HIV-Infected or -Exposed Children Exhibit Lower Immunogenicity to Hepatitis B Vaccine in Yaoundé, Cameroon: An Appeal for Revised Policies in Tropical Settings?

Abstract

BackgroundSince 2005, anti-hepatitis B virus (anti-HBV) vaccine is part of the Expanded Program on Immunization (EPI) for infants born in Cameroon, with 99% anti-HBV coverage. In a context of generalized HIV epidemiology, we assessed paediatric anti-HBV vaccine response according to HIV status, feeding option and age in a tropical context.MethodologyProspective, observational and cross-sectional study conducted among 82 children (27 [IQR: 9–47] months, min-max: 6–59), after complete anti-HBV vaccination (Zilbrix Hepta: 10μg AgHBs) at the Essos Health Centre in Yaounde, Cameroon, classified as group-A: HIV unexposed (28), group-B: HIV-exposed/uninfected (29), group-C: HIV-infected (25). Quantitative anti-HBs ELISA was interpreted as “no”, “low-” or “protective-response” with <1, 1–10, or ≥10 IU/L respectively; with p-value<0.05 considered significant.ResultsChildren were all HBV-unexposed (AcHBc-negative) and uninfected (HBsAg-negative). Response to anti-HBV vaccine was 80.49% (66/82), with only 45.12% (37/82) developed a protective-response (≥10IU/L). According to HIV status, 60.71% (17/28) developed a protective-response in group-A, vs. 51.72% (15/29) and 20% (5/25) in group-B and group-C respectively, Odds Ratio (OR): 2.627 [CI95% 0.933–7.500], p = 0.041. According to feeding option during first six months of life, 47.67% (21/45) developed a protective-response on exclusive breastfeeding vs. 43.24% (16/37) on mixed or formula feeding, OR: 1.148 [CI95% 0.437–3.026], p = 0.757. According to age, protective-response decreased significantly as children grow older: 58.33% (28/48) <24 months vs. 26.47% (9/34) ≥24 months, OR: 3.889 [CI95% 1.362–11.356], p = 0.004; and specifically 67.65% (23/34) ≤6 months vs. 0%, (0/5) 33–41 months, p = 0.008.ConclusionsAnti-HBV vaccine provides low rate of protection (<50%) among children in general, and particularly if HIV-exposed, infected and/or older children. Implementing policies for early vaccination, specific immunization algorithm for HIV-exposed/infected children, and monitoring vaccine response would ensure effective protection in tropical settings, pending extensive/confirmatory investigations.

Antibody response to hepatitis B vaccine in HIV‐exposed infants in Malawi and correlation with HBV infection acquisition

“…We observed a strong antibody response to HBV vaccine in HIV‐exposed infants, with more than 90% with protective levels at 6 months (approximately 1 month post‐final vaccination) in line with the data obtained by Li et al in China and by others in sub‐Saharan Africa . Controversial results had been previously reported for HIV‐exposed infants: some have found a lower response, while other did not find significant differences in the immune response in comparison with HIV‐unexposed infants. In the study by Ndlend et al conducted in Cameroon 60% of HIV‐unexposed infants had anti‐HBs protective levels, compared to a proportion of 37% of HIV‐exposed (among them 20% were HIV‐positive) who had protective levels.…”

“…In agreement with others our data show that HIV‐exposure does not seem to have a major impact on the development of the immune response to HBV vaccine. However, it has to be underlined that anti‐HBs titers (and proportion with protective levels) significantly decreased at 12 months and further at 24 months, as reported by others, but differently from what reported for healthy adults who, 20 years after vaccination, had anti‐HBs antibodies >10 mIU/mL in more than 90% of the cases . We observed a diminished response in HIV‐infected children (as reported by others) although the numbers were too small in our cohort to draw definitive conclusions The only other significant factor associated to HBV immune response was male sex.…”

“…However, it has to be underlined that anti‐HBs titers (and proportion with protective levels) significantly decreased at 12 months and further at 24 months, as reported by others, but differently from what reported for healthy adults who, 20 years after vaccination, had anti‐HBs antibodies >10 mIU/mL in more than 90% of the cases . We observed a diminished response in HIV‐infected children (as reported by others) although the numbers were too small in our cohort to draw definitive conclusions The only other significant factor associated to HBV immune response was male sex. The impact of sex on the immune response is unclear with some studies including ours reporting a lower response for males and othersshowing no effect, indicating that larger studies are probably needed to assess the significance of this finding.…”

“…Controversial results had been previously reported for HIV‐exposed infants: some have found a lower response, while other did not find significant differences in the immune response in comparison with HIV‐unexposed infants. In the study by Ndlend et al conducted in Cameroon 60% of HIV‐unexposed infants had anti‐HBs protective levels, compared to a proportion of 37% of HIV‐exposed (among them 20% were HIV‐positive) who had protective levels. However, the main limitation for the study was the very small sample size since it was conducted on only 82 children.…”

“…However, limited information is available on the proportion of infants who have an adequate response to the vaccine and reach anti‐HBs levels which are considered protective . This is particularly important for infants born to HIV‐positive mothers in whom a decreased response could be observed and in whom HBV transmission may more frequently occur due to high HBV‐DNA levels in co‐infected mothers . Maternal HBV co‐infection could also be potentially associated with a lower response to HBV vaccine since maternal specific antibody can interfere with the infant's own response to vaccination …”