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Incomplete development and persistence.In productive chlamydial infection, a cell infected by a chlamydial elementary body (EB), produces lots more infectious EBs through the normal developmental cycle. The fact that infectious EBs can frequently be recovered from patients, plus the direct observation of EBs in clinical specimens, suggests that productive chlamydial infection is the norm. However Moulder and his colleagues showed that, in chlamydial infected cells which had been maintained in the laboratory over many weeks, there was a great variation in the amount and type of chlamydial infection. Sometimes, virtually all the cells were productively infected, with lots of inclusions [lay reader: vacuoles containing chlamydiae] evident, eventually killing the host cells. However, if the surviving cells were permitted to multiply in culture, eventually there was very little evidence of infection. That many of these cells were infected, however, was shown by the fact that if they continued to be cultured over weeks, a whole new round of productive infection occurred [1]. Electron microscopy studies showed that, in the intervening period when many of the cells appeared not to be infected, there were sometimes chlamydiae present. However, these chlamydiae consisted of structurally abnormal reticulate bodies (RBs). Effectively, the growth cycle was halted prior to the conversion of RBs to infectious EBs. As RBs are normally non-infectious, how then is infection maintained? It seems likely that the aberrant chlamydiae can be transferred to new host cells at cell division [2]. Indeed, cell to cell transfer of C. pneumoniae and C. trachomatis infection has been maintained for two and three years respectively [3,4]. Factors subsequently found to favour incomplete, persistent chlamydial infection in laboratory culture included: treatment with penicillin (an antibiotic not normally used for chlamydial infection); the depletion of host cell tryptophan (an amino acid essential for the production of chlamydial proteins); and the action of gamma interferon, one of the key factors in immunity to chlamydial infection. Comment: It has to be remembered that these observations are from highly artificial laboratory model systems. Their clinical relevance is discussed later. Nevertheless, there are three important concepts which arise:
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What do we mean by persistence?
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