Correspondence

Miltefosine for Indian Visceral Leishmaniasis

N Engl J Med 2003; 348:857-858February 27, 2003

Article

To the Editor:

The study by Sundar et al. (Nov. 28 issue)1 regarding oral miltefosine for the treatment of Indian visceral leishmaniasis is very promising. However, the reason for excluding from the study patients with a platelet count below 50,000 per cubic millimeter or coinfection with the human immunodeficiency virus (HIV) is not clear. Thrombocytopenia is very common among patients with Indian visceral leishmaniasis, and coinfection with HIV and the parasite that causes visceral leishmaniasis is an emerging problem. The authors also fail to report any complications related to the use of a splenic aspirate for diagnosis and follow-up. Hemorrhage is a not infrequent complication of splenic aspiration.

Pradeep K. Agarwal, M.D.
West Jefferson Medical Center, Marrero, LA 70072

1 References

1. 1

   Sundar S, Jha TK, Thakur CP, et al. Oral miltefosine for Indian visceral leishmaniasis. N Engl J Med 2002;347:1739-1746
   Full Text | Web of Science | Medline

To the Editor:

Because of the risk of bleeding, splenic aspiration is considered by some clinicians an unsafe diagnostic procedure, and a bone marrow aspirate is commonly used for the diagnosis of leishmaniasis.1 Could Sundar et al. explain the technique used for splenic aspiration in their study (e.g., whether an intercostal or abdominal route was used, whether ultrasonography was used for guidance, and the gauge of needle chosen)? A report of possible complications, if any, would also be relevant.

In addition, Sundar et al. do not explain why they chose a ratio of 3:1 for the assignment of patients to miltefosine or amphotericin treatment. With a 1:1 ratio, they would have needed fewer patients to achieve identical power to detect differences between the groups, with a substantial reduction in cost.

Bernardino Roca, M.D., Ph.D.
Hospital General, 12004 Castellon, Spain
brocav@meditex.es

1 References

1. 1

   Sinha R, Datta U, Sehgal S. Importance of bone marrow culture for diagnosis of Kala azar. Scand J Infect Dis 1993;25:787-789
   CrossRef | Web of Science | Medline

Author/Editor Response

We appreciate the interest of Agarwal and Roca. Patients with a low platelet count were excluded to protect against possible complications of splenic aspiration. Visceral leishmaniasis in HIV-infected patients characteristically relapses — hence the exclusion of HIV-infected patients. We are considering combination therapy for such patients.

The most common complication of splenic aspiration is slight hemorrhage, with or without local peritonitis; it occurs approximately once per 500 to 700 patients but did not occur in our 400-patient study. Deaths are rare, occurring at a rate of 2 per 9612 aspiration procedures.1 However, skin infections can occur if conditions are not aseptic.

The usual route for splenic aspiration in an enlarged spleen is abdominal. The patient's spleen is identified by palpation, and the patient is instructed in how to hold his or her breath. After the skin has been pierced with a 21-gauge, 37-mm needle attached to a 10-ml syringe, the patient is asked to hold his or her breath. Suction of 2 to 3 ml is created in the syringe, which is then pushed into and pulled out of the spleen while the suction is maintained. Pressure is applied externally over the area to prevent oozing. The small amount of splenic material obtained is placed on a glass slide, from which smears are made and which are cultured if needed. In the less common situation in which the spleen is only slightly enlarged, it is located by percussion, and then splenic aspiration is performed over that area intercostally.

We chose a 3:1 ratio of miltefosine-treated patients to amphotericin-treated patients because the larger number of miltefosine-treated patients would better establish a safety profile for this novel agent.

Shyam Sundar, M.D.
Banares Hindu University, Varanasi, India

Jonathan Berman, M.D., Ph.D.
National Center for Complementary and Alternative Medicine, Bethesda, MD 20892
bermanjo@mail.nih.gov

1 References

1. 1

   Sundar S, Rai M. Laboratory diagnosis of visceral leishmaniasis. Clin Diagn Lab Immunol 2002;9:951-958
   Medline

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