New Approaches to Prevent Mother-to-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 (%)

Timing No Breastfeeding

Breastfeeding through 6 months

Breastfeeding through 18-24

months

During pregnancy 5 to 10 5 to 10 5 to 10

During labour 10 to 20 10 to 20 10 to 20

Through breastfeeding

Early (first 2 months) 2 to 10 2 to 10

Late (after 2 months) 1 to 5 5 to 10

Overall 15 to 30 25 to 35 30 to 45

(source: DeCock, KM, et al., 2000)

OTHER MTCT CONCERNS

• Risk increased /w mixed feeding (Coutsoudis et al., 2001)

• Risk decreased with perinatal antivirals

• Formula-feeding reduced postnatal transmission by 40%, yet no ⁂ in mortality between breast and formula (Nduati et al., 2000)

• 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 BreastmilkSecretory 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 factorPromotes 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 HIV-influenced 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 complements C3, C4

Several forms of casein and lactotransferrin

Summary of NAF Proteomic Analysis: Milk or Immune

Proteins • Albumin

• a-1-Antichymotrypsin

• a-1-Antitrypsin

• a-, b-, k-Casein

• Coagulation factor II

• Complement C3

• Complement C4

• Complement C7

• Complement factor B

• Complement factor D

• Ferroxidase (ceruloplasmin)

Summary of NAF Proteomic Analysis: Milk or Immune

Proteins • Fibrinogen gamma-B

chain

• Haptoglobin

• Ig alpha chain (heavy)

• Ig gamma chain (heavy)

• Ig kappa chain (light)

• Ig lambda chain (light)

• a-Lactalbumin

• Lactoferrin

• b-2-microglobulin, pI 5.3

• Polymeric-immunoglobulin receptor

• 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 AIDS-impacted 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