Maternal HIV and malaria infection during pregnancy reduces tetanus antibody levels in newborns and mothers thereby exposing them to an increased risk of tetanus, according to the findings of a study published in the August 15th edition of the Journal of Infectious Diseases.
According to the paper and an accompanying editorial, the control of these diseases in child-bearing women have an important role to play in the elimination of maternal and neonatal tetanus which causes 213,000 deaths annually. About 85 % of the mortality is in newborns and 7-14 % is in women during the early period after birth.
Clostridium tetani produces a toxin, tetanospasmin, which causes the characteristic muscle spasms of tetanus. Maternal tetanus is caused by the introduction of C. tetani spores during unclean delivery or abortion while neonatal tetanus results from the use of unclean instruments to cut the umblical cord or inappropriate cord care.
The eradication of tetanus is not feasible because of the unique biology of C. tetani; it is found in the intestines of animals throughout the world and its spores are viable for long periods in soil and dust.
Public health efforts are therefore aimed at the reduction of newborn tetanus to less than 1 case/1000 live births per district through improved cleanliness during childbirth, proper cord care, and tetanus toxoid (TT) vaccination of child-bearing women. Newborns are protected against tetanus through placentally acquired maternal neutralizing antibodies against tetanospasmin.
Many countries in Africa and South-east Asia have co-endemic malaria and HIV-1. However, there is conflicting evidence about the impact of HIV and malaria on immunisation programs in these countries. A team of British and Kenyan researchers re-examined this issue by studying the effect of maternal malaria and HIV infection on placental transfer of tetanus antibodies in a rural Kenyan population.
The study population was women delivering between January 1996 and July 1997 at the Maternity Department of Kilifi District Hospital. On admission, peripheral blood was obtained for the determination of the HIV and malaria infection status. After delivery, cord blood and placental blood and biopsy were collected. Placental biopsy samples were classified as active acute, active chronic, past, or negative malarial infections, respectively, according to pre-defined criteria.
A standard questionnaire was administered to collect demographic and socioeconomic data, pregnancy history, and a history of TT vaccination which was confirmed from antenatal clinic records. Tetanus antitoxin antibody levels were measured using an enzyme-linked immunoadsorbent assay (ELISA) which provided antibody concentrations in IU/ml. Seronegative individuals were those with an antibody level of less than 0.1 IU/ml.
A total of 704 paired maternal-cord serum samples of women with a confirmed history of TT vaccination were tested for tetanus antibodies. The geometric mean titer (GMT) for seropositive women was 4.23 while in seronegative women it was 0.04. Of the 704 women, 12 % were HIV positive, 44 % had placental malaria, and 7 % had both malaria and HIV.
Thirty seven women (5.3 %) and 55 newborns (7.8%) were seronegative for tetanus antibodies. The seronegative women tended to be younger, primigravid, and had not received TT vaccination during the index pregnancy. Of the 37 babies born to seronegative mothers, 35 (94.5 %) were seronegative. The remaining 20 seronegative infants were born to tetanus seropositive mothers who had a low median tetanus antibody titre and were younger, primigravid, and had HIV or placental malaria.
Tetanus antibody levels were significantly reduced by 36 and 41% in women with active chronic or past placental malaria, respectively. Antibody levels were 38 % lower in HIV-infected than HIV-uninfected women (P = 0.009) and 33 % lower in those who had both HIV and malaria. Multivariate analyses confirmed that HIV and placental malaria reduced newborn tetanus antibody levels. Malnutrition, pre-term delivery, parity, and the type of housing for mothers also had an impact on newborn tetanus antibody levels.
Placental transfer of maternal antibodies was assessed by calculating the ratio of cord and maternal tetanus antibody levels (CMR). CMR was 30 % lower in unvaccinated than in vaccinated women. HIV infection, active chronic and past placental malaria were associated with a 22, 17, and 11 % reduction, respectively, in CMR.
These findings confirm that malaria and HIV infections may hinder efforts to eliminate maternal and neonatal tetanus. However, the high seropositivity in women who received the TT vaccine during the index pregnancy confirms the usefulness of vaccination in women of childbearing age in areas with co-endemic HIV and malaria.
The policy implication is that provision of ART to HIV-infected women, malaria prevention during pregnancy using intermittent presumptive treatment and insecticide-impregnated bednets in malaria-prone areas, provision of additional doses of TT during childhood, and the promotion of neonatal health and clean deliveries are strategies that would collectively contribute to the elimination of maternal and neonatal tetanus, say the authors of this paper and the editorial.
Cumberland P et al. Maternal HIV infection and placental malaria reduce transplacental antibody transfer and tetanus antibody levels in new borns in Kenya. J. Infect. Dis 196:550-557,2007.
Moss WJ and Halsey NA. The effects of maternal malaria and HIV-1 infection on the effort to eliminate neonatal tetanus. J. Infect. Dis 196:502-504,2007.