in the decrease of white cells is statistically significant (p ,0.001); this points to leucopenia as an important side effectof combination therapy.
Francesca Russo, M.D.Marco Bacosi, M.D.
Lucia Miglioresi, M.B.Bs.Giovanni L. Ricci, M.D., Ph.D.
Gastroenterology UnitDepartment of Clinical Sciences
Univ. La SapienzaRome, Italy
1. Davis GL, Esteban-Mur R, Rustgi V, et al. Interferon alfa-2balone or in combination with ribavirin for the treatment ofrelapse of chronic hepatitis C. N Engl J Med 1998;339:14939.
2. Brillanti S, Migliolo M, Barbara L. Combination antiviral therapywith ribavirin and interferon a in interferon a relapsers and non-responders: Italian experience. J Hepatol 1995;23(suppl 2):136.
3. Kakumu S, Yoshioka K, Wakita T, et al. A pilot study ofribavirin and interferon b for the treatment of chronic hepatitisC. Gastroenterology 1993;105:50712.
4. Scotto G, Fazio V, Tantimonaco G. Pilot study of a short courseof ribavirin and alfa interferon in the treatment of chronic activehepatitis C not responding to alfa interferon alone. Ital J Gas-troenterol 1996;28:50511.
Reprint requests and correspondence: Giovanni L. Ricci, M.D.,Ph.D., Gastroenterology Unit, Department of Clinical Sciences,Policlinico, 00161 Rome, Italy.
Received Nov. 17, 1999; accepted Nov. 30, 1999.
Re: Drug-Resistant FalciparumMalaria With Bowel SymptomsTO THE EDITOR: I wish to bring to the notice of thereaders of your esteemed journal the following clinicopath-ological experience, which deserves attention for the bettermanagement of cases of drug-resistant falciparum malariawith bowel symptoms.
A 22-yr-old man developed intermittent fever of 5 daysduration with peripheral blood smear positivity for plasmo-dium falciparum. Culture for Salmonella typhi was negative;Widal test and HIV were also negative. The patient wasstarted on chloroquine and symptomatic therapy. The fever,as high as 103F before institution of therapy, decreased to100F. CBC was noncharacteristic; but blood smear wasstill positive for falciparum rings on day 8. On day 8, hedeveloped clinical features of acute abdomen, and an emer-gent exploratory laparotomy was performed because of sus-picion of bowel perforation. Because of concern that thismay represent undiagnosed typhoid fever (endemic in thisregion), intravenous ciprofloxacin was started, along withgentamicin and metronidazole. Exploratory laparotomy re-vealed two discrete punched-out perforations of 1.5 cm and
1.0 cm in the last 6 inches of terminal ileum, close to theantimesenteric border, with markedly congested smallbowel and enlarged, congested mesenteric nodes. Histopa-thology of the sites of perforations showed neutrophils andmacrophage response with vascular congestion and serosi-tis. Lymph nodes showed marked congestion and areas ofinfarction also. Despite the continuation of broad spectrumantibiotics including ciprofloxacin, the patient developedrecurrent features of acute abdomen on the second postop-erative day. The fever (100F) continued to persist.
A repeat blood smear revealed persisting parasite in theblood. Based on the suspicion that this represented chloro-quine-resistant falciparum malaria, a decision was made togive quinine 600 mg i.v. every 8 h instead of chloroquine.Dramatically, from the next morning onwards the patientwas afebrile, and abdominal complaints also regressed com-pletely, without necessitating further surgery. The patient wasdischarged on day 14, afebrile and with normal wound healing.
Gastrointestinal ischemia is a known problem with falci-parum malaria. However, small bowel perforation due tofalciparum malaria infection has not been reported in theliterature. This patient did not respond to antityphoid med-ications or chloroquine. Dramatic clinical improvement wasnoted with the institution of quinine. Subsequently, twoother patients with an identical presentation were treatedsuccessfully with quinine, with minimal morbidity at ourinstitution.
It is our impression that drug-resistant strains of falcipa-rum malaria produce accelerated or aggressive ischemicchanges of organs and, in particular, the gastrointestinaltract, because of microvascular occlusion, by the parasitizedand nonparasitized RBC causing a local hyperviscosity ofmicrovasculature that can lead to frank perforation insteadof an ischemic ooze. Molecular biological events incited bythe drug-resistant forms of falciparum deserve study ingreater detail apart from the already known role of ICAM-1,CD 36, and thrombospondin receptors, red cell rosette for-mation, and vasculo-occulsion.
CH.V. Ramana Murty, M.D.Y.V.S. Prabhakar, M.D.Guntur Medical College
Guntur, IndiaV. Bala Bhaskara Rao, M.S.
Guntur, IndiaSreenivasa S. Jonnalagadda, M.D.
Division of GastroenterologyWashington University School of Medicine
St. Louis, Missouri
Reprint requests and correspondence: CH.V. Ramana Murty,M.D., Professor of Pathology, Guntur Medical College, House No.6, Pragati Apartments, 5/2 Chandramouli Nagar, Guntur, AndhraPradesh, India 522007.
Received Nov. 23, 1999; accepted Nov. 30, 1999.
1101AJG April, 2000 Letters to the Editor