Natural protection
The World Health Organization estimates that last year 570 000 children across the globe were infected with HIV. Over 90 per cent of them were born to HIV-positive women and acquired the virus either at birth or through their mother’s breast milk, and almost 90 per cent of these cases occurred in sub-Saharan Africa - amounting to some 450 000 cases of mother-to-child transmission of HIV in the region. This huge problem is the focus of research being carried out by scientists at the Trust-funded (see box below) in the Hlabisa District of KwaZulu-Natal in South Africa.
The problem of mother-to-child transmission during delivery has largely been alleviated by the introduction of cheap antiretrovirals. A course of Nevirapine costs under £3, and one dose each given to both the mother and child has reduced infection through exposure at birth by 50 per cent. "It is a morning-after intervention," explains the Africa Centre’s Professor Hoosen Mohamed Coovadia. Transmission through breast-feeding is more problematic, however: "The single most important question in developing countries is how do we resolve the problem of breast-feeding transmission, because there is no study which shows that this has been adequately addressed," says Professor Coovadia.
In the West the answer has been simple: HIV-infected women are advised to avoid breast-feeding altogether, and on the whole, thanks to the availability of good-quality formula foods, that is what they have done. But as Professor Coovadia points out, in developing countries this is simply not an option. "For very many reasons, either through lack of freedom to choose or cultural factors or cost, the majority of women in Africa - even after testing and counselling about the benefits and dangers of their feeding choice, which is either breast-feeding or formula feeding - still choose breast-feeding."
Clearly, telling women in these countries not to breast-feed is not an answer. Instead, says Professor Coovadia, "in the same way that we advise the practice of safe sex, we must encourage women in developing countries to practise safe breast-feeding - and this means finding ways of making breast-feeding safe."
Various ideas for safe breast-feeding have been put forward, none of which has yet been proven. However, a chance observation made by researchers at the Africa Centre may point to a possible solution. "If women gave breast milk only and nothing else - no other contaminants in food or water - then the transmission was not dissimilar to that seen in women given formula," says Professor Coovadia. This finding suggests that exclusively breast-feeding carries no greater risk of transmission than not breast-feeding at all - indicating that the greatest risk of transmission occurs when breast-milk is supplemented with formula food (mixed breast-feeding).
The explanation may lie in the fact that much of the food and water in developing countries contains microbial contaminants that may damage the baby’s bowel. Therefore, if breast-feeding is mixed with formula feeding, the HIV in breast milk - which on its own appears to contain protective factors that prevent the virus infecting the baby - could breach the damaged gut and enter the baby’s system.
If this observation is tested in a scientific study of a suitable size and proved to be correct, it would point to a natural, effective and cost-free intervention against mother-to-child transmission: to encourage women to breast-feed, exclusively without supplementing breast milk with other foods or water. "We now have to take the observation we have made, which would have a major public health policy impact if it turns out to be right, and prove it once and for all or disprove it once and for all," says Professor Coovadia.
Testing the theory
The hypothesis will be put to the test in a three-year study to be conducted in the Hlabisa Health District. Preliminary work has already started and researchers hope to enrol patients into the main study by October. "Six thousand women will be screened for participation, approximately 2000 of whom will be HIV positive and the study will focus on these," explains Michael Bennish, Director of the Africa Centre.
In fact the size of the cohort will enable researchers to address a whole range of problems, including the growth and development of infants, and the impact of other infections on their development, but the issue of transmission of HIV during breast-feeding will take priority. "The first issue that we’ll be addressing in this cohort is whether HIV is transmitted in breast milk, whether exclusively breast-feeding is less dangerous than mixed breast-feeding, or carries no danger at all," says Dr Bennish.
The Africa Centre has decided against conducting a randomised controlled trial to test this hypothesis. "Breast-feeding is a deeply rooted cultural practice," asserts Professor Coovadia. "And in an environment like Africa, where HIV is prevalent, any deviation from a deeply rooted cultural practice will always be hazardous, because people will immediately suspect that the woman has something wrong with her, and that something wrong could well be HIV, and she could then be subjected to stigma, discrimination, expulsion, even murder. In that context, to imagine you will be able to randomise women to formula feeding or breast-feeding is unrealistic."
Instead, the women in the study will all be encouraged to breast-feed exclusively. "We will follow them up very closely to see if they do indeed follow that advice and, if they don’t, what happens to the vertical transmission when they cease to exclusively breast-feed," says Professor Coovadia. "So at the end of the day we’ll have vertical transmission rates in women who have exclusively breast-fed for varying periods of time - and for when those practices were stopped and women used mixed breast-feeding."
By comparing these groups, the researchers hope to be able to come to a firm conclusion about the safety and efficacy of exclusively breast-feeding as an intervention against mother-to-child transmission of HIV. "The answers that we will hopefully be able to arrive at have important implications throughout Africa and other areas where HIV infection is common," says Dr Bennish.
Professor Coovadia agrees. "I think it will have tremendous impact, especially in Africa and Asia, where breast-feeding practices are almost universal to start with." He points out that the intervention would also tie in perfectly with maternal and child health promotion programmes throughout the world. "The encouragement to breast-feed exclusively is one of the major components of these health promotion programmes. It’s a fundamental good."
In addition to the many advantages of exclusively breast-feeding - its cultural appropriateness, simplicity and well-documented health benefits - another major plus is the fact that breast milk is, of course, free. "There couldn’t be a more exquisite intervention because it costs nothing and because the option is to otherwise give formula - and formula costs money," asserts Professor Coovadia. He adds that in South Africa, the cost of formula food would be a major obstacle in a mother-to-child transmission prevention programme that advocated the avoidance of breast-feeding as an option, instead of exclusively breast-feeding. "So we are going to save millions of rands and we will be providing a wonderfully natural alternative to the option of formula feeding or feeding food," says Professor Coovadia. "So it’s got a symmetry in it which is very attractive."
See also
- T-cell tango: Article outlining the understanding of the host’s immune response to HIV
- A Moving target: Article describing HIV heterogeneity and vaccine development
- AIDS and Auntie Stella: Article describing HIV and sex education programmes in Zimbabwe
- The generation gap: Article describing HIV and AIDS over the past twenty years
External links
Further reading
Professor Hoosen Mohamed Coovadia
Dilraj A, Cutts F T, de Castro J F, Wheeler J G, Brown D, Roth C, Coovadia H M, Bennett J V (2000). Response to different measles vaccine strains given by aerosol and subcutaneous routes to schoolchildren: a randomised trial. Lancet. 355(9206): 798-803.
Coutsoudis A, Pillay K, Spooner E, Kuhn L, Coovadia H M (1999). Influence of infant-feeding patterns on early mother-to-child transmission of HIV-1 in Durban, South Africa: a prospective cohort study. South African Vitamin A Study Group. Lancet. 354(9177): 471-6.
Coovadia H M, Jeena P, Wilkinson D (1998). Childhood human immunodeficiency virus and tuberculosis co-infections: reconciling conflicting data. [Review] [60 refs] International Journal of Tuberculosis & Lung Disease. 2(10): 844-51.
Jeena P M, Coovadia H M, Hadley L G, Wiersma R, Grant H, Chrystal V (2000). Lymph node biopsies in HIV-infected and non-infected children with persistent lung disease. International Journal of Tuberculosis & Lung Disease. 4(2): 139-46.
Coovadia H M (1999). Sanctions and the struggle for health in South Africa. American Journal of Public Health. 89(10): 1505-8.
Bobat R, Coovadia H, Moodley D, Coutsoudis A (1999). Mortality in a cohort of children born to HIV-1 infected women from Durban, South Africa. South African Medical Journal. 89(6): 646-8.
Bhimma R, Coovadia H M, Kramvis A, Adhikari M, Kew M C, Connolly C A (1999). HBV and proteinuria in relatives and contacts of children with hepatitis B virus-associated membranous nephropathy. Kidney International. 55(6): 2440-9.
Taylor M, Coovadia H M, Kvalsvig J D, Jinabhai C C, Reddy P (1999). Helminth control as an entry point for health-promoting schools in KwaZulu-Natal. South African Medical Journal. 89(3): 273-9.
Dilraj A, Cutts F T, Bennett J V, Coovadia H M (1999). Adverse reactions possibly associated with the use of Emla cream. South African Medical Journal. 89(4): 419-20.
Jeena P M, Wesley A G, Coovadia H M (1999). Admission patterns and outcomes in a paediatric intensive care unit in South Africa over a 25-year period (1971-1995). Intensive Care Medicine. 25(1): 88-94.
Bobat R, Coovadia H, Coutsoudis A, Moodley D, Gouws E (1999). Neonatal characteristics and outcome in a cohort of infants born to HIV-1-infected African women from Durban, South Africa. JAIDS: Journal of Acquired Immune Deficiency Syndromes. 20(4): 408-9.
Wilkinson D, Karim S S, Coovadia H M (1999). Short course antiretroviral regimens to reduce maternal transmission of HIV. BMJ. 318(7182): 479-80.
Coutsoudis A, Pillay K, Spooner E, Kuhn L, Coovadia H M (1999). Randomized trial testing the effect of vitamin A supplementation on pregnancy outcomes and early mother-to-child HIV-1 transmission in Durban, South Africa. South African Vitamin A Study Group. AIDS. 13(12): 1517-24.
Bobat R, Moodley D, Coutsoudis A, Coovadia H, Gouws E (1998). The early natural history of vertically transmitted HIV-1 infection in African children from Durban, South Africa. Annals of Tropical Paediatrics. 18(3): 187-96.
Topley J M, Bamber S, Coovadia H M, Corr P D (1998). Tuberculous meningitis and co-infection with HIV. Annals of Tropical Paediatrics. 18(4): 261-6.
Bhimma R, Coovadia H M, Adhikari M (1998). Hepatitis B virus-associated nephropathy in black South African children. Pediatric Nephrology. 12(6): 479-84.
Moodley J, Moodley D, Pillay K, Coovadia H, Saba J, van Leeuwen R, Goodwin C, Harrigan P R, Moore K H, Stone C, Plumb R, Johnson M A (1998). Pharmacokinetics and antiretroviral activity of lamivudine alone or when coadministered with zidovudine in human immunodeficiency virus type 1-infected pregnant women and their offspring. Journal of Infectious Diseases. 178(5): 1327-33.
Jeena P M, Coovadia H M, Thula S A, Blythe D, Buckels N J, Chetty R. Persistent and chronic lung disease in HIV-1 infected and uninfected African children. AIDS. 12(10): 1185-93.
Jeena P M, Wesley A G, Coovadia H M (1998). Infectious diseases at the paediatric isolation units of Clairwood and King Edward VIII Hospitals, Durban. Trends in admission and mortality rates (1985-1996) and the early impact of HIV (1994-1996). South African Medical Journal. 88(7): 867-72.
Pillay K, Coovadia H M (1998). Should South Africa be preparing for interventions to reduce mother-to-infant transmission of HIV-1? South African Medical Journal. 88(4): 434-6.
Moodley D, Moodley J, Coovadia H M (1998). Preventing perinatal HIV transmission in developing countries - do we know enough? South African Medical Journal. 88(4): 431-2.
Dr Michael Bennish
Engels E A, Bennish M L. Falagas M E, Lau J (2000). Typhoid fever vaccines. Vaccine. 18(15): 1433-4.
Salam M A, Khan W A, Dhar U, Ronan A, Rollins N C, Bennish M L (1999). Vitamin A for treating shigellosis. Study did not prove benefit. BMJ. 318 (7188): 939-40.
Bennish M L (1999). Animals, humans, and antibiotics: implications of the veterinary use of antibiotics on human health. Advances in Pediatric Infectious Diseases. 14: 269-90.
Khan W A, Dhar U, Salam M A, Griffiths J K, Rand W, Bennish M L (1999). Central nervous system manifestations of childhood shigellosis: prevalence, risk factors, and outcome. Pediatrics. 103(2): E18.
Salam M A, Dhar U, Khan W A, Bennish M L (1998). Randomized comparison of ciprofloxacin suspension and pivmecillinam for childhood shigellosis. Lancet. 352(9127): 522-7.
Engels E A, Falagas M E, Lau J, Bennish M L (1998). Typhoid fever vaccines: a meta-analysis of studies on efficacy and toxicity. BMJ. 316(7125): 110-6.
Khan W A. Seas C. Dhar U. Salam M A. Bennish M L (1997). Treatment of shigellosis: V. Comparison of azithromycin and ciprofloxacin. A double-blind, randomized, controlled trial. Annals of Internal Medicine. 126(9): 697-703.
Ronan A, Azad A K, Rahman O, Phillips R E, Bennish M L (1997). Hyperglycemia during childhood diarrhoea. Journal of Pediatrics. 130(1): 45-51.