Abstract
In the wake of the HIV epidemic, visceral leishmaniasis (VL), a disseminated protozoan infection caused by the Leishmania donovani complex, has been re-emerging, particularly in North Ethiopia where up to 40% of patients with VL are co-infected with HIV. Management of VL in HIV co-infection is complicated by increased drug toxicity, and high treatment failure and relapse rates with all currently available drugs, despite initiation of antiretroviral treatment. Tackling L. donovani infection before disease onset would thus be a logical approach. A screen-and-treat approach targeting latent or the early stage of infection has successfully been implemented in other HIV-associated opportunistic infections. While conceptually attractive in the context of VL–HIV, the basic understanding and evidence underpinning such an approach is currently lacking. Prospective cohort studies will have to be conducted to quantify the risk of VL in different risk groups and across CD4 cell count levels. This will allow developing clinical prognostic tools, integrating clinical, HIV and Leishmania infection markers. Interventional studies will be needed to evaluate prophylactic or pre-emptive treatment strategies for those at risk, ideally relying on an oral (combination) regimen. Issues like tolerability, emergence of resistance and drug interactions will require due attention. The need for maintenance therapy will have to be assessed. Based on the risk–benefit data, VL risk cut-offs will have to be identified to target treatment to those most likely to benefit. Such a strategy should be complemented with early initiation of antiretroviral treatment and other strategies to prevent HIV and Leishmania infection.
Highlights
Population to be screened and aim of the strategyScreen-and-treat strategy for cryptococcal infection (WHO rapid advice 2010) [12]
Whereas HIV has contributed to the re-emergence of Visceral leishmaniasis (VL) in Europe in the 90s, the problem of VL–HIV co-infection is especially marked in some regions of Ethiopia, where up to 40% of patients with VL are co-infected with HIV [9]
It is clear that once VL is established in HIV-infected individuals—meaning that L. donovani infection has evolved to the disease stage—prognosis at the individual level is dire, despite initiation of antiretroviral treatment (ART) [2]
Summary
Screen-and-treat strategy for cryptococcal infection (WHO rapid advice 2010) [12]. Asymptomatic ARV naıve HIV-infected individuals with baseline CD4 counts ,100 cells/mL before ART initiation. Latex agglutination test for cryptococcal antigen in serum: technically demanding; cost: 717 USD/test. Fluconazole 800 mg/d for 8 weeks followed by fluconazole 200 mg/d until CD4 counts .200 cells/mL. Active cryptococcal infection to prevent progression to overt cryptococcal disease; (meningitis is associated with high mortality). Prototype dipstick developed (point of care): for serum/urine: cost: 2.5 USD/test. HIV-infected individuals, irrespective of ART use, with active tuberculosis (TB) ruled out Tuberculosis skin test. Isoniazid prophylactic treatment (IPT) 300 mg/d for 6 months; Longer duration if high TB transmission: effect weans off after IPT interruption
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