Abstract:
Malaria is one of the most important infectious diseases with high morbidity rates particularly in young children and in pregnant women in Sub-Saharan Africa. Intermittent preventive treatment in pregnancy (IPTp) is an effective way to reduce morbidity of malaria in pregnancy and to reduce neonatal morbidity. Sulphadoxine/pyrimethamine (SP) is the recommended drug for IPTp in sub-Saharan Africa. Because of increasing resistance against SP there is a need to develop alternative drugs to replace SP for IPTp. Among the most promising candidate drugs in clinical development are mefloquine and azithromycin. Besides their antimalarial activity, these antimalarial drugs show significant antibacterial activity when given as IPTp. This antibacterial activity may offer several additional public health benefits when used as IPTp in pregnant women. These drugs may– besides protecting from malaria in pregnancy - treat and prevent often undetected sexually transmitted diseases (STDs) and urinary tract infections (UTIs).
In this thesis, three studies are presented focusing on infectious diseases highly prevalent in sub-Saharan Africa. In the first study, the activity of mefloquine and azithromycin was assessed in vitro in comparison to sulphadoxine-pyrimethamine against bacterial pathogens with clinical importance in pregnancy. Results of this study demonstrated that SP was highly active against Staphylococcus aureus and Streptococcus pneumoniae. All tested Gram-positive bacteria, except Enterococcus faecalis, were sensitive to azithromycin. Additionally, azithromycin was active against Neisseria gonorrhoeae. Mefloquine showed good activity against pneumococci but lower in vitro activity against all other tested pathogens. These data indicate that the use of azithromycin may be associated with most collateral benefit in curing and preventing concomitant bacterial infections.
In the second study the impact of routine IPTp with mefloquine (MQ) and SP on Streptococcus agalactiae (GBS) was evaluated. GBS is an important cause of early neonatal infections leading to considerable morbidity and mortality. In this nested randomized controlled clinical trial GBS colonization rates in pregnant women were assessed. The overall prevalence of recto-vaginal GBS colonization was comparable to published findings in industrialized countries. Demographic characteristics showed significant association between GBS colonization and literacy. No difference of maternal GBS colonization was observed between SP- and MQ-IPTp regimes. This finding indicates that SP-IPTp was not superior to MQ-IPTp in preventing GBS colonization in pregnant women in Gabon.
In another analysis of the above described IPTp study, the prevalence of human herpes virus 8 (HHV-8) infections was assessed in Gabon. HHV-8 infection is associated with Karposi-sarcoma, Castleman disease and other malignant conditions and is known to be highly prevalent in Central Africa. In this sero-epidemiological study it was shown that 39% of pregnant women were seropositive for HHV-8 infections. Among 35% of seropositive women, real time PCR showed one pregnant women with detectable viraemia in peripheral blood. In analysis of cord blood samples of sero-positive women, no vertical transmission of HHV-8 was observed.
Finally, a pharmacokinetic analysis of albendazole for the treatment of extra-hepatic echinococcosis is presented. Echinococcosis is highly prevalent in sub-Saharan Africa and medical treatment is one option in resource limited settings. Here the ability of albendazole and its active metabolite albendazole sulphoxide to penetrate into Echinococcus granulosus cysts of patients with non-liver cysts was investigated. Analysis of two patients with lung and soft tissue cysts demonstrated a satisfactory penetration of albendazole sulphoxide into Echinococcus cysts. These data underline the usefulness of albendazole therapy in extra-hepatic cystic echinococcosis.
Malaria in pregnancy
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