BCG vaccination in southern rural Mozambique: an overview of coverage and its determinants based on data from the demographic and health surveillance system in the district of Manhiça

The study was conducted in the district of Manhiça, Maputo Province, a rural area of Southern Mozambique, where the Manhiça Health Research Centre (CISM) runs a Health and Demographic Surveillance System (HDSS) since its foundation in 1996 [31]. It is a high TB and HIV burden area [32, 33]. In 2014, the HDSS was expanded to cover the entire district, an area of 2380 km² that comprises around 38,000 enumerated and geo-positioned households, and about 178,000 individuals. Compared to the official census, DHS, health service data and civil registrations, the HDSS is considered a gold standard tool for population indicators and cross-national comparisons [1, 34].

In Mozambique, where high pediatric TB rates and low case detection rates have been reported [35, 36], children receive a national health card (also called “vaccination card”) at birth or in their first contact with the health system, where immunization, anthropometric and basic health data are registered. All children born in the district of Manhiça participate in the HDSS.

In every HDSS round, demographic information about births, deaths and migration is updated. This is a cross-sectional study performed at the time of the HDSS census rounds of 2014 and 2015, which included a specific form to collect information about vaccination status. In each round, information was collected for children who were up to 3 years of age, thus in the round of 2014, children born in 2011, 2012 and 2013 were evaluated; and from 2012 onwards for the round of 2015. Information for all children who were less than 36 months of age at the HDSS census rounds was selected. Health cards, whenever available, were evaluated by the field worker, who collected information about administration of all vaccines. In order to estimate BCG and other EPI vaccines coverage through the assessment of vaccination card, we only included children who presented the card at the time of the interview; in order to assess BCG vaccination coverage through the presence of scar, we included all children observed at the visits.

Data cleaning, prior to data analysis, included deletion of duplicated records or incomplete variables. Duplicated observations occurred because the questionnaire was administered to every child irrespective of having or not responded to previous rounds. This allowed to have the most updated information for missed children in previous visits and newborns. When duplicate observations were present, those observations with the most complete data for all variables were preserved.

BCG vaccination coverage (VC) was defined as the proportion of children with recorded BCG vaccine in their health card divided among children whose health card was assessed and readable. VC was calculated as a proportion of children receiving a BCG or other EPI vaccines divided by the total number of eligible children (those who should have received it according to their age at the time of the visit and whose health card was assessed, readable and without missing dates). VC was calculated as a proportion, with 95% confidence intervals (CI). Information about children included variables such as sex, number of siblings, season of birth and area of residence. Mothers’ data was obtained from other HDSS questionnaires in which information about family members is routinely collected, including religion, education or marital status. Variables at household level, such as wealth index and distance to nearest health centre were also included. The variable wealth index was estimated using principal component analysis (PCA) with variables related to the household assets following the recommendations of Vyas et al. [37].

To measure the coverage of BCG through scar assessment, the number of children who presented a BCG scar was divided by the total number of children assessed for scarring. The coverage was also measured among children with and without health cards and among children with BCG according to their health card. Delay in BCG administration was defined as a child receiving BCG vaccine after the first 28 days of life.

In the descriptive analysis absolute and relative frequencies were calculated. The description included qualitative variables and quantitative variables categorized according to the objective of the study.

The analysis was conducted using Stata 13 (StataCorp LP, College Station, TX, USA). Graphs and tables were produced with Excel (Microsoft Office 2016, USA).

According to CISM’s HDSS database, 11,537 children were born between 1st January 2011 and 31st December 2014 in the district of Manhiça. From the 10,875 eligible children (born in that period and under 36 months at the time of annual visits), 9512 children were visited. Around 72.9% (7903/10,875) of children presented a health card to the field workers for transcription of the information on vaccination. Of 2972 children whose card was not available, 48.9% of cases declared the reason was that the adult responding to the HDSS questions could not find the card and, in almost a quarter, 23.1%, no reason was recorded.

Among children with a health card, information about BCG vaccination (either yes or no) was recorded in 98.9% of the cases and, from those, 91.9% were present at the time of the interview allowing the evaluation of their arm to see the scar post BCG vaccination (see Fig. 1). Regardless of having the vaccination card, 8298 children were evaluated for presence of BCG scar. Characteristics of study participants are described in Table 1. Additional file 1 presents the characteristics of infants with and without health card.

A total of 7612 children under the age of 36 months whose national health card was evaluated were BCG vaccinated in the district of Manhiça, yielding a BCG coverage of 97.4%. Table 2 and Fig. 2 show the vaccination coverage for all EPI vaccines administered in the district of Manhiça in the first year of life during the years 2011 to 2014. Coverage for each of the four doses of Oral Polio Vaccines were: 96.3%, 95.6%, 93.8% and 92.1%. For the pentavalent DPT/HepB/Hib vaccine, coverage was 96%, 94.5% and 93%. Measles vaccine was received around month 9 of life by 85.6% of infants. Around 90.2% of all study children had received all four doses of Oral Polio Vaccine and 91.8% of the doses of the pentavalent vaccine DPT/HepB/Hib. We found no differences in coverage for any of the vaccines by year of vaccination.

The multivariable logistic regression model revealed that children born in the municipality of Maluana had 89% higher odds of not receiving the vaccine compared to those born in central Manhiça (OR = 1.89, 95% CI: 1.18-3.00). Mothers’ marital status (divorced or not living with a male companion vs married or living with a male companion) showed a weak association with lack of vaccination: OR = 1.66 95% CI: 0.81-3.37) (Table 3). No other factors were associated with lack of BCG vaccination.

From the 9512 adults who responded to the interview, irrespective of whether they presented the national health card or not, 8298 children could be directly observed for the presence of BCG-compatible scar. Coverage was 99.0% and 97.9% among children with and without a health card respectively. Therefore, when children are vaccinated with BCG (according to the health card), failure to develop the typical scar would occur in less than 1% in this population. We did not find any statistically significant association with lack of BCG scar. There were 174 children who were not BCG vaccinated according to the card, but 144 of them presented a BCG-compatible scar (82.8%).

Figure 3 represents the distribution of BCG vaccines administered to children starting from the day of birth onwards. The results indicate that 93.4% of vaccinated children received BCG within the first 28 days of life. The factors associated with the administration of BCG in the first 28 days of life are described in Table 4. The only factor associated with a timely BCG administration is not being born by a cesarean section (for which OR = 0.40, p-value 0.021). In other words, children born through a cesarean section are 60% less likely to have an adequate administration of BCG vaccine.

This study provides population estimates of BCG administration by two different methods in a large cohort of children. It shows that vaccine coverage in Manhiça district was very high for all vaccines administered in the first year of life, surpassing the international targets for EPI vaccine coverage. This finding is in line with results presented from similar studies about EPI vaccine coverage in Mozambique [29].

This is the first vaccination coverage study in the country using data collected by a HDSS. This preliminary information could be very relevant for future vaccine trials and a proxy for other health interventions. It is also important to highlight the importance of data registries in LMIC to monitor health systems’ performance, resource allocation planning and progress in immunization strategies. These findings call for an improved system to collect information to be used for assessing vaccine coverage, and which could hopefully be used to compare across different countries.

In the period from 2011 to 2014, BCG coverage was 97.4%, higher than the estimation of 86.3% in Maringue District, Sofala Province (centre Mozambique) [12] and the nationwide 94% estimation by WHO [28]. The results of high coverage could be explained because of the likely better health infrastructure in the district than national standards, which include two referral hospitals plus the existence of a research centre (the CISM, which conducts operational and translational research). The latter, conducts at least one visit per year to each household for the purpose of HDSS work rounds of data collection in the district, which could potentially affect vaccination-seeking behaviour in the community. However, selection bias might have occurred since there is a proportion of subjects who fail to provide a health card. Although the main stated reason was that the caregivers could not find the card, if those who did not find the card had lower vaccine coverage, our estimates might represent a slight overestimation of the true coverage. An extra source of potential selection bias is that those born in that period who died before the HDSS census rounds might have had lower BCG coverage. However, the effect of this bias, albeit unknown, could be limited, since those with and without vaccination card had similar coverages measured by the presence of scar.

We found no statistically significant associations with lack of BCG vaccination, except living in the municipality of Maluana. These findings might be explained by the small number of non-vaccinated individuals (random error) or other social factors that will require qualitative approaches in order to be identified.

Very few BCG vaccinated children (according to their health cards) in the district of Manhiça fail to develop the scar. These results are comparable with findings of scar failure in other countries, ranging from 1 to 20% [13, 38, 39]. Potential observer bias could have taken place, since field workers were not blind to the child heath card information. Nonetheless, the proportion of scar formation in children with and without health card was similar to that of BCG vaccinated infants. If these findings were a true overestimation, the reason behind could be a systematic poor evaluation of the presence of BCG scar. Conversely, the fact that many children with no record of BCG in their card presented BCG scar could lead to a potential underestimation of coverage estimates based solely on immunization card. This could be due to bad documentation of BCG vaccination in the immunization card (or cases where the card was lost and replaced, and information could not be updated). Unfortunately these potential explanations cannot be verified.

Recent studies showing scar beneficial effects, such as lower mortality in infants with scar [5, 11], have opened the debate about re-vaccination [5, 40] among those failing to develop a scar. Some have suggested that scarring could be a method to monitor vaccination performance in resource-poor settings. On the other hand, BCG is not recommended in HIV suspected cases and HIV-related immunosuppression may play a role in scar response. In a high HIV burden country such as Mozambique, where most children are BCG vaccinated regardless of their HIV status, we expected a lower scar formation rate.

The timing of vaccination is very important in order to reach the maximum protection, but also for being a proxy of non-adherence and reduce of vaccination. [16, 17, 20, 22]. In order to measure if BCG was appropriately administered, we consider a timely vaccination if it occurred within the 28 days of life, as recommended by WHO [19]. The results show a low proportion of delayed BCG vaccination (6.6%), compared to 33% found in Tanzanian the year 2004 [15]. However, the definition of delayed BCG vaccination differs from author to author, [19] some consider it happens only after 8 weeks or even after 56 days [17] after birth, thus comparability with other studies needs to be cautious. The only factor associated with timely BCG vaccination was being delivered through a caesarean section. It is closely related with being born in a health facility, with a skilled birth attendant, where they will have the BCG vaccine ready to be administered after birth.

This study had several limitations. First, selection bias could have occured since we could only visit children whose adults were present at the moment of the interview and presented the card (for evaluation of the registration) and/or the children were present (for scar assessment). There were 16.9% (1609/9512) of children who did not present a health card. Although most of them argued that adults had lost the card, these children might live in families with more difficulties in accessing the health system or not able to have a proper follow-up of their children’s health status, thus our vaccination coverage could be overestimating the real one. Secondly, children who died before the first round visit were not included and might have different (potentially lower) vaccine coverage. Thirdly, given the discrepancies found about BCG vaccination assessed through health card and presence of scar, poor BCG documentation in the card or poor evaluation of BCG scar, cannot be ruled out. Last, due to the low number of non-vaccinated individuals identified, the study had little power to detect potential factors associated with absence of vaccination.