Post 00791e : Other Interventions With Vaccination

POST 00791E : OTHER INTERVENTIONS WITH VACCINATION 21 May 2005 _____________________________________ In the previous posting (Post 00790E), we shared a presentation by Juan Ortiz and Bob Davis on "EPI and Accelerated Child Survival". As Bob had circulated the Lancet article quoted in slide 17 through Tech Updates, I thought it would be good to share it with TechNet members. You will thus find it attached. I do not deny the benefits of anthelminthic treatments, quite the contrary, but I wish to draw your attention to this article. There are millions of article published in the scientific literature every year and one has to be very critical. Unfortunately, this study is seriously flawed. One cannot draw the conclusions as the authors did with such a protocol. When results presented in any research article are so incredible, one has to be suspicious. I also copy below another article that Bob Davis circulated in the Tech Updates, related to the same topic. This is a review article, not the original article. However, I also have some questions because such in the study, the number of 192 women (barely above significance level for studies of common events) seems to be very small to draw any conclusion on a relatively rare event. This may be debatable but I would rely myself on other evidence. The moderator _____________________________________ "Use of anthelminthic drugs during pregnancy," Amer J Obstet Gynecol, 2003, Vol. 188, 5-6 Lorenzo Savioli, MD, DWT Crompton, OBE, and Maria Neira, MD Geneva, Switzerland, and Glasgow, UK The burden of disease that is associated with schistosome and soil-transmitted helminth infections remains a massive health problem in developing countries. Approximately 2 billion people are affected, and approximately 300 million people have severe morbidity. The World Health Organization (WHO) estimated that these infections caused at least 40% of the burden of ill health from tropical diseases, excluding malaria. In 1990, approximately 44 million pregnancies were reckoned to be complicated by hookworm infections. Impaired iron status, iron deficiency anaemia, low birth weight, and neonatal and maternal deaths are some of the outcomes of hookworm infection during pregnancy. Currently, 85% of the 200 million people who are plagued by schistosomiasis live in Africa, where 10 million women annually have the infection during pregnancy. Women in developing countries may be pregnant or lactating for as much as one half of their reproductive lives. Excluding such women from treatment may have the effect of denying them treatment for years. Until recently, their exclusion from treatment against hookworm, schistosome, and other helminth infections resulted from a combination of understandable anxieties that were based on a lack of relevant information and a failure to carry out appropriate risk:benefit analyses about the use of anthelminthic drugs during pregnancy and lactation. Key questions include whether pregnancy outcomes would improve if anthelminthic treatment were to be available for mothers, whether birth defect rates would increase if anthelminthic treatment were to be given during pregnancy, and whether breast-feeding infants could be affected adversely by their mothers having taken anthelminthic drugs. Generally, praziquantel, a WHO-recommended drug, has not been used to treat pregnant and lactating women who were infected with schistosomes. Similarly, adolescent girls have not been treated in case they were pregnant. Health professionals have been reluctant to treat although these blood flukes impair growth and fitness, exacerbate the appearance of iron deficiency and anemia, and in the case of schistosomiasis haematobium, cause genital lesions in about one third of the infected women. Recent evidence suggests that female genital schistosomiasis may facilitate spread of the human immunodeficiency virus. This reluctance stems from the fact that answers to questions, such as those posed earlier, were not available. Praziquantel was released by Bayer AG (Leverkusen, Germany) in 1979 after mandatory toxicologic tests and trials. Despite little reason to indicate any potential adverse effects on pregnancy, praziquantel was not tested on pregnant and lactating women before its release. Accordingly, praziquantel was classified as a pregnancy category B drug, which should be presumed to be safe on the basis of animal studies but should be used with caution during pregnancy. The prescribing advice during lactation was to cease breast-feeding for up to 72 hours after treatment to avoid any possible toxicity to the infant. Such advice was impractical; food cannot be withheld from infants for such a long period. The practice of excluding women (and adolescents) of childbearing age from drug safety trials has led to unwarranted restrictions on the treatment of those women who might be pregnant. Women must be protected from unnecessary exposure to the deleterious effects of chemotherapy, but they should not be denied treatment without sound reason. The situation concerning schistosomiasis, pregnancy, and lactation has now been addressed by a meeting of experts held at the WHO in Geneva in April 2002. After reviewing two decades of clinical experience with praziquatel and examining new data and the results of an extensive risk/benefit analysis, the experts recommended that, in areas where schistosomiasis is endemic, all pregnant and lactating women should be considered as a high-risk group and that treatment should be available for them either individually or during wider campaigns to reduce and control morbidity. In this issue of the American Journal of Obstetrics and Gynecology, Diav-Citrin and colleagues present the results of a prospective study into the use of mebendazole in 192 pregnant women who were infected with Enterobius vermicularis. This is the first report of the use of this drug during pregnancy against an irritating helminthiasis that rarely induces severe morbidity. However, this infection tends to be more troublesome in women and girls with genital complications. In the study, the dosage of mebendazole varied between a single dose of 100mg and a dose of 100mg on each of 3 consecutive days. Many of the women were exposed to the drug during the first trimester. The results revealed no difference in the birth defect rate between the treated group and a matched group who were exposed to nonteratogens. The authors concluded that mebendazole does not represent a major teratogenic risk in humans when it is used as recommended for the treatment of enterobiasis. Mebendazole and albendazole are benzimidazole derivatives and are known to have teratogenic effects in animals when they are given in high doses under experimental conditions. In 1994, a WHO consultation was convened to review the significance of hookworm infection in women and to assess the risks of the use of such drugs to treat hookworm infections during pregnancy. Unlike the other common species of soil-transmitted nematodes, the intensity of hookworm infections tends to rise steadily during the teenage years and then remains steady. Chronic blood loss from the intestinal mucosa caused by the feeding activity of the worms is often a fact of life for people who live where the infections persists. The 1994 consultation recommended that anthelminthic drugs could be used against hookworm infection in pregnant women, although as a general rule treatment should be delayed until after the first trimester. The attendees of both this consultation and the 2002 meeting called for stronger pharmacovigilance and the publication of observations that are relevant to the issue of the use of anthelminthic drugs when necessary during pregnancy. In the case of soil-transmitted nematode infections, the essential drugs are albendazole, levamisole, mebendazole and pyrantel. It should be noted that the recommended treatments involve a single oral dose with a drug that must have been manufactured to the standards of high quality. The implementation of the 1994 consultation recommendation has already had a beneficial impact on the health of some pregnant women. In Sierra Leone, an additive effect was detected when anthelminthic treatment was combined with iron and folate supplements in a study that was designed to reduce the intensity of hookworm infection and to control maternal anaemia during pregnancy. In Sri Lanka, the same combined intervention was linked to improvements in the health of mothers, and a follow-up study of several thousand women found no difference in the birth defect rate between those women who were given anthelminthic drug and those women who were not treated. Recently Bradley and Horton reviewed case histories in which albendazole was prescribed for the treatment of various helminth infections and found no evidence of congenital abnormalities in infants who were born to mothers who had received treatment. The WHO has concluded, through its various consultations and expert committees, that the health benefits that are gained from the treatment of schistosomiasis and soil-transmitted helminthiasis with the WHO-recommended drugs outweigh any risks to a mother or her unborn child or breast-fed infant. Risks will diminish even further if the first trimester can be avoided. New policies have been developed on the basis of the available evidence. These policies should be implemented across all endemic areas; their impact on the health of women and children should be monitored, and the experience that is gained in this way should be made available to public health professionals. ______________________________________________________________________________ Visit the TECHNET21 Website at http://www.technet21.org You will find instructions to subscribe, a direct access to archives, links to reference documents and other features. ______________________________________________________________________________ To UNSUBSCRIBE, send a message to : mailto:[email protected] Leave the subject area BLANK In the message body, write unsubscribe TECHNET21E ______________________________________________________________________________ The World Health Organization and UNICEF support TechNet21. The TechNet21 e-Forum is a communication/information tool for generation of ideas on how to improve immunization services. 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