in the decrease of white cells is statistically significant (p
,0.001); this points to leucopenia as an important side effectof
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
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
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
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
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
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
Guntur, IndiaV. Bala Bhaskara Rao, M.S.
Guntur, IndiaSreenivasa S. Jonnalagadda, M.D.
Division of GastroenterologyWashington University School of
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
Received Nov. 23, 1999; accepted Nov. 30, 1999.
1101AJG April, 2000 Letters to the Editor