br In their Comment on
In their Comment on the use of antenatal corticosteroids to reduce preterm infant deaths, Kishwar Azad and Anthony Costello advise “extreme caution” before scale-up in low-income settings. They emphasise maternal sepsis as a concern but cite only one trial in which dexamethasone resulted in a significant increase in fever that required antibiotic treatment compared with controls (relative risk [RR] 2·05, 95% CI 1·14–3·69; 118 women). We suggest that this finding alone does not reflect a balanced assessment of the paucity of evidence available. In a systematic review of antenatal corticosteroid treatment to accelerate fetal lung maturation, only four of 21 randomised controlled trials report on puerperal sepsis outcomes for dexamethasone versus no antenatal corticosteroids and these show moderate heterogeneity ( 38%) (RR 1·74, 95% CI 1·04–2·89; 536 women). Only two trials were in low-income to middle-income countries and had very different results: the Dexiprom trial from South Africa (0·57, 0·17–1·89; 204 women) and one trial from Jordon (4·19, 0·94–18·68; 139 women). Incidence of maternal postnatal fever did not differ in two trials, the US Collaborative trial (0·93, 0·56–1·53; 682 women) and the Dexiprom trial in South Africa (1·00, CI 0·36–2·75; 204 women). Most reassuringly, no significant difference was reported in the incidence of chorioamnionitis in four trials of dexamethasone (1·35, 0·89–2·05; 575 women) or postnatal fever in two trials of dexamethasone (0·94, 0·60–1·47; 886 women). No trials of dexamethasone reported on maternal intrapartum fever when BMS-650032 were given. Trials of betamethasone versus dexamethasone in accelerating fetal lung maturation have not reported on maternal infectious outcomes. We are currently undertaking a large-scale trial to compare the efficacy of intramuscular dexamethasone versus betamethasone in reducing childhood neurosensory disability, with maternal infection as a secondary outcome. Currently, no published data suggest a major risk of maternal infection with the use of antenatal corticosteroids and none are available to allow confident assertion that dexamethasone increases the risk. According to present recommendations, the major safety concern surrounding the use of antenatal corticosteroids is repeat doses.
In response to the promising results of a single dose of liposomal amphotericin B (AmBisome) to treat visceral leishmaniasis in Bangladesh, Nilima Kshirsagar (April issue), suggests that an alternative form—Fungisome—might soon qualify for similar use and application. AmBisome was the first formulation of amphotericin B that maximised efficacy in visceral leishmaniasis while minimising toxic effects. Fungisome is the brand name of a liposomal amphotericin B product developed in Kshirsagar\'s own laboratory and marketed by LifeCare Innovations. It cannot be considered a generic of AmBisome because the liposomal compositions are not comparable. To transform multilamellar vesicles into small unilamellar vesicles, Fungisome requires sonication for 45 min before administration, which is technically very challenging in programmatic settings for visceral leishmaniasis. Moreover, published evidence on the efficacy and safety of Fungisome in visceral leishmaniasis, either in single-dose or multidose regimens, is very limited. The phase 2–3 clinical trials that Kshirsagar mentions were actually in fungal infections. An ongoing is assessing single-dose Fungisome for visceral leishmaniasis in India. Beyond Fungisome, other products could be considered as generics of liposomal amphotericin B. Bioequivalence to AmBisome has to be established then through adapted processes. Before any generic product can be used for visceral leishmaniasis, liposomal amphotericin B suppliers should submit their products to the WHO Prequalification Programme, the remit of which has been expanded to liposomal amphotericin B, to determine which medicines are quality-assured and bioequivalent to AmBisome. This is the only safeguard to avoid exposing visceral leishmaniasis patients to products with an unassessed safety and efficacy profile.