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BCG coverage and barriers to BCG vaccination in Guinea-Bissau: an observational study

  • Sanne Marie Thysen1, 2Email author,
  • Stine Byberg1, 2,
  • Marie Pedersen1, 2,
  • Amabelia Rodrigues1,
  • Henrik Ravn2, 3,
  • Cesario Martins1,
  • Christine Stabell Benn2, 3,
  • Peter Aaby1, 2, 3 and
  • Ane Bærent Fisker1, 2
BMC Public Health201414:1037

DOI: 10.1186/1471-2458-14-1037

Received: 23 May 2014

Accepted: 29 September 2014

Published: 4 October 2014

Abstract

Background

BCG vaccination is recommended at birth in low-income countries, but vaccination is often delayed. Often 20-dose vials of BCG are not opened unless at least ten children are present for vaccination (“restricted vial-opening policy”). BCG coverage is usually reported as 12-month coverage, not disclosing the delay in vaccination. Several studies show that BCG at birth lowers neonatal mortality. We assessed BCG coverage at different ages and explored reasons for delay in BCG vaccination in rural Guinea-Bissau.

Methods

Bandim Health Project (BHP) runs a health and demographic surveillance system covering women and their children in 182 randomly selected village clusters in rural Guinea-Bissau. BCG coverage was assessed for children born in 2010, when the restricted vial-opening policy was universally implemented, and in 2012–2013, where BHP provided BCG to all children at monthly visits in selected intervention regions. Factors associated with delayed BCG vaccination were evaluated using logistic regression models. Coverage between intervention and control regions were evaluated in log-binomial regression models providing prevalence ratios.

Results

Among 3951 children born in 2010, vaccination status was assessed for 84%. BCG coverage by 1 week of age was 11%, 38% by 1 month, and 92% by 12 months. If BCG had been given at first contact with the health system, 1-week coverage would have been 35% and 1-month coverage 54%. When monthly visits were introduced in intervention regions, 1-month coverage was higher in intervention regions (88%) than in control regions (51%), the prevalence ratio being 1.74 (1.53-2.00). Several factors, including socioeconomic factors, were associated with delayed BCG vaccination in the 2010-birth cohort. When BCG was available at monthly visits these factors were no longer associated with delayed BCG vaccination, only region of residence was associated with delayed BCG vaccination.

Conclusion

BCG coverage during the first months of life is low in Guinea-Bissau. Providing BCG at monthly vaccination visits removes the risk factors associated with delayed BCG vaccination.

Keywords

BCG Coverage Timeliness of vaccines Implementation of the vaccination programme

Background

Bacillus Calmette Guérin (BCG) vaccine is recommended at birth to normal-birth-weight children in Guinea-Bissau. However, BCG vaccination is often delayed for several reasons, one of them being the “restrictive vial-opening policy”: BCG is a freeze-dried vaccine supplied in vials with 20 infant doses [1] and once reconstituted, the vaccine should only be used for a maximum of six hours. In Guinea-Bissau and other low-income countries [2, 3], the focus on not wasting vaccines [4] has led to a policy of not opening a BCG vial unless 10 children are present to be vaccinated [5]. Previous studies have shown that BCG has beneficial non-specific or heterologous effects, providing protection also against many non-tuberculosis causes of death [615]. In two randomised trials among low-birth-weight (<2500 g, LBW) neonates, BCG at birth compared with the usual delayed BCG, lowered neonatal mortality by 48% (95% CI: 18%-67%) [6, 7], the reduction being 58% (8%-81%) the first three days after vaccination [6, 7]. The rapidly occurring effect suggests that BCG stimulates the innate immune system. This is supported by recent immunological studies showing that BCG induces epigenetic changes which reprogram monocytes to increased pro-inflammatory responses against unrelated pathogens [16, 17].

Most infant deaths occur during the neonatal period, particularly in the first week of life [18] and thus any delays in BCG vaccination may have major consequences because children do not benefit from BCG when their mortality risk is highest. Hence, it is important to identify obstacles to early BCG vaccination, as this will help target interventions to lower the age at vaccination.

We assessed BCG coverage at different ages among children born in 2010 in rural Guinea-Bissau to identify factors associated with delayed BCG vaccination in a context with a restrictive vial-opening policy. In 2012, we implemented monthly visits and provided BCG vaccination to newborns in three intervention regions (Oio, Biombo and Cacheu) but not in six control regions. We evaluated how not adhering to the restrictive vial-opening policy affected BCG coverage and affected factors associated with delayed BCG vaccination.

Methods

Setting and study population

The study was conducted in the rural study area of the Bandim Health Project (BHP) in Guinea-Bissau. The BHP maintains a health and demographic surveillance system following 182 randomly selected clusters of 100 women and their children in rural Guinea-Bissau. The clusters were initially selected using the Expanded Programme on Immunizations (EPI) methodology for immunisation surveys sampling 20 clusters of 100 women in each of the eight larger health regions, and 10 and 12 clusters in the two smallest regions. Later two regions have been joined and rural Guinea-Bissau now has nine health regions; Oio, Biombo, Gabu, Cacheu, Bafata, Quinara, Tombali, Bubaque, and Bolama. All women of fertile age and children below the age of 5 years are followed through home visits every four to six months.

At the home visits women of fertile age are registered and information on ethnicity and schooling is collected. If a pregnancy is registered, a special form is completed collecting information on prenatal consultations and socioeconomic factors. For all newborn children information on date of birth, place of birth, and prenatal consultations is collected. At all visits the child’s vaccination card is inspected and vaccination dates are recorded. If the child has no vaccination card a vaccination card is provided from the BHP team.

BCG vaccination possibilities

Children in Guinea-Bissau should receive BCG and oral polio vaccine (OPV) at birth, pentavalent vaccine (diphtheria-tetanus-pertussis-H. influenza type B-Hepatitis B vaccine) and OPV at 6, 10, and 14 weeks, and measles and yellow fever vaccines at 9 months. These vaccines are provided free of charge at the health centres as part of the national programme and during outreach to villages when additional funding is available. Due to the restricted vial-opening policy some vaccines are only provided once a week at health centres and only if there is a sufficient number of eligible children present.

Since 2007 the BHP teams visiting the surveyed villages in all regions have been accompanied by a nurse, who offered OPV, pentavalent vaccine, measles vaccine, and yellow fever vaccine to all children below the age of 1 year. The vaccines were supplied through the national programme and the BHP nurse had to follow the national policy. Hence she did not bring BCG as she would very rarely encounter sufficient eligible children in a village.

In 2012 the BHP increased the frequency of visits from four-six-monthly visits to monthly visits in three regions (Oio, Biombo and Cacheu). In these intervention regions BCG vaccination was offered to all children below the age of 1 year regardless of the number of children present, thus a BCG vial was opened for one child. In the remaining control regions national policy was followed and BCG was not offered during village visits.

Information about reasons for delay of BCG vaccination

During the year from 1st July 2012 to 30th June 2013 mothers of BCG unvaccinated infants in all regions were interviewed on their BCG vaccination attempts/experiences during home visits. They were asked if they knew that their child was due to receive BCG and whether they had taken the child for vaccination. Mothers who reported to have sought vaccination were asked why the child had not been vaccinated. Mothers who had not sought BCG vaccination were interviewed about the reasons.

Ethical approval

BHP’s HDSS which has been in place in Guinea-Bissau since 1978 and is conducted by request from the Guinean Ministry of Health. The current surveillance system in the rural areas has been approved by the National Ethics Committee in Guinea-Bissau and the Central Ethics Committee in Denmark. No separate ethical and consent approval was sought.

Statistical analyses

Assessing BCG coverage in the 2010-birth cohort
Standard estimates for vaccination coverage are usually based on vaccinations obtained by 12 months of age, assessed among children aged 12 to 23 months [19, 20]. In the 2010-birth cohort we assessed BCG coverage by 1 month of age in children aged 1–12 months at the time of the home visit, the coverage by 3 months of age in children aged 3–14 months, the coverage by 6 months in children aged 6–17 months, and the coverage by 12 months in children aged 12–23 months (Table 1). Since most neonatal deaths occur within the first week of life, we also assessed the 1-week coverage using vaccination status assessed within the 12 months after day 7. Vaccination status was determined at the first visit in the relevant time period at which the vaccination card was seen. Children who had lost their vaccination card or for whom the vaccination card was not seen were excluded from the analysis.
Table 1

Coverage assessment methods for standard coverage estimates and coverage estimates in the 2010-birth cohort and the 2012 cohort

 

Standard coverage estimates

Coverage in 2010-birth cohort

Coverage in 2012 cohort

Children

 

Children born in 2010

Children aged 1, 3, 6, or 12 months of age, when visited from 1st July 2012 to 30th June 2013

Assessment ages

12 months

1 week, 1, 3, 6 and 12 months

1, 3, 6, and 12 months

Vaccination status

12-23 months

First visit with seen vaccination card within 12 months after assessment age

Visit with seen vaccination card in the month after the assessment age

Missed opportunities among BCG unvaccinated children were defined as contact with the health system, either being born at a health facility or having received other vaccines (based on the registered date of another vaccination on the vaccination card). We calculated the potential coverage if BCG had been given at the first contact with the health system.

Assessing BCG coverage after implementation of monthly visits, 2012 cohort

In 2012 monthly visits were introduced in the intervention regions, whereas four-six-monthly visits continued in control regions. We considered a village as belonging to the intervention regions when there was less than 6 weeks between two subsequent visits. BCG coverage was assessed among all children visited from 1st July 2012 to 30th June 2013. Like in the 2010-birth cohort, we assessed BCG coverage at 1, 3, 6, and 12 months of age. To take into account that children in intervention regions with monthly visits had a larger possibility of having their card seen within a 12 months period compared with children in control regions with four-six-monthly visits, we considered only data collected in the month after 1, 3, 6, and 12 months, respectively (Table 1).

Comparisons of coverage between regions with different BCG provision strategies were evaluated in log-binomial regression models providing prevalence ratios (PR).

Factors associated with delayed BCG vaccination

Factors associated with delayed BCG vaccination (vaccination after 1 month of age) were assessed in the 2010-birth cohort and after implementation of monthly visits separately for intervention and control regions in 2012/2013. This study focused on background factors assessed among the users of the vaccination services. The factors evaluated were: sex, birth place, antenatal care, region, type of roof, toilet, household possessions (radio, cell phone, and generator), ethnic group (Fula, Pepel, Balanta, Manjaco, and other), age of mother, and education of caretaker. All continuous variables were tested for linear relationship with BCG coverage by inspecting the BCG coverage in quintiles of the variable. Where inspection suggested a linear relationship, the quadratic value of the continuous variable was included in the model to assess departure from linearity. We tested all variables one by one in a simple model using logistic regression to calculate the odds ratio (OR) of being unvaccinated. As children were not individually sampled but selected for the study based on residence within a geographical cluster, we adjusted the standard error for cluster. In a larger multivariable model we included all factors associated with delayed BCG. In this large model we excluded ethnic group since ethnic group and region were highly correlated with more than 90% of the Pepels living in Biombo, and more than 75% of the Manjacos living in Cacheu. We chose to include region rather than ethnicity since region would be feasible to target through interventions.

Results

BCG coverage in the 2010-birth cohort

We assessed vaccination status at a visit within the first 2 years of life for 84% (3318/3951) of all children (Additional file 1). In the 2010-birth cohort, the BCG coverage by 1 week of age was 11% (327/3020) and 38% (1140/2984) by 1 month of age but increased to 92% (2385/2594) coverage by 12 months of age (Figure 1). If all children had received BCG vaccine at their first contact with the healthcare system, coverage would have been at least 35% by 1 week of age, 54% by 1 month of age and 99% by 12 months of age (Figure 1). The median age of BCG vaccination among children vaccinated within the first 12 months of life was 39 days. This could be reduced to 27 days if BCG vaccine had been given at first contact with the healthcare system.
Figure 1

Observed BCG coverage and potential BCG coverage by different ages. Observed BCG coverage (blue) and potential BCG coverage if all vaccination opportunities had been used (purple). Bandim Health Project, Guinea-Bissau, 2010-birth cohort.

BCG coverage after implementation of monthly visits, 2012 cohort

In the 2010-birth cohort, BCG coverage did not differ significantly between the regions which subsequently became intervention regions compared with the control regions (PR = 1.03 (0.85-1.24)) (data not shown). After implementation of monthly visits, we assessed BCG coverage among a total of 2812 children (Additional file 2). Coverage by 1 month of age was 88% (769/872) in intervention regions and 51% (141/279) in control regions (Figure 2), the PR being 1.74 (1.53-2.00). The 3-months coverage was 99% (769/776) in intervention regions and 85% (304/359) in control regions. By 12 months of age, it had increased to 99% (257/259) in intervention regions and 95% (284/299) in control regions. The potential 1-month coverage if BCG vaccine had been given at first contact with the healthcare system was 93% in intervention regions and 65% in control regions.
Figure 2

Observed BCG coverage by different ages in intervention and control regions. Bandim Health Project, Guinea-Bissau, 2012 cohort.

Factors associated with delayed BCG vaccination in the 2010-birth cohort

A number of factors were associated with being BCG vaccinated by 1 month of age (Table 2). Region of residence was strongly associated; only 25% of children in Oio had received BCG compared with 60% on Bolama. Caretaker’s education was significantly associated with delayed BCG vaccination in both the univariate analysis (OR = 1.15 (1.10-1.20) per year of schooling), and the multivariable analysis (OR = 1.07 (1.02-1.12)). Previous contact with the health system was associated with higher BCG coverage in both the univariate and the multivariable analysis: Children born at health centres or hospitals were more likely to be BCG vaccinated (OR = 1.70 (1.26-2.30) and OR = 2.88 (2.06-4.01), respectively) than children born at home. Also, children of mothers who attended prenatal consultation were more likely to be BCG vaccinated (OR = 1.78 (1.23-2.57). The children born to mothers with better economic status reflected in possession of a latrine and possession of a cell phone had higher coverage; however, other socioeconomic factors were not significantly associated with coverage in the multivariable analysis. Maternal age was not associated with BCG coverage, and finally BCG coverage did not differ significantly for girls compared with boys (OR = 1.19 (0.99-1.43)) (Table 2).
Table 2

Factors associated with BCG vaccination by 1 month of age

 

Total number of children

BCG by 1 month n (%)

OR of BCG vaccination1

Multivariable analysis OR (95%CI)1

P-value for the univariate/multivariable analyses

Gender

    

0.202/0.063

Male

1493

553 (37)

Ref

Ref

 

Female

1491

587 (39)

1.10 (0.95-1.28)

1.19 (0.99-1.43)

 

Age of mother 2

    

0.616/0.662

1.quartile (<21)

763

304 (40)

Ref

Ref

 

2. quartile (21–24)

614

239 (39)

0.96 (0.77-1.21)

1.06 (0.80-1.40)

 

3. quartile (25–30)

825

306 (37)

0.89 (0.71-1.11)

1.08 (0.82-1.43)

 

4. quartile (>30)

745

275 (37)

0.88 (0.71-1.10)

1.18 (0.90-1.55)

 

Education of caretaker 3,4

    

<0.001/0.006

None

1889

627 (33)

1.15 (1.10-1.20)

1.07 (1.02-1.12)

 

1-4 years

648

286 (44)

  

5+ years

347

185 (53)

  

Region 5

    

<0.001/0.007

Oio

416

102 (25)

0.37 (0.21-0.64)

0.39 (0.21-0.73)

 

Biombo

445

183 (41)

0.79 (0.50-1.24)

0.90 (0.60-1.35)

 

Gabu

459

132 (29)

0.45 (0.28-0.75)

0.50 (0.30-0.82)

 

Cacheu

582

274 (47)

Ref

Ref

 

Bafata

370

122 (33)

0.55 (0.31-0.98)

0.49 (0.27-0.89)

 

Quinara

277

143 (52)

1.20 (0.69-2.09)

1.07 (0.61-1.87)

 

Tombali

277

105 (38)

0.69 (0.46-1.03)

0.84 (0.55-1.29)

 

Bubaque

86

36 (42)

0.81 (0.46-1.42)

0.50 (0.24-1.01)

 

Bolama

72

43 (60)

1.67 (0.98-2.84)

0.59 (0.33-1.04)

 

Ethnic group 6

    

<0.001/NA

Balanta

739

265 (36)

1.27 (0.88-1.82)

  

Mandinga/Fula

1116

342 (31)

Ref

  

Manjaco

254

149 (59)

3.21 (1.89-5.44)

  

Pepel

391

151 (39)

1.42 (0.92-2.20)

  

Other

481

231 (48)

2.09 (1.46-2.99)

  

Contact with the health system

     

Birth place 7

    

<0.001/<0.001

At home

1888

576 (31)

Ref

Ref

 

Healthcare centre

527

263 (50)

2.27 (1.68-3.07)

1.70 (1.26-2.30)

 

Hospital

380

228 (60)

3.42 (2.61-4.48)

2.88 (2.06-4.01)

 

Other

29

4 (14)

0.36 (0.13-1.02)

0.43 (0.16-1.18)

 

Prenatal consultations 8

    

<0.001/0.002

Yes

2313

942 (41)

2.88 (2.06-4.02)

1.78 (1.23-2.57)

 

No

301

58 (19)

Ref

Ref

 

Socioeconomics

     

Type of roof 9

    

<0.001/0.324

Straw

1427

482 (34)

Ref

Ref

 

Hard

1522

649 (43)

1.46 (1.17-1.81)

1.13 (0.89-1.43)

 

Toilet 10

    

0.001/0.005

None

903

286 (32)

Ref

Ref

 

Latrine/ toilet in house

2037

839 (41)

1.51 (1.18-1.94)

1.54 (1.14-2.08)

 

Household possessions

     

Cell phone 11

    

<0.001/0.025

Yes

1339

571 (43)

1.41 (1.20-1.64)

1.24 (1.03-1.49)

 

No

1575

545 (35)

Ref

Ref

 

Radio 12

    

0.211/0.192

Yes

2104

825 (39)

1.13 (0.94-1.36)

0.87 (0.71-1.07)

 

No

810

295 (36)

Ref

Ref

 

Generator 13

    

0.025/0.563

Yes

187

88 (47)

1.47 (1.05-2.07)

1.14 (0.73-1.80)

 

No

2753

1036 (38)

Ref

Ref

 

Bandim Health Project, Guinea-Bissau, 2010-birth cohort.

1Standard error adjusted for clustering by robust variance estimates.

2Numbers do not add up due to some not living with their mother.

3Education of caretaker per year’s schooling; linear.

4100 had missing information on years of schooling.

5When including ethnic group rather than region in the final model the estimates changed less than 10% for all parameters assessed.

63 had missing information on ethnic group.

7160 had missing information on place of birth.

8370 had missing information on prenatal consultations.

935 had missing information on type of roof.

1044 had missing information on possession of a latrine.

1170 had missing information on possession of a cell phone.

1270 had missing information on possession of a radio.

1344 had missing information on possession of a generator.

Note: significant (p < 0.05) findings in bold.

The risk factor analysis for BCG coverage by 3, 6, and 12 months identified the same factors but most associations were weaker. Prenatal consultation was significantly associated with BCG coverage at all ages (data not shown).

Factors associated with delayed BCG vaccination after implementation of monthly visits, 2012 cohort

After implementation of monthly visits, factors associated with delayed BCG vaccination were studied among the 2812 children who had a vaccination status assessed by 1, 3, 6, or 12 months of age. In the control regions (n = 1147) the factors strongest associated with being BCG vaccinated by 1 month of age in the 2012 cohort were region, contact with the healthcare system (being born at a hospital; OR = 1.81 (1.20-2.73)), and living in a house with hard roof (OR = 1.74 (1.30-2.32)). Other factors were significantly associated with delayed BCG in the univariate analysis, but not when adjusted for the other factors (Table 3). When the visit frequency was increased to monthly visits (n = 1665) socioeconomic factors and contact with the healthcare system were no longer significantly associated with BCG coverage, only region was significantly associated with BCG coverage in the multivariable analysis (Table 3).
Table 3

Factors associated with BCG vaccination by 1 month of age after implementation of monthly visits in intervention regions

 

Intervention regions

Control regions

 

BCG by 1 month n (%)

OR of early BCG vaccination1

Multivariable analysis OR (95% CI)1

P-value for the univariate/multivariable analyses

BCG by 1 month n (%)

OR of early BCG vaccination1

Multivariable analysis OR (95% CI)1

P-value for the univariate/multivariable analyses

Gender 2

   

0.492 / 0.662

   

0.099/0.070

Male

658 (77)

Ref

Ref

 

284 (50)

Ref

Ref

 

Female

620 (76)

0.93 (0.75-1.15)

1.05 (0.84-1.32)

 

260 (45)

0.82 (0.65-1.04)

0.78 (0.59-1.02)

 

Age of mother 3

   

0.582 / 0.615

   

0.998/0.979

1.quartile (<21)

339 (78)

Ref

Ref

 

125 (47)

Ref

Ref

 

2. quartile (21–26)

244 (78)

1.01 (0.68-1.49)

0.95 (0.59-1.53)

 

113 (47)

1.00 (0.69-1.47)

1.09 (0.69-1.71)

 

3. quartile (27–31)

357 (76)

0.90 (0.64-1.27)

0.86 (0.60-1.25)

 

153 (48)

1.01 (0.71-1.45)

1.03 (0.65-1.63)

 

4. quartile (>31)

335 (75)

0.83 (0.59-1.17)

0.80 (0.53-1.22)

 

153 (48)

1.03 (0.75-1.40)

1.07 (0.72-1.59)

 

Education of caretaker 4, 5

   

0.003 / 0.377

   

0.018/0.771

None

607 (73)

1.08 (1.03-1.14)

1.03 (0.96-1.10)

 

317 (46)

1.07 (1.01-1.13)

0.99 (0.92-1.07)

 

1-4 years

323 (79)

118 (47)

5+ years

270 (83)

84 (59)

Region 6

   

<0.001 / 0.002

   

0.003/0.161

Oio

271 (70)

0.67 (0.46-0.95)

0.70 (0.49-1.02)

 

81 (40)

0.49 (0.31-0.77)

0.67 (0.40-1.09)

 

Biombo

528 (81)

1.21 (0.87-1.68)

1.34 (0.91-1.98)

 

42 (47)

0.67 (0.41-1.11)

0.92 (0.56-1.51)

 

Gabu

 

NA

NA

 

83 (40)

0.50 (0.31-0.82)

0.63 (0.36-1.10)

 

Cacheu

479 (77)

Ref

Ref

 

148 (57)

Ref

Ref

 

Bafata

 

NA

NA

 

42 (39)

0.48 (0.27-0.88)

0.54 (0.30-0.98)

 

Quinara

 

NA

NA

 

112 (57)

1.01 (0.59-1.73)

1.18 (0.68-2.04)

 

Tombali

 

NA

NA

 

24 (37)

0.44 (0.17-1.15)

0.69 (0.26-1.89)

 

Bubaque

 

NA

NA

 

6 (60)

1.13 (0.43-2.95)

1.61 (0.43-6.07)

 

Bolama

 

NA

NA

 

7 (70)

1.75 (0.52-5.94)

1.82 (0.30-10.99)

 

Ethnic group 7

   

0.109 / NA

   

<0.001/NA

Balanta

401 (73)

Ref

  

124 (41)

Ref

  

Mandinga/Fula

194 (76)

1.18 (0.81-1.73)

  

175 (39)

0.92 (0.66-1.28)

  

Manjaco

140 (79)

1.37 (0.79-2.38)

  

64 (67)

2.84 (1.49-5.40)

  

Pepel

426 (81)

1.60 (1.12-2.27)

  

35 (48)

1.31 (0.80-2.13)

  

Other

115 (74)

1.07 (0.66-1.73)

  

147 (63)

2.45 (1.65-3.65)

  

Contact with the health system

        

Birth place 8

   

0.369 / 0.515

   

<0.001/<0.001

At home

793 (76)

Ref

Ref

 

337 (43)

Ref

Ref

 

Healthcare centre

255 (81)

1.38 (0.95-1.99)

1.30 (0.83-2.03)

 

82 (53)

1.48 (1.01-2.16)

1.15 (0.76-1.74)

 

Hospital

192 (78)

1.17 (0.83-1.66)

0.96 (0.64-1.44)

 

106 (62)

2.18 (1.54-3.08)

1.81 (1.20-2.73)

 

Prenatal consultations 9

   

0.410 / 0.504

   

0.057/0.558

Yes

1093 (79)

1.16 (0.81-1.66)

0.86 (0.55-1.34)

 

460 (49)

1.55 (0.99-2.44)

1.20 (0.71-2.05)

 

No

124 (76)

Ref

Ref

 

42 (38)

Ref

Ref

 

Socioeconomics

        

Type of roof 10

   

0.048 / 0.128

   

<0.001/<0.001

Straw

493 (74)

Ref

Ref

 

151 (37)

Ref

Ref

 

Hard

777 (79)

1.35 (1.00-1.83)

1.28 (0.93-1.77)

 

386 (54)

1.97 (1.50-2.58)

1.74 (1.30-2.32)

 

Toilet 11

   

0.039 / 0.188

   

0.136/0.706

None

445 (74)

Ref

Ref

 

100 (44)

Ref

Ref

 

Latrine/ toilet in house

819 (79)

1.32 (1.01-1.73)

1.24 (0.90-1.71)

 

439 (49)

1.23 (0.94-1.62)

0.93 (0.67-1.30)

 

Household possessions

        

Cell phone 12

   

0.011 / 0.136

   

0.009/0.347

Yes

747 (80)

1.38 (1.08-1.78)

1.25 (0.93-1.66)

 

311 (51)

1.39 (1.08-1.79)

1.15 (0.84-1.55)

 

No

501 (74)

Ref

Ref

 

221 (43)

Ref

Ref

 

Radio 13

   

0.183 / 0.303

   

0.159/0.841

Yes

958 (78)

1.21 (0.91-1.59)

1.17 (0.87-1.56)

 

422 (49)

1.24 (0.92-1.67)

1.05 (0.75-1.48)

 

No

295 (74)

Ref

Ref

 

109 (43)

Ref

Ref

 

Generator 14

   

0.020 / 0.083

   

0.234/0.636

Yes

149 (83)

1.51 (1.07-2.13)

1.46 (0.95-2.24)

 

53 (53)

1.27 (0.86-1.87)

0.89 (0.54-1.47)

 

No

1115 (76)

Ref

Ref

 

485 (47)

Ref

Ref

 

Bandim Health Project, Guinea-Bissau, 2012 cohort.

1Standard error adjusted for clustering by robust variance estimates.

21 had missing information on gender.

3Numbers do not add up due to some not living with their mother.

4Education of caretaker per year’s schooling; linear.

5157 had missing information on years of schooling.

6When including ethnic group rather than region in the final model the estimates changed less than 10% for all parameters assessed.

73 had missing information on ethnic group.

856 had missing information on place of birth, 26 were born elsewhere and have been excluded due to small numbers.

9202 had missing information on prenatal consultations.

1033 had missing information on type of roof.

1136 had missing information on possession of a latrine.

1271 had missing information on possession of a cell phone.

1358 had missing information on possession of a radio.

1437 had missing information on possession of a generator.

Note: significant (p < 0.05) findings in bold.

Information about reasons for not being BCG vaccinated

The year following implementation of monthly visits in intervention regions, 1470 interviews were conducted with mothers of BCG unvaccinated children from all regions. Among the mothers 229 (16%) reported to have sought vaccination for their child, 135 (59%) recalled to be told to return another day to get the vaccine, and 76 (33%) had received other vaccines (Additional file 3). Among the 1239 mothers, who reported not to have sought vaccination, 760 (61%) reported that their main reason was lack of money whereas 481 (39%) said that the distance to the vaccination post kept them from seeking vaccination (Additional file 3).

Discussion

Main findings

In 2010, BCG coverage by 1 week of age was only 11% in rural Guinea-Bissau. By 1 month of age the coverage was 38%, increasing to 73% by 3 months of age and 92% by 12 months of age. Contact with the health system was one of the main factors associated with BCG vaccination, but socioeconomic factors also played a role. When monthly visits were introduced in intervention regions and BCG was available for all children the inequity was reduced and the 1-month BCG coverage was 88% compared with 51% in control regions.

Strengths and weaknesses

A major strength of this study is the set-up in the form of the health and demographic surveillance system covering a representative part of the population in rural Guinea-Bissau. Data was collected through frequent home visits by experienced field workers. Weaknesses include that children who died before the assessment age did not enter the coverage analysis; however, children dying before 12 months of age usually do not enter the standard coverage estimation either. Also it should be noted that the vaccination coverage was estimated using slightly different approaches in the 2010-birth cohort and the 2012 cohort. However, we do not directly compare coverage between the cohorts, but only compare coverage between intervention and control regions within the 2012 cohort. Information on reasons for not being vaccinated was collected based on the mothers’ recall.

Consistency with other studies

Vaccination coverage is usually reported by 12 months of age. We found 92% BCG coverage by 12 months in 2010, which corroborates the 94% coverage from 2009 reported by WHO [21]. Others have found that the median vaccination coverage across 31 low- and middle-income countries was 98% and ranged from 56% to 100% [19].

We found a much lower coverage by 1 and 3 months, which concurs with reports of a median coverage across the 31 countries of 65% by age of 4.3 weeks, ranging from 15% to 97% [19]. This supports the need for assessing BCG coverage at earlier ages to disclose the delay in BCG vaccination.

Other studies [2224] defined timely BCG vaccination as vaccinated before 8 weeks of age. The percentage of timely vaccinated children ranged from 69% vaccinated [22] in a large survey in 45 low-income and middle-income countries, to 99% [24] in a study from three areas in South Africa. This still does not fully disclose the poor coverage in the neonatal period, with only 49% coverage by 4 weeks [22], quite similar to the 1-month coverage of 38% in the present study.

We found that giving birth at a hospital or health centre increased the likelihood of being BCG vaccinated. Similarly, a study from South Africa found that birth at a health facility reduced the risk of being unvaccinated by 47% (26%-42%) [24]. In Ethiopia there was also higher BCG coverage for those born at a health facility [25]. In Guinea-Bissau it is not general practice that children born at a hospital or health centre are vaccinated before they leave the health facility, however, they are often told to return to the health centre for vaccination.

It has previously been reported from South Africa [24] and 31 low- and middle-income countries [19] that low socioeconomic status was related to delay in BCG vaccination. We found a similar tendency, especially during the first month of life. Importantly, this inequity in getting BCG vaccinated was no longer apparent when we provided BCG at monthly village visits.

Interpretation and implications

WHO vaccination coverage estimates are reported as the coverage by 12 months of age not taking into account the timeliness of vaccines received. This does not disclose delays in administration of the BCG vaccine. It has been shown that BCG vaccination can reduce neonatal mortality by 48% in LBW children when administered at birth [6]. When donors only ask for BCG coverage by 12 months of age, there is no incentive to provide BCG in the neonatal period. Therefore the 1-month coverage or the median age at vaccination would be better indicators of BCG coverage and its likely effect on child survival.

Obstacles to timely BCG were identified through the interview with mothers of unvaccinated children. Among the mothers having sought vaccination but had not obtained BCG more than half the mothers recalled being told to return another day. We speculate that the restricted vial-opening policy is one of the main obstacles to early BCG vaccination but the information disclosed to the mothers does not allow any final conclusion. Among the mothers who had not sought vaccination not having money and distance to health facility were the main obstacles to taking their child for vaccination. Routine childhood vaccinations are provided free of charge in Guinea-Bissau, but health workers charge fees (~1$) for vaccination cards.

Twenty-five percent of BCG unvaccinated children had been in contact with a health facility by 1 month of age. The potential coverage by 1 month of age was 54% in 2010, if all children had been BCG vaccinated at first contact with the health system. Monthly village visits with BCG vaccination for all children significantly increased BCG vaccination coverage, especially at early ages, and would provide a very efficient tool for increasing especially coverage among the youngest children.

Conclusions

Our study showed a large delay in BCG vaccination in Guinea-Bissau with less than half of the children being BCG vaccinated by 1 month and only 11% being BCG vaccinated by 1 week of age. Our risk factor analysis identified many factors associated with delay of BCG vaccination, including a number of socioeconomic factors, but these factors were no longer associated with delayed BCG vaccination when BCG-vaccination became available to all children at monthly visits.

Abbreviations

BCG: 

Bacillus Calmette-Guérin vaccine

BHP: 

Bandim Health Project

CI: 

Confidence interval

LBW: 

Low-birth-weight

OPV: 

Oral polio vaccine

OR: 

Odds ratio

PR: 

Prevalence ratio

WHO: 

World Health Organization.

Declarations

Acknowledgements

Funding: The study was funded by Aarhus University, Aase og Ejnar Danielsens Fond, Dagmar Marshalls Fond, Direktør Michael Hermann Nielsens Fond, Fonden til lægevidenskabens fremme and European Union FP7 support for OPTIMUNISE (grant: Health-F3-2011-261375). The Bandim Health Project received support from Danish National Research Foundation via support to CVIVA (grant: DNRF108). PA holds a research professorship grant from the Novo Nordisk Foundation, CSB an ERC stating grant (grant: ERC-2009-StG-243149 and ABF a postdoc grant from the Danish Council for Independent Research (DFF – 1333–00192). The funding agencies had no role in the study design, in the data collection, analysis, and interpretation, or in the writing of the report.

Authors’ Affiliations

(1)
Bandim Health Project, INDEPTH network
(2)
Research Center for Vitamins and Vaccines (CVIVA), Statens Serum Intitut
(3)
Institute of Clinical Research, University of Southern Denmark/Odense University Hospital

References

  1. Immunization standards: WHO prequalified vaccines. http://www.who.int/immunization_standards/vaccine_quality/PQ_vaccine_list_en/en/index.html,
  2. Drain PK, Nelson CM, Lloyd JS: Singe-dose versus multi-dose vaccine vials for immunization programmes in developing countries. Bull World Health Organ. 2003, 81 (10): 726-731.PubMedPubMed CentralGoogle Scholar
  3. Hutchins SS, Jansen HA, Robertson SE, Evans P, Kim-Farley RJ: Studies of missed opportunities for immunization in developing and industrialized countries. Bull World Health Organ. 1993, 71 (5): 549-560.PubMedPubMed CentralGoogle Scholar
  4. Immunizations, vaccines and biologicals. Effective Vaccine Management (EVM) initiative. http://www.who.int/immunization/programmes_systems/supply_chain/evm/en/index.html,
  5. Fisker AB, Hornshoj L, Rodrigues A, Balde I, Fernandes M, Benn CS, Aaby P: Effects of the introduction of new vaccines in Guinea-Bissau on vaccine coverage, vaccine timeliness, and child survival: an observational study. Lancet Global Health. 2014, 2 (8): e478-e487. 10.1016/S2214-109X(14)70274-8.View ArticlePubMedGoogle Scholar
  6. Biering-Sorensen S, Aaby P, Napirna BM, Roth A, Ravn H, Rodrigues A, Whittle H, Benn CS: Small randomized trial among low-birth-weight children receiving bacillus Calmette-Guerin vaccination at first health center contact. Pediatr Infect Dis J. 2012, 31 (3): 306-308. 10.1097/INF.0b013e3182458289.View ArticlePubMedGoogle Scholar
  7. Aaby P, Roth A, Ravn H, Napirna BM, Rodrigues A, Lisse IM, Stensballe L, Diness BR, Lausch KR, Lund N, Biering-Sørensen S, Whittle H, Benn CS: Randomized trial of BCG vaccination at birth to low-birth-weight children: beneficial nonspecific effects in the neonatal period?. J Infect Dis. 2011, 204 (2): 245-252. 10.1093/infdis/jir240.View ArticlePubMedGoogle Scholar
  8. Shann F: Commentary: BCG vaccination halves neonatal mortality. Pediatr Infect Dis J. 2012, 31 (3): 308-309. 10.1097/INF.0b013e3182465be8.View ArticlePubMedGoogle Scholar
  9. Roth A, Jensen H, Garly M-L, Djana Q, Martins CL, Sodemann M, Rodrigues A, Aaby P: Low birth weight infants and calmette-guerin bacillus vaccination at birth: community study from Guinea-Bissau. Pediatr Infect Dis J. 2004, 23 (6): 544-550. 10.1097/01.inf.0000129693.81082.a0.View ArticlePubMedGoogle Scholar
  10. Roth A, Sodemann M, Jensen H, Poulsen A, Gustafson P, Weise C, Gomes J, Djana Q, Jakobsen M, Garly ML, Rodrigues A, Aaby P: Tuberculin reaction, BCG scar, and lower female mortality. Epidemiology. 2006, 17 (5): 562-568. 10.1097/01.ede.0000231546.14749.ab.View ArticlePubMedGoogle Scholar
  11. Garly ML, Martins CL, Bale C, Balde MA, Hedegaard KL, Gustafson P, Lisse IM, Whittle HC, Aaby P: BCG scar and positive tuberculin reaction associated with reduced child mortality in West Africa. a non-specific beneficial effect of BCG?. Vaccine. 2003, 21 (21–22): 2782-2790.View ArticlePubMedGoogle Scholar
  12. Velema JP, Alihonou EM, Gandaho T, Hounye FH: Childhood mortality among users and non-users of primary health care in a rural west African community. Int J Epidemiol. 1991, 20 (2): 474-479. 10.1093/ije/20.2.474.View ArticlePubMedGoogle Scholar
  13. Niobey FM, Duchiade MP, Vasconcelos AG, de Carvalho ML, Leal Mdo C, Valente JG: Risk factors for death caused by pneumonia in children younger than 1 year old in a metropolitan region of southeastern Brazil. a case- control study. Rev Saude Publica. 1992, 26 (4): 229-238.View ArticlePubMedGoogle Scholar
  14. Kristensen I, Aaby P, Jensen H: Routine vaccinations and child survival: follow up study in Guinea-Bissau, West Africa. BMJ. 2000, 321 (7274): 1435-1438. 10.1136/bmj.321.7274.1435.View ArticlePubMedPubMed CentralGoogle Scholar
  15. Aaby P, Vessari H, Nielsen J, Maleta K, Benn CS, Jensen H, Ashorn P: Sex differential effects of routine immunizations and childhood survival in rural Malawi. Pediatr Infect Dis J. 2006, 25 (8): 721-727. 10.1097/01.inf.0000227829.64686.ae.View ArticlePubMedGoogle Scholar
  16. Netea MG, Quintin J, van der Meer JW: Trained immunity: a memory for innate host defense. Cell Host Microbe. 2011, 9 (5): 355-361. 10.1016/j.chom.2011.04.006.View ArticlePubMedGoogle Scholar
  17. Kleinnijenhuis J, Quintin J, Preijers F, Joosten LAB, Ifrim DC, Saeed S, Jacobs C, van Loenhout J, de Jong D, Stunnenberg HG, Xavier RJ, van der Meer JW, van Crevel R, Netea MG: Bacille Calmette-Guerin induces NOD2-dependent nonspecific protection from reinfection via epigenetic reprogramming of monocytes. Proc Natl Acad Sci U S A. 2012, 109 (43): 17537-17542. 10.1073/pnas.1202870109.View ArticlePubMedPubMed CentralGoogle Scholar
  18. Lawn JE, Cousens S, Zupan J: 4 million neonatal deaths: when? where? why?. Lancet. 2005, 365: 891-900. 10.1016/S0140-6736(05)71048-5.View ArticlePubMedGoogle Scholar
  19. Akmatov MK, Mikolajczyk RT: Timeliness of childhood vaccinations in 31 low and middle-income countries. J Epidemiol Community Health. 2012, 66 (7): e14-10.1136/jech.2010.124651.View ArticlePubMedGoogle Scholar
  20. Burton A, Monasch R, Lautenbach B, Gacic-Dobo M, Neill M, Karimov R, Wolfson L, Jones G, Birmingham M: WHO and UNICEF estimates of national infant immunization coverage: methods and processes. Bull World Health Organ. 2009, 87 (7): 535-541. 10.2471/BLT.08.053819.View ArticlePubMedPubMed CentralGoogle Scholar
  21. WHO vaccine-preventable diseases: monitoring system. 2013 global summary. http://apps.who.int/immunization_monitoring/globalsummary/countries?countrycriteria%5Bcountry%5D%5B%5D=GNB&commit=OK,
  22. Clark A, Sanderson C: Timing of children’s vaccinations in 45 low-income and middle-income countries: an analysis of survey data. Lancet. 2009, 373 (9674): 1543-1549. 10.1016/S0140-6736(09)60317-2.View ArticlePubMedGoogle Scholar
  23. Fadnes L, Nankabirwa V, Sommerfelt H, Tylleskär T, Tumwine J, Engebretsen I: Is vaccination coverage a good indicator of ageappropriate vaccination? a prospective study from Uganda. Vaccine. 2011, 29 (19): 3564-3570. 10.1016/j.vaccine.2011.02.093.View ArticlePubMedGoogle Scholar
  24. Fadnes LT, Jackson D, Engebretsen IM, Zembe W, Sanders D, Sommerfelt H, Tylleskar T, Group P-ES: Vaccination coverage and timeliness in three South African areas: a prospective study. BMC Public Health. 2011, 11: 404-10.1186/1471-2458-11-404.View ArticlePubMedPubMed CentralGoogle Scholar
  25. Moyer CA, Tadesse L, Fisseha S: The relationship between facility delivery and infant immunization in Ethiopia. Int J Gynecol Obstet. 2013, 123 (3): 217-220. 10.1016/j.ijgo.2013.06.030.View ArticleGoogle Scholar
  26. Pre-publication history

    1. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/14/1037/prepub

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© Thysen et al.; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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