Leishmaniosis – new perspectives on an underappreciated opportunistic infection

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Visceral leishmaniosis (VL) is an important opportunistic infection in patients with advanced HIV infection living in France, Italy, Spain, and Portugal. More than 500 cases of HIV-associated VL have been reported from these countries [1]. Currently almost 50% of all adult cases of VL in Spain are HIV associated, making VL the third most common opportunistic infection (OI) in some areas of Spain and Portugal [2]. Our understanding regarding the complex interaction between both pathogens, however, is regrettably incomplete. Part of the problem is that despite good arguments to the contrary VL [3] is not an AIDS-defining OI according to the Center for Disease Control - World Health Organization classification. Moreover, most available data were generated in retrospective case series and prospective studies of the interaction between leishmaniosis and HIV are lacking.
In this issue Kubar et al. present an interesting study of a French cohort of patients co-infected with Leishmania infantum and HIV [4]. They use serological markers to distinguish between primary and reactivated VI and compare the evolution of CD4 cell counts between both groups.
Whereas asymptomatic VL has previously been reported in HIV-infected individuals [5,6] the ratio between latent/subclinical infection overt disease has never been established in HIV-infected patients. The ratio of 10 : 1 reported by the authors is remarkably close to ratios that have been reported for immuno-competent persons in endemic areas such as Brazil [7] and Kenya [8]. This ratio, on the other hand, is several magnitudes higher than ratios that have been documented for immunocompetent patients in France [4].
This important finding obviously has implications for the management of HIV-infected patients living in or visiting areas endemic for leishmaniosis where sero-prevalence rates range from 2 to 17%.
The authors also provide evidence that AIDS patients with Vl may still be capable of maintaining or even generating a specific antibody to leishmanial antigens. In contrast to these results most previous studies had failed to detect an adequate humoral response in most of their dually infected patients [1,9–12]. How to explain this discrepancy?
The authors, acknowledged experts in the study of the pathophysiology and diagnosis of leishmaniosis, cite the use of different antibody assays as the most likely reason for their intriguing findings. While I believe this is indeed the most likely reason, it should be acknowledged that there is another possible explanation for the surprisingly high seropositivity rate among their AIDS patients with overt VL. It cannot be excluded with certainty that Kubar's group may have missed some patients with subclinical VL who never generated a specific humoral response. In order to study the true sensitivity of this assay in HIV-infected patients routine bone marrow cytology or examination of a buffy coat specimen would have had to be performed on seronegative patients.
Another potential problem will prove more difficult to resolve. The authors definition of latent leishmaniosis is entirely based on the performance of their serological assay, namely the presence of 14- and/or 18-lDa bands on Western blotting. The Western blot used by the authors has been extensively validated in immunocompetent hosts and in that setting probably represents one of the most reliable serological test systems available. It remains to be shown, however, that results indicative of past infection in immunocompetent patients (i.e. a single band in the Western blot) have the same relevance in HIV-seropositive patients. The consistency of the serological findings over time seem to indicate that the serological diagnosis of latent leishmaniosis is probably also valid in HIV-infected patients. This important observation, however, should be corroborated by other investigators and longer observation periods.
An important limitation relates to the timing of the study.
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