[DU-WATCH] Baghdad Boil festers as new enemy of G.I.s

1. Baghdad Boil festers as new enemy of G.I.s
2. Visceral Leishmaniasis Treatment, Italy

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Baghdad Boil festers as new enemy of G.I.s
Juan Gonzalez   [EMAIL PROTECTED]

Iraqis call it the Baghdad Boil or Black Fever - and it's attacking
American soldiers.  In its most virulent form, the rare parasitic
disease, known officially as Visceral Leishmaniasis, or VL, infects
the kidneys and spleen and is usually fatal if left untreated.

A milder form leaves ugly lesions on the skin that can lead to
permanent scarring.  Last month the Pentagon announced that 22 U.S.
soldiers from the Middle East have come down with the milder form
of the disease during the past year - 18 of them in Iraq, mostly
around Baghdad and Nassiriya in the south. The others got sick in
Afghanistan or Kuwait.

But the number infected could be much higher than military brass
is admitting, two Army medics recently returned from Iraq told the
Daily News last week.

"A lot of people are being medivacked for Leishmaniasis," said one
medic, an Army sergeant back in the states on leave who asked not
to be identified.  "In briefing sessions several months ago, we
were told the number of in-country cases was almost 800," he said.

And the most dangerous time for catching the disease is during the
month of November.

According to the second medic, who also is a sergeant, some commanders
are so strapped for manpower, they've started to resist shipping
out all but the sickest soldiers.

Pentagon officials, after revealing the first cases of the disease
among U.S. troops, have banned donations of blood by G.I.s from the
Middle East for at least a year after soldiers return home. "The
issue with those who are exposed is that there is an incubation
period before any symptoms appear," Lt. Col. Ruth Sylvester of the
Armed Services Blood Program said recently.

Any soldier who contracts the disease becomes a carrier and can no
longer donate blood.  With the mild form of the disease, multiple
sores typically form on the legs, arms or face several weeks after
the victim is bitten by an infected sand fly.  Those sores can
persist for years if not treated and eventually form scabs that
leave ugly scars.

Those struck by the virulent form typically experience high fever,
weight loss and an enlarged spleen and liver. Soldiers with confirmed
cases are being shipped to Walter Reed Medical Center, where they
are treated for at least three weeks with intravenous drugs.

Leishmaniasis is prevalent throughout Southwest Asia and Africa,
with about 1.5 million people infected each year, but Iraq has seen
increased outbreaks of the virulent form of the disease in recent
years.

In August, the World Health Organization warned of "a sharp increase
of Visceral Leishmaniasis in various parts of the country."

During the first Persian Gulf War, where far more U.S. soldiers
were deployed than in Iraq, 32 cases of Leishmaniasis were reported,
12 of them the acute form of the disease.

But those troops spent much of their time in unpopulated areas of
the desert during the coolest part of the year, and they dedicated
considerable time to eradicating mosquitoes and flies.

In Iraq, on the other hand, the troops have spent much time in
cities in unbearable heat, amid a population that has seen basic
sanitary systems decimated.

Iraq's cities have become a breeding ground for disease. It may
take years before we know the toll Leishmaniasis and other diseases
have taken on U.S. soldiers.

Originally published on November 25, 2003

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Visceral Leishmaniasis Treatment, Italy
Luigi Gradoni,* Marina Gramiccia,* and Aldo Scalone*
*Istituto Superiore di Sanit`, Rome, Italy
Suggested citation for this article: Gradoni L, Gramiccia M, Scalone A.
Visceral leishmaniasis treatment, Italy. Emerg Infect Dis [serial online]
2003 Dec [date cited]. Available from: URL:
http://www.cdc.gov/ncidod/EID/vol9no12/03-0178.htm

First-line drug treatment was recorded in 573 immunocompetent patients with
visceral leishmaniasis in Italy. In the past 12 years, the proportion of
antimonial treatments decreased from 100% to 2.8%, while the proportion of
amphotericin B treatments increased from 0% to 97.2%. The countrywide change
in therapy is a response to both disease reemergence and increasing
antimonial failure.

Zoonotic visceral leishmaniasis is a life-threatening disease caused by the
multiplication of the protozoan parasite Leishmania infantum in the
phagocytes of the reticuloendothelial system. Infections are widespread in
the Mediterranean subregion, where the parasite is transmitted in summer by
the bites of phlebotomine sand flies, and canids serve as reservoir hosts
(1).

Figure 1

Click to view enlarged image

Figure 1. Reemergence of zoonotic visceral leishmaniasis in Italy: human
cases recorded from 1987 through 2001 by passive reports and active
surveillance...

Figure 2

Click to view enlarged image

Figure 2. Annual proportion of immunocompetent patients with visceral
leishmaniasis...
In the first half of the 20th century, visceral leishmaniasis was a typical
infantile syndrome in Italy with high incidence in southern regions and
islands. After World War II, the incidence dropped to 10 to 20 cases per
year for 4 decades; the disease reemerged with approximately 200 cases in
2000 and 2001 (Figure 1). This trend can be explained by the following: 1)
the appearance of cases in immunocompetent adults that might be attributable
to a general decrease in acquired immunity after the reduction of the
phlebotomine-vector populations, determined by the massive antimosquito
insecticide campaigns for malaria eradication 50 years ago (2); 2) the
spreading of the disease from traditional areas of transmission to new
stable foci in central and northern regions of Italy, as evidenced by recent
colonization of these areas by sand flies and by increased Leishmania
diffusion and prevalence among the canine reservoir (3); and 3) the
occurrence of Leishmania infections in immunosuppressed persons, such as
those co-infected with HIV (4). Incidence of visceral leishmaniasis in these
patients, however, has recently decreased after the introduction of highly
active antiretroviral therapy (Figure 1) (5).
Since the 1940s through 1990, meglumine antimoniate has been the only
first-line drug for visceral leishmaniasis treatment in Italy (6). >From
1991 through 1994, a total of 90 patients of all ages, representing one
third of all immunocompetent visceral leishmaniasis case-patients reported
in Italy during that period, were enrolled in clinical trials of liposomal
amphotericin B (L-AmB), which led to a novel, safe, short course of visceral
leishmaniasis treatment as an alternative to meglumine antimoniate (7,8). In
the same period, other lipid-associated AmB drugs were registered in Italy
for the treatment of fungal infections, i.e., AmB colloidal dispersion
(ABCD) and AmB lipid complex (ABLC). Because no official policy exists for
visceral leishmaniasis therapy in Italy (physicians can prescribe any
registered drug under their own responsibility) and information on drug
regimens used is not included in visceral leishmaniasis case reports, we
aimed to assess whether changes have occurred, and to what extent, in
first-line drug regimens adopted in Italy after lipid-associated AmB was
introduced into clinical practice.
The Study
A retrospective analysis was performed on data collected at the Unit of
Protozoology of Istituto Superiore di Sanit`, Rome, the main reference
center for visceral leishmaniasis surveillance in Italy. Diagnosis of
visceral leishmaniasis in patients with clinically suspected cases was
routinely performed on serum and bone marrow aspirate samples sent by
hospitals, mainly from pediatrics, internal medicine, and infectious
diseases wards, from throughout the country. If visceral leishmaniasis was
confirmed, relevant information on patients was recorded, which included
drug regimens used and posttherapy results. Two datasets were analyzed: the
first included information from patients in whom leishmaniasis was diagnosed
from 1986 to 1990, i.e., before the mass enrollment of patients in the
aforementioned study on L-AmB; the second from patients in whom
leishmaniasis was diagnosed from 1995 to 2001, i.e., after that study.
Immunosuppressed patients (e.g., HIV co-infected persons or transplant
recipients), who usually respond poorly to antileishmanial treatments, were
not included in our analysis. Fisher exact test was used for comparisons.
For the 19861990 period, we recorded treatments used for 40 patients in 22
hospitals, representing 29.2% of 137 immunocompetent persons with visceral
leishmaniasis. Fourteen (35.0%) were children <14 years of age. As expected,
all patients were treated with meglumine antimoniate, given at the standard
dose of 20 mg pentavalent antimony (Sbv)/kg/day for 3 to 4 weeks (6), either
alone (37 patients) or in combination with allopurinol at the daily dose of
15 mg/kg (3 patients). Two patients treated with meglumine antimoniate alone
(5.4%) had a visceral leishmaniasis relapse within 6 months from treatment
and have been retreated successfully with meglumine antimoniate in
combination with allopurinol.
For the 19952001 period, we recorded treatment information for 533
patients, representing a large proportion (56.4%; annual range 43.3% to
69.1%) of 945 immunocompetent visceral leishmaniasis patients. About half
were children (267; annual range in proportion 42.1% to 64.8%). Every year,
patients were referred by 19 to 42 hospitals, with a range of 1 to 30
patients per hospital. Drug regimens recorded are shown in the Table and
summarized in Figure 2. Meglumine antimoniate was the first-line drug used
in 158 patients (29.6%) at the Sbv dosages noted previously; 6 also received
allopurinol (the drug combination was used until 1997). The proportion of
meglumine antimoniate-treated patients has steadily decreased from 55.9% in
1995 to 2.8% in 2001. AmB drugs have been the only alternative drugs used in
the remaining 375 patients (70.4%). Of those patients, L-AmB accounted for
most regimens (348, 92.8%); this drug was administered to both children and
adults at the standard dose of 3 mg/kg/day for 5 consecutive days plus an
additional 3 mg/kg dose on day 10 (7). Slight variations from this regimen
(e.g., 3 mg/kg/day for 710 consecutive days) were recorded in some
case-patients. ABCD and ABLC were given only to adult patients (21 and 3
cases, respectively) both at the dosage of 2 mg/kg/day for 7 days. Thus,
lipid-associated AmB was used to treat 372 patients (69.8%). Finally, three
adult patients were treated with the conventional AmB deoxycholate
formulation (dosages unreported). The proportion of patients treated with
any AmB-based drugs increased from 44.1% in 1995 to 97.2% in 2001.
We recorded the failure of drug therapy in 16 (10.1%) of 158 patients
treated with meglumine antimoniate, equally distributed in children and
adults and with no association with particular geographic location. Five
patients showed primary unresponsiveness or experienced acute toxicity,
which required suspension from treatment, while 11 patients who responded
initially to treatment had a relapse after a variable period of time (range
311 months). All patients were successfully retreated with the standard
L-AmB regimen. Altogether, the rate of meglumine antimoniate failures
recorded in 1995 to 2001 did not differ significantly from that of the
failures in 1986 to 1990. However, the rate significantly increased in
recent years, from 3 (5.3%) of 57  in 1995 to 4 (36.4%) of 11  in 2000 (p =
0.01). Drug treatment was unsuccessful in 12 (3.2%) of 375 AmB-treated
patients, in 2 patients the infection was unresponsive, and 10 patients had
a relapse at 3 to 10 months. This rate was significantly lower than the
meglumine antimoniate failure rate (p = 0.002). Eight of 10 L-AmB treatments
failed in children from different geographic locations. All AmB treatment
failures but one (retreated with meglumine antimoniate) were successfully
retreated with a high-dose L-AmB regimen of 3 mg/kg/day for 10 consecutive
days.
Conclusions
A range of treatment options exists in visceral leishmaniasis, which include
two pentavalent antimonials (meglumine antimoniate and sodium
stibogluconate), four formulations of AmB, aminosidine (paromomycin),
pentamidine, and the new oral agent miltefosine (9,10). For the clinician,
the choice of treatment depends on several factors, such as the clinical
features of the disease, as well as drug safety, efficacy, and cost. In the
absence of any official drug policy for visceral leishmaniasis in Italy and
in consideration of the large sample of patients surveyed, our study may be
the first observational investigation on visceral leishmaniasis therapy at
the national level from 1986 through 2001.
Results have shown a countrywide change in therapy over the period
considered. Even though the change was relatively gradual over a 16-year
period, a traditionally effective drug (meglumine antimoniate) has been
almost fully replaced by a new compound, L-AmB, in an epidemiologic context
of disease reemergence. Possible explanations for this change include the
following: 1) mild or severe adverse reactions (e.g., pancreatitis, cardiac
abnormalities) are commonly seen in meglumine antimoniatetreated patients,
especially in adults, when the recommended dosages are increased even
slightly. A recent investigation in Sicily showed that the
antimony-associated death rate was 7% among HIV-negative adults with or
without underlying diseases (11). On the other hand, the toxicity of
lipid-associated AmB drugs, especially L-AmB, was negligible in all
categories of patients at the dosages used for visceral leishmaniasis
therapy (9). 2) The efficacy of meglumine antimoniate for the treatment of
Mediterranean visceral leishmaniasis has been high (approximately 95%) for
>50 years. However, in the past few years, meglumine antimoniate treatment
failures have increased in visceral leishmaniasis patients from southern
Europe. This treatment failure could be attributable to the widespread use
of meglumine antimoniate in treating infected dogs, which may have caused
the spread of L. infantum strains less susceptible to antimony (1214).
Efficacy of AmB drugs is very high and, so far, decreased Leishmania
susceptibility to this compound (AmB is rarely used in veterinary practice)
has not been indicated. 3) Although L-AmB and other lipidic formulations of
AmB are 30- to 50-fold more expensive than meglumine antimoniate for
visceral leishmaniasis therapy at the dosages reported above, in Western
countries most of the costs of treating visceral leishmaniasis are inpatient
hospitalization expenses rather than drug costs. Therefore, short courses of
6 to 7 days, as required for L-AmB, ABCD, or ABLC (9), are highly
cost-effective if compared with 21- to 28-day courses needed for meglumine
antimoniate treatment.
Dr. Gradoni is the head of the Protozoology Unit in the Parasitology
Department of Istituto Superiore di Sanit` in Rome. His main research
interests are in the epidemiology and control of leishmaniases.
References
Desjeux P. The increase in risk factors for leishmaniasis worldwide. Trans R
Soc Trop Med Hyg 2001;95:23943.
Mansueto S, Barba G, Cerrito B, Farinella E, Orsinis S, Di Rosa S. Visceral
leishmaniasis of adults in Sicily: a truce interrupted? Trans R Soc Trop Med
Hyg 1987;81:1612.
Gradoni L. Epizootiology of canine leishmaniasis in southern Europe. In: R.
Killick-Kendrick, editor. Canine leishmaniasis: an update. Proceedings of
the Canine Leishmaniasis Forum, Barcelona, Spain. Wiesbaden, Germany:
Hoechst Roussel Vet; 1999. p. 329.
Gradoni L, Scalone A, Gramiccia M. Epidemiological surveillance of
leishmaniasis in HIV-1-infected individuals in Italy. AIDS 1996;10:78591.
del Giudice P, Mary-Krause M, Pradier C, Grabar S, Dellamonica P, Marty P,
et al. Impact of highly active antiretroviral therapy on the incidence of
visceral leishmaniasis in a French cohort of patients infected with human
immunodeficiency virus. J Infect Dis 2002;186:136670.
Gradoni L, Bryceson A, Desjeux P. Treatment of Mediterranean visceral
leishmaniasis. Bull World Health Organ 1995;73:1917.
Davidson RN, di Martino L, Gradoni L, Giacchino R, Gaeta GB, Pempinello R,
et al. Short course treatment of visceral leishmaniasis with liposomal
amphotericin B (AmBisome). Clin Infect Dis 1996;22:93843.
Meyerhoff A. U.S. Food and Drug Administration approval of AmBisome
(lipsomal amphotericin B) for treatment of visceral leishmaniasis. Clin
Infect Dis 1999;28:428.
Davidson RN. Practical guide for the treatment of leishmaniasis. Drugs
1998;56:100918.
Jha TK, Sundar S, Thakur CP, Bachmann P, Karbwang J, Fisher C, et al.
Miltefosine, an oral agent, for the treatment of Indian visceral
leishmaniasis. N Engl J Med 1999;341:1795800.
Cascio A, Gradoni L, Scarlata F, Gramiccia M, Giordano S, Russo R, et al.
Epidemiologic surveillance of visceral leishmaniasis in Sicily, Italy. Am J
Trop Med Hyg 1997;57:758.
Gramiccia M, Gradoni L, Orsini S. Decreased sensitivity to meglumine
antimoniate (Glucantime) of Leishmania infantum isolated from dogs after
several courses of drug treatment. Ann Trop Med Parasitol 1992;86:613-20.
Faraut-Gambarelli F, Piarroux R, Deniau M, Giusiano B, Marty P, Michel G, et
al. In vitro and in vivo resistance of Leishmania infantum to meglumine
antimoniate: a study of 37 strains collected from patients with visceral
leishmaniasis. Antimicrob Agents Chemother 1997;41:82730.
Carris J, Portzs M. In vitro susceptibility to pentavalent antimony in
Leishmania infantum strains is not modified during in vitro or in vivo
passages but is modified after host treatment with meglumine antimoniate.
BMC Pharmacol 2002;2:11.

Table. First-line drugs used for treatment of visceral leishmaniasis in 533
immunocompetent patients in Italy and drug treatment failures recordeda

YMA (%)L-AmBABCDABLCdAmBAny AmB drugs (%)

199557 (55.9)
3 R45
1 R00045 (44.1)
1 R
199635 (50.0)
2 R35
1 R00035 (50.0)
1 R
199726 (39.4)
3 U, 1 R34
2 R50140 (60.6)
2 R
199814 (28.0)
1 R32
1 R40036 (72.0)
1 R
199913 (21.0)
1 U, 1 R45
2 R 21149 (79.0)
2 R
200011 (9.8)
1 U, 3 R89
1 U, 1 R10
1 U1
1 R1101 (90.2)
2 U, 2 R
20012 (2.8)68
1 R01069 (97.2)
1 R
Total158 (29.6) 5 U, 11 R348
1 U, 9 R21
1 U3
1 RS3375 (70.4)
2 U, 10 R

aMA, meglumine antimoniate; L-AmB, liposomal amphotericin B; ABCD,
amphotericin B colloidal dispersion; ABLC, amphotericin B lipid complex;
dAmB, amphotericin B desoxycholate; U, unresponsiveness and/or acute
toxicity; R,

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