Download Feasibility of Grandmother Surrogate Lactation to Prevent

New Approaches to Prevent Motherto-Child Transmission of HIV in Kenya
RESEARCH TEAM
• Chandice Covington,PhD,RN
• Mohamed Abdullah, MD
• Richard Zangar PhD
• Lynne McEnroe,MA,MSN,RN
Estimated risk & timing of mother-to-child transmission of HIV
Transmission rate (%)
No
Breastfeeding
Breastfeeding
through 6
months
Breastfeeding
through 18-24
months
5 to 10
5 to 10
5 to 10
10 to 20
10 to 20
10 to 20
Early (first 2 months)
2 to 10
2 to 10
Late (after 2 months)
1 to 5
5 to 10
25 to 35
30 to 45
Timing
During pregnancy
During labour
Through breastfeeding
Overall
(source: DeCock, KM, et al., 2000)
15 to 30
OTHER MTCT CONCERNS
• Risk increased
/w
•
mixed feeding
(Coutsoudis et al., 2001)
(Nduati et al., 2000)
• Risk decreased
with perinatal
antivirals
Formula-feeding reduced
postnatal transmission by
40%, yet no ⁂ in mortality
between breast and formula
•
About 50% infants who
acquire HIV succumb in the
first 18 months of life
LONG TERM CONSEQUENCES
•
Life expectancy for
Japan = 77 years for
women, sub-Saharan
Africa it is 32 years
•
Over 1-million children
orphaned in Kenya by
AIDS, in Africa > than
12,000,000
LONGER TERM CONSEQUENCES
•
Youth are our future
•
Along with parents,
loss of teachers and
nurses—social carriers.
•
Novel approaches
needed to reduce this
loss of life and our
future
WHO RECOMENDS EXCLUSIVE
BREASTFEEDING
DEFENSIVE CELLS IN BREASTMILK
COMPONENT
ACTION
B Lymphocytes
Give rise to antibodies targeted against specific
microbes.
Macrophages
Kill microbes outright in the baby's gut, produce
lysozyme and activate other components of the
immune system.
Neutrophils
May act as phagocytes, injecting bacteria in baby's
digestive system.
T lymphocytes
Kill infected cells directly or send out chemical
messages to mobilize other defenses. Proliferate in
the presence of organisms that cause serious infant
illness. Also manufacture compounds that can
strengthen child's immune response.
Molecules in Breastmilk
Secretory IgA class
Bind to microbes in infant digestive tract, prevent
from passing through gut walls into body's tissues.
B12 binding protein
Reduces amount of vitamin B-2, which bacteria need
in order to grow.
Bifidus factor
Promotes growth of Lactobacillus bifidus bacterium in
gut., helps to crowd out dangerous varieties.
Fatty acids
Disrupt membranes surrounding some viruses and
destroy them.
Fibronectin
Increases antimicrobial activity of macrophages; helps
to repair tissues that have been damaged by immune
reactions in baby's gut.
PURPOSE
• Surrogate nursing is a tradition across cultures
• Grandmother/elder relatives appreciate low rates
of HIV infection & function as extended family
caregivers
• Examine the feasibility of grandmother-aged
women’s nipple aspirate fluid (NAF) as a
replacement or supplemental feeding for HIVinfluenced neonates
SURROGATE DEFINED
•
Non-puerperal not so novel:
200,000 years old; Margaret
Mead 1950s, Slome1 described
GM in 1956.
•
Slome, Cecil (1956).
Nonpuerperal lactation in
grandmothers. Journal of
Pediatrics, 49(5), 550-552.
•
The process of re-lactation or
induced for the purpose of
feeding a related or non-related
child.
Grandmother ~ age 50. Natal, South Africa ~ 1956.
SETTING AND SAMPLE
• Clinics attended by 60 women (N=48)
• Villages coastal Kenya (Vipingo & Rabai)
• Weaned* women ≥ 35 -70 years (*) of age
• Not pregnant or hypertensive, no “wasting” disease symptoms
(n=12)
• Youthful multiparity & extensive lactation histories, some
previous surrogate nursing
PROCEDURES
• Clinic notices; 10 miles
• Informed consent, pregnancy
test, interview, venipuncture,
anthropometrics, breast
examination, non-invasive,
patented aspirator system
• Incentives: Dry milk, maize,
“Beads for Life”, cloth
ASSAYS (Proteomics)
• Mass spectrometric analysis of peptides
(Thermofinnigan LCQ Deca) with pooled NAF
• Identification parent proteins (Sequest
analysis software)
• Minimum 3 separate peptide matches (Sequest
Xcorr values > 1.5 (1/3 e > 2.0) to confirm the
presence of the parent protein in NAF
RESULTS
•Quantity of NAF range <10 µl to >250 µl. *
•Proteomic analysis: Most abundant proteins
 Immunoglobins, accounting
for ~40% of the
total protein content
 Immune
 Several
complements C3, C4
forms of casein and lactotransferrin
Summary of NAF Proteomic Analysis:
Milk or Immune Proteins
• Albumin
• Complement C3
• a-1Antichymotrypsin
• Complement C4
• a-1-Antitrypsin
• Complement factor B
• a-, b-, k-Casein
• Complement factor D
• Coagulation factor
II
• Ferroxidase
(ceruloplasmin)
• Complement C7
Summary of NAF Proteomic Analysis:
Milk or Immune Proteins
• Fibrinogen gamma-B chain
• Lactoferrin
• Haptoglobin
• b-2-microglobulin, pI 5.3
• Ig alpha chain (heavy)
• Polymericimmunoglobulin receptor
• Ig gamma chain (heavy)
• Ig kappa chain (light)
• Ig lambda chain (light)
• a-Lactalbumin
• Prolactin-induced
protein
• Transferrin
Grandmother Hypothesis: Re-visited
• The data support that
grandmothers may serve a
"evolutionary loophole"
function to circumvent
disasters
• Maternal-child morbidity
& mortality in AIDSimpacted populations is a
disaster
OBSTACLES/CONCERNS
•Availability of female relative caretaker
(GM currently feeding grandchildren)
•Competing infections: e.g. malaria,
tuberculosis, hookworm, parasites,
hepatitis
•Health problems of elder women: e.g.
nutrition, anemia, osteoporosis,
hypertension
OBSTACLES/CONCERNS
•New HIV infection in surrogate
•Risk of reverse transmission HIV infection
to women low but potentially possible
•Stigma
Next Step: Test Feasibilty in Community
• Community Acceptability
• Potential for elder women
to re-lactate &
functionality of immune
proteins
• Risk/Cost-benefit model
for infant, mother,
surrogate, family,
community