccine delivered (US$0.10) [80].

Reminder/recall
Three studies have shown varying levels of success in the use of text message (SMS) systems. In Bangladesh, the use of SMS reminder system in both urban street dwellers and a rural 'hard-to-reach' population was evaluated [89]. The results showed an increase in coverage in both populations, with an adjusted odds ratio of complete immunization of 3.0 (95% confidence interval (CI): 1.4-6.4) among the urban children. In Pakistan, an SMS system was successfully used to monitor provision of polio immunization by asking urban community members to report whether their children had been immunized by vaccinators [83]. A proof-of-concept study in an urban poor community in Guatemala City showed that an SMS system to remind mothers to receive pentavalent vaccine was feasible and acceptable, but found no difference in vaccine uptake [94].
A study in a slum community in Uganda showed that children born at a health facility, or whose mother was unwell during the pregnancy were more likely to have an immunization reminder card, and that these children were 10 times more likely to be up to date for all immunizations when compared to children without cards [91].

Education
Two studies considered the effect of an intervention focussing on education or information provision to parents in Pakistan. An RCT conducted in Karachi involved community health workers delivering pictorial messages to encourage immunization [84]. The intervention resulted in a 39% increase (OR 1.39, 95% CI: 1.06-1.81) of DTP3/Hepatitis B completion, although 27% of sampled women declined to take part. A randomized controlled before-and-after study of the provision of education sessions by medical students to mothers in a squatter settlement found an increase in complete immunization in the intervention group [86]. However, health centre utilisation for vaccination in intervention and control groups was significantly different at baseline (30% vs 13% respectively), suggesting participants were poorly matched. Additionally, this study was excluded from a related Cochrane Review due to its poor study design [26], and thus provides only weak evidence for this intervention.

Incentives
Two studies considered the effect of incentives on increasing vaccination uptake. A study of the Bolsa Familia program of conditional cash transfers in slums in Salvador City, Brazil, found that recipient families had higher use of health clinics and increased odds of vaccination uptake (OR 2.8; 95% CI: 1.4-5.2) [93]. A study conducted in Pakistan involving nearly 4000 children investigated the effect of providing a coupon redeemable for food or medicine (worth US$2) to incentivize attendance amongst low-income mothers in Karachi at follow-up immunization appointments [82]. The results showed increase (OR 2.2, 95% CI: 1.95-2.48) in timely completion of the DTP immunization series Discussion A wide range of socio-economic and behavioural factors have been associated with immunization status in different slum and urban poor contexts. While some of this diversity may result from differences in study methods, much may also be from true differences in the factors in the underlying populations. One included study from Pakistan applied the same methods in multiple settings simultaneously and reached the conclusion that 'one size does not fit all' , which is supported by the evidence in this review [60].
Further qualitative work is required to better understand the interlinking socioeconomic and demographic factors that influence immunisation coverage inequalities identified through analysis of surveys or population level data sources. The application of intersectionality theory, a method of systematically considering the multiple social labels individuals hold (e.g. ethnic group, gender, social class, migration status), may also provide additional useful detail in slum populations [97].

Improving immunization coverage
The evidence presented here demonstrates the relatively small number of interventional studies that have been conducted in slum populations. In addition, several of the studies have significant methodological flaws, requiring caution in the interpretation of the results. However, when comparing the evidence base identified here with the wider literature, it is notable that no interventions consider the importance of providing services to new migrants from rural areas in slum communities and that community involvement may be especially useful when designing interventions in slum areas.
A Cochrane review of interventions to improve coverage of childhood immunisation in low and middle income countries in all populations was published in 2014 also found a limited evidence base [26]. Of the studies described here, only one evaluating a maternal education programme was also included in the Cochrane review [84]. However, a comparison of the effectiveness for the type of interventions identified in this paper and in the Cochrane review are presented in Table 4.
Multi-component interventions that tackle multiple factors that can contribute to low coverage have some evidence for effectiveness [77,81,85,88,92,95]. An important component was community involvement, which enables the individual context of a slum to be considered, although this was not identified separately in the Cochrane review. This should include consideration of minority ethnic groups, who may suffer from lower coverage [59,67]. This matches similar research conducted in deprived urban communities in high-income countries [98].
The outreach programs identified in the literature focused specifically on reducing physical distance between communities and health services have evidence of effectiveness [74,78,80,90]. This finding matches that of a recent systematic review looking at improving immunization in LMIC urban areas generally, which concluded that outreach visits worked well in densely populated areas [99]. However, overall the authors identified fewer papers than are included in this study despite having a broader topic and longer time-frame. Outreach may be particularly relevant for slum communities, where there may be a lower density of health facilities, and should be a focus of further research.
No interventions were identified that reduced the social distance that some slum residents may experience when accessing health services. Specifically, no interventions were identified that provided services to migrants from rural areas, despite that migration was identified as having a universally negative effect on immunization coverage. Slums are often the first entry point of new migrants to an urban area [23], and the process of migration leads to an understandable disruption in parents' ability to access health services, leading to lower coverage [53,71].
Reminder/recall systems have good evidence for effectiveness in high-income countries and are considered as a core component of any immunization programme [100]. However, the provision of reminder/recall systems in LMICs is challenging, especially in slums, due to informal road systems, lack of addresses and limited access to electronic communications. However, of the three studies presented here, two show that SMS reminders can be effective in a slum context, [83,89] and the other showed feasibility as part of a pilot RCT, although found no difference in coverage [94].
Of the two studies evaluating education programmes identified here, one showed some evidence of effectiveness [84], but the other was compromised by methodological limitations [86]. However, community-based education programmes have evidence for effectiveness in increasing immunization uptake in LMICs generally and warrant further investigation in slum contexts [26]. The use of incentives is not supported by evidence from a recent Cochrane review of interventions to improve immunization in LMICs generally, unless incentives are combined with outreach [26]. However, both studies identified here had positive effects that also warrant further investigation [82,93].

Limitations
The quality of the included studies was only poor to medium, with no high quality randomised trials, making assessment for risk of bias challenging. We included studies conducted in slums alongside other urban poor communities, which may not be commensurate. Few studies reported negative results, suggesting publication bias overall. Several studies reported in Chinese were excluded. No evidence was identified for many countries with significant slum-dwelling populations, such as Indonesia, the Philippines, Sudan, Mozambique and Madagascar.

Conclusions
Different factors affect immunization coverage in different urban poor and slum contexts. Immunization services should be designed and provided to slum-dwelling communities in consultation with the people living there, considering the local context and avoiding constructing barriers to access, such as geographic and social distance, cost and timing. Interventions should be designed and tested to increase immunization in new migrants from rural areas.