IPV in Moderate to Severe Chronic Malnourished 9-12 Month Old Children in Karachi.
Condition: Immunity to Polio Vaccines in Malnourished Infants; Immunity to Polio Vaccines in Non-malnourished Infants
MeSH terms: Poliomyelitis; Malnutrition
Study type: Interventional
Phase: Phase 4

Summary: 
      Chronic malnutrition is associated with lack of effective gut immunity which is a possible
      explanation for why we see polio cases among a proportion of children who have received 7 or
      more doses of OPV.Our proposed idea is to evaluate if IPV antigen given later in life may act
      together to boost humoral and mucosal immunity in children belonging to low-income background
      in Karachi who have moderate to severe chronic malnutrition (height for age Z score less than
      -2SD). We also intend to compare eIPV + OPV with OPV only in non-malnourished infants at 9
      -12 month of age. Thus, the proposed study is a combination of two trials, with study
      population stratified by nutritional status, each with a reference arm (bOPV) and an
      experimental arm (bOPV plus IPV).
    

Detailed description: 
      The development of chronic malnutrition is a complex interplay of multiple factors; including
      genetic predisposition and a whole host of environmental insults. In the urban squatter and
      peri-urban settlement environments of Karachi where the Aga Khan University (AKU) has
      established surveillance programs, half of all infants have moderate to severe chronic
      malnutrition (height for age Z score less than -2 SD) by the time they are 9 -12 months old.
      IPV has the advantage of parenteral route, thereby bypassing the damaged gut mucosa of
      malnourished children. It also does not cause the rare vaccine-associated paralysis. Its
      effectiveness depends on stimulation of serum (blood) neutralizing antibodies that block the
      spread of poliovirus to the central nervous system. The main disadvantages that have
      precluded IPV use in low-income countries is high cost, difficulty in adding another
      injectable vaccine in the EPI schedule at 6, 10, and 14 weeks, and lack of ability to induce
      a strong mucosal immune response and therefore prevent enteral infection. Additionally,
      maternal antibodies at this early age neutralize IPV quite effectively. However, as the
      median age of polio in Pakistan is 15 months for poliovirus type 1 and 18 months for
      poliovirus type 3, it may be feasible to give a single IPV dose at an older age, avoiding the
      effects of maternal antibodies and boosting immunity against polio before the majority of
      these children enter their risk period in Pakistan. Enhanced potency IPV (eIPV) with higher
      antigen content yields greater than 90% seropositivity against all 3 types after one dose and
      100% seropositivity after two doses. Thus using eIPV combined with OPV at 9 - 12 months in
      moderate to severe chronically malnourished infants may provide improved seroconversion as
      well as some stimulation of the mucosal immune response. Our proposed idea is to evaluate if
      IPV antigen given later in life may act together to boost humoral and mucosal immunity in
      children belonging to low-income background in Karachi who have moderate to severe chronic
      malnutrition (height for age Z score less than -2SD). We also intend to compare eIPV + OPV
      with OPV only in non-malnourished infants at 9 -12 month of age. Thus, the proposed study is
      a combination of two trials, with study population stratified by nutritional status, each
      with a reference arm (bOPV) and an experimental arm (bOPV plus IPV).
    

Intervention name(s): Injectable polio vaccine and Bivalent oral polio vaccine
Intervention type(s): Biological
Intervention description(s): One dose of IPV given IM (arm, thigh) to infant aged 9-12 month after randomization.
There will be two groups Chronic Malnourished group and Non-Malnourished group. Each group has two arms, which were randomized on IPV+bOPV and bOPOV alone
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: poliomyelitis; oral polio vaccine; OPV; seroconversion; mucosal immunity; malnutrition; IPV; Inactivated polio vaccine; Pakistan