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Although flucytosine is a key component of WHO-recommended induction treatment for HIV-associated cryptococcal meningitis, this antifungal agent is not widely available in low-income and middle-income countries due to limited production and cost. In 2018, a national flucytosine access programme was initiated in South Africa. We aimed to determine the effectiveness of flucytosine-containing induction regimens in routine care to motivate for the urgent registration of flucytosine and its inclusion in treatment guidelines.In this cross-sectional study, we compared outcomes of adults aged 18 years and older with incident laboratory-confirmed cryptococcal meningitis treated with or without flucytosine-containing regimens at 19 sentinel hospitals in South Africa. A case of cryptococcosis was defined as illness in an adult with: (1) positive cerebrospinal fluid (CSF) India ink microscopy; (2) a positive CSF cryptococcal antigen test; or (3) culture of Cryptococcus neoformans or Cryptococcus gattii from CSF or any other specimen. We excluded patients without a case report form, those with an unknown or negative HIV serology result, those with a recurrent episode, and those who did not receive antifungal treatment in hospital. We assessed cumulative in-hospital mortality at 14 days and 30 days and calculated the overall crude in-hospital case-fatality ratio. We used random-effects logistic regression to examine the association between treatment group and in-hospital mortality.From July 1, 2018, to March 31, 2020, 10 668 individuals were diagnosed with laboratory-confirmed cryptococcal meningitis, 7787 cases diagnosed at non-enhanced surveillance sites and 567 cases from eight enhanced surveillance sites with no access to flucytosine were excluded. Of 2314 adults with a first episode of cryptococcosis diagnosed at 19 facilities with access to flucytosine, 1996 had a case report form and of these, 1539 received induction antifungal treatment and were confirmed HIV-seropositive first-episode cases. Of 1539 patients who received antifungal therapy, 596 (38·7%) individuals received a flucytosine-containing regimen and 943 (61·3%) received another regimen. The median age was 36 years (IQR 32-43) and 906 (58·9%) participants were male and 633 (41·1%) were female. The crude in-hospital case-fatality ratio was 23·9% (95% CI 20·0-27·0; 143 of 596) in those treated with flucytosine-containing regimens and 37·2% (95% CI 34·0-40·0; 351 of 943) in those treated with other regimens. Patients admitted to non-academic hospitals (adjusted odds ratio [aOR] 1·95 [95% CI 1·53-2·48]; p0·0001) and those who were antiretroviral treatment-experienced (aOR 1·30 [1·02-1·67]; p=0·033) were more likely to receive flucytosine. After adjusting for relevant confounders, flucytosine treatment was associated with a 53% reduction in mortality (aOR 0·47 [95% CI 0·35-0·64]; p0·0001). Among survivors, the median length of hospital admission in the flucytosine group was 11 days (IQR 8-15) versus 17 days (13-21) in the comparison group (p=0·0010).In-hospital mortality among patients treated with a flucytosine-containing regimen was comparable to reduced mortality reported in patients receiving a flucytosine-containing regimen in a recent multicentre African clinical trial. Flucytosine-based treatment can be delivered in routine care in a middle-income country with a substantial survival benefit.National Institute for Communicable Diseases, a Division of the National Health Laboratory Service.For the Zulu translation of the abstract see Supplementary Materials section.

Most writers on Vico have concentrated their efforts on his important final work, La scienza nuova, to the exclusion of his earlier writings; yet, within these works — which include an autobiography, orations, an unfinished book on the wisdom of the ancient Italians, a book on law, and the first two editions of La scienza nuova itself — Vico addressed the fundamental issues of imagination and history. Many crucial insights regarding these and other issues raised there do not reappear in his later works. Consequently a fully-rounded understanding of Vico’s thought is not possible without consulting the 1699–1730 works. The autobiography gives the most detailed description we have of Vico’s life and intellectual development. De nostri studiorum ratione and De antiquissima sapientia italorum are much undervalued as sources of Vico’s growing preoccupation with imagination in particular, and it is in Il diritto universale and the first two editions of La scienza nuova that Vico expressed his ideas on social groups and human history in the most sophisticated form. Thus this chapter is designed to- introduce these important works, which will form an integral part of the analysis of Vico’s thought in later chapters.

Vico was not concerned with poetry as either art or literature; rather it was man’s innate desire to create representations of the past which was his primary consideration. Neither did poetry in Vico’s thought have anything to do with the products of sensitive, perceptive or refined imaginations, nor was it the work of individuals.1 Vico showed no interest in the great artistic traditions which often accompany extravagant and decadent civilizations. His emphasis was always on the spontaneous creations of social groups rather than well-planned individual works of great genius. He did not discuss la questione della lingua (the question of language), which runs throughout the history of Italian culture and concerns the variety of language most appropriate for literary use.2 For Vico early poetry was produced by necessity, not for pleasure. Croce was absolutely correct; it is necessary to understand Vico’s idea of poetry if one wishes to comprehend La scienza nuova.3

Vico wrote three versions of his last work, La scienza nuova, all of which were published in Naples in 1725, in 1730 and in 1744, the year of his death.1 With very few exceptions, it has been the final version which has been considered the definitive edition, to the exclusion not only of the two previous editions but also of all of Vico’s other writings. Only in this century has this overemphasis been somewhat rectified in the Italian-speaking world by research on Vico’s early works, especially in their specific Neapolitan or Italian cultural contexts,2 and in addition, more recently, by the 1981 publication by Lessico Intellettuale Europeo of a concordance of the 1725 edition3 (with concordances of the rest of his works to follow shortly) and the release in 1987 by the Centro di Studi Vichiani of the orations as the first volume of the long-awaited scholarly edition of Vico.4

Virtually all recent work on Vico is based on the premise that there was an epistemological break in his thought in 1710, at which point he became suddenly and dramatically anti-Cartesian.1 One reason for this is that most previous studies have restricted themselves to an analysis of the third and final version of Vico’s best known work, La scienza nuova (1744). Little effort has been made to trace the development of his ideas not only in the important first (1725) and almost unknown second (1730) editions of La scienza nuova, but also throughout his autobiographical and earlier theoretical writings. The exception to this practice is the attention given to De antiquissima italorum sapientia, the publication of which in 1710 is held to mark his supposed intellectual conversion. Quite to the contrary, however, it can be argued that no such major shift in his thought occurred at any point. Yet this is not to deny Vico’s anti-Cartesian stance. The year 1710 was not a dramatic turning point in Vico’s intellectual development; rather, it was the year that he wrote the first of his works which was to receive significant attention.

One can hardly fail to notice in Vico’s writings the quite amazing jumble of ideas and terms. The danger when one is presented with such an inchoate mixture of the startlingly new and the prosaic is to read into it an interpretation which is not dissimilar to that held before reading Vico. But even if Vico’s lack of precise terminology is to be greatly regretted, the continuation of such an approach would be intolerable. There is no doubt this has hindered a proper understanding of the Vichian view of fantasia, for much of the confusion regarding Vico’s views on this pivotal issue is because it has been relegated to a subordinate position, as simply the means of creating mythology and early poetry. Thus the only hope of understanding the profound implications of Vico’s discussion of fantasia is to begin by dividing into categories the three main ways in which he used this not uncommon term.