Treatment of young patients with lupus nephritis using calcineurin inhibitors

Recent advances in the management of lupus nephritis, together with earlier renal biopsy and selective use of aggressive immunosuppressive therapy, have contribut-ed to a favorable outcome in children and adolescents with systemic lupus erythematosus （SLE）. Neverthe-less, we believe that a more effective and less toxic treatment is needed to attain an optimal control of the activity of lupus nephritis. Recent published papers and our experiences regarding treatment of young patients with lupus nephritis using calcineurin inhibitors are re-viewed. Although it has been reported that intermittent monthly pulses of intravenous cyclophosphamide （IVCY） are effective for preserving renal function in adult pa-tients, CPA is a potent immunosuppressive agent thatinduces severe toxicity, including myelo- and gonadal toxicity, and increases the risk of secondary malig-nancy. Thus, treatment for controlling lupus nephritis activity, especially in children and adolescents, remains challenging. Cyclosporine A （CsA） and tacrolimus （Tac） are T-cell-specific calcineurin inhibitors that prevent the activation of helper T cells, thereby inhibiting thetranscription of the early activation genes of interleu-kin （IL）-2 and suppressing T cell-induced activation of tumor necrosis factor-α, IL-1β and IL-6. Therefore, both drugs, which we believe may be less cytotoxic, are attractive therapeutic options for young patients with lupus nephritis. Recently, a multidrug regimen of prednisolone （PDN）, Tac, and mycophenolate mofetile （MMF） has been found effective and relatively safe in adult lupus nephritis. Since the mechanisms of action of MMF and Tac are probably complementary, multidrug therapy for lupus nephritis may be useful. We propose as an alternative to IVCY, a multidrug therapy with mizoribine, which acts very similarly to MMF, and Tac, which has a different mode of action, combined with PDN for pediatric-onset lupus nephritis. We also believe that a multidrug therapy including CsA and Tac may bean attractive option for young patients with SLE and lupus nephritis

Current challenges in treatment options for visceral leishmaniasis in India: a public health perspective

Visceral leishmaniasis(VL)is a serious parasitic disease causing considerable mortality and major disability in the Indian subcontinent.It is most neglected tropical disease,particularly in terms of new drug development for the lack of financial returns.An elimination campaign has been running in India since 2005 that aim to reduce the incidence of VL to below 1 per 10,000 people at sub-district level.One of the major components in this endeavor is reducing transmission through early case detection followed by complete treatment.Substantial progress has been made during the recent years in the area of VL treatment,and the VL elimination initiatives have already saved many lives by deploying them effectively in the endemic areas.However,many challenges remain to be overcome including availability of drugs,cost of treatment(drugs and hospitalization),efficacy,adverse effects,and growing parasite resistance.Therefore,better emphasis on implementation research is urgently needed to determine how best to deliver existing interventions with available anti-leishmanial drugs.It is essential that the new treatment options become truly accessible,not simply available in endemic areas so that they may promote healing and save lives.In this review,we highlight the recent advancement and challenges in current treatment options for VL in disease endemic area,and discuss the possible strategies to improve the therapeutic outcome.