Published Date: 2001-07-28 23:50:00
Subject: PRO/EDR> Malaria, chloroquine resistant, fatal - USA ex Africa
Archive Number: 20010728.1475

MALARIA, CHLOROQUINE RESISTANT, FATAL - USA EX AFRICA
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See Also

2001
---
Malaria, chloroquine resistant - Burundi 20010628.1233
Malaria, chloroquine resistant - Tanzania 20010514.0935
2000
----
Malaria, chloroquine resistant - Tanzania 20000430.0657
Malaria, chloroquine resistant - Tanzania (02) 20000706.1120
1999
----
Malaria, chloroquine resistant - Kenya 19990719.1213
Malaria, chloroquine resistant - Kenya (04) 19990726.1264
Malaria, drug resistant - Africa: overview 19990320.0444
Date: Sun, 22 Jul 2001
From: ProMED-mail <promed@promedmail.org>
Source: MMWR 50(28);597-9 [edited
<http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5028a1.htm>

During January-March 2001, 2 U.S. citizens died from malaria after
taking chloroquine alone or with proguanil for malaria
chemoprophylaxis in countries with known chloroquine-resistant
_Plasmodium falciparum_ malaria.
Chloroquine-containing chemoprophylaxis regimens are not recommended
by CDC for persons traveling to areas with known
chloroquine-resistant _P. falciparum_. This report summarizes the
investigation of the 2 cases and underscores the need for clinicians
and travelers to know the recommended options for malaria
chemoprophylaxis when traveling to locations with
chloroquine-resistant malaria.
Case Reports
----------------
Case 1. On 11 Jan 2001, a 12-year-old was taken to a clinic with a
2-day history of fever with chills, malaise, fatigue, cough, and one
episode of vomiting. At the clinic, the patient had a temperature of
102 F (39 C). The clinician noted that the patient had returned from
Africa on 6 Jan 2001. Upper respiratory tract infection was diagnosed
with nausea and vomiting, and the patient was prescribed an oral
cephalosporin antibiotic and an antiemetic agent. The symptoms
continued, and on 14 Jan 2001, the patient collapsed, was transported
to a local hospital, and died in the emergency
department shortly thereafter.
Examination of a peripheral blood film on stored blood from 11 Jan
2001 and a film from blood taken 14 Jan 2001 demonstrated _P.
falciparum_ parasites with 0.8% parasitemia and 14.0%, respectively.
The patient had been born in Nigeria, had emigrated to the United
States in 1991, and had returned to Nigeria for 3 weeks during
December 2000--January 2001. The patient and 5 other family members
who had traveled to Nigeria had been prescribed weekly chloroquine for
malaria chemoprophylaxis. On 1 Dec 2001, the patient had taken the
initial 500 mg dose and subsequently had followed the weekly regimen;
the last dose was taken 11 Jan 2001.
A blood sample taken postmortem revealed a chloroquine level of 1782
ng/ml whole blood, a level consistent with recent ingestion of
chloroquine and sufficient to inhibit
_P. falciparum_ parasites sensitive to the drug (1,2). The patient's
mother also had taken chloroquine for chemoprophylaxis, had _P.
falciparum_ malaria diagnosed in January, and later recovered.
Case 2. On 7 Mar 2001, a 47-year-old returned to the United States
after 11 days in east Africa. Chloroquine was taken before and during
the trip and proguanil was added on arrival in Africa. On returning to
the United States, proguanil was discontinued, and on 11 Mar 2001,
the scheduled dose of chloroquine was taken. On 17 Mar 2001, the
patient developed a persistent headache, and on 19 Mar 2001, sought
care for headache and dark urine at a hospital emergency department.
On admission, the patient's temperature was 102 F (39 C); physical
examination did not reveal any abnormalities.
A thick blood film obtained on admission initially was read as
Plasmodium species (_P. falciparum_ versus _P. malariae_), and later
was confirmed as _P. falciparum_. The patient was admitted and treated
with oral quinine and doxycycline; however, the patient developed
cerebral edema and respiratory failure and died 6 days after
admission.
The patient had traveled to Africa with a group of 13 persons; 9 had
taken mefloquine for prophylaxis and 4 had followed the same regimen
as the patient. No other malaria cases were reported from the group.
CDC Editorial Note:
A total of 7 malaria-related deaths among U.S. citizens who had
traveled abroad following inappropriate chemoprophylaxis regimens have
been reported to CDC since 1992. In all cases, the travelers received
prescriptions for chloroquine compounds to be taken for travel to
sub-Saharan Africa, where antimalarial resistance to this drug is
widespread. The geographic spread of _P. falciparum_resistance to
chloroquine is increasing.
Chloroquine resistance exists throughout sub-Saharan Africa, southeast
Asia, the Indian subcontinent, and over large portions of South
America, including the Amazon basin (3). Among 4685 cases of imported
malaria in U.S. civilian travelers during 1992--2001, 893 (19%) took
an inappropriate chemoprophylaxis regimen and 2616 (56%) took no
chemoprophylaxis.
Among 505 persons who took an inappropriate chemoprophylaxis regimen
during
1995--2001, 351 (70%) took chloroquine for travel to an area with
known chloroquine resistance. Since 1990, CDC has recommended
mefloquine as antimalarial prophylaxis in regions with
chloroquine-resistant malaria; doxycycline has been the recommended
alternative (4). Chloroquine, ideally taken with daily proguanil (an
antimalarial not marketed in the United States except in coformulation
with atovaquone), had been recommended only for persons unable to take
mefloquine or doxycycline. In July 2000, Malarone (Glaxo Wellcome
Inc., Research Triangle Park, North Carolina), a combination of
atovaquone and proguanil, was approved for use in the United States.
*****
Since November 2000, CDC has recommended Malarone, mefloquine, or
doxycycline as options for malaria chemoprophylaxis in areas with
chloroquine-resistant malaria and *no* longer recommends chloroquine
combined with proguanil (5).
*****
Travelers and health-care workers who provide medical advice to
travelers should be aware that chloroquine is effective for malaria
prophylaxis only in a few areas of the world. Recommending and
prescribing inappropriate chemoprophylaxis can result in travelers
becoming ill or dying from malaria. Information on malaria prevention
and
chemoprophylaxis is available in Health Information for International
Travel, CDC's handbook for travelers, which is published bi-annually
and is available and updated online at <http://www.cdc.gov/travel>.
Information also is available by telephoning (877) FYI-TRIP ([877
394-8747).
References
(1) Hellgren U, Kihamia CM, Mahikwano LF, Bjorkman A, Eriksson O,
Rombo L.
Response of _Plasmodium falciparum_ to chloroquine treatment: relation
to whole blood concentrations of chloroquine and desethylchloroquine.
Bull World Health Organ 1989;67:197--202.
(2) Krishna S, White NJ. Pharmacokinetics of quinine, chloroquine, and
amodiaquine: clinical implications. Clin Pharmacokinet
1996;30:263--92.
(3) CDC. Health information for international travel 1989. Atlanta,
Georgia: US
Department of Health and Human Services, Public Health Service, 1989.
(4) CDC. Information for health care providers: Malarone for malaria
treatment and prophylaxis, October 2000. Available at
<http://www.cdc.gov/travel/diseases/malaria/malarone.htm>. Accessed 3
Jan
2001.
(5) CDC. Health information for international travel 2001--2002.
Atlanta, Georgia: US Department of Health and Human Services, Public
Health Service,
2001.
--
ProMED-mail
<promed@promed.org>
[The 2 cases sadly illustrate the need for physicians in non-endemic
countries to think of malaria and ask for the travel history in every
febrile patient. It's noteworthy that one of the cases travelled to
East Africa, where chloroquine is no longer used for treatment due to
low efficacy. Clearly from the results presented in CDC's editorial
note, 75% of imported malaria cases in the USA were potentially
preventable.
European statistics show that the case fatality rate of _P.
falciparum_ malaria imported to Europe varies between 0.5% and 4%;
there is no data on the case fatality rate in travellers and the
number of deaths during travel. Europe imported pproximately 20 000
malaria cases in 1999 and the United States about 1500 in 1997.
Chloroquine resistance has been spreading in tropical Africa, and
malaria prophylaxis has become more complicated. - Mods.EP, MPP
.............................................mpp/ep/pg/jw

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